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Monte Carlo validation of a multireader method for receiver operating characteristic discrete rating data: factorial experimental design.

RATIONALE AND OBJECTIVES: The authors conducted a series of null-case Monte Carlo simulations to evaluate the Dorfman-Berbaum-Metz (DBM) method for comparing modalities with multireader receiver operating characteristic (ROC) discrete rating data. MATERIALS AND METHODS: Monte Carlo simulations were performed by using discrete ratings on fully crossed factorial designs with two modalities and three, five, and 10 hypothetical readers. The null hypothesis was true for all simulations. The population ROC areas, latent variable structures, case sample sizes, and normal/abnormal case sample ratios used in another study were used in these simulations. RESULTS: For equal allocation ratios and small (Az = 0.702) and moderate (Az = 0.855) ROC areas, the empirical type I error rate closely matched the nominal alpha level. For very large ROC areas (Az = 0.961), however, the empirical type I error rate was somewhat smaller than the nominal alpha level. This conservatism increased with decreasing case sample size and asymmetric normal/abnormal case allocation ratio. The empirical type I error rate was sometimes slightly larger than the nominal alpha level with many cases and few readers, where there was large residual, relatively small treatment-by-case interaction and relatively large treatment-by-reader interaction. CONCLUSION: The results suggest that the DBM method provides trustworthy alpha levels with discrete ratings when the ROC area is not too large and case and reader sample sizes are not too small. In other situations, the test tends to be somewhat conservative or slightly liberal.

Diagnostic Imaging↗

Development of the pulmonary surfactant system in non-mammalian amniotes.

Pulmonary surfactant (PS) is a complex mixture of phospholipids, neutral lipids and proteins that lines the inner surface of the lung. Here, it modulates surface tension thereby increasing lung compliance and preventing the transudation of fluid. In mammals, the PS system develops towards the end of gestation, characterized by an increase in the saturation of phospholipids in lung washings and the appearance of surfactant proteins in amniotic fluid. Birth, the transition from in utero to the external environment, is a rapid process. At this time, the PS system is important in opening and clearing the lung of fluid in order to initiate pulmonary ventilation. In oviparous vertebrates, escape from an egg can be a long and exhausting process. The young commence pulmonary ventilation and hatching by 'pipping' through the eggshell, where they remain for some time, presumably clearing their lungs. This paper relates changes in the development of the pulmonary surfactant system within the non-mammalian amniotes in response to birth strategy, lung morphology and phylogeny in order to determine the conservatism of this developmental process. Total phospholipid (PL), disaturated phospholipid (DSP) and cholesterol (Chol) were quantified from lung washings of embryonic and hatchling chickens, bearded dragons (oviparous), sleepy lizards (viviparous), snapping turtles and green sea turtles throughout the final stages of incubation and gestation. In all cases, the pattern of development of the pulmonary surfactant lipids was consistent with that of mammals. PL and DSP increased throughout the latter stages of development and Chol was differentially regulated from the PLs. Maximal secretion of both PL and DSP occurred at 'pipping' in oviparous reptiles, coincident with the onset of airbreathing. Similarly, the amount of DSP relative to total PL was maximal immediately after the initiation of airbreathing in chickens. The relative timing of the appearance of the lipids differed between groups. In the oviparous lizard, surfactant lipids were released over a relatively shorter time than that of the sleepy lizard, turtles, birds and mammals. Thus, despite temporal differences and vastly different lung morphologies, birth strategies and phylogenies, the overall development and maturation of the PS system is highly conserved amongst the amniotes.

Animals↗

Membrane heredity and early chloroplast evolution.

Membrane heredity was central to the unique symbiogenetic origin from cyanobacteria of chloroplasts in the ancestor of Plantae (green plants, red algae, glaucophytes) and to subsequent lateral transfers of plastids to form even more complex photosynthetic chimeras. Each symbiogenesis integrated disparate genomes and several radically different genetic membranes into a more complex cell. The common ancestor of Plantae evolved transit machinery for plastid protein import. In later secondary symbiogeneses, signal sequences were added to target proteins across host perialgal membranes: independently into green algal plastids (euglenoids, chlorarachneans) and red algal plastids (alveolates, chromists). Conservatism and innovation during early plastid diversification are discussed.

Biological Evolution↗

An engineering view of pharmaceutical powder mixing.

Can the pharmaceutical industry learn anything from other powder processing industries? Although essential regulatory processes have ensured that the pharmaceutical industry is a leader in quality assurance, they have also led to a conservative approach to process technology. Conservatism is advantageous when the dosage form and profit margins are stable; however, for most other industries, form, price and quality of product are all subject to fickle customer requirements. Other powder industries have used a sequential questioning approach to elicit new technical responses to change. Perhaps the time is ripe for this to be introduced to the pharmaceutical industry?

Journal Article↗

Determinants of the ability of general practitioners to detect psychiatric illness.

This study of psychiatric illness among 4098 patients attending 91 general practitioners compares 2 methods of case identification: 'conspicuous morbidity' by the doctor's own assessments, and 'probable prevalence' by the patients' responses to the General Health Questionnaire (GHQ). In general, the latter gives somewhat higher estimates than the former, but there are wide variations in morbidity between practices. The ability of each general practitioner to detect psychiatric illness was measured by computing Spearman's correlation coefficient between his assessments and the GHQ scores of his patients. The mean correlation coefficient was + 0.36, but the range was very wide (0.09-0.60). The first part of the study deals with various demographic characteristics of the patients themselves which are associated with an increased likelihood of the doctor detecting a psychiatric illness; such factors include unemployment, female sex, and marriages which have ended by separation, divorce or death. The second part of the study examines characteristics of the doctors themselves in an attempt to account for the wide variation between them in their ability to detect psychiatric illness. A research psychiatrist made detailed observations on 2098 interviews carried out by 55 general practitioners. Each doctor's verbal and non-verbal styles were recorded minutely, and in addition various global ratings were made. The doctors completed personality inventories and supplied details of training and professional background. It was possible to account for 67% of the variance of correlation coefficient mainly in terms of 2 dimensions: 'interest and concern' and 'conservatism'. The way in which the doctor interviews his patients is shown to be important, but there are interactions between interview style and the doctor's personality.

Adolescent↗

A multiple process solution to the logical problem of language acquisition.

Many researchers believe that there is a logical problem at the centre of language acquisition theory. According to this analysis, the input to the learner is too inconsistent and incomplete to determine the acquisition of grammar. Moreover, when corrective feedback is provided, children tend to ignore it. As a result, language learning must rely on additional constraints from universal grammar. To solve this logical problem, theorists have proposed a series of constraints and parameterizations on the form of universal grammar. Plausible alternatives to these constraints include: conservatism, item-based learning, indirect negative evidence, competition, cue construction, and monitoring. Careful analysis of child language corpora has cast doubt on claims regarding the absence of positive exemplars. Using demonstrably available positive data, simple learning procedures can be formulated for each of the syntactic structures that have traditionally motivated invocation of the logical problem. Within the perspective of emergentist theory (MacWhinney, 2001), the operation of a set of mutually supportive processes is viewed as providing multiple buffering for developmental outcomes. However, the fact that some syntactic structures are more difficult to learn than others can be used to highlight areas of intense grammatical competition and processing load.

Child Language↗

Who favors legalizing physician-assisted suicide? The vote on Michigan's Proposal B.

At the November 1998 general election, Michigan citizens were given the opportunity to vote on Proposal B, an initiative that would have legalized physician-assisted suicide (PAS). PAS initiatives also have been held in Washington State, California, Oregon, and Maine, with only Oregon's passing. We use exit poll data to analyze the vote on Proposal B. Attributes associated with social liberalism -- Democratic Party identification, less frequent church attendance, more education, and greater household income -- led to increased odds of a "yes" vote. Attributes associated with social conservatism -- Republican Party identification and frequent church attendance -- led to decreased odds of a "yes" vote. Similar to the abortion issue, PAS's supporters strongly value personal autonomy, whereas its opponents strongly value the sanctity of life. Voter alignments like those in Michigan will likely appear in other states with the initiative process if PAS reaches their ballots.

Data Collection↗

Isolation and characterization of the histone variants in chicken erythrocytes.

Chicken erythrocyte histones 2A, 2B, and 3 can be resolved into nonallelic primary structure variants by polyacrylamide gel electrophoresis in the presence of Triton X-100. These variants were isolated and characterized by analysis of their tryptic and thermolytic peptides. The major variants of chicken H2A and H2B differ from the analogous component of calf thymus by a small number of conservative amino acid substitutions in the basic terminal regions, which interact with DNA. This moderate rate of allelic evolution of the slightly lysine-rich histones contrasts with the complete conservatism found in the arginine-rich histones. Chicken H4 and both chicken H3 variants are identical with their corresponding components in mammals. The amino acid substitutions distinguishing histone variants are located within the highly conserved hydrophobic regions, which are involved in histone--histone interactions.

Amino Acids↗

Histone-histone interactions in a lower eukaryote, Tetrahymena thermophila.

The six pairwise interactions of Tetrahymena macronuclear histones H2A (formerly HX), H2B, H3, and H4 have been studied using the techniques of circular dichroism and continuous variation. Parallel experiments have been performed with calf thymus histones as controls, and the 12 possible interspecies pairs have also been examined. The behavior of three of the ciliate histones, H2A, H2B, and H3 is virtually identical with that of their vertebrate counterparts. Tetrahymena H4 exhibits a pattern of interactions identical with that of calf thymus H4, but displays significant quantitative differences in the strength of those interactions. Although we have not entirely eliminated the possibility that these differences may be artifactual, we suggest that they reflect the unique primary structure of Tetrahymena H4. These results extend the pattern of histone-histone interactions defined for plants, animals, and fungi to include the protists as well and imply the strong evolutionary conservatism of this pattern in spite of the electrophoretic and compositional differences which exist between homologous histones of different organisms. In addition, they demonstrate conclusively that histone HX should be redefined as Tetrahymena H2A.

Animals↗

Reliability analysis for hazardous waste treatment processes.

The reliability of a treatment process is addressed in terms of achieving a regulatory effluent concentration standard and the design safety factors associated with the treatment process. This methodology was then applied to two aqueous hazardous waste treatment processes: packed tower aeration and activated sludge (aerobic) biological treatment. The designs achieving 95 percent reliability were compared with those designs based on conventional practice to determine their patterns of conservatism. Scoping-level treatment costs were also related to reliability levels for these treatment processes. The results indicate that the reliability levels for the physical/chemical treatment process (packed tower aeration) based on the deterministic safety factors range from 80 percent to over 99 percent, whereas those for the biological treatment process range from near 0 percent to over 99 percent, depending on the compound evaluated. Increases in reliability per unit increase in treatment costs are most pronounced at lower reliability levels (less than about 80 percent) than at the higher reliability levels (greater than 90 percent, indicating a point of diminishing returns. Additional research focused on process parameters that presently contain large uncertainties may reduce those uncertainties, with attending increases in the reliability levels of the treatment processes.

Aerobiosis↗

Bioinformatics and molecular modeling in chemical enzymology. Active sites of hydrolases.

Comparison and multiple alignments of amino acid sequences of a representative number of related enzymes demonstrate the existence of certain positions of amino acid residues which are permanently reproducible in all members of the whole family. The use of the bioinformatic approach revealed conservative residues in each of the related enzymes and ranked amino acid conservatism for the overall enzymatic catalysis. Glycine and aspartic acid residues were shown to be the most essential for structure and catalytic activity of enzymes. Amino acid residues forming catalytic subsite of the active site of enzymes are always highly conservative. Analysis revealed that aspartic acid carboxyl group is the most frequently employed nucleophilic (in deprotonated form) and electrophilic (in protonated form) agent involved in activation of molecules by the mechanism of general base and acidic catalyses in the catalytic sites of enzymes. Glycine is a unique amino acid possessing the highest possibilities for rotation along C-C and C-N bonds of the polypeptide chain. The conservative fixation of the glycine residue in polypeptide chains of related enzymes provides a possibility for directed assembly of amino acid residues into the catalytic subsite structure. It is possible that the conservative glycines provide known conformational mobility of the protein and the active site. Methods of molecular modeling were used for analysis of structural substitutions of conservative and non-conservative glycines and their effects on geometry of catalytic site of typical hydrolases. The substitution of glycine(s) for alanine significantly altered the catalytic site structures.

Binding Sites↗

The "mad" vs. the "bad" revisited: managing predatory behavior.

Ever since the Englightenment, western democracies have maintained separate institutions for the "mad" and for the "bad." For the mad they provided protection and treatment, and for the bad, deterrence and punishment. During the past decade, however, increasing social conservatism and the apparent failure of the criminal justice system have resulted in a series of changes in social policy. In order to protect the public adequately from repeatedly violent predators, legislation has been introduced in several states that remands those predators to mental institutions on completion of their prison terms. Challenges to this legislation, based on ex post facto, double jeopardy, and civil rights considerations were effectively dismissed by the U.S. Supreme Court in Kansas v Hendricks in June, 1997. An effect, however unintended, of upholding these laws and of policy changes leading up to them, is that they have effectively blurred the separation between mad and bad. This paper details the following: 1) the events that have led to these changes in policy and law; 2) the preparations being made in New York State's mental health system to prepare for managing such predators when and if such laws are enacted; 3) the dangers and drawbacks these changes have brought in states where they have already been legislatively mandated; and 4) suggestions for alternatives that would reaffirm the separation between mad and bad.

Adult↗

Characterization of furanocoumarin metabolites in parsnip webworm, Depressaria pastinacella.

Although metabolites of furanocoumarins have been characterized in a wide range of organisms, to date they have been identified in only a single insect species, Papilio polyxenes. Depressaria pastinacella, the parsnip webworm, like P. polyxenes a specialist on Apiaceae, routinely consumes plant tissues higher in furanocoumarin content than does P. polyxenes and is capable of faster cytochrome P-450-mediated detoxification of these compounds. In this study, we characterized metabolites of xanthotoxin, a linear furanocoumarin, and sphondin, an angular furanocoumarin, in midguts and frass of parsnip webworms. Two metabolites were isolated and identified from webworms fed artificial diet containing xanthotoxin. LC-ESI-MS analysis resulted in the determination of a MW of 266 for the compound in the frass and one of the compounds in the midgut; 1H NMR confirmed its structure as 6-(7-hydroxy-8-methoxycoumaryl)-hydroxyacetic acid (HCHA). The second compound from the midgut had a MW of 252 and was identified by 1H NMR and 13C NMR analysis as 6-(7-hydroxy-8-methoxycoumaryl)-hydroxyethanol) (HMCH). Whereas HCHA has been found in frass of Papilio polyxenes fed xanthotoxin, HMCH has not been reported previously in insects. Although the first step of metabolism of xanthotoxin in webworms as well as P. polyxenes is likely the formation of an epoxide on the furan ring, angular furanocoumarin metabolism in webworms appears to differ. The principal metabolite of sphondin was identified as demethylated sphondin (6-hydroxy-2H-furo[2,3-h]-1-benzopyran-2-one) by LC-ESI-MS and confirmed by 1H NMR and 13C NMR analyses. That webworms produce metabolites of xanthotoxin in common not only with other Lepidoptera (e.g., HCHA) but with other vertebrates (e.g., HMCH) suggests a remarkable conservatism in the metabolic capabilities of cytochrome P-450s and raises the possibility that insects may share other detoxification reactions with vertebrates with respect to toxins in foodplants.

Animals↗

College student perceptions of crime and casino gambling: a preliminary investigation.

To gain insight into how attitudes toward casino gambling vary by an area's experience with gambling, a survey was given to 415 university students at the University of Nevada, Reno, and 420 students at the University of Memphis. Casino gambling has been legal in Reno since 1931, but was introduced in the Memphis area in 1992. Given the differences in duration and degree of integration of casinos in each area, significant differences were expected by area in respondents' perceptions of casinos and casino gambling. While some significant differences were found, the most prominent finding is the degree of similarity of attitudes of students in each university and the high percentage in each sample that associated casino gambling with types of crime. Where significant differences did exist, the findings are interpreted as supporting either an exposure hypothesis or a cultural conservatism hypothesis.

Journal Article↗

Solidarity, society and the welfare state in the United Kingdom.

Political argument and institutions in the United Kingdom have frequently been represented as the products of a blend of nationalistic conservatism, liberal individualism and socialism, in which consensus has been prized over ideology. This situation changed, as the standard story has it, with the rise of Thatcherism in the late 1970s, and again with the arrival of Tony Blair's "New Labour" pragmatism in the late 1990s. Solidarity as an element of political discourse makes its appearance in the UK late in the day. It has been most strongly linked to the Third Way debate, as framed most influentially in the work of Prof. Anthony Giddens. In this paper we review the history and pre-history of the debate on solidarity in the UK, focussing mostly on its implications for welfare state reform. In particular we discuss the proposals for the long-term care of the Elderly issued by the Royal Commission on long-term care in 1999. In this context we critically examine the idea that solidarity is a new concept in British political culture, and that it is a concept which has real political "bite" in the project of welfare reform. We examine this through a consideration of Gidden's attempted synthesis of political argument and social theory.

Aged↗

Molecular characterization of contaminant-indicative RAPD markers.

This paper describes genetic markers which can be used to study selection and genetic adaptation of organisms to radionuclide and other types of contaminant stress. Previous research using the randomly amplified polymorphic DNA (RAPD) technique has identified several markers which revealed genetic differences between contaminated and reference western mosquitofish (Gambusia affinis) populations. Experimental evidence suggested that these markers may be associated with loci involved in determining relative fitness in radionuclide-contaminated environments ("contaminant-indicative markers"). In the present study, Southern blot analyses show these markers to be highly conserved in DNA sequence and molecular length in sea urchins, mosquitofish, herring gulls and humans. Such conservation is thought to be rare among RAPD bands. Results of DNA sequencing efforts did not provide definitive evidence as to the identity of these loci, but indicated that short segments (<40 bp) of known DNA sequences were homologous to various regions of the RAPD sequences. Furthermore, the regions of homology seemed to be non-randomly distributed along the length of the RAPD markers. Although the identity of these bands is still unknown, the high degree of conservatism suggests that these loci might play an important role in molecular processes.

Animals↗

Comparative analysis (Hippotragini versus Caprini, Bovidae) of X-chromosome's constitutive heterochromatin by in situ restriction endonuclease digestion: X-chromosome constitutive heterochromatin evolution.

The Bovidae X-chromosome shows a considerable variation, in contrast to the preservative autosomal conservatism. The X-chromosome variation is mostly a consequence of the constitutive heterochromatin (CH) variation; in what respect to its amount and position. This is especially common among the non-Bovinae subfamilies and tribes. In order to characterize the X-chromosome CH in non-Bovinae species--Hippotragini and Caprini tribes--we have used restriction endonuclease digestion on fixed chromosomes and sequential C-banding. With these techniques we were able to distinguish between the two X-chromosome types (Hippotragini and Caprini) CH, in what respect to its position and molecular nature. Moreover, we define at least, six subclasses of CH in both X-chromosome types analyzed. Evolutionary considerations were draw based on the results obtained. The technology used here for the analysis of the Bovidae X-chromosome CH showed to be more evolutionary informative than the classical approaches.

Animals↗

[Kidney and urinary tract diseases in pregnancy].

Management of urologic disorders in pregnant patients often increases the anxiety of all involved. Based on a thorough understanding of the physiologic changes seen in various organ systems the urologist has to assume the responsibility for the well-being of the mother and the fetus. Apart from the urinary tract infection, which occurs as frequent as in non-pregnant patients but has a significantly higher risk of acute bacterial pyelonephritis, it is mainly the pregnancy-associated symptomatic hydronephrosis and the urolithiasis which are complicating approximately 1 of every 1000-1500 pregnancies. Urinary tract infections should be treated in any case by antibiotics according to a antibiogram. High risk patients with history of vesicoureteral reflux or recurrent pyelonephritis should be treated prophylactically. Following parturition these patients should be investigated urologically to exclude structural abnormalities of the genitourinary system. In case of symptomatic hydronephrosis and calculous disease the first approach should be a watchful conservatism with symptomatic relief. If the symptoms persist insertion of a double-J-stent or in case of live-threatening situations (e.g. urosepsis) when urgent decompression and rapid evacuation is mandatory a percutaneous nephrostomy can be brought in place under sonographic monitoring completely thereby avoiding any radiation exposure.

Adult↗