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PubMed1996

The corporate practice of health care ... a panel discussion.

The pros and cons of treating health care as a profit-making business got a lively airing in Boston May 16, when the Harvard School of Public Health's "Second Conference on Strategic Alliances in the Evolving Health Care Market" presented what was billed as a "Socratic panel." The moderator was Charles R. Nesson, J.D., a Harvard Law School professor of 30 years' standing whose knack for guiding lively discussions is well known to viewers of such Public Broadcasting Service series as "The Constitution: That Delicate Balance. "As one panelist mentioned, Boston was an interesting place for this conversation. With a large and eminent medical establishment consisting mostly of traditionally not-for-profit institutions, the metropolis of the only state carried in 1972 by liberal Presidential candidate George McGovern is in one sense a skeptical holdout against the wave of aggressive investment capitalism that has been sweeping the health care industry since the 1994 failure of the Clinton health plan. In another sense, though, managed care-heavy Boston is an innovative crucible of change, just like its dominant HMO, the not-for-profit but merger-minded Harvard Pilgrim Health Care. Both of these facets of Beantown's health care psychology could be discerned in the comments heard during the panel discussion. With the permission of the Harvard School of Public Health--and asking due indulgence for the limitations of tape-recording technology in a room often buzzing with amateur comment--MANAGED CARE is pleased to present selections from the discussion in the hope that they will shed light on the business of health care.

Community-Institutional Relations↗

PubMed2006

Cyto-nuclear epistasis: two-locus random genetic drift in hermaphroditic and dioecious species.

We report the findings of our theoretical investigation of the effect of random genetic drift on the covariance of identity-by-descent (ibd) of nuclear and cytoplasmic genes. The covariance in ibd measures of the degree to which cyto-nuclear gene combinations are heritable, that is, transmitted together from parents to offspring. We show how the mating system affects the covariance of ibd, a potentially important aspect of host-pathogen or host-symbiont coevolution. The magnitude of this covariance influences the degree to which the evolution of apparently neutral cytoplasmic genes, often used in molecular phylogenetics, might be influenced by selection acting on unlinked nuclear genes. To the extent that cyto-nuclear gene combinations are inherited together, genomic conflict is mitigated and intergenomic transfer it facilitated, because genes in both organelle and nuclear genomes share the same evolutionary fate. The covariance of ibd also affects the rate at which cyto-nuclear epistatic variance is converted to additive variance necessary for a response to selection. We find that conversion is biased in species with separate sexes, so that the increment of additive variance added to the nuclear genome exceeds that added to the cytoplasmic genome. As a result, the host might have an adaptive advantage in a coevolutionary arms race with vertically (maternally) transmitted pathogens. Similarly, the nuclear genome could be a source of compensatory mutations for its organellar genomes, as occurs in cytoplasmic male sterility in some plant species. We also discuss the possibility that adaptive cytoplasmic elements, such as favorable mitochondrial mutations or endosymbionts (e.g., Wolbachia), have the potential to release heritable nuclear variation as they sweep through a host population, supporting the view that cytoplasmic introgression plays an important role in adaptation and speciation.

Alleles↗

PubMedDate not supplied

Linear sweep voltammetric studies on the interaction of brilliant cresyl blue with nucleic acids and its analytical application.

In this paper, the interaction of brilliant cresyl blue (BCB) with nucleic acids was studied and further applied for the microdetermination of nucleic acids. In aqueous Britton-Robinson (B-R) buffer solution, BCB can be easily reduced on the hanging mercury drop electrode (HMDE) and had a sensitive voltammetric reduction peak at -0.09 V (vs. SCE). The reduction peak current of BCB could be greatly decreased by the addition of DNA. The results of voltammetric measurements had indicated that a binding reaction was occurred between BCB and DNA and a new supramolecular complex was formed, which resulted in the decrease of the diffusion coefficient of the reaction solution and the decrease of the reduction peak current correspondingly. The conditions of interaction and the electrochemical detection were carefully investigated. Under the selected conditions, the calibration curves for the detection of fish sperm (fs)DNA, calf thymus (ct)DNA and yeast (y)RNA were established. The linear range of this assay was 1.0-30.0 microg/mL for fsDNA, 1.0-45.0 microg/mL for ctDNA and 1.0-25.0 microg/mL for yRNA, respectively. The detection limits were 0.38 microg/mL fsDNA, 0.43 microg/mL ctDNA, 0.64 microg/mL yRNA. The interaction parameters such as the equilibrium constant and the binding number were calculated by electrochemical method. The results showed that the 2:3 type of complex was formed in the fsDNA-BCB complex with the binding constant as 2.51 x 10(7). The proposed method was further applied to the synthetic samples determination with satisfactory results.

Animals↗

PubMed2005

Acoustic reflexes to Schroeder-phase harmonic complexes in normal-hearing and hearing-impaired individuals.

Harmonic complexes generated with positive or negative Schroeder-phases may result in differences in cochlear excitation, even though their long-term spectra and amplitudes are equal. As a measure of possible differences in cochlear excitation resulting from these harmonic complexes, thresholds and growth of the acoustic reflex were assessed in normal-hearing and hearing-impaired subjects. Harmonic complexes with fundamental frequencies of 50, 100, and 200 Hz were constructed with positive and negative-Schroeder phases. In normal-hearing subjects, acoustic reflex thresholds for the 50- and 100-Hz fundamental waveforms were typically lower for negative Schroeder-phase complexes than for positive Schroeder phase stimuli. At the highest fundamental frequency of 200 Hz, there were no significant threshold differences due to phase. Hearing-impaired subjects showed a similar pattern for thresholds between the two phase selections, but with smaller differences than those observed in normal-hearing subjects. At levels above reflex threshold, the magnitude of the acoustic reflex was greater for the negative-phase than the positive-phase stimuli for the lowest fundamental frequency, but no significant differences were observed at fundamental frequencies of 100 and 200 Hz. These results are consistent with generally greater cochlear excitation in response to negative than to positive Schroeder-phase stimuli when the fundamental frequency is sufficiently low. Increased excitation may reflect a synchronization of response across a wide band of frequencies in the cochlea when the rate of frequency sweep within periods of these harmonic complexes is appropriately matched to timing characteristics of the traveling wave.

Acoustic Stimulation↗

PubMed1981

ONe-step isolation of human chopionic ganadotropin in milligram amounts, using selective steady-state stacking on polyacrylamide gel.

Human chorionic gonadotropin (hCG) has been isolated in a single step from a crude, commercially available urinary preparation. The isolated hormone, and highly purified standard hormone preparations, each exhibit on PAGE (pH 5.5), as on electrofocusing, 3 to 5 major "change isomeric" species within preparations. In addition, PAGE (pH 5.5) detects differences in molecular size between charge isomeric species of identical net charge occurring in the various preparations. For the purposes of isolation by Steady-State Stacking, each of these charge isomeric families of hCG components was collectively separated from faster migrating proteins in crude, commercial hCG by first allowing them to unstack while the more highly mobile contaminating proteins in the preparation remained stacked and were eluted as a stack from an elution-PAGE apparatus. After some time of electrophoresis the unstacked hCG components were then combined ("restacked") by sweeping them into a second moving boundary and eluted from a preparative elution-PAGE apparatus in a single zone. The product exhibits on PAGE re-run molecular species related to hCG standard as either "size-" or "charge-isomers". After dissociation into subunits, all preparations yield a protein indistinguishable in size or net charge from a standard preparation of the beta-chain of hCG. The alpha- and beta-chains derived from the isolated preparations exhibited dose-response curves parallel to those of standard hCG alpha and hCG beta respectively. The biological activity of the product was 8-12.000 IU/mg, as compared to 3,000 IU/mg for the starting material. The total yield was 20% by dry weight of the crude starting material.

Buffers↗

PubMed2006

Voltammetric determination of tyrosine based on an L-serine polymer film electrode.

A novel film electrode for the voltammetric determination of tyrosine has been constructed based on electropolymerization of L-serine on a glassy carbon electrode. Voltammetric behaviour of tyrosine on the poly-L-serine film electrode was investigated with cyclic voltammetry and linear sweep voltammetry, and electrochemical parameters were calculated from chronocoulometry. In optimal conditions, the oxidation peak current of tyrosine on the poly-L-serine film electrode was enhanced greatly. A sensitive oxidation peak at 0.90 V was employed to determine tyrosine. A linearity between the oxidation peak current and the tyrosine concentration was obtained in the range of 3.0 x 10(-7) to 1.0 x 10(-4) mol L(-1) with a detection limit of 1.0 x 10(-7)mol L(-1). The practical application of the film electrode in the determination of tyrosine in a commercial amino acid oral solution demonstrated that it has good selectivity and high sensitivity.

Amino Acids↗

PubMed1993

The relationship between sound transfer functions from free sound field to the eardrum and temporary threshold shift.

Three groups of 12 subjects were utilized for an experiment in which the temporary threshold shift due to a free-field exposure was measured and compared to the sound transfer functions from free-sound field to the subjects' eardrums. Subject selection was based upon their sound transfer functions and the requirement of normal hearing. The subjects were assigned to one of three groups depending on their dominantly sound transfer function frequency: Low, middle, or high. A probe tube with a miniature microphone was used for the measurement of the sound transfer functions in 1/3-oct bands. The measurements were performed in frequency bands from 0.2 to 20 kHz with one direction of sound incidence: 0 degree azimuth and 0 degree elevation. The subjects were exposed twice to a 2-kHz and twice to a 4-kHz narrow-band noise monotonically on four different occasions. Pre- and postexposure sweep Békésy audiograms were recorded and the temporary threshold shift calculated as the difference between the two. The averaged temporary threshold shifts differed significantly among groups.

Acoustic Stimulation↗

PubMed2005

Electrochemical characteristics of zafirlukast and its determination in pharmaceutical formulations by voltammetric methods.

Simple, rapid, reliable and fully validated voltammetric methods were developed for the determination of zafirlukast in pharmaceutical formulations, based on its electrochemical reduction at a hanging mercury drop electrode. Its electrochemical behavior in borate buffer (pH 8.0) was investigated using cyclic voltammetry, linear sweep voltammetry and chronoamperometry. The linear sweep voltammetric study of zafirlukast was carried out using glassy carbon electrode. A well-defined cathodic peak at -1326 mV without the adsorptive accumulation time and at -1312 mV with 20 s of accumulation time versus Ag/AgCl reference electrode in square-wave and square-wave adsorptive stripping voltammetric methods, respectively, was observed. The experimental and instrumental parameters affecting the peak current of zafirlukast were investigated and optimized for the zafirlukast determination. The detection limits of square-wave and square-wave adsorptive stripping voltammetric methods were 50 and 5 ngmL(-1) with R.S.D. of 6.79 and 5.72%, respectively. The methods showed good sensitivity, accuracy, precision, selectivity, robustness and ruggedness. The proposed methods were applied for the determination of zafirlukast in its pharmaceutical formulations. The results obtained from developed methods were compared with a spectrophotometric method reported in the literature and no significant difference was found statistically.

Adsorption↗

PubMed2005

Song types and their structural features are associated with specific contexts in the banded wren.

We studied the use of song types and their acoustic features in different social contexts in the banded wren (Thryothorus pleurostictus), a resident tropical songbird in which males possess about 20 distinctive song types varying in duration, bandwidth, note composition, and trill structure. We recorded six focal males intensively for four days each while we observed context information such as during versus after dawn chorus, presence of the female, counter-versus solo-singing, location at the edge versus centre of the territory, and proximity to the nest. All males used at least some song types differentially during each of these pairs of alternative contexts. Males also preferentially used the song types they shared with a given neighbour when interacting with that bird. Songs delivered during dawn chorus were significantly longer, wider in bandwidth, often compound (double songs), and more likely to contain a rattle or buzz and an up-sweeping trill, compared to songs delivered after dawn chorus. Similar features were also more commonly observed when birds were engaged in intense male-male interactions and boundary disputes after dawn chorus, especially when countersinging at the edge of the territory. The presence of the female caused the male to deliver song types with narrower whole-song and trill bandwidth and fewer rattles and buzzes, and song-type diversity and fraction of compound songs were higher when the female was present. Thus, in addition to using type matching and variations in song-type switching and diversity to signal different levels of aggressive intention, male banded wrens also select song types based on their acoustic structure in different social contexts.

Journal Article↗

PubMed1985

A functional measure of front-to-back ratio.

Monaural hearing aid users (aged 26-75 yrs; mn: 52 yrs) with moderate to severe bilateral sensorineural losses tracked free field sweep-frequency Bekesy thresholds from .25-4 kc/s in a typical audiological test booth. Each S was fitted, on the ear on which S usually wore an aid, with successively 3 directional microphone hearing aids (DMHAs) now commonly issued, with similar frequency response and gain characteristics but with a range, as shown by the manikin KEMAR in an anechoic chamber, of 8 db in FBR. Warbled tones were presented from a loudspeaker either 1 m directly ahead of or 1 m directly behind S's head. The difference in thresholds (180 degrees data subtracted from 0 degree data) in db was taken as functional front-to-back ratio (FBR) at selected frequencies. These were compared with FDRs from KEMAR. The functional FBR was shown to be sensitive enough (p less than .001) to differentiate among DMHAs, and the aids were on the average ordered similarly from highest to lowest by both KEMAR and functional FBRs. It was found that the data at 1 kc/s were predominately useful to test. However, individual differences were such that it was concluded that more reliance should be placed on a functional test of FBR. In addition, a significant Pearson r of 0.42 (p less than .01) was obtained between functional FBR and monosyllabic DS (S/N: 0 db). These results suggest that the functional FBR may play an important role in measuring hearing aid selection.

Adult↗

PubMed2000

Molecular epidemiology of Entamoeba spp.: evidence of a bottleneck (Demographic sweep) and transcontinental spread of diploid parasites.

Entamoeba histolytica causes amebic colitis and liver abscess in developing countries such as Mexico and India. Entamoeba dispar is morphologically identical but is not associated with disease. Here we determined the ploidy of E. histolytica and developed PCR-based methods for distinguishing field isolates of E. histolytica or E. dispar. Fluorescence in situ hybridization showed that E. histolytica trophozoites are diploid for five "single-copy" probes tested. Intergenic sequences between superoxide dismutase and actin 3 genes of clinical isolates of E. histolytica from the New and Old Worlds were identical, as were those of E. dispar. These results suggest a bottleneck or demographic sweep in entamoebae which infect humans. In contrast, E. histolytica and E. dispar genes encoding repeat antigens on the surface of trophozoites (Ser-rich protein) or encysting parasites (chitinase) were highly polymorphic. chitinase alleles suggested that the early axenized strains of E. histolytica, HM-1 from Mexico City, Mexico, and NIH-200 from Calcutta, India, are still present and that similar E. dispar parasites can be identified in both the New and Old Worlds. Ser-rich protein alleles, which suggested the presence of the HM-1 strain in Mexico City, included some E. histolytica genes that predicted Ser-rich proteins with very few repeats. These results, which suggest diversifying selection at chitinase and Ser-rich protein loci, demonstrate the usefulness of these alleles for distinguishing clinical isolates of E. histolytica and E. dispar.

Actins↗

PubMedDate not supplied

Religious hiring exemption upheld: anatomy of a Supreme Court ruling.

In 1980 the Church of Jesus Christ of the Latter-day Saints (LDS Church) notified five employees that they could no longer continue in church employment because they would not or could not attend the temple as members in good standing. Together, the five filed suit in federal district court in Utah, alleging that the LDS Church discriminated against them on religious grounds in violation of Title VII of the federal Civil Rights Act of 1964, which generally prohibits discrimination in employment on the basis of religion. The plaintiffs said the statutory exemption for religious organizations in Section 702 operated as a religious preference and penalized their personal choices of religion in violation of the First Amendment. The case ended up in the Supreme Court, which upheld the provision exempting religious organizations from Title VII with respect to employing people of a particular religion for all not-for-profit activities. Evidence in the case included: Legislative history. As first enacted in 1964, Section 702 provided a limited exemption to religious corporations. In 1972 Congress enacted a broader exemption, effectively exempting from the sweep of Title VII employment decisions made by religious employers with respect to members of that religion in any work connected with the religious corporation. District court proceedings. The Utah court borrowed from several earlier cases, including one that avoided the constitutional issue by deciding that the function challenged was uniquely religious and, thus, exempted. Briefs amicus curiae. Four religious organizations filed briefs amicus curiae.

Civil Rights↗

PubMed2005

Simulations of photomodulated solute transport in doubly illuminated liquid membranes containing photoactive carriers.

A steady-state model describing photofacilitated transport in liquid membranes under double illumination is presented. The model allows for the exploration of the effects of a wide range of thermodynamic and kinetic carrier properties on the control of photoinduced transport rates of solutes, called photomodulation. Most previous experimental and theoretical studies have explored the illumination of only the feed or sweep side of the membrane, while this study examines the effects of illuminating both sides simultaneously. Under double illumination, solute transport rates can be as much as five times greater than those measured in the dark and 2.5 times greater than rates obtained under single illumination. Carriers that are predominantly in the weakly binding form in the dark generally provide slightly better performance at lower light intensities than do carriers that are predominantly in the strongly binding form in the dark. The greatest enhancement in solute transport under double illumination is seen for carriers with very slow interconversion rate constants between the strongly and weakly binding forms. These results provide guidelines to help those studying photofacilitated membranes select or design photoactive molecules that will act as optimal carriers in liquid membranes under double illumination.

Journal Article↗

PubMed2003

Heterogeneity of cag genotypes in Helicobacter pylori isolates from human biopsy specimens.

The Helicobacter pylori chromosomal cluster of genes known as the cytotoxin-associated gene (cag) island may have different compositions in infecting strains. In this study, we analyzed 150 single colonies obtained from gastric biopsy specimens from 10 patients infected with cagA-positive H. pylori strains and sweep isolates (isolates harvested with sweep in different points of the plate) from 6 patients infected with cagA-negative strains. Three loci in the cag island (cagA, cagE, and virB11) and the conserved gene glmM (ureC) were investigated by PCR. The levels of anti-H. pylori and anti-CagA antibodies in patient sera were also measured. For subjects infected with cagA-negative strains, all sweep isolates were also negative for cagE and virB11, suggesting the complete absence of the cag island. For subjects infected with cagA-positive strains, most of the isolates were positive for all three genes studied, whereas 24.7% of the isolates had a partial or total deletion of the cag island. cagA, cagE, and virB11 were, respectively, present in 87.3, 77.3, and 90% of the colonies. The deletion of virB11 was always associated with the deletion of cagA and/or cagE. H. pylori colonies with different cag genotypes were isolated within a single gastric biopsy specimen from 3 of the 10 patients and were further characterized by random amplified polymorphic DNA (RAPD) analysis and by sequencing of an arbitrarily selected gene segment. Although the colonies had different cag genotypes, their RAPD profiles were highly similar within each patient, and the nucleotide sequences of the selected gene segment were identical. All of the patients had detectable antibodies against H. pylori, and 9 of 10 had anti-CagA antibodies. In conclusion, we show that a single infecting H. pylori strain may include variable proportions of colony subtypes with different cag genotypes. The extension of our analysis to patients with well-characterized gastric diseases may provide significant information on the relationship between cag genotypes and clinical outcomes of H. pylori infections.

Antibodies, Bacterial↗

PubMed2005

Evidence for a global Wolbachia replacement in Drosophila melanogaster.

Wolbachia are maternally inherited intracellular alpha-Proteobacteria found in numerous arthropod and filarial nematode species. They influence the biology of their hosts in many ways. In some cases, they act as obligate mutualists and are required for the normal development and reproduction of the host. They are best known, however, for the various reproductive parasitism traits that they can generate in infected hosts. These include cytoplasmic incompatibility (CI) between individuals of different infection status, the parthenogenetic production of females, the selective killing of male embryos, and the feminization of genetic males. Wolbachia infections of Drosophila melanogaster are extremely common in both wild populations and long-term laboratory stocks. Utilizing the newly completed genome sequence of Wolbachia pipientis wMel, we have identified a number of polymorphic markers that can be used to discriminate among five different Wolbachia variants within what was previously thought to be the single clonal infection of D. melanogaster. Analysis of long-term lab stocks together with wild-caught flies indicates that one of these variants has replaced the others globally within the last century. This is the first report of a global replacement of a Wolbachia strain in an insect host species. The sweep is at odds with current theory that cannot explain how Wolbachia can invade this host species given the observed cytoplasmic incompatibility characteristics of Wolbachia infections in D. melanogaster in the field.

Animals↗

PubMed2006

Cage trials using an endogenous meiotic drive gene in the mosquito Aedes aegypti to promote population replacement.

Control of arthropod-borne diseases based on population replacement with genetically modified non-competent vectors has been proposed as a promising alternative to conventional control strategies. Due to likely fitness costs associated with vectors manipulated to carry anti-pathogen effector genes, the effector genes will need to be coupled with a strong drive system to rapidly sweep them into natural populations. Endogenous meiotic drive systems have strong and stable population replacement potential, and have previously been reported in two mosquito species: Aedes aegypti and Culex pipiens. To investigate the influence of an endogenous meiotic drive gene on Ae. aegypti population dynamics, we established three experimental population types that were initiated with 100%, 10%, and 1% male mosquitoes carrying a strong meiotic driver (T37 strain) and 100% sensitive females (RED strain), respectively. Among the 100% and 10% populations, early generations were highly male biased, which reflected the effects of the meiotic driver, and remained more than 60% male by the F(15). A genetic marker tightly linked with the meiotic driver on chromosome 1 showed strong selection for the T37 strain-specific allele. Similar but reduced effects of the meiotic driver were also observed in the 1% populations. These results suggest that release of Ae. aegypti males carrying a strong meiotic driver into drive sensitive populations can be an effective tool for population replacement, and provide a foundation for additional studies including both experimental populations and simulations by mathematical modeling.

Aedes↗

PubMed2001

Effects of auditory stimulus context on the representation of frequency in the gerbil inferior colliculus.

Prior studies of dynamic conditioning have focused on modulation of binaural localization cues, revealing that the responses of inferior colliculus (IC) neurons to particular values of interaural phase and level disparities depend critically on the context in which they occur. Here we show that monaural frequency transitions, which do not simulate azimuthal motion, also condition the responses of IC neurons. We characterized single-unit responses to two frequency transition stimuli: a glide stimulus comprising two tones linked by a linear frequency sweep (origin-sweep-target) and a step stimulus consisting of one tone followed immediately by another (origin-target). Using sets of glide and step stimuli converging on a common target, we constructed conditioned response functions (RFs) depicting the variability in the response to an identical stimulus as a function of the preceding origin frequency. For nearly all cells, the response to the target depended on the origin frequency, even for origins outside the excitatory frequency response area of the cell. Results from conditioned RFs based on long (2-4 s) and short (200 ms) duration step stimuli indicate that conditioning effects can be induced in the absence of the dynamic sweep, and by stimuli of relatively short duration. Because IC neurons are tuned to frequency, changes in the origin frequency often change the "effective" stimulus duty cycle. In many cases, the enhancement of the target response appeared related to the decrease in the "effective" stimulus duty cycle rather than to the prior presentation of a particular origin frequency. Although this implies that nonselective adaptive mechanisms are responsible for conditioned responses, slightly more than half of IC neurons in each paradigm responded significantly differently to targets following origins that elicited statistically indistinguishable responses. The prevailing influence of stimulus context when discharge history is controlled demonstrates that not all the mechanisms governing conditioning depend on the discharge history of the recorded neuron. Selective adaptation among the neuron's variously tuned afferents may help engender stimulus-specific conditioning. The demonstration that conditioning effects reflect sensitivity to spectral as well as spatial stimulus contrast has broad implications for the processing of a wide range of dynamic acoustic signals and sound sequences.

Acoustic Stimulation↗

PubMed2006

The FDA and drug safety: a proposal for sweeping changes.

The current Food and Drug Administration (FDA) system of regulating drug safety has serious limitations and is in need of changes. The major problems include the following: the design of initial preapproval studies lets uncommon, serious adverse events go undetected; massive underreporting of adverse events to the FDA postmarketing surveillance system reduces the ability to quantify risk accurately; manufacturers do not fulfill the majority of their postmarketing safety study commitments; the FDA lacks authority to pursue sponsors who violate regulations and ignore postmarketing safety study commitments; the public increasingly perceives the FDA as having become too close to the regulated pharmaceutical industry; the FDA's safety oversight structure is suboptimal; and the FDA's expertise and resources in drug safety and public health are limited. To address these problems, we urge Congress, which is ultimately responsible for the FDA's performance, to implement the following 5 recommendations: (1) give the FDA more direct legal authority to pursue violations, (2) authorize the adoption of a conditional drug approval policy, at least for selected drugs, (3) provide additional financial resources to support the safety operations, (4) mandate a reorganization of the agency with emphasis on strengthening the evaluation and proactive monitoring of drug safety, and (5) require broader representation of safety experts on the FDA's advisory committees.

Drug Approval↗