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R Dawkins

Publications and source records attributed to R Dawkins.

At least 19 recordsLinked to original sources
PubMed2001

What is science good for?

A nonbusiness discipline can provide a useful framework for thinking about old problems in new ways. People who study management, for instance, freely borrow from many fields of science to theorize about organizational behavior and business strategy. Evolutionary psychology and biology are especially popular sources of inspiration. But should they be? Evolutionary biologist Richard Dawkins has spent much of his career explaining science to the public. More than 20 years ago, his book The Selfish Gene shattered the popular belief that evolution necessarily favors altruism and self-sacrifice. In a conversation with HBR senior editor Diane Coutu, Dawkins discusses the role of science in our lives and identifies some of the more glaring public misperceptions of scientific theories. In particular, he disentangles the current notion that certain behaviors are in some way preprogrammed and explodes some contemporary myths about the Human Genome Project. Dawkins says much of the popular fear surrounding genetic manipulation is unfounded. "Humans have been practicing it for thousands of years, to no obvious ill effect," he says. Modern foot-long corncobs, the result of more than 1,000 years of artificial selection, are "quite Frankenstein-like" compared to their half-inch-long progenitors, he points out. He also touches on agriculture giant Monsanto and the media: "Part of the reason for Monsanto's troubles is that the company came up against an extraordinary amount of unfortunate, even malevolent, media hype," he says. "And people were more or less misled, by one scare story after another, into stampeding." A staunch defender of science as a haven of rational thought, Dawkins counsels businesspeople to recognize the limitations--as well as the beauty--of science.

Commerce↗
PubMed1999

A critical evaluation of enzyme immunoassays for detection of antinuclear autoantibodies of defined specificities. I. Precision, sensitivity, and specificity.

OBJECTIVE: To determine the performance characteristics of enzyme-based immunoassay (EIA) kits for the detection of antinuclear and other autoantibodies of defined specificities. METHODS: Nine manufacturers of EIA kits to detect antibodies of defined specificities participated in a study in which they received coded sera from the Centers for Disease Control and Prevention. These coded sera contained different dilutions of antibody of one specificity mixed with sera containing antibodies of other specificities. The manufacturers were asked to use their standard technology to determine antibody content and send the data to a committee of the International Union of Immunological Societies for analysis. The data were analyzed for sensitivity and specificity in the detection of anti-double-stranded DNA (anti-dsDNA), anti-single-stranded DNA, antihistone, anti-Sm, anti-U1 RNP, anti-SSA/Ro, anti-SSB/La, anti-Scl-70 (DNA topoisomerase I), anticentromere, and anti-Jo-1 antibodies. In addition, replicate samples were included in the coded sera to evaluate the precision of each EIA method. RESULTS: Lack of sensitivity and specificity was most evident in the anti-dsDNA and anti-Sm kits, although 2 kits for anti-dsDNA achieved acceptable sensitivity and specificity. Generally, anti-SSA/Ro, anti-SSB/La, anti-Scl-70, anticentromere, and anti-Jo-1 kits performed well. Many false-positive results were obtained with a multiple myeloma serum containing cryoprecipitates, but multiple myeloma sera without cryoprecipitates presented no problem in the EIA system. Precision, based on evaluation of replicate samples, varied from very good to poor. CONCLUSION: No single manufacturer was clearly superior to others in terms of their products' overall sensitivity, specificity, and precision. Areas that needed improvement were in kits for the detection of antibodies to dsDNA and to Sm antigen. Some EIA kits achieved good sensitivity and specificity. Individual manufacturers were informed of the performance of their respective kits so they could take measures to correct perceived deficiencies and thus improve the reliability of a group of important diagnostic assays used in the evaluation of systemic rheumatic diseases.

Antibodies, Antinuclear↗
PubMed1999

Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease.

The genomic region encompassing the Major Histocompatibility Complex (MHC) contains polymorphic frozen blocks which have developed by local imperfect sequential duplication associated with insertion and deletion (indels). In the alpha block surrounding HLA-A, there are ten duplication units or beads on the 62.1 ancestral haplotype. Each bead contains or contained sequences representing Class I, PERB11 (MHC Class I chain related (MIC) and human endogenous retrovirus (HERV) 16. Here we consider explanations for co-occurrence of genomic polymorphism, duplication and HERVs and we ask how these features encode susceptibility to numerous and very diverse diseases. Ancestral haplotypes differ in their copy number and indels in addition to their coding regions. Disease susceptibility could be a function of all of these differences. We propose a model of the evolution of the human MHC. Population-specific integration of retroviral sequences could explain rapid diversification through duplication and differential disease susceptibility. If HERV sequences can be protective, there are exciting prospects for manipulation. In the meanwhile, it will be necessary to understand the function of MHC genes such as PERB11 (MIC) and many others discovered by genomic sequencing.

Animals↗
PubMed1998

Reference typing report for complement component C4.

During the 7th Complement Genetics Workshop, Mainz, Germany, May 1998, a complement component C4 typing exercise took place with the aim of applying present technologies to the definition of reference C4 alleles/phenotypes and the recognition of nonexpressed (Q0) C4 alleles within expressed haplotypes. Eleven samples were submitted from 3 laboratories and tested by 14 participating laboratories with basic protein-typing technologies; in addition, each laboratory contributed data from local expertise. The samples were introduced to the reference typing for one or more characteristic allotype or for partial or total nonexpression of one isotype. The blinded samples were centrally evaluated and the results discussed among the participants at a plenum meeting. From the results, the samples could be classified into a group of common, easy to diagnose pheno-/allotypes, less common but still unanimously recognised variants, and a third group with difficult pheno-/allotypes. Within the latter group, the allotypes were either new (C4A '92'; C4B '93') and/or showed partial or total reversed antigenicity and unusual Rodgers/Chido (Rg/Ch) PCR subtypes (C4A '92'; C4A 12; C4B '35'; C4B '13'). Semiquantitative C4-alpha-chain estimates of relative isotype levels correlated well with the number of alleles seen at each locus by agarose gel electrophoresis, and were superior to other isotype quantitation methods. From the evaluation of the reference typing it was concluded that the recognition of rare, aberrant or hybrid C4 alleles with partial or total reversed Rg/Ch antigenicity or monoclonal reactivity is still difficult in most instances; besides isotype-dependent lysis, relative migration values, immunoblots with Rg- and Ch-specific monoclonal antibodies, Rg/Ch PCR typing, side-by-side comparison with already described allotypes will ultimately be required. The recognition of nonexpressed alleles within C4A and C4B expressed phenotypes remains the major obstacle in C4 genetic typing. Finally, a conclusive interpretation of DNA typing results will be achieved only in the context of complete allotyping results at the protein level, and at present cannot replace conventional protein allotyping.

Alleles↗
PubMed1997

Range of antinuclear antibodies in "healthy" individuals.

OBJECTIVE: To determine the range of antinuclear antibodies (ANA) in "healthy" individuals compared with that in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatism (STR). METHODS: Fifteen international laboratories experienced in performing tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above. Except for the stipulation that HEp-2 cells should be used as substrate, each laboratory used its own in-house methodology so that the data might be expected to reflect the output of a cross-section of worldwide ANA reference laboratories. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320. RESULTS: In healthy individuals, the frequency of ANA did not differ significantly across the 4 age subgroups spanning 20-60 years of age. This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320. In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specificity) could have diagnostic value, since it would classify virtually all patients with SLE, SSc, or SS as ANA positive. Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensitivity) would be useful to confirm the presence of disease in only a portion of cases, but would be likely to exclude 95% of normal individuals. CONCLUSION: It is recommended that laboratories performing immunofluorescent ANA tests should report results at both the 1:40 and 1:160 dilutions, and should supply information on the percentage of normal individuals who are positive at these dilutions. A low-titer ANA is not necessarily insignificant and might depend on at least 4 specific factors. ANA assays can be a useful discriminant in recognizing certain disease conditions, but can create misunderstanding when the limitations are not fully appreciated.

Adult↗
PubMed1997

Abbreviated educational session improves cranial computed tomography scan interpretations by emergency physicians.

STUDY OBJECTIVE: Previously published research (phase I) demonstrated a concerning misinterpretation rate of cranial computed tomography (CT) scans by emergency physicians. This study (phase II) determined whether an abbreviated educational session would improve emergency physician interpretation skills of cranial CT scans. METHODS: Participants in this prospective, interventional study in a county hospital ED were patients undergoing cranial CT scanning during ED evaluations and attending level emergency physicians. An abbreviated educational session on cranial CT interpretation skills was given to the same attending emergency physicians who participated in phase I. The educational session included basic CT interpretation skills and misinterpreted CT scans from phase I. We determined the postsession accuracy rate of the emergency physicians on 324 ED patient CT scans. The CT interpretation accuracy rates were then compared between phase I and phase II to determine the effectiveness of the educational session. RESULTS: The radiology/ED CT scan concordance rate improved from 61.3% (kappa = .22) to 88.6% (kappa = .70; P < .0001). Potentially clinically significant CT scan misinterpretations decreased from 24.1% to 4.0% (P < .0001). Most importantly, major missed findings on CT scans decreased from 11.4% to 2.8% (P < .0001). Continuous quality improvement monitoring found no instance of clinically significant patient mismanagement. CONCLUSION: Within the limits of this study, we conclude that emergency physicians' interpretation skills of cranial CT scans may be improved using a 1-hour educational session.

Brain Diseases↗
PubMed1997

Computerised estimation of the baseline fetal heart rate in labour: the low frequency line.

OBJECTIVE: To develop and evaluate a computerised algorithm for the estimation of the fetal heart rate baseline (low frequency line) during labour. DESIGN: Retrospective observational study. METHODS: Fetal heart rate signals were obtained from women in labour using the Nottingham fetal ECG monitor. The computerised algorithm for the baseline estimation was developed for intrapartum applications and is based on averaging modal fetal heart rate values. Evaluation was carried out on sixty cardiotocographic recordings by 12 experts and by the computer. These estimates were compared with those obtained from the computerised system using paired differences and intraclass correlation. RESULTS: The study showed that it is possible to produce a low frequency line from data obtained from intrapartum records. The system could not estimate the low frequency line in four records, whereas experts were also unable to estimate between one and seven tracings. The 95% CI for the paired differences between computer and experts was -12 to 15 bpm, whereas between the experts this was -10 to 10. With the exception of one expert, there was a high concordance between experts and between computer and experts (intraclass correlation > 0.9). CONCLUSIONS: The performance of this computerised algorithm cannot be distinguished from that of experienced clinicians. There were no significant differences between baseline values obtained by the computerised algorithm and those by the clinicians.

Algorithms↗
PubMed1996

Antibody reactivity profiles following immunization with diverse peptides of the PERB11 (MIC) family.

PERB11 (MIC) is a gene family possessing multiple copies located within the MHC. Structurally, PERB11 is related to the MHC class I, neonatal IgG Fc receptor (FcRn) and Zn-alpha 2-glycoprotein molecules. The MHC class I family is complex in terms of its genomic arrangement, expression and function, and available evidence suggests that the PERB11 family may be similarly complex. We have adopted an approach to study the expression of such complex gene families by immunizing with multiple peptides and by screening the resulting antibodies against a large range of tissues. The amino acid sequences of PERB11.1 and PERB11.2 as well as those of other related molecules were analysed and compared. Peptides were chosen for immunization based upon (i) loop formation within the equivalent known structure of the MHC class I molecules; (ii) immunogenicity by computer analysis; and (iii) evolutionary relationships. Antibodies in serum from immunized rabbits bound to three out of six peptides used for immunization. ELISA and immunoprecipitation demonstrated binding both to the peptides and to the PERB11.2 recombinant protein. By immunofluorescent staining of various tissues of several species, the three antisera generated overlapping profiles of activity. These included reactions with kidney, small and large intestine, oesophagus, testis, ovary and human neutrophils. This is the first description of antibodies induced by the PERB11 peptides. The extreme complexity of these profiles requires further investigation, but may be explained in terms of antibodies against diverse products of the PERB11 gene family and/or related molecules.

Amino Acid Sequence↗
PubMed1995

Severity of infections in IgA deficiency: correlation with decreased serum antibodies to pneumococcal polysaccharides and decreased serum IgG2 and/or IgG4.

In order to define abnormalities of humoral immunity which determine susceptibility to respiratory tract infections in IgA-deficient adults, serum IgG subclass concentrations, and serum concentrations of pneumococcal antibodies and Haemophilus influenzae type B (Hib) antibodies sera from IgA-deficient adults with and without susceptibility to respiratory tract infections were compared. Infection susceptibility was not related to the degree of IgA deficiency, but was related to deficiency of IgG4 and, to a lesser extent, IgG2, as well as to low basal serum concentrations of pneumococcal polysaccharide antibodies. The combination of IgG2 and/or IgG4 deficiency and a non-protective basal serum concentration of antibody against two or more pneumococcal polysaccharides was present in the serum of six of 12 (50%) patients with severe infections, but only one of 44 (2%) patients without infections. Furthermore, the preservation of antibody responses against the most immunogenic pneumococcal polysaccharide type 3, but not against the less immunogenic types 7F, 9N and 14, in patients with severe infections suggested that abnormalities of pneumococcal polysaccharide antibody responses might include defects of affinity maturation.

Adolescent↗
PubMed1994

Diuretic effects, pharmacokinetics, and safety of a new centrally acting kappa-opioid agonist (CI-977) in humans.

The diuretic effects, pharmacokinetics, and safety of CI-977, a new centrally acting selective kappa-opioid agonist, were determined in 16 healthy subjects. Subjects received single intramuscular doses of CI-977 (5, 15, or 25 micrograms) or placebo 1 week apart according to a randomized, double-blind, placebo-controlled, four-period, crossover design. Serial blood and urine specimens were collected after each dose. Significant dose-related decreases in negative free water clearance and urine osmolality and increases in urine volume were observed after administration of 15- and 25-micrograms doses of CI-977. CI-977 had no effect on urine electrolyte excretion or serum antidiuretic hormone. Absorption of CI-977 was rapid with individual tmax values ranging from 0.17 to 1.5 hours. Cmax and AUC(0-infinity) increased proportionally with dose. Individual elimination half-life values ranged from 0.6 to 3.3 hours and were independent of dose. Changes in free water clearance were related to CI-977 Cmax (r2 = 0.29, P = 0.0001) and AUC(0-4 hr) (r2 = 0.32, P = 0.0001) values. The most frequently reported adverse events after CI-977 administration were dizziness, fatigue, paresthesia, headache, vasodilatation (facial flushing), emotional lability, high feeling, and abnormal thinking. The frequency and intensity of adverse events increased with increasing CI-977 dose. In conclusion, CI-977 Cmax and AUC(0-infinity) increased in proportion to dose over the range of 5 to 25 micrograms; decreases in negative free water clearance were related to CI-977 dose and Cmax and AUC(0-4 hr) values; and the frequency and intensity of adverse events increased with increasing CI-977 dose.

Adult↗
PubMed1994

Congenital Candida pneumonia in a preterm infant.

A 24 week gestation survivor of congenital Candida pneumonia who received prompt antifungal treatment and modern neonatal intensive care is reported. It was an unusual case in that fungal chorioamnionitis occurred without a foreign body in the maternal genital tract. Early diagnosis and treatment of congenital fungal pneumonia was possible because of prior knowledge of the obstetric history. Amphotericin B was successfully used for the treatment of this condition but combination with fluconazole (a fungistatic agent) was unsatisfactory and may be undesirable. Dexamethasone therapy to assist extubation was instituted once the fungal infection had been successfully controlled.

Bronchopulmonary Dysplasia↗
PubMed1991

Association of the complement allele C4AQ0 with primary Sjögren's syndrome in Japanese patients.

We studied allotypes of the fourth component of complement (C4) and factor B in 76 patients with Sjögren's syndrome (SS) and in 63 normal subjects. C4A-null (C4AQ0) was found in 10 of 28 patients who had primary SS, compared with 1 of 63 control subjects (P less than 0.005). In contrast, no significant difference in the frequency of any C4 allotype was observed between patients with secondary SS and control subjects. An association of HLA-DRw53 with primary SS in Japanese patients has been reported. Since there is no linkage disequilibrium between DRw53 and C4AQ0, it is possible that at least 2 genes in the major histocompatibility complex may determine susceptibility to the development of primary SS in the Japanese population.

Autoimmune Diseases↗
PubMed1990

C4 nomenclature statement (1990).

A common and revised nomenclature of the allotypes of the fourth component (C4) of human complement has been proposed. It is based on the results of the C4 Reference Typing of the VIth Complement Genetics Workshop and Conference, Mainz, FRG, 1989, the previous C4 nomenclature and the guidelines for human gene nomenclature (ISGN). The designation of allotypes derives from their relative electrophoretic mobility, the distinction between C4A and C4B proteins from their relative hemolytic activity. Common alleles retain their single digit numeric designation, intermediate variants their two- or three-digit designations; newly discovered alleles should not interfere with already described variants. At least 13 C4A alleles, 16 C4B alleles as well as non-expressed genes at each C4 locus are presently known. There are also duplicated loci of each C4 gene; they should be designated by repetition of the locus symbol at the haplotype or genotype level. As a phenotype they will be placed in parenthesis without repetition of the locus symbol. Aberrant allotypes or hybrid genes should be explained by a special suffix. No special nomenclature is recommended for restriction fragment length polymorphisms. Their designation should follow the general rules of the ISGN.

Alleles↗