Analysis of EEG Data Using Complex Geometric Structurization.

Electroencephalogram (EEG) is a common tool used to understand brain activities. The data are typically obtained by placing electrodes at the surface of the scalp and recording the oscillations of currents passing through the electrodes. These oscillations can sometimes lead to various interpretations, depending on, for example, the subject's health condition, the experiment carried out, the sensitivity of the tools used, or human manipulations. The data obtained over time can be considered a time series. There is evidence in the literature that epilepsy EEG data may be chaotic. Either way, the Embedding Theory in dynamical systems suggests that time series from a complex system could be used to reconstruct its phase space under proper conditions. In this letter, we propose an analysis of epilepsy EEG time series data based on a novel approach dubbed complex geometric structurization. Complex geometric structurization stems from the construction of strange attractors using Embedding Theory from dynamical systems. The complex geometric structures are themselves obtained using a geometry tool, the α-shapes from shape analysis. Initial analyses show a proof of concept in that these complex structures capture the expected changes brain in lobes under consideration. Further, a deeper analysis suggests that these complex structures can be used as biomarkers for seizure changes.

Antimicrobial-resistant Salmonella is detected more frequently in feed milling equipment than in raw feed components or processed animal feed.

Food for human and animal consumption can provide a vehicle for the transfer of pathogenic and antimicrobial-resistant bacteria into the food chain. We investigated the antimicrobial susceptibility of 453 Salmonella isolates collected from raw feed components, equipment and finished feed from 17 commercial feed mills in Australia between 2012 and 2021. Previous studies have found Salmonella prevalence and the diversity of Salmonella serotypes are greatest in the raw feed components. We, therefore, hypothesised that we would find a greater proportion of antimicrobial-resistant Salmonella isolates in the raw feed components compared to other sample types. We found that of 453 isolates tested, 356 (0.80) were susceptible to all antimicrobials tested, 49 (0.11) were nonsusceptible to streptomycin only and 48 (0.11) were resistant to two or more antimicrobials. Of the 48 antimicrobial-resistant isolates, 44 were found in feed milling equipment, two in raw feed components and two in finished feed. Statistical analysis, using a logistic regression with random effects model, found that the population-adjusted mean probability of detecting antimicrobial-resistant Salmonella isolates from feed milling equipment of 0.39, was larger than the probability of detecting resistant isolates in raw feed components 0.01, (P < 0.001) and in finished feed, 0.11, (P = 0.006). This propensity for antimicrobial-resistant bacteria to colonise feed milling equipment has not been previously reported. Further studies are required to understand the ecology of antimicrobial-resistant Salmonella in the feed milling environment.

Th17/Th1 phenotype in demyelinating disease.

BACKGROUND: Th17 cells are thought to contribute to the immunopathology of allergic and autoimmune conditions. Their role in multiple sclerosis (MS) pathology remains to be fully elucidated. OBJECTIVE: To assess peripheral blood Th17 responses in patients with MS compared to controls. METHODS: We isolated peripheral blood mononuclear cells from 41 MS patients and 23 healthy controls, which were then stimulated using phorbol ester and ionomycin, labelled for CD3, CD8, CD154, IL-17 and IFN-gamma and analysed using flow cytometry. RESULTS: Minimal IL-17 was detectable in unstimulated cells. Following stimulation with phorbol ester and ionomycin, PBMCs taken from MS patients in relapse developed a more inflammatory profile than those taken from controls or non-relapse patients, with greater expression of CD154, IL-17 and dual expression of IL-17/IFN-gamma. CONCLUSION: We suggest a greater tendency to Th17 and Th1/Th17 response to non-specific stimulation in MS patients in relapse compared to controls and non-relapse patients.

Is the type of neuraxial anesthesia associated with adverse neonatal outcomes among patients with preeclampsia?

OBJECTIVE: Both preeclampsia and neuraxial anesthesia can alter placental perfusion, potentially affecting the neonatal status. The objective of our study is to quantify the association between type of neuraxial anesthetic and short-term neonatal morbidity among preeclamptic patients undergoing cesarean delivery. METHODS: We performed a secondary analysis of a prospective observational cohort study. Women with singleton gestations and a diagnosis of preeclampsia who underwent cesarean delivery with neuraxial anesthesia were included in the analysis. Short-term neonatal morbidities, defined as neonatal intensive care unit (NICU) admission, arterial cord gas pH ≤7.2 and 5-minute Apgar <7, were compared based on type of neuraxial anesthetic. RESULTS: A total of 4100 patients were included in the analysis, 1696 (41.4%) received spinal anesthesia 1848 (45.1%) received epidural anesthesia and 556 (13.5%) received a combined spinal-epidural (CSE). Antepartum and intrapartum characteristics significantly differed between the groups (p≤0.02). After adjusted analysis, spinal anesthesia was associated with reduced odds of NICU admission, compared with epidural or CSE (OR; 95% CI: 0.79; 0.63-0.98, 0.71; 0.53-0.94, respectively). Spinal anesthesia was also associated with lower odds of a 5-minute Apgar <7 compared with epidural anesthesia (OR 0.59; 95% CI; 0.43-0.83). We found no association between type of anesthesia and arterial cord pH ≤7.2. In stratiifed analysis by gestational age, no association between the type of neuraxial anesthesia and neonatal outcomes was noted among term infants, but associations persisted in preterm infants. CONCLUSIONS: Among women with preeclampsia undergoing cesarean delivery, spinal anesthesia may be associated with reduced short-term neonatal morbidity in preterm infants, compared with epidural or CSE.

Calcareous septa formed in snail shells by larvae of snail-killing flies.

Larvae of 13 species of Pherbellia and Colobaea that feed in exposed aquatic snails uitilize a product of the Malpighian tubules before they pupate to form a plate-like structure within the shell or to reinforce the anterior end of the puparium. The substance is partly calcium carbonate, and carbonic anhydrase may be involved in its production.

Salmonella monitoring programs in Australian feed mills: a retrospective analysis.

The availability of safe, commercially prepared stock feed for production animals is an important step in ensuring animal health and welfare and the safety of food animal products for human consumption. Animal feed quality assurance programs include microbiological monitoring of raw materials, mill equipment and finished feed. Over a period of 16 years, 23,963 samples for Salmonella culture and serotyping were collected from 22 stock feed mills. A multivariable generalized linear mixed model (GLMM) was used to identify mill and sample type factors that increase the odds of detecting Salmonella. The odds of detecting a Salmonella positive sample was greatest in samples from raw materials and in mills that processed restricted animal material (RAM). The percentage of positive samples ranged from 7.2% in 2003 to 2.8% in 2017. Of the 1,069 positive samples, 976 were serotyped with 61 different Salmonella serotypes isolated. The serotype most frequently isolated from raw materials was S. Agona, (n = 108) whilst S. Anatum was the serotype most frequently isolated from equipment and finished feed (n = 156). The diversity of Salmonella serotypes differed between mills and different stages of the production line. Microbiological monitoring in the commercial preparation of animal feed in Australian stock feed mills guides the implementation of quality control measures and risk mitigation strategies thereby reducing the prevalence and diversity of potentially zoonotic bacteria such as Salmonella, enhancing food safety for both animal and consumer.

Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.

AIMS: To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro-inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS). CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown. METHODS: Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2. RESULTS: Pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α (the latter likely NF-κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL-1ß, IL-6 and TNF-α mRNA in blood of patients with MS compared with controls. CONCLUSION: The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.

Responses of the fetal pituitary-adrenal axis to acute and chronic hypoglycemia during late gestation in the sheep.

We investigated the response of the fetal pituitary-adrenal axis to acute and chronic hypoglycemia before and after the normal prepartum activation of this axis at around 135 days gestation (term = 147 +/- 3 days). Pregnant ewes were either well nourished (control group; n = 22) or undernourished (UN; 50% reduction in maternal nutrient intake; n = 23) during the last 30 days of pregnancy. Acute hypoglycemia was induced by intrafetal administration of insulin between 125 and 130 days gestation (control, n = 7; UN, n = 12) and between 138 and 141 days gestation (control, n = 6; UN = 9). Fetal plasma glucose concentrations were significantly lower (P < 0.005) in the UN compared with the control group throughout the insulin infusion period at both gestational age ranges. In the control group, there was no fetal ACTH response to insulin infusion before 135 days gestation, but there was a significant (P < 0.001) response after 136 days gestation. In the UN group, there was a significant ACTH response to insulin infusion both before and after 135 days gestation, and there was no difference in the fetal ACTH response between the two gestational age ranges. The plasma cortisol responses to insulin were greater (P < 0.001) after 136 days compared with before 135 days gestation in both the UN and control groups. In the control group there was no significant relationship between basal fetal plasma ACTH and glucose concentrations between 115-135 days gestation or between 136-145 days gestation. In the UN group, fetal glucose ranged from 0.5-2.0 mM, and plasma ACTH and glucose concentrations were inversely related at 115-135 days gestation [log ACTH = -0.31 (glucose) + 2.21; r = -0.37; P < 0.001] and at 136-145 days gestation [log ACTH = -0.40 (glucose) + 2.50; r = -0.54; P < 0.001]. When the UN and control groups were combined, fetal plasma ACTH concentrations were significantly greater (F = 13.5; P < 0.05) when plasma glucose concentrations were less than 1.0 mM at either 115-135 days or 136-147 days gestation. Similarly, fetal plasma cortisol concentrations were also significantly greater (F = 18.7; P < 0.05) when plasma glucose concentrations were less than 1.0 mM at each gestational age range. Therefore, there is an increased sensitivity of the fetal hypothalamo-pituitary axis to acute falls in glucose concentrations below 1.2 mM after 135 days compared with earlier in gestation. The fetal hypothalamo-pituitary axis can respond, however, when plasma glucose concentrations fall below 1.0 mM, before and after 135 days gestation, independently of whether the low glucose concentrations are a consequence of insulin-induced hypoglycemia or maternal nutrient restriction.

Depression and other determinants of values placed on current health state by stroke patients: evidence from the VA Acute Stroke (VASt) study.

BACKGROUND AND PURPOSE: This prospective study examined the determinants of the utility (value) placed on health status among a sample of patients with acute ischemic and intracerebral hemorrhagic stroke. METHODS: Data were from the VA Acute Stroke (VASt) study, a nationwide prospective cohort of 1073 acute stroke patients admitted at any of 9 Department of Veterans Affairs Medical Center sites between April 1, 1995, and March 31, 1997. The primary outcome was the patient's health status utility as measured by the time-tradeoff method. Data were obtained by telephone interviews at 1, 6, and 12 months and by medical record review. General linear mixed modeling was used to assess the effects of social, psychological, and physical factors on patients' valuations of their current health state. The analysis was confined to the 327 patients who were able to provide self-reports at >/=2 time points. RESULTS: Patients' valuations of their health state status over the initial 12 months after stroke were very stable over time, with only a slight improvement at 6 months, followed by a slight decline at 12 months. In adjusted analyses, living alone, being institutionalized, decreased physical function, and depression were independently associated with lower levels of patient health status utility over time. CONCLUSIONS: Stroke patient health status utilities are relatively stable during the initial year after stroke. In addition to physical function, psychological health and social environment are important determinants of patient health status utility. These factors need to be considered when conducting stroke decision analyses if more accurate conclusions are to be drawn regarding preferred patterns of care.

Improving the reliability of stroke subgroup classification using the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria.

BACKGROUND AND PURPOSE: We sought to improve the reliability of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of stroke subtype for retrospective use in clinical, health services, and quality of care outcome studies. The TOAST investigators devised a series of 11 definitions to classify patients with ischemic stroke into 5 major etiologic/pathophysiological groupings. Interrater agreement was reported to be substantial in a series of patients who were independently assessed by pairs of physicians. However, the investigators cautioned that disagreements in subtype assignment remain despite the use of these explicit criteria and that trials should include measures to ensure the most uniform diagnosis possible. METHODS: In preparation for a study of outcomes and management practices for patients with ischemic stroke within Department of Veterans Affairs hospitals, 2 neurologists and 2 internists first retrospectively classified a series of 14 randomly selected stroke patients on the basis of the TOAST definitions to provide a baseline assessment of interrater agreement. A 2-phase process was then used to improve the reliability of subtype assignment. In the first phase, a computerized algorithm was developed to assign the TOAST diagnostic category. The reliability of the computerized algorithm was tested with a series of synthetic cases designed to provide data fitting each of the 11 definitions. In the second phase, critical disagreements in the data abstraction process were identified and remaining variability was reduced by the development of standardized procedures for retrieving relevant information from the medical record. RESULTS: The 4 physicians agreed in subtype diagnosis for only 2 of the 14 baseline cases (14%) using all 11 TOAST definitions and for 4 of the 14 cases (29%) when the classifications were collapsed into the 5 major etiologic/pathophysiological groupings (kappa=0.42; 95% CI, 0.32 to 0.53). There was 100% agreement between classifications generated by the computerized algorithm and the intended diagnostic groups for the 11 synthetic cases. The algorithm was then applied to the original 14 cases, and the diagnostic categorization was compared with each of the 4 physicians' baseline assignments. For the 5 collapsed subtypes, the algorithm-based and physician-assigned diagnoses disagreed for 29% to 50% of the cases, reflecting variation in the abstracted data and/or its interpretation. The use of an operations manual designed to guide data abstraction improved the reliability subtype assignment (kappa=0.54; 95% CI, 0.26 to 0.82). Critical disagreements in the abstracted data were identified, and the manual was revised accordingly. Reliability with the use of the 5 collapsed groupings then improved for both interrater (kappa=0.68; 95% CI, 0.44 to 0.91) and intrarater (kappa=0.74; 95% CI, 0.61 to 0.87) agreement. Examining each remaining disagreement revealed that half were due to ambiguities in the medical record and half were related to otherwise unexplained errors in data abstraction. CONCLUSIONS: Ischemic stroke subtype based on published TOAST classification criteria can be reliably assigned with the use of a computerized algorithm with data obtained through standardized medical record abstraction procedures. Some variability in stroke subtype classification will remain because of inconsistencies in the medical record and errors in data abstraction. This residual variability can be addressed by having 2 raters classify each case and then identifying and resolving the reason(s) for the disagreement.

A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome.

OBJECTIVES: The authors report the results of a prospective, placebo-controlled, randomized study to evaluate the effectiveness of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS) and to determine the acute and long-term side effects of DAP. METHODS: Twenty-six patients with LEMS completed a two-arm parallel treatment protocol in which DAP, 20 mg three times daily, or placebo was given blindly for 6 days, and a quantitative examination of muscle strength (the quantitative myasthenia gravis [QMG] score) was used as the primary measure of efficacy. After the blinded study, patients were given open-label DAP and monitored for side effects as long as there was symptomatic improvement. RESULTS: Twelve patients took DAP, and 14 took placebo. There was no difference in the age of LEMS onset, gender distribution, incidence of lung cancer, or baseline muscle strength between the patients who were randomly assigned to receive placebo and those randomly assigned to DAP. Statistical analysis using the Wilcoxon's rank sum test demonstrated that patients who received DAP had a significantly greater improvement in the QMG score and in the summated amplitude of compound muscle action potentials recorded from three sentinel limb muscles. All but one LEMS patient had significant symptomatic improvement from subsequent open-label DAP. Side effects of DAP were negligible, consisting of perioral and digital paresthesia. Laboratory measurements demonstrated no evidence of toxicity affecting liver, renal, hematologic, endocrinologic, encephalographic, or electrocardiologic function acutely or after 6 months of open-label DAP. CONCLUSIONS: This study corroborates previous studies and many years of clinical experience showing that DAP is an effective and safe treatment for LEMS.

Significance of blood stream infection after lung transplantation: analysis in 176 consecutive patients.

BACKGROUND: Although infection is a leading cause of death after lung transplantation, very little is known about the incidence, epidemiology, and clinical significance of bloodstream infections in lung transplant recipients. METHODS: All blood cultures were reviewed in 176 consecutive lung transplant recipients over a 6-year period. Data were obtained from a prospectively collected microbiological database. RESULTS: Bloodstream infection (BSI) occurred in 25% (44/176) of all lung transplant recipients over the 6-year study period. Staphylococcus aureus, Pseudomonas aeruginosa, and Candida species were the most common bloodstream isolates after lung transplantation. The epidemiology of posttransplant BSI, however, varied considerably between early and late posttransplant time periods and also differed between cystic fibrosis (CF) and non-CF patients. BSI infection after transplantation was associated with significantly worse survival by Kaplan-Meir analysis (P value log rank test=0.0001). In a multivariable logistic regression model, posttransplant BSI was a significant predictor of posttransplant death (odds ratio 5.62, CI 2.41-13.11, P=0.001), independent of other pre- and posttransplant factors. CONCLUSIONS: Bloodstream infection represents a serious complication after lung transplantation, occurring more frequently than previously recognized, and independently contributing to posttransplant mortality.

Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection.

BACKGROUND: Although the use of mycophenolate mofetil (MMF) has reduced the incidence of acute rejection in heart and kidney allograft recipients, its role in lung transplantation remains controversial. Therefore, we conducted a randomized, prospective, open-label, multicenter study in lung transplant recipients to determine whether MMF decreases episodes of acute allograft rejection when compared with azathioprine (AZA). METHODS: Between March of 1997 and January of 1999, 81 consecutive lung transplant recipients from two centers were prospectively randomized to receive cyclosporine, corticosteroids, and either 2 mg/kg per day of AZA or 1 g twice daily of MMF. The primary study endpoint was biopsy-proven acute allograft rejection over the first 6 months posttransplant. Secondary endpoints included clinical rejection, cytomegalovirus (CMV) infection, adverse events, and survival. Surveillance bronchoscopies were performed at 1, 3, and 6 months, or if clinically indicated. Pathologists interpreting the biopsy results were blinded to the randomization. Results were analyzed according to intention-to-treat. Between group comparisons of means and proportions were made by using two sample t tests and Fisher's exact tests, respectively. Six-month survival was calculated by the Kaplan-Meier method and compared by the log rank test. RESULTS: Thirty-eight patients were prospectively randomized to receive AZA, and 43 MMF. The incidence of biopsy proven grade II or greater acute allograft rejection at 6 months was 58% in the AZA group and 63% in the MMF group (P=0.82). The 6-month survival rates in the MMF and AZA groups were 86% and 82%, respectively (P=0.57). Rates of CMV infection and adverse events were not significantly different between the two groups. CONCLUSIONS: Acute rejection rates and overall survival at 6 months are similar in lung transplant recipients treated with either MMF- or AZA-based immunosuppression.

Maternal undernutrition throughout pregnancy increases adrenocorticotrophin receptor and steroidogenic acute regulatory protein gene expression in the adrenal gland of twin fetal sheep during late gestation.

We have previously demonstrated that maternal undernutrition during either the 'periconceptional' (i.e. from 60 days (d) before until 7 d after mating) or 'gestational' periods (i.e. from 8 d after mating until the end of pregnancy) have differential effects on the subsequent development of the hypothalamo-pituitary-adrenocortical (HPA) axis and on adrenal growth and steroidogenesis in the sheep fetus during late gestation (term=147+/-3 d gestation). The specific mechanisms by which periconceptional or gestational undernutrition result in activation of the fetal HPA axis in late gestation are unclear. We have therefore investigated the impact of maternal nutrient restriction imposed either during the periconceptional period, or between 8 and 147 d gestation on the expression of specific genes in the fetal pituitary and adrenal which regulate adrenal steroidogenesis in late gestation. Ewes were maintained on either a Control (C) or Restricted (R, 70% of C) diet from 60 d before until 7 d after mating (periconceptional period) and then maintained on either a Control or Restricted diet from 8 d after mating for the remainder of pregnancy (gestational period). Four nutritional treatment groups were therefore generated (C-C, C-R, R-R and R-C). Whilst periconceptional undernutrition (R-R and R-C groups) resulted in higher fetal plasma adrenocorticotrophic hormone (ACTH) at 135-146 d gestation, there was no change in the relative level of expression of the ACTH receptor (MC2R), steroidogenic acute regulatory protein (StAR) or steroidogenic enzyme mRNAs in the fetal adrenal in late gestation. Exposure to gestational undernutrition (R-R and C-R groups), however, resulted in a stimulation in the relative level of expression of MC2R mRNA (P=0.001) and StAR mRNA (P=0.007) in the fetal adrenal during late gestation. This study provides new insights into the potential mechanisms by which alterations of the nutrient environment of the fetus at different stages of gestation may result in differential activation of the fetal HPA axis.

Nontuberculous mycobacteria in adult patients with cystic fibrosis.

Because patients with cystic fibrosis (CF) may be predisposed to airway infections with unusual microorganisms, we screened the sputum of adult CF patients for mycobacterial organisms. Acid-fast bacilli (AFB) smears and mycobacterial culture were performed on 297 sputum specimens from 87 patients. Cultures for mycobacteria were frequently overgrown with other bacteria; 22.6 percent of cultures were contaminated. Despite this limitation of mycobacterial culture, 17 patients had at least one positive culture for a Mycobacterium other than tuberculosis (MOTT). Eleven patients were positive for Mycobacterium avium-intracellulare (MAI), two for MAI and M chelonei, three for M chelonei, and one for M fortuitum. None was positive for M tuberculosis. Patients with CF with MOTT were similar to patients with CF without MOTT; only a slightly different (older) age distribution was recognized. The clinical significance of MOTT was difficult to determine in any individual patient, but patients with positive AFB smears appeared more likely to suffer pathogenic effects. We conclude that MOTT is frequently recovered from adult CF patients in the southeastern United States. A specific risk factor for colonization and/or pathogenic infection in this patient group was not evident. The general prevalence and clinical pathogenesis in CF patients in the United States remains to be determined.

Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters.

Oral ulcerative mucositis is a common toxicity associated with drug and radiation therapy for cancer. It impacts on quality of life and economic outcomes, as well as morbidity and mortality. Mucositis is often associated with dose limitations for chemotherapy or is a cause for dose interruption for radiation. The complexity of mucositis as a biological process has only been recently appreciated. It has been suggested that the condition represents a sequential interaction of oral mucosal cells and tissues, pro-inflammatory cytokines and local factors such as saliva and the oral microbiota. The recognition that the pathophysiology of mucositis is a multifactorial process was partially suggested by the observation that interleukin-11 (IL-11), a pleotropic cytokine, favorably altered the course of chemotherapy-induced mucositis in an animal model. In the current study, we evaluated a series of biologic and morphologic outcomes to determine their roles and sequence in the development of experimental radiation-induced mucositis and to evaluate the effects of IL-11 in attenuating them. Our results suggest that IL-11 favorably modulates acute radiation-induced mucositis by attenuating pro-inflammatory cytokine expression. Data are also presented which help define the pathobiological sequence of mucositis.

Modern statistical techniques for the analysis of longitudinal data in biomedical research.

Longitudinal study designs in biomedical research are motivated by the need or desire of a researcher to assess the change over time of an outcome and what risk factors may be associated with the outcome. The outcome is measured repeatedly over time for every individual in the study, and risk factors may be measured repeatedly over time or they may be static. For example, many clinical studies involving chronic obstructive pulmonary disease (COPD) use pulmonary function as a primary outcome and measure it repeatedly over time for each individual. There are many issues, both practical and theoretical, which make the analysis of longitudinal data complicated. Fortunately, advances in statistical theory and computer technology over the past two decades have made techniques for the analysis of longitudinal data more readily available for data analysts. The aim of this paper is to provide a discussion of the important features of longitudinal data and review two popular modern statistical techniques used in biomedical research for the analysis of longitudinal data: the general linear mixed model, and generalized estimating equations. Examples are provided, using the study of pulmonary function in cystic fibrosis research.

Modeling development of sleep-wake behaviors. II. Results of two cohorts of preterms.

A mixed general linear model analysis of the development of sleep-wake states was conducted on 37 high-risk preterm infants and replicated with a second cohort of 34 infants. Most dependent variables showed significant development over the preterm period: active sleep decreased, and active waking, quiet waking, and the organization of active sleep and quiet sleep increased over the preterm period in both cohorts. The amount of quiet sleep also increased over age, but this change was significant only for Cohort 1. Seven infant characteristics used as covariates had only minor effects. There were no significant differences in the developmental trajectories (slopes) of the two cohorts. The amounts of four variables differed between cohorts: Cohort 2 infants had less sleep-wake transition, more active sleep, less active sleep without REM, and more regular quiet sleep. These findings suggest that developmental patterns of sleep wake states are stable enough in the preterm period that deviant individual patterns might be used to identify infants with neurological problems.

Modeling development of sleep-wake behaviors: I. Using the mixed general linear model.

The purpose of this paper is to demonstrate the use of the mixed general linear model (MixMod) for modeling development of sleep-wake behaviors in preterm infants. The mixed general linear model allows the concurrent identification of both group and individual developmental patterns in longitudinal data sets with inconsistently timed data, irregularly timed data, and randomly missing values. This statistical technique is well suited to data from preterm infants because these infants enter and leave longitudinal studies at varying times depending on their health status. One sleep organizational variable--the regularity of respiration in quiet sleep--obtained from a study of 37 preterm infants was used as an example. Seven infant characteristics were used as covariates. The various steps involved in conducting a mixed model analysis of this variable are illustrated. The strengths and limitations of this technique are discussed.

Measurement error in dietary data: implications for the epidemiologic study of the diet-disease relationship.

OBJECTIVES: To examine the effect of measurement error in dietary data on the relationship between diet and body mass index (BMI). To correct for the effect of measurement error on diet-BMI association by using replicate measurements of diet. The effect of measurement error on diet--BMI relationship was simulated, and its implications are discussed. DESIGN: Prospective study design. SETTING: The first and second China Health and Nutrition Survey conducted in 1989 and 1991, respectively. SUBJECTS: Three thousand, four hundred and seventy-nine adults age 20-45 y at the 1989 survey. METHODS: Statistical methods were used to demonstrate the effect of measurement error in dietary data on the diet-BMI association. RESULTS: By using the average of three replicate 24 h dietary recalls, the attenuation of diet-BMI association was reduced substantially. The regression coefficients of fat and energy intakes differed markedly from those computed by using only single measurement of diet. CONCLUSIONS: Measurement error in dietary data may significantly attenuate the diet-disease association. Where appropriate, specific emphasis may be needed to address the problem of measurement error in the study of diet-disease relationship.