Biomedical subjects
Publications and source records attributed to J E Kolassa.
Applications of saddlepoint approximations to distribution functions are reviewed. Calculations are provided for marginal distributions and conditional distributions. These approximations are applied to problems of testing and generating confidence intervals, particularly in canonical exponential families.
Influenza epidemics are associated with significant morbidity and mortality in the elderly, with a substantial proportion of deaths due to cardiovascular events. Elevations of acute-phase proteins have been associated with an increased risk of atherosclerotic events. Therefore, serum amyloid A (SAA) and C-reactive protein (CRP) were measured during influenza illness and 4 weeks later in 7 young persons, 15 elderly outpatients, and 36 hospitalized adults. Striking elevations were seen in mean acute SAA and CRP levels in all groups, but hospitalized patients had the highest levels (SAA, 503 vs. 310 microg/mL [P=.006]; CRP, 120 vs. 34 microg/mL [P<.001]). The presence of dyspnea, wheezing, and fever was also associated with high CRP levels. Influenza infection is associated with significant elevations of SAA and CRP levels in elderly patients, especially those who require hospitalization. It is possible that direct effects of CRP may exacerbate preexisting atherosclerotic lesions and may help explain cardiovascular events associated with acute influenza.
Little information about immunity to respiratory syncytial virus (RSV) and disease pathogenesis in elderly persons exists. Humoral immunity to RSV was assessed in 41 young, 56 healthy elderly, and 49 frail elderly adults by measuring baseline RSV specific IgG by enzyme immunoassay (EIA) and microneutralization assay (MNA) in serum. A comparison of the immune response of 11 young and 28 elderly persons with natural RSV infection was also performed. Despite significant differences in age and functional status, no decreases in RSV antibody levels by either EIA or MNA were noted in the elderly compared with the young. Mean baseline MNA titers expressed as log2 were 10.5 +/- 1.1 for the young, 10.5 +/- 1.5 for the healthy elderly, and 10.9 +/- 1.6 for the frail elderly. The frail elderly who attend a daycare had the highest RSV titers to F by EIA at 16.6 +/- 2.0, compared with 15.4 +/- 1.4 and 15.1 +/- 1.4 in the healthy elderly and young, respectively. This finding may reflect recent infection due to their communal setting or increased production of non-neutralizing antibody. The immune response of older persons to RSV infection was as vigorous as the younger subjects, with 79% having a >/=fourfold rise in MNA titers compared to 64% in the young. These data suggest that the severe clinical manifestations of RSV in the elderly are not due to a significant defect in humoral immunity.
To decrease respiratory infections in senior day care, staff were educated on viral transmission and the value of hand washing. Fanny packs with alcohol foam supplemented hand washing and were alternated monthly between centers. Infection rates were unchanged with alcohol foam use. The intervention year's infection rate was significantly lower than the previous 3 years, suggesting a benefit of education.
This article presents an algorithm for approximate frequentist conditional inference on two or more parameters for any regression model in the Generalized Linear Model (GLIM) family. We thereby extend highly accurate inference beyond the cases of logistic regression and contingency tables implimented in commercially available software. The method makes use of the double saddlepoint approximations of Skovgaard (1987, Journal of Applied Probability 24, 875-887) and Jensen (1992, Biometrika 79, 693-703) to the conditional cumulative distribution function of a sufficient statistic given the remaining sufficient statistics. This approximation is then used in conjunction with noniterative Monte Carlo methods to generate a sample from a distribution that approximates the joint distribution of the sufficient statistics associated with the parameters of interest conditional on the observed values of the sufficient statistics associated with the nuisance parameters. This algorithm is an alternate approach to that presented by Kolassa and Tanner (1994, Journal of the American Statistical Association 89, 697-702), in which a Markov chain is generated whose equilibrium distribution under certain regularity conditions approximates the joint distribution of interest. In Kolassa and Tanner (1994), the Gibbs sampler was used in conjunction with these univariate conditional distribution function approximations. The method of this paper does not require the construction and simulation of a Markov chain, thus avoiding the need to develop regularity conditions under which the algorithm converges and the need for the data analyst to check convergence of the particular chain. Examples involving logistic and truncated Poisson regression are presented.
This article presents an algorithm for small-sample conditional confidence regions for two or more parameters for any discrete regression model in the generalized linear interactive model family. Regions are constructed by careful inversion of conditional hypothesis tests. This method presupposes the use of approximate or exact techniques for enumerating the sample space for some components of the vector of sufficient statistics conditional on other components. Such enumeration may be performed exactly or by exact or approximate Monte Carlo, including the algorithms of Kolassa and Tanner (1994, Journal of the American Statistical Association 89, 697-702; 1999, Biometrics 55, 246-251). This method also assumes that one can compute certain conditional probabilities for a fixed value of the parameter vector. Because of a property of exponential families, one can use this set of conditional probabilities to directly compute the conditional probabilities associated with any other value of the vector of the parameters of interest. This observation dramatically reduces the computational effort required to invert the hypothesis test to obtain the confidence region. To construct a region with confidence level 1 - alpha, the algorithm begins with a grid of values for the parameters of interest. For each parameter vector on the grid (corresponding to the current null hypothesis), one transforms the initial set of conditional probabilities using exponential tilting and then calculates the p value for this current null hypothesis. The confidence region is the set of parameter values for which the p value is at least alpha.
Evaluation of alveolar development beyond the postnatal period of rapid septation has generally involved alveolar counting. We used an alternate approach to assess postseptation parenchymal development: measurement of the lengths of various types of alveolar septal borders. This technique directly addresses changes in the elastin fiber network that determines parenchymal complexity. Lungs from weanling and adult ferrets, inflated to 15 cmH2O, were perfusion fixed and dehydrated, and 2-micrometer sections were stained with Miller's elastin stain for light microscopy. We used standard morphometric methods to measure the lengths of the various types of alveolar septal borders. Three types comprised >90% of all septal borders: 1) free septal ends ("ends") containing an elastin cable; 2) angled meetings of two alveolar septa ("bends"), also with a cable; and 3) the near-symmetrical intersections of three septa ("junctions") devoid of elastin. When scaled for lung volume, ends and bends were 23 and 37% greater in adults (P < 0.001), reflecting the increase in parenchymal complexity with growth. The 17% difference in scaled junction lengths was not significant (P = 0.10). Bends increased out of proportion to the increase in ends, and both bends and ends increased to a greater degree than any possible increase in junctions (P < 0.001 for all comparisons). Although the interpretation of changes in the distribution of alveolar border lengths is not straightforward, an increase in bends resulting in an increase in the complexity of individual alveoli may contribute to the increase in alveolar gas-exchanging surface area with growth. Septation, the process responsible for the rapid early postnatal increase in parenchymal complexity in many species, should tend to increase the lengths of ends and junctions and decrease the lengths of bends. Therefore, these data suggest that septation is not the predominant mechanism of later postnatal parenchymal development in the ferret.
OBJECTIVE: To evaluate the incidence and impact of rhinovirus and coronavirus infections in older persons attending daycare. DESIGN: Prospective descriptive study. SETTING: Three senior daycare centers in Rochester, New York. PATIENTS: Frail older persons and staff members of the daycare centers who developed signs or symptoms of an acute respiratory illness. MEASUREMENTS: Demographic, medical, and physical findings were recorded on subjects at baseline and during respiratory illness. Nasopharyngeal specimens for viral culture as well as acute and convalescent sera for coronavirus 229E enzyme immunoassay (EIA) were obtained for all illnesses. RESULTS: During the 44 months of study, 352 older persons experienced 522 illnesses. Thirty-five (7%) of 522 cultures were positive for rhinovirus and 37 (8%) of 451 serologies were positive for coronavirus 229E infection. The clinical syndromes associated with rhinovirus and coronavirus infection were similar and characterized by nasal congestion, cough, and constitutional symptoms. No patient died or was hospitalized, but approximately 50% had evidence of lower respiratory tract involvement. The average illness lasted 14 days. During the same period, 113 staff developed 338 respiratory illnesses. Eight percent were identified as coronavirus and 9% as rhinovirus. Cough, sputum production, and constitutional symptoms were significantly more common among older persons. CONCLUSIONS: Rhinovirus and coronavirus 229E are common causes of moderately debilitating acute respiratory illnesses among older persons attending daycare.
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OBJECTIVE: To evaluate the rate of specific pathogens and clinical syndromes associated with acute respiratory tract infections (ARTI) in frail older persons attending daycare. DESIGN: Prospective descriptive study, without intervention. SETTING: Two sites of a senior daycare program providing all-inclusive care for the older persons in Rochester, New York. PARTICIPANTS: Staff members and participants of the day-care. MEASUREMENTS: Demographic, medical, and physical findings were collected from older subjects at baseline and while ill with respiratory illnesses. Nasopharyngeal specimens for viral and Chlamydia culture and sputum for bacterial culture were obtained from subjects when ill. Acute and convalescent sera were also collected with each illness and examined for viral, chlamydial, and mycoplasma infection. MAIN RESULTS: One hundred sixty-five illnesses were documented in 165 older daycare participants as well as 113 illnesses among 67 staff members during the 15-month study. The rate of ARTI in the elderly group was 10.8 per 100 person months. The most common etiologies in both the staff and elderly participants were respiratory syncytial virus (RSV), Influenza A, and coronavirus. The etiologies of illnesses in the staff compared with those in elderly group were similar except that bacterial infections were significantly more common among the elderly (7% vs. 0, P = 0.05). Multiple pathogens were found to cocirculate within centers, and no clear outbreak of a predominant organism was noted. Cough and nasal congestion characterized most illnesses. The elderly experienced significantly more cough, dyspnea, and sputum production than did the staff. There were 10 hospitalizations related to respiratory infections and four deaths during the acute illness among the elderly group and none in staff.
This paper analyzes data from a study conducted by the United States Office of Naval Research on the effects of pulsed magnetic fields on chick embryos. The experiment involved incubation of eggs under carefully controlled conditions in six different laboratories. The original analysis included inappropriate statistical methodology for analyzing the experimental results. Since the conclusions from this study rest so heavily on the results of statistical analyses, choosing the proper methodology is imperative. The major aim of this paper then is to introduce more appropriate analytic tools and illustrate their use in the present context. Qualitatively our results agree with those of the original analysis; our findings about interactions between effects, however, makes interpretation of these effects more subtle. We apply linear logistic modeling to counts of damaged embryos, using as covariates factors corresponding to exposure, laboratory, incubator, run, and measurements of background radiation. This facilitates estimation of the size of the effects. The effects of laboratory, incubator, and run are explored both as fixed and random effects. We find statistically significant exposure and laboratory effects, in accordance with the original study. However, we also find that the inter-laboratory variation in exposure effect is at least as large as the exposure effect itself. The presence of such effects fundamentally alters the interpretation of the fitted model, as is graphically presented.