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Estimation of genetic parameters based on individual and group mean records in laying hens.

(1) The study was conducted to estimate the heritability, genetic correlations and breeding values of laying hens based on individual records and group mean records. (2) Records of two pure lines from a commercial breeding programme of White Leghorns from three generations housed in single cages and in group cages were used. A total of 8483 and 8817 individual records of lines A and D, respectively, and a total of 1358 (line A) and 1161 (line D) group mean records were analysed. (3) An animal model using Restricted Maximum Likelihood (REML) was used to estimate variance components of individual records. Group mean records were analysed using the sire model, taking heterogeneity of error variance and correlated residual effects into account. Breeding values of sires were estimated based on the BLUP method using a multivariate sire model. Spearman Rank correlations were used to compare sire breeding values estimated from individual records and from group mean records. The traits studied were monthly egg production, cumulative production and egg weight. (4) Heritability estimates based on individual records were higher than from group mean records. Heritabilities for cumulative production records were higher than for monthly production, based on individual as well as group mean records. The estimates of genetic correlations between monthly egg production and cumulative production were moderate to high. Egg production and egg weight recorded individually were highly genetically correlated with those recorded on group means. Sire breeding values estimated from individual records showed high correlations with those from group mean records. (5) Differences in the ranking of sire breeding values estimated from individual vs group mean records were negligible, indicating that no genotype x environment interaction exists. Selection based on individual performance records of laying hens housed in single cages could give a good response on performance of laying hens housed in group cages. Cumulative egg production over periods 1 to 6 is the best trait for the selection programme.

Animals↗

INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS.

The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled gamma-globulin and for the localization of these determinants on the gamma-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of gamma-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum. The antigenic determinants responsible for the individual specificity were localized in all cases studied solely to the Fab fragment produced by papain digestion. After reductive cleavage, three patterns of localization were observed. Individual specificity could be localized either to; (a) isolated heavy chains, (b) isolated light chains, (c) antigenic determinants present only when light and heavy chains were recombined. After immunization with whole myeloma proteins, individual specificity was localized in part at least to the isolated heavy chain in four of six proteins studied. It was localized to the light chains in three of five type L proteins but in none of six type K proteins. In the instances where individual specificity of the myeloma protein was present on the light chains, it was shown that the Bence Jones protein from the same patient also contained the individual specificity. Immunization with isolated heavy or light chains furnished further evidence for the individual specificity of both types of chains. These studies on myeloma proteins furnished evidence concerning the portions of the gamma-globulin molecule subject to individual antigenic variation. The light chains, particularly the L type and the Fd portion of the heavy chains were primarily involved. Evidence for the importance of the quaternary structure was also obtained from the necessity in some instances for light and heavy chains to be associated in order for individual specificity to be observed. The Fc fragment of the heavy chains on the other hand showed very limited variation which was related to subgroup specificity.

Antigens↗

Effect of sodium arsenite on peripheral lymphocytes in vitro: individual susceptibility among a population exposed to arsenic through the drinking water.

Arsenic (As) contamination in ground water has affected more than 19 countries. Approximately 36 million people in the Bengal delta alone are exposed to this toxicant via drinking water (>50 microg/l) and are at potential health risk. Chronic ingestion of As via drinking water is associated with occurrence of skin lesions, cancer and other arsenic-induced diseases in West Bengal, India. An in vitro cytogenetic study was performed utilizing chromosomal aberrations (CA) in lymphocytes treated with sodium arsenite (0-5 microM) in six symptomatic (having arsenic-related skin lesions) individuals, six age- and sex-matched As-exposed asymptomatic (no arsenic-related skin lesions) individuals and six control individuals with similar socio-economic status residing in non-affected districts of West Bengal with no evidence of As exposure. The mean As content in nails and hair was 9.61 and 5.23 microg/g in symptomatic, 3.48 and 2.17 microg/g in asymptomatic and 0.42 and 0.33 microg/g in the control individuals, respectively. The main aim of our study was to determine whether genotoxic effects differed in the lymphocytes of the control (no exposure to arsenic), asymptomatic and symptomatic individuals after in vitro treatment with sodium arsenite. Although both the exposed groups had chronic exposure to As through the drinking water, individuals with skin lesions accumulated more As in their nails and hair and excreted less in urine (127.80 versus 164.15 microg/l). The results show that sodium arsenite induced a significantly higher percentage of aberrant cells in the lymphocytes of control individuals than in the lymphocytes of both the exposed groups. Within the two exposed groups As induced higher incidences of CA in the symptomatic than the asymptomatic individuals. These results suggest that asymptomatic individuals have relatively lower sensitivity and susceptibility to induction of genetic damage by As compared with the symptomatic individuals.

Adult↗

Circulating amylin in human essential hypertension: heritability and early increase in individuals at genetic risk.

BACKGROUND: Human essential hypertension is a complex trait with poorly understood genetic determination. Insulin resistance is frequently associated with this trait. OBJECTIVE: To determine whether a potentially pathogenic feature of the insulin-resistant state, circulating amylin (islet amyloid polypeptide, co-released with insulin from pancreatic islet beta-cells), is already increased in prehypertensive individuals (normotensive persons at genetic risk of hypertension because of family history), whether such individuals already differ in their amylin response to beta-cell stimulation, and whether plasma amylin concentration is heritable. Such features could establish increased circulating amylin as a hereditary 'intermediate phenotype' useful in genetic analyses of hypertension. METHODS: Plasma amylin and insulin were measured in 283 medication-free individuals stratified by blood pressure status (82 hypertensive and 201 normotensive), and genetic risk (family history) of hypertension. Differences in means were tested by ANOVA, variances by F test, and frequency distributions by maximum likelihood analysis. Co-release of amylin and insulin was provoked by intravenous infusion of mixed amino acids. The effect of antihypertensive treatment was evaluated after monotherapy with either angiotensin converting enzyme inhibition or calcium-channel blockade in hypertension. RESULTS: Plasma amylin was increased in hypertension (P= 0.027), and body mass index was a strong predictor of increased circulating amylin (P = 0.0001). Plasma amylin and plasma renin activity were not correlated (P = 0.395), and effective antihypertensive monotherapy with either angiotensin converting enzyme inhibition or calcium-channel blockade did not affect either amylin (P = 0.87-0.97) or insulin (P= 0.55-0.59). Among normotensive individuals, those at genetic risk of hypertension (with positive family history) already had increased concentrations of amylin (P< 0.001), despite exhibiting no difference in blood pressure or body mass index compared with the family-history-negative group; however, among normotensive individuals, both family history (P = 0.043) and body mass index (P= 0.0059) were significant predictors of increased concentrations of amylin. By maximum likelihood analysis, plasma amylin was distributed heterogeneously in the normotensive individuals, with two modes best explaining the distribution (chi2 = 77.4, P< 0.001), and family-history-positive individuals completely accounting for the upper mode (chi2 = 4.63, P = 0.031). Family-history-positive normotensive individuals showed greater plasma amylin concentrations both before and during beta-cell stimulation by amino acid infusion (P = 0.014). Black (n = 111) and white (n = 172) individuals did not differ in mean (P = 0.946) or variance (P = 0.172) of plasma amylin concentrations. CONCLUSIONS: These results suggest that plasma amylin concentration is in part determined by heredity. Both basal and stimulated plasma amylin excess may identify a subgroup of individuals bearing an inherited predisposition to hypertension. Measurement of amylin might identify a useful 'intermediate phenotype' in the genetic analysis of essential hypertension and its relationship to insulin resistance.

Adult↗

Computer-assisted orthopedic surgery with individual templates and comparison to conventional operation method.

STUDY DESIGN: Comparison was made of the accuracy of a pedicle bore performed by conventional technique and by using an individual template in the lumbar spine of cadavers. OBJECTIVES: The fixation of pedicle screws necessitates a high amount of surgical skill and experience to avoid lesions of nerves and vessels. By using individual templates in a cadaver study the goal was to prove the accuracy and efficiency of this less-invasive image-guided surgery in comparison with the conventional technique by fluoroscopy and computed tomographic (CT) scan. SUMMARY OF BACKGROUND DATA: Based on three-dimensional models generated from CT scans of the lumbar spine, precise preoperative planning of the position and trajectory of pedicle screws is possible. In comparison with other means of computer-assisted spine surgery with navigation systems, in which a time-consuming intraoperative matching of the bone surface structure is necessary, the use of individual templates enables the surgeon to reduce the operation time considerably. METHODS: Individual templates are customized on the basis of three-dimensional reconstructions of the bone structures extracted from CT image data and depending on the individual preoperative surgical planning, which uses the desktop image processing system for orthopedic surgery (DISOS). A desktop-computer-controlled milling device is used as a three-dimensional printer to automatically mold the shape of small reference areas of the bone surface into the body of the template. Postoperative CT scans were obtained and the accuracy of the pedicle bore rated by two independent observers. RESULTS: The preparation time with the individual template lasted slightly longer than with the conventional operation technique (555 seconds and 482 seconds, respectively). Fluoroscopic study took a mean time of 31.5 seconds, with the conventional operation technique and 5.5 seconds with the individual template. The assessment of the postoperative CT scans demonstrated a higher accuracy of the pedicle bore with the individual template. CONCLUSIONS: This cadaveric study has shown that overall operation time including the fluoroscopy time can be shortened by using the individual template for the pedicle bore. The individual template is an alternative to the computer-assisted navigation systems with a good cost-performance ratio without excessive technical workload on the physicians or the surgical personnel. Further investigations must be conducted to validate the clinical applicability of this system.

Bone Screws↗

Serious adverse cutaneous and hepatic toxicities associated with nevirapine use by non-HIV-infected individuals.

BACKGROUND: Nevirapine is a nonnucleoside reverse transcriptase antiretroviral agent. Among HIV-infected individuals, rare instances (<1%) of serious cutaneous and hepatic toxicity have been reported. Because of its favorable pharmacokinetic profile, non-HIV-infected individuals have received nevirapine-containing postexposure prophylaxis (PEP). OBJECTIVE: To describe the clinical features of cutaneous and hepatic toxicity that occurred when nevirapine was administered to non-HIV-infected individuals. METHODS: Reports of nevirapine-associated cutaneous or hepatic toxicity occurring among non-HIV-infected individuals were obtained from the US Food and Drug Administration's adverse event reporting system, the pharmaceutic manufacturer, occupational health programs in Chicago, physicians, and case reports. The Eastern Cooperative Oncology Group (ECOG) scoring system was used to grade toxicity. RESULTS: Twelve non-HIV-infected individuals developed severe cutaneous toxicity, including 3 with Stevens-Johnson syndrome, after 7 to 12 days of nevirapine-containing PEP regimens. Thirty non-HIV-infected individuals developed hepatotoxicity after 8 to 35 days of single-agent nevirapine (n = 8) or a nevirapine-containing PEP regimen (n = 22). Findings included ECOG grade 3 or 4 hepatotoxicity (n = 14), fevers (n = 11), skin rashes (n = 8), eosinophilia (n = 6), and fulminant hepatic necrosis requiring an orthotopic liver transplant (n = 1). Rates of severe hepatotoxicity (grade 3 or 4) in non-HIV-infected individuals ranged from 10% (4/41) to 62% (5/8). Liver biopsy material from 2 individuals was consistent with a hypersensitivity syndrome. CONCLUSIONS: Serious hepatic and cutaneous toxicities can occur in non-HIV-infected individuals who receive short-term nevirapine therapy. The rate of severe hepatotoxicity appears to be greater in non-HIV-infected individuals than in HIV-infected persons and may be associated with higher CD4 counts. The use of PEP regimens containing nevirapine should be discouraged.

Adult↗

Integrating individual-based indices of contaminant effects. How multiple sublethal effects may ultimately reduce amphibian recruitment from a contaminated breeding site.

Habitat contamination can alter numerous biological processes in individual organisms. Examining multiple individual-level responses in an integrative fashion is necessary to understand how individual health or fitness reflects environmental contamination. Here we provide an example of such an integrated perspective based upon recent studies of an amphibian (the bullfrog, Rana catesbeiana ) that experiences several, disparate changes when larval development occurs in a trace element-contaminated habitat. First, we present an overview of studies focused on specific responses of individuals collected from, or transplanted into, a habitat contaminated by coal combustion residues (CCR). These studies have reported morphological, behavioral, and physiological modifications to individuals chronically interacting with sediments in the CCR-contaminated site. Morphological abnormalities in the oral and tail regions in contaminant-exposed individuals influenced other properties such as grazing, growth, and swimming performance. Behavioral changes in swimming activities and responses to stimuli appear to influence predation risk in the contaminant-exposed population. Significant changes in bioenergetics in the contaminated habitat, evident as abnormally high energetic expenditures for survival (maintenance) costs, may ultimately influence production pathways (growth, energy storage) in individuals. We then present a conceptual model to examine how interactions among the affected systems (morphological, behavioral, physiological) may ultimately bring about more severe effects than would be predicted if the responses were considered in isolation. A complex interplay among simultaneously occurring biological changes emerges in which multiple, sublethal effects ultimately can translate into reductions in larval or juvenile survival, and thus reduced recruitment of juveniles into the population. In systems where individuals are exposed to low concentrations of contaminants for long periods of time, research focused on one or few sublethal responses could substantially underestimate overall effects on individuals. We suggest that investigators adopt a more integrated perspective on contaminant-induced biological changes so that studies of individual-based effects can be better integrated into analyses of mechanisms of population change.

Animals↗

Is There a Fly in My Soup? To What Extent Do Metabarcoding and Individual Barcoding Tell the Same Story?

Metabarcoding has become the method of choice for characterizing complex arthropod communities. The extent to which metabarcoded bulk samples will recover the same community composition as individual sequencing of all individuals in the sample remains poorly quantified. Biases such as unequal extraction of DNA from different taxa, primer mismatches and non-random PCR may cause the selective drop-out of species from metabarcoding data. At the same time, DNA metabarcoding may reveal arthropod taxa present not as individuals, but as DNA residues on the surface or in the gut of insects. To quantify the consistency in sample contents established by different means, we metabarcoded 45 bulk insect samples, then extracted all arthropods and sequenced them individually. Metabarcoding targeted 418&#x2009;bp at the 3' end of the Folmer barcoding region, while individual barcodes captured the entire 658&#x2009;bp Folmer region. The metabarcoding workflow, including PCR amplification, sequencing and bioinformatics, was performed in three replicates from three separate lysate aliquots per sample. For the main analyses, sequences were assigned to Barcode Index Numbers (BINs) as identical taxonomic categories across data types, thereby allowing the detection of even rare but biologically true taxa. Since such reference-based validation will be unavailable to any researcher dealing with metabarcoding data alone, we validated our key findings through an alternative workflow, i.e., de novo clustering of sequences. We found that metabarcoding is replicable, as different replicates of the same sample recover similar species richness and composition. Individual barcoding and metabarcoding provide similar impressions of relative differences in community structure: species-rich vs. species-poor samples rank similarly among data types (Spearman's &#x2374;&#x2009;=&#x2009;0.88-0.99) as do differences in relative dissimilarity between sample pairs (Spearman's &#x2374;&#x2009;=&#x2009;0.55-0.90). Dissimilarity between data types varies with BIN richness in the sample, but this relationship reflects nestedness rather than turnover: metabarcoding recovers the same set of core species as individual barcoding but adds hundreds of species on top. Any BIN recovered as an individual occurred with high probability in the metabarcoding data, and any BIN found in high read abundances by metabarcoding was likely found as an individual (p&#x2009;>&#x2009;0.8). In terms of abundances, the number of individual insects per BIN was well predicted by the number of metabarcoding reads (R2&#x2009;>&#x2009;0.68 for a model including taxonomy as a random effect). Our analysis suggests that metabarcoding data will be informative of the sample contents in terms of arthropod species richness, composition and taxon-specific abundances. Taxa recovered in low copy numbers in metabarcoding sequence data will likely represent DNA left as residues from past biotic interactions. Barring sequencing errors, both types of data yield biologically relevant insights into the taxa present in the source community.

Animals↗

Two-sample tests for comparing intra-individual genetic sequence diversity between populations.

Consider a study of two groups of individuals infected with a population of a genetically related heterogeneous mixture of viruses, and multiple viral sequences are sampled from each person. Based on estimates of genetic distances between pairs of aligned viral sequences within individuals, we develop four new tests to compare intra-individual genetic sequence diversity between the two groups. This problem is complicated by two levels of dependency in the data structure: (i) Within an individual, any pairwise distances that share a common sequence are positively correlated; and (ii) for any two pairings of individuals which share a person, the two differences in intra-individual distances between the paired individuals are positively correlated. The first proposed test is based on the difference in mean intra-individual pairwise distances pooled over all individuals in each group, standardized by a variance estimate that corrects for the correlation structure using U-statistic theory. The second procedure is a nonparametric rank-based analog of the first test, and the third test contrasts the set of subject-specific average intra-individual pairwise distances between the groups. These tests are very easy to use and solve correlation problem (i). The fourth procedure is based on a linear combination of all possible U-statistics calculated on independent, identically distributed sequence subdatasets, over the two levels (i) and (ii) of dependencies in the data, and is more complicated than the other tests but can be more powerful. Although the proposed methods are empirical and do not fully utilize knowledge from population genetics, the tests reflect biology through the evolutionary models used to derive the pairwise sequence distances. The new tests are evaluated theoretically and in a simulation study, and are applied to a dataset of 200 HIV sequences sampled from 21 children.

Base Sequence↗

Psychosocial investigation of individual and community responses to the experience of Ovine Johne's Disease in rural Victoria.

OBJECTIVE: This paper explores the psychosocial outcomes for individuals and communities in rural Victoria who experienced the outbreak of Ovine Johne's Disease (OJD). DESIGN: The study uses a qualitative methodology to analyse the minutes of evidence provided by the inquiry into the control of OJD to identify the psychosocial events, experiences and outcomes associated with the control of this outbreak. The inquiry was undertaken by the Environment and Natural Resources Committee of the Victorian State Government. SETTING: Public hearings were undertaken by the committee across several rural Victorian communities and the state capital, Melbourne. SUBJECTS: The transcripts detail 136 submissions from 98 individuals and 23 organisations. OUTCOME MEASURES: The analysis aimed to provide insight into the impact of the disease on individuals and communities and also to explore the factors individuals perceived as associated with these outcomes. RESULTS: While the paper identifies that aspects of stock loss associated with the outbreak caused substantial emotional and economic distress, for farmers the most significant finding was the impact of the government control program on individuals, families and rural communities. The control program was perceived as having very limited scientific credibility and its implementation was described as heartless, inflexible and authoritarian. Involvement with the program resulted in farmers reporting emotions, such as, trauma, shame, guilt and stigma. Families became discordant and the sense of community within rural townships fragmented. Psychological outcomes of grief, depression and anxiety emerged as prevalent themes within families and communities. CONCLUSIONS: These data highlight the need for significant attention to the management of rural disasters, such as, the OJD program. WHAT THIS PAPER ADDS: There is an acknowledgement in the literature that rural disasters have a significant impact on the well-being of individuals, families and communities. The major focus of the previous research has, however, been on the impact of economic losses with less recognition of the other psychosocial loss experiences that accompany the experience of rural disaster. This paper achieves a clear description of the experiences for individuals (trauma, stigma, sense of personal failure, loss of identity, diminished self esteem and family disruption) and communities (destroyed social cohesion, economic disharmony) caught up in the OJD disaster and explores the factors that individuals perceive as responsible for these outcomes. The mental health outcomes for individuals, such as, loss, grief and depression are also explored within this paper. This paper highlights the psychosocial complexity of the experience of rural disaster for individuals and communities significantly extending the current knowledge base in this area.

Anecdotes as Topic↗

Human herpesvirus-6-specific interleukin 10-producing CD4+ T cells suppress the CD4+ T-cell response in infected individuals.

Human herpesvirus-6 (HHV-6) infection normally persists for the lifetime of the host and may reactivate with immunosuppression. The mechanism behind HHV-6 latent infection is still not fully understood. In this study, we observed that decreased proliferation of CD4+ T cells and PBMCs but not CD8+ T cells from HHV-6-infected individuals was stimulated with HHV-6-infected cell lysates. Moreover, HHV-6-stimulated CD4+ T cells from HHV-6-infected individuals have suppressive activity on naïve CD4+ T and CD8+ T cells from HHV-6-uninfected individuals. However, no increased proportion of CD4+ CD25+ Treg cells from HHV-6-infected individuals contributed to the suppressive activity of the HHV-6-stimulated CD4+ T cells from HHV-6-infected individuals. Transwell experiments, ELISA and anti-IL-10 antibody blocking experiment demonstrated that IL-10 may be the suppressive cytokine required for suppressive activity of CD4+ T cells from HHV-6-infected individuals. Results of intracellular interleukin (IL)-10 and IL-4 further implicated the HHV-6-specific IL-10-producing CD4+ T cells in the suppressive activity of CD4+ T cells from HHV-6-infected individuals. Results of intracellular interferon (IFN)-gamma demonstrated a decreased frequency of HHV-6-specific IFN-gamma-producing CD4+ T, but not CD8+ T cells in HHV-6-infected individuals, indicating that it was the CD4+ Th1 responses in HHV-6-infected individuals that were selectively impaired. Our findings indicated that HHV-6-specific IL-10-producing CD4+ T cells from HHV-6-infected individuals possess T regulatory type 1 cell activity: immunosuppression, high levels of IL-10 production, with a few cells expressing IFN-gamma, but none expressing IL-4. These cells may play an important role in latent HHV-6 infection.

Adult↗

A measure of food seeking in individuals with Prader-Willi syndrome.

BACKGROUND: Individuals with Prader-Willi syndrome (PWS), a chromosome 15 genetic disorder, often have a significant preoccupation with food and problem behaviour related to food seeking is often prevalent. METHODS: In the present study, we compared how individuals with PWS responded on a survey regarding the acceptability of food in various locations that varied according to degree of appropriateness for human consumption (e.g. food on a plate, food in a garbage can). For a subgroup of participants, we observed how they actually responded when placed in a room with food items placed in the same locations depicted in the survey. In the first part of the study, three groups (25 typically developing individuals, 7 individuals with intellectual disability (ID), and 19 individuals with PWS) responded to a visual survey to determine the degree of acceptability of food items in various locations (e.g. on a table near a hairbrush, on the floor behind a toy box, in a trash can). In the second part of the study, these food items (popcorn, jelly beans) were placed in the 12 locations described above. Nine individuals diagnosed with PWS (deletion type) and three individuals with ID were given some break time in the room for 15 min. The amount of food consumed, the time spent food seeking, and time spent interacting with materials were measured. RESULTS: Results of the survey indicated that the PWS group differed significantly with regard to how they responded on the survey from the typically developing group, but did not differ significantly from the ID group. Results of the food seeking observations indicated that only three individuals with PWS ate a significant number of items. The three individuals did not differ from the rest of the group according to IQ or compulsivity score; however, they had significantly lower body mass index (BMI) scores and were younger than the other participants. CONCLUSIONS: The findings from the survey indicate that individuals with PWS are able to discriminate the appropriateness of eating items in more or less contaminated areas; however, the amount of time spent seeking food and the amount of food covertly consumed appeared to depend more directly on age and BMI.

Adolescent↗

Subsidies and the demand for individual health insurance in California.

OBJECTIVE: To estimate the effect of changes in premiums for individual insurance on decisions to purchase individual insurance and how this price response varies among subgroups of the population. DATA SOURCE: Survey responses from the Current Population Survey (http://www.bls.census.gov/cps/cpsmain.htm), the Survey of Income and Program Participation (http://www.sipp.census.gov/sipp), the National Health Interview Survey (http://www.cdc.gov/nchs/nhis.htm), and data about premiums and plans offered in the individual insurance market in California, 1996-2001. STUDY DESIGN: A logit model was used to estimate the decisions to purchase individual insurance by families without access to group insurance. This was modeled as a function of premiums, controlling for family characteristics and other characteristics of the market. A multinomial model was used to estimate the choice between group coverage, individual coverage, and remaining uninsured for workers offered group coverage as a function of premiums for individual insurance and out-of-pocket costs of group coverage. PRINCIPAL FINDINGS: The elasticity of demand for individual insurance by those without access to group insurance is about -.2 to -.4, as has been found in earlier studies. However, there are substantial differences in price responses among subgroups with low-income, young, and self-employed families showing the greatest response. Among workers offered group insurance, a decrease in individual premiums has very small effects on the choice to purchase individual coverage versus group coverage. CONCLUSIONS: Subsidy programs may make insurance more affordable for some families, but even sizeable subsidies are unlikely to solve the problem of the uninsured. We do not find evidence that subsidies to individual insurance will produce an unraveling of the employer-based health insurance system.

Adult↗

Risk assessment of Listeria monocytogenes: impact of individual cell variability on the exposure assessment step.

Recently, the lag phase research in predictive microbiology is focusing more on the individual cell variability, especially for pathogenic microorganisms that typically occur in very low contamination levels, like Listeria monocytogenes. In this study, the effect of this individual cell lag phase variability was introduced in an exposure assessment study for L. monocytogenes in a liver pâté. A basic framework was designed to estimate the contamination level of pâté at the time of consumption, taking into account the frequency of contamination and the initial contamination levels of pâté at retail. Growth was calculated on pâté units of 150 g, comparing an individual-based approach with a classical population-based approach. The two different protocols were compared using simulations. If only the individual cell lag variability was taken into account, important differences were observed in cell density at the time of consumption between the individual-based approach and the classical approach, especially at low inoculum levels, resulting in high variability when using the individual-based approach. Although, when all variable factors were taken into account, no significant differences were observed between the different approaches, allowing the conclusion that the individual cell lag phase variability was overruled by the global variability of the exposure assessment framework. Even in more extreme conditions like a low inoculum level or a low water activity, no differences were created in cell density at the time of consumption between the individual-based approach and the classical approach. This means that the individual cell lag phase variability of L. monocytogenes has important consequences when studying specific growth cases, especially when the applied inoculum levels are low, but when performing more general exposure assessment studies, the variability between the individual cell lag phases is too limited to have a major impact on the total exposure assessment.

Animals↗

Calcium concentration of individual coronary calcified plaques as measured by multidetector row computed tomography.

BACKGROUND: Characteristics of individual calcified plaques, especially calcium concentration (CC), may provide incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and evaluation of therapeutic intervention. In this study, therefore, we assessed the characteristics of individual calcified plaques and their relationship to other parameters derived from CT analysis of coronary calcium in a community-based cross-sectional cohort. METHODS AND RESULTS: Coronary artery calcium (CAC) was analyzed in 612 participants of the Framingham Heart Study (third-generation and offspring cohorts) using prospectively ECG-triggered multidetector CT. We determined the CC, Agatston score, calcified volume, and mineral mass of individual calcified plaques in each subject. Heterogeneity of CC was defined as the standard deviation of CC of all individual calcified plaques in a subject. CAC was detected in 274 of 605 subjects. After excluding 57 subjects (21%) because of motion artifacts, we identified a total of 956 calcified coronary plaques in 217 subjects (74 women, 143 men; mean age, 57.1+/-10.8 years) with detectable CAC and no image artifacts. CC of individual calcified plaques was independent of subject age (P=0.76) and sex (197.8+/-74.8 versus 183.6+/-52.8 mg/cm3 for men versus women; P=0.21). Among a subgroup of 125 subjects with multiple (> or =3) individual calcified plaques, CC was heterogeneous within individual subjects (mean SD of CC, 43.6+/-23.1 mg/cm3). The degree of heterogeneity of CC in these subjects was independent of age (P=0.60), sex (P=0.99), and number of plaques (P=0.06). CONCLUSIONS: The CC of individual calcified plaques is independent of age and sex but heterogeneous within a subject, which may reflect that the pathological process of calcified plaque formation and progression is the same in men and women regardless of age. CC may have incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and the evaluation of therapeutic intervention. Further studies are warranted to confirm that individual plaque analysis is preferable to global CAC scores to evaluate progression of atherosclerosis and to assess whether individual plaque analysis may be complementary to global CAC measures to assess coronary event risk.

Age Factors↗

The semi-individual study in air pollution epidemiology: a valid design as compared to ecologic studies.

The assessment of long-term effects of air pollution in humans relies on epidemiologic studies. A widely used design consists of cross-sectional or cohort studies in which ecologic assignment of exposure, based on a fixed-site ambient monitor, is employed. Although health outcome and usually a large number of covariates are measured in individuals, these studies are often called ecological. We will introduce the term semi-individual design for these studies. We review the major properties and limitations with regard to causal inference of truly ecologic studies, in which outcome, exposure, and covariates are available on an aggregate level only. Misclassification problems and issues related to confounding and model specification in truly ecologic studies limit etiologic inference to individuals. In contrast, the semi-individual study shares its methodological and inferential properties with typical individual-level study designs. The major caveat relates to the case where too few study areas, e.g., two or three, are used, which render control of aggregate level confounding impossible. The issue of exposure misclassification is of general concern in epidemiology and not an exclusive problem of the semi-individual design. In a multicenter setting, the semi-individual study is a valuable tool to approach long-term effects of air pollution. Knowledge about the error structure of the ecologically assigned exposure allows consideration of the impact of ecologically assigned exposure on effect estimation. Semi-individual studies, i.e., individual level air pollution studies with ecologic exposure assignment, more readily permit valid inference to individuals and should not be labeled as ecologic studies.

Air Pollutants↗

Analysis of aspirin-associated risks in healthy individuals.

BACKGROUND: Aspirin therapy is widely accepted for patients with documented cardiovascular disease, but there is a growing trend among healthy individuals to use aspirin as primary prevention for both cardiovascular disease and cancer. OBJECTIVE: To determine the impact of the complications of aspirin therapy on quality-adjusted life-years (QALYs) in healthy individuals. METHODS: A computer-based decision-analytic model was constructed. In this model, healthy individuals taking aspirin were assumed to receive no advantages from the aspirin, but were at risk of developing its associated complications. Individuals took 325 mg of enteric-coated aspirin every day until death, discontinuing therapy only if an aspirin-induced complication occurred. The analysis was performed from a societal perspective, starting at age 50 years. Extensive sensitivity analyses were performed. RESULTS: In the absence of any beneficial effect, aspirin reduced QALYs by 0.03 per individual. Unadjusted life expectancy was decreased by 0.04 years (2 wk). Lifetime aspirin use cost an average of $460/healthy person. The total complication rate over a lifetime of aspirin therapy was 6.79%, with a mortality rate of 0.18%. Alternatively stated, there was one complication for every 15 individuals treated and one death for every 556 individuals treated. Extensive sensitivity analysis showed the range of results possible when varying age, gender, length of follow-up, and other key parameters. CONCLUSIONS: Assuming no benefits, aspirin therapy in healthy individuals leads to a small reduction in QALYs at an overall low cost per person. However, approximately 1 in 15 individuals will experience an aspirin-induced complication and 1 in 556 individuals will die.

Adult↗

Physician conceptions of responsibility to individual patients and distributive justice in health care.

PURPOSE: Physicians' values may be shifting under managed care, but there have been no empirical data to support this claim. We describe physician conceptions of responsibility to individual patients and distributive justice in health care, and explore whether these values are associated with type of managed care practice and professional satisfaction. METHODS: We mailed a questionnaire to 500 primary care physicians from 80 out-patient clinics in 11 managed care organizations (MCOs) who were participating in 4 studies designed to improve the quality of depression care in primary care. RESULTS: We received 414 responses (response rate 83%). Twenty-eight percent of physicians strongly agreed that their main responsibility was to the individual patient rather than to society (strong sense of responsibility to individual patients). Physicians with a strong sense of responsibility to individual patients were older (43% of physicians older than 50 years reported a strong sense of responsibility to individual patients, compared with 26% of physicians aged 36 to 50 years, and 21% of physicians younger than 35 years, P = .009) and tended to practice in network- rather than staff-model MCOs (33% of physicians in network-model MCOs reported a strong sense of responsibility to individual patients compared with 24% in staff-model MCOs, P = .077). Scores on a scale measuring egalitarian conceptions of distributive justice within the health care system were similar for physicians regardless of whether they reported a strong sense of responsibility to individual patients. When we controlled for physician and practice characteristics, physicians with a strong sense of responsibility to individual patients and physicians with higher scores on an egalitarian scale were more likely to be very satisfied overall with their practices (adjusted odds ratio [AOR] = 2.23, 95% confidence interval [CI], 1.11-4.49, and AOR = 1.18, 95% CI, 1.09-1.29, respectively). CONCLUSIONS: Physicians with a strong sense of responsibility to individual patients are older and less likely to practice in staff-model MCOs. Stronger commitment to an egalitarian health care system and a strong sense of responsibility to individual patients are independently associated with greater practice satisfaction among physicians. The impact of these values on patient care should be a priority for future research and the subject of professional education and debate.

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