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Description and validation of a method for simultaneous estimation of effective population size and mutation rate from human population data.

A method is presented for utilizing population data on electrophoretic variants of proteins to estimate simultaneously the effective sizes (Ne values) of the populations in question and the rate of mutation resulting in electromorphs at the loci whose products were surveyed. The method is applied to data from 12 relatively unacculturated Amerindian tribes for whom census data and independent estimates of the number of different electrophoretic variants at 27 loci are available. Because of tribal demographic structure, Ne should be less than the current number of reproductive-aged adults. In fact, it is substantially greater for 7 tribes, most likely due to intertribal migration and a recent decrease in tribal size. Estimates of locus mutation rates for the 27 loci vary by more than a factor of 20, with an average of 1.1 x 10(-5) per locus per generation. This latter estimate is in satisfactory agreement with the results of other indirect approaches to the estimation of mutation rates in these tribes but about two times higher than the results of direct estimates based on these same loci in studies on civilized populations. This discrepancy could be due to the above-hypothesized migration and to decreases in tribal size.

Adult↗

Life cycle assessment of wastewater treatment technologies treating petroleum process waters.

This paper describes the implementation of life cycle assessment to investigate the environmental impact of 20 technologies suitable for treating extensive volumes of water produced during the oil and gas extraction processes. Data on the physical and operational attributes of technologies under consideration were assembled and their life cycle environmental impacts estimated over 15 year time period. The results were then incorporated in a decision support system which allows identification and prioritisation of potential technology combinations capable of producing water for nine designated industrial and agricultural end uses. In total, more than 618 technology combinations were investigated for their environmental impacts. The identification and prioritisation of technologies were done on the basis of their environmental and technical performance. This analysis showed that dissolved air flotation, absorbents, dual media filtration and reverse osmosis technologies offer relatively low environmental impact parts of systems for cleaning such process waters. Furthermore, the environmental assessment combined within the decision support system has revealed potentially valuable indirect downstream "benefits" from effects such as evaporative losses from wetlands in terms of the overall environmental impact of a treatment system.

Extraction and Processing Industry↗

Potassium activities in epithelia.

In general, intracellular K+ appears to be compartmentalized. This phenomenon does not seem to characterize cytoplasm per se, but probably reflects the processes of sequestration and ion exclusion characterizing certain as yet unidentified organelles. The cell nucleus does not appear to participate significantly in these processes. Measurement of intracellular potassium activity (alpha K)c in small epithelial cells is complicated by significant technical problems. Recent experimental maneuvers designed to circumvent these problems have led to substantially higher estimates of (alpha K)c under baseline conditions. The time courses of short circuit current (SCC) and (alpha K)c in toad urinary bladder have been correlated under two experimental conditions. After removing external K+ or after adding ouabain, both parameters are depressed. However, the time courses of SCC and (alpha K)c are very different following return to baseline conditions. The data suggest: 1) that the processes of cell K+ accumulation and transepithelial Na+ transport are not linked with a fixed stoichiometry, and 2) if a reduction in cytosolic K+ activity does inhibit transepithelial Na+ transport, its role is indirect.

Animals↗

[Use of purified antigens in the serodiagnosis and epidemiologic studies of human malaria. Importance of the ELISA technic for determining specific IgG and IgM].

A purified antigen was isolated from the red blood cells of Saimiri sciureus which was experimentally infected by Plasmodium falciparum. An enzyme immunoassay (ELISA) was carried out thanks to this antigen. The results obtained with the test were evaluated from two series of sera: one coming from an endemic area, the other taken out of it. The results were compared with those obtained with indirect fluorescent antibody test (IFAT) which is considerated as reference test. There is a good correlation between the two tests when anti-IgG conjugate is used for ELISA but there is no correlation with anti-IgM conjugate. One of the advantages of the ELISA, is that it allows a separate evaluation of specific IgG and IgM. Consequently distinction between recent and past infection would be possible. This may be useful for estimating the efficiency of an antimalaric campaign.

Animals↗

Heart transplants: need versus availability.

Every year in the US heart failure accounts for roughly 60,000 deaths and is the contributing cause in another 300,000 deaths. The two-year survival rate for patients with advanced heart failure is less than 50%, with the incidence of death at 106 in 100,000, more than that for AIDS and breast cancer combined. As these figures attest, the economic burden is quite extensive. The Centers for Medicaid and Medicare estimate a cost of $10 billion a year for this diagnosis alone. Both the human and financial cost have impelled doctors and researchers to improve their capacity to treat heart failure both through conventional methods and, in the most serious cases, through transplantation. Many pioneers have either directly or indirectly contributed to our ability to treat heart failure. Among these early researchers were: Dr Alexis Carrel, who was awarded the Nobel Prize for his pioneering work in vascular anastomosis; Dr John Gibbon, who did important work in the development of the cardiopulmonary bypass machine; Drs Normal Shumway, Richard Lower, and Demikhov, who developed heart transplant procedures in the canine model; Dr Christian Barnaard, who performed the first technically successful human-to-human heart transplant (1967); and Dr Thomas Hardy, who attempted the first xenotransplant (1963). While these achievements were phenomenal advances, long-term survival for transplant recipients was minimal until progress was made in immunosuppressive techniques.

Cost-Benefit Analysis↗

[Extended outcome assessment in endonasal sinus surgery].

BACKGROUND: Endonasal optically guided surgery has gained wide acceptance for treatment of chronic sinusitis. However, irrespective to the advent of minimally-invasive techniques, standard outcome assessment has not always reflected the increased technical and conceptual efforts. "Psychometric" instruments offer additional information on patients' perceptions of health. We analyzed the practical value of an extended outcome assessment. METHODS: Standardized interviews were carried out with 103 patients pre- and postoperatively applying several psychometrical instruments ("SF-36" and other valid general health-status instruments besides disease-specific questionnaires, providing 124 items/questions altogether). RESULTS: The diverse changes of subtle health status subscores as a rule paralleled each other and were concordant with traditional self-estimated global ratings of the surgical success by the patient. Significant postoperative changes of the "SF-36" questionnaire were especially seen in the subscale "bodily pain" and "level of energy". With few exceptions only, items reflecting any indirect burden of chronic sinusitis revealed less pronounced improvements postoperatively. CONCLUSION: It appears legitimate to question the special benefits of extended psychometric outcome research in comparison to traditional global ratings for daily surgical practice.

Adult↗

Antiperinuclear factor in an Italian series of patients with rheumatoid arthritis.

Serum samples from 90 cases of rheumatoid arthritis (RA), 218 control patients and 100 healthy controls were tested by indirect immunofluorescence for the presence of the antiperinuclear factor (APF), an autoantibody to the keratohyaline granules of human buccal mucosal cells. The sensitivity and specificity of the APF test for RA were 82 and 90%, respectively, slightly higher than those obtained when the same serum samples were tested for rheumatoid factor (RF) using a latex agglutination method. The diagnostic gain of APF in the RF-negative RA cases was greater than that of RF in the APF-negative cases (54% vs. 37%). In spite of a few technical disadvantages, the APF test should be therefore performed in the serological routine examination of rheumatic diseases. As APF was also found in 11% of degenerative joint disease (DJD) cases and the estimated prevalence ratio RA/DJD is, in Italy, 1/11, the predictive value of a negative APF test proved to be much higher than that of a positive test (98% vs. 40%) for the diagnosis of RA. APF was significantly associated with other autoantibodies (RF and antinuclear antibody).

Antibodies, Antinuclear↗

Detection and persistence of specific IgM antibody to Coxiella burnetii by enzyme-linked immunosorbent assay: a comparison with immunofluorescence and complement fixation tests.

An enzyme-linked immunosorbent assay (ELISA) for specific IgM antibody to Coxiella burnetii was compared with the indirect immunofluorescence (FA) test in studies of 130 serum samples from 38 patients with Q fever. The IgM fractions obtained after rate zonal-density gradient ultracentrifugation of 37 serum samples from 12 patients were also studied in a complement fixation test (CF-DG). Specific IgM antibody to C burnetii was detected by all three methods in sera collected two to eight weeks after the onset of symptoms. The longest period for which specific IgM was shown to persist was 17 weeks by ELISA and FA and 10 weeks by CF-DG. The ELISA is performed with a single dilution of convalescent-phase serum and offers advantages over the subjective FA and the technically tedious CF-DG methods. The estimation of C burnetii-specific IgM by ELISA or FA is useful for the confirmation of infection when a rising titer of complement-fixing antibody cannot be demonstrated because acute-phase blood samples are not available.

Antibodies, Bacterial↗

[The concept of risk and its estimation].

The concept of risk, in relation to human health, is a topic of primary interest for occupational health professionals. A new legislation recently established in Italy (626/94) according to European Community directives in the field of Preventive Medicine, called attention to this topic, and in particular to risk assessment and evaluation. Motivated by this context and by the impression that the concept of risk is frequently misunderstood, the present paper has two aims: the identification of the different meanings of the term "risk" in the new Italian legislation and the critical discussion of some commonly used definitions; and the proposal of a general definition, with the specification of a mathematical expression for quantitative risk estimation. The term risk (and risk estimation, assessment, or evaluation) has mainly referred to three different contexts: hazard identification, exposure assessment, and adverse health effects occurrence. Unfortunately, there are contexts in the legislation in which it is difficult to identify the true meaning of the term. This might cause equivocal interpretations and erroneous applications of the law because hazard evaluation, exposure assessment, and adverse health effects identification are completely different topics that require integrated but distinct approaches to risk management. As far as a quantitative definition of risk is of concern, we suggest an algorithm which connects the three basic risk elements (hazard, exposure, adverse health effects) by means of their probabilities of occurrence: the probability of being exposed (to a definite dose) given that a specific hazard is present (Pr(e[symbol: see text]p)), and the probability of occurrence of an adverse health effect as a consequence of that exposure (Pr(d[symbol: see text]e)). Using these quantitative components, risk can be defined as a sequence of measurable events that starts with hazard identification and terminates with disease occurrence; therefore, the following formal definition of risk is proposed: the probability of occurrence, in a given period of time, of an adverse health effect as a consequence of the existence of an hazard. In formula: R(d[symbol: see text]p) = Pr(e[symbol: see text]p) x Pr(d[symbol: see text]e). While Pr(e[symbol: see text]p) (exposure given hazard) must be evaluated in the situation under study, two alternatives exist for the estimation of the occurrence of adverse health effects (Pr(d[symbol: see text]e)): a "direct" estimation of the damage (Pr(d[symbol: see text]e) through formal epidemiologic studies conducted in the situation under observation; and an "indirect" estimation of Pr(d[symbol: see text]e) using information taken from the scientific literature (epidemiologic evaluations, dose-response relationships, extrapolations, ...). Both conditions are presented along with their respective advantages, disadvantages, and uncertainties. The usefulness of the proposed algorithm is discussed with respect to commonly used applications of risk assessment in occupational medicine; the relevance of time for risk estimation (both in the term of duration of observation, duration of exposure, and latency of effect) is briefly explained; and how the proposed algorithm takes into account (in terms of prevention and public health) both the etiologic relevance of the exposure and the consequences of exposure removal is highlighted. As a last comment, it is suggested that the diffuse application of good work practices (technical, behavioral, organizational, ...), or the exhaustive use of check lists, can be relevant in terms of improvement of prevention efficacy, but does not represent any quantitative procedure of risk assessment which, in any circumstance, must be considered the elective approach to adverse health effect prevention.

Humans↗

Elastase and alkaline protease production by Pseudomonas aeruginosa strains: comparison of two procedures.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause fatal infections in immunocompromised hosts. The virulence of P. aeruginosa is associated with the presence of various extracellular factors like elastase and alkaline protease. These enzymes are suggested to contribute to tissue destruction and assist bacterial invasion during infection. Therefore it seems likely that determination of these virulence factors will be an important prognostic marker in the near future especially for follow up of cystic fibrosis patients, to start antimicrobial agents that are directly or indirectly inhibit microbial growth or virulence factor production. Herein, we suggest a simple test procedure to be used in routine laboratories for estimation of elastase and alkaline protease levels and compare them with quantitative methods in the literature. We detected the amount of elastase and alkaline protease in 49 clinical P. aeruginosa isolates by comparing agar plate method and colorimetric assay. The resulting values were in the range reported in the literature and differed from one strain to another(elastase: 0-1390 mg/ml, alkaline protease: 0- 770 mg/ml). Linear relationships were found when assays compared in pairs and significant correlation coefficients were obtained(r>0.788 for alkaline protease, p<0.0001- r>0.926 for elastase, p<0.0001). Our method can be applied in laboratories regardless of the availability of technical equipment.

Bacterial Proteins↗

Socioeconomic inequalities in child mortality: comparisons across nine developing countries.

This paper generates and analyses survey data on inequalities in mortality among infants and children aged under five years by consumption in Brazil, Côte d'Ivoire, Ghana, Nepal, Nicaragua, Pakistan, the Philippines, South Africa, and Viet Nam. The data were obtained from the Living Standards Measurement Study and the Cebu Longitudinal Health and Nutrition Survey. Mortality rates were estimated directly where complete fertility histories were available and indirectly otherwise. Mortality distributions were compared between countries by means of concentration curves and concentration indices: dominance checks were carried out for all pairwise intercountry comparisons; standard errors were calculated for the concentration indices; and tests of intercountry differences in inequality were performed.

Child, Preschool↗

[Phonosurgical treatment of vocal cord polyps].

INTRODUCTION: A vast majority of polyps appear at the predilection site of the vocal fold and therefore belong to the functional-traumatic group of vocal fold lesions. According to their size, vocal fold polyps may severely interfere with the glottal closure, and induce hoarseness, vocal fatigue, and frequently hyperkynetic pattern of voice production. MATERIAL AND METHOD: A series of 699 polyps was operated by direct microlaryngoscopy (DML), indirect microstroboscopy (IMS), and indirect videostroboscopu (IVS). Postoperative functional results were estimated by stroboscopy. Based on the functional results, specific indications were established for the use of each operative technique. RESULTS: Functional results in our series were satisfactory. We used DML in 152 patients, IMS in 432 cases, and IVS in 115 phonosurgical procedures. Indirect surgery was used in 547 patients (78.2%). It was established that indirect procedures were very suitable for small vocal fold lesions with narrow base, and good demarcation towards the normal vocal fold tissue. Direct procedures should be used for massive growths with wide base, and poor demarcation towards the normal vocal fold tissue. The patient's preference for a particular technique and possible contraindications for either direct of indirect procedure, should also be considered. DISCUSSION: Direct and indirect procedures are complementary, and each has its own indications. IVS technique is technically simpler in comparison with IMS procedure. Each phonosurgeon must be able and skilled to use both direct and indirect phonosurgical techniques.

Endoscopy↗

Reliability and validity of the combined heart rate and movement sensor Actiheart.

UNLABELLED: Accurate quantification of physical activity energy expenditure is a key part of the effort to understand disorders of energy metabolism. The Actiheart, a combined heart rate (HR) and movement sensor, is designed to assess physical activity in populations. OBJECTIVE: To examine aspects of Actiheart reliability and validity in mechanical settings and during walking and running. METHODS: In eight Actiheart units, technical reliability (coefficients of variation, CV) and validity for movement were assessed with sinusoid accelerations (0.1-20 m/s(2)) and for HR by simulated R-wave impulses (25-250 bpm). Agreement between Actiheart and ECG was determined during rest and treadmill locomotion (3.2-12.1 km/h). Walking and running intensity (in J/min/kg) was assessed with indirect calorimetry in 11 men and nine women (26-50 y, 20-29 kg/m(2)) and modelled from movement, HR, and movement + HR by multiple linear regression, adjusting for sex. RESULTS: Median intrainstrument CV was 0.5 and 0.03% for movement and HR, respectively. Corresponding interinstrument CV values were 5.7 and 0.03% with some evidence of heteroscedasticity for movement. The linear relationship between movement and acceleration was strong (R(2) = 0.99, P < 0.001). Simulated R-waves were detected within 1 bpm from 30 to 250 bpm. The 95% limits of agreement between Actiheart and ECG were -4.2 to 4.3 bpm. Correlations with intensity were generally high (R(2) > 0.84, P < 0.001) but significantly highest when combining HR and movement (SEE < 1 MET). CONCLUSIONS: The Actiheart is technically reliable and valid. Walking and running intensity may be estimated accurately but further studies are needed to assess validity in other activities and during free-living. SPONSORSHIP: The study received financial support from the Wellcome Trust and SB was supported by a scholarship from Unilever, UK.

Adult↗

Guidelines for rapid estimation of the direct and indirect costs of HIV infection in a developing country.

The economic impact of AIDS may be especially severe in developing nations because of the additional burden on scarce health care resources and the potential loss of human capital. We describe a methodology for estimating the direct and indirect costs of HIV infection. Our approach is designed for the typical environment of international economic consulting, where time is short, and data sparse. We focus on HIV rather than AIDS because the only way now known to prevent AIDS is to prevent HIV infection.

Acquired Immunodeficiency Syndrome↗

An overview to CERSSO's self evaluation of the cost-benefit on the investment in occupational safety and health in the textile factories: "a step by step methodology".

INTRODUCTION: The Pan American Health Organization (PAHO) and CERSSO collaborated to develop a new Tool Kit (TK), which became available in May 2002. PAHO already had a TK in place, and CERSSO requested that one be developed for their needs. CERSSO wanted to enable managers and line workers in garment factories to self-diagnose plant and workstation hazards and to estimate the costs and benefits of investing in occupational safety and health (OSH) as a way to improve productivity and competitiveness. METHODS: For consistency, the collaborating organizations agreed to construct the TK according to PAHO's methodology. The instrument was developed to be comprehensive enough that any user can collect the data easily. It integrates epidemiologic, risk assessment, clinic, engineering, and accountability issues, organized to include step-by-step training in: (a) performing risk assessments in the workplaces (risk factors); (b) making cause-effect relationships; (c) improving decision making on OSH interventions; (d) doing calculations of direct and indirect costs and savings; and (e) doing calculation of the overall cost-benefit of OSH interventions. RESULTS AND CONCLUSIONS: Since July 2002, about 2,400 employees and officials from 736 garment factories, Ministries of Labor, Health, Social Security Institutes, and Technical Training Institutions of Central America and the Dominican Republic have used this instrument. Systematically, they have calculated a positive relationship of the investment (3 to 33 times). Employers are now aware of the financial rewards of investing in OSH. The TK is available in Spanish, Korean, and English. In July 2003, a software program in Spanish and English was developed (180 persons have been trained in the region), which requires less time to execute with better reliability.

Central America↗

Relating pulmonary oxygen uptake to muscle oxygen consumption at exercise onset: in vivo and in silico studies.

Assessment of the rate of muscle oxygen consumption, UO(2m), in vivo during exercise involving a large muscle mass is critical for investigating mechanisms regulating energy metabolism at exercise onset. While UO(2m) is technically difficult to obtain under these circumstances, pulmonary oxygen uptake, VO(2p), can be readily measured and used as a proxy to UO(2m). However, the quantitative relationship between VO(2p) and UO(2m) during the nonsteady phase of exercise in humans, needs to be established. A computational model of oxygen transport and utilization--based on dynamic mass balances in blood and tissue cells--was applied to quantify the dynamic relationship between model-simulated UO(2m) and measured VO(2p) during moderate (M), heavy (H), and very heavy (V) intensity exercise. In seven human subjects, VO(2p) and muscle oxygen saturation, StO(2m), were measured with indirect calorimetry and near infrared spectroscopy (NIRS), respectively. The dynamic responses of VO(2p) and StO(2m) at each intensity were in agreement with previously published data. The response time of muscle oxygen consumption, tauUO(2m) estimated by direct comparison between model results and measurements of StO(2m) was significantly faster (P < 0.001) than that of pulmonary oxygen uptake, tauVO(2p) (M: 13 +/- 4 vs. 65 +/- 7 s; H: 13 +/- 4 vs. 100 +/- 24 s; V: 15 +/- 5 vs. 82 +/- 31 s). Thus, by taking into account the dynamics of oxygen stores in blood and tissue and determining muscle oxygen consumption from muscle oxygenation measurements, this study demonstrates a significant temporal dissociation between UO(2m) and VO(2p) at exercise onset.

Adolescent↗

High-resolution analysis of DNA replication in released chromatin fibers containing 5-bromodeoxyuridine.

A strategy has been devised to physically map replication sites in released chromatin of mammalian cells. When added to the culture medium, 5-bromodeoxyuridine (BrdU) is incorporated into replicating DNA, partially replacing thymidine. BrdU pulses as short as one minute can be visualized on preparations of straightened chromatin fibers from protein-extracted nuclei by means of monoclonal anti-BrdU antibody. Short BrdU pulses (< 10 min) appear as strings of fluorescent signals that are 50-300 kb in length. This corresponds to the estimated size of individual replication units. Pulse chase experiments reveal that replicating DNA is tightly associated with the residual nuclear matrix, whereas newly replicated DNA is positioned on the released loop chromatin of nuclear halo preparations. Simultaneous fluorescence in situ hybridization (FISH) on BrdU-substituted released chromatin fibers suggests that replication can initiate at multiple sites anywhere within an alpha-satellite array of several Mb.

Bromodeoxyuridine↗

Infant mortality trends and differentials in Nepal.

Infant mortality trends and differentials are estimated from the 1981 Nepal Contraceptive Prevalence Survey (NCPS) and compared with similar estimates from the 1976 Nepal Fertility Survey (NFS) and the 1981 Census of Nepal. The analysis indicates that infant mortality rates derived directly from the NFS maternity histories are the most accurate. Infant mortality rates derived directly from the NCPS maternity histories are severely underestimated and yield a strongly biased trend that is the reverse of the true downward trend. Indirect estimates of infant mortality trends derived from child survivorship data do not result in a consistent pattern. Infant mortality differentials, when expressed in relative rather than absolute terms, are generally consistent with findings from earlier studies. Possible reasons for data quality differences among the three data sources are discussed.

Actuarial Analysis↗