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PubMed2005

Electrostatically driven spatial patterns in lipid membrane composition.

To explore the physical mechanisms that can guide spatial organization at biological membranes, we have constructed simple, cell-free intermembrane junctions. We find that the mechanically driven patterning of proteins uncovered in our earlier work can electrostatically generate spatial patterns in the distribution of charged membrane lipids. Tuning the magnitude of the interaction as a function of composition and ionic strength, and analyzing the interplay between thermodynamics and electrostatics via a Poisson-Boltzmann approach, we are able to determine the charge density and surface potential of the junction components. Surprisingly, the electrostatic potential of the proteins is a minor factor in the lipid reorganization; the protein size and its modulation of the junction topography play the dominant role in driving the electrostatic patterns.

Lipid Bilayers↗
PubMed2003

Significance analysis of lexical bias in microarray data.

BACKGROUND: Genes that are determined to be significantly differentially regulated in microarray analyses often appear to have functional commonalities, such as being components of the same biochemical pathway. This results in certain words being under- or overrepresented in the list of genes. Distinguishing between biologically meaningful trends and artifacts of annotation and analysis procedures is of the utmost importance, as only true biological trends are of interest for further experimentation. A number of sophisticated methods for identification of significant lexical trends are currently available, but these methods are generally too cumbersome for practical use by most microarray users. RESULTS: We have developed a tool, LACK, for calculating the statistical significance of apparent lexical bias in microarray datasets. The frequency of a user-specified list of search terms in a list of genes which are differentially regulated is assessed for statistical significance by comparison to randomly generated datasets. The simplicity of the input files and user interface targets the average microarray user who wishes to have a statistical measure of apparent lexical trends in analyzed datasets without the need for bioinformatics skills. The software is available as Perl source or a Windows executable. CONCLUSION: We have used LACK in our laboratory to generate biological hypotheses based on our microarray data. We demonstrate the program's utility using an example in which we confirm significant upregulation of SPI-2 pathogenicity island of Salmonella enterica serovar Typhimurium by the cation chelator dipyridyl.

2,2'-Dipyridyl↗
PubMed2005

Mortality and cancer incidence in Korean patients with systemic lupus erythematosus: results from the Hanyang lupus cohort in Seoul, Korea.

The rates of mortality and cancer have not been compared between Korean systemic lupus erythematosus (SLE) patients and the general population. The objective of this study was to compare the observed mortality and cancer incidence rates of SLE patients with the expected age-, sex- and calendar-matched incidence rates of a comparable general control population. This study included 466 SLE patients who were in the Hanyang Lupus Cohort, Seoul and we excluded the males from the analyses because the number of males was too small to expect any incidence of cancer or death. We used the national female mortality rates from 1992 to 2001 as recorded by the Korean National Statistical Office as the standard mortality rates, and the Seoul Cancer Registry data as the standard cancer incidence rate. Ten of the females in our study died, giving a crude mortality rate of 596.0/100 000 person-years (PY) and a standardized mortality ratio (SMR) of 3.02. The crude cancer incidence was 179.3/100 000 PYand the standard incidence ratio was 1.04. These results demonstrate that the SMR is significantly higher in SLE patients than in the general population, whereas the incidence of cancer is the same in these two groups.

Adolescent↗
PubMed2004

Intussusception in early childhood: a cohort study of 1.7 million children.

OBJECTIVE: To describe incidence and temporal trends of intussusceptions in Danish children during 1980 to 2001. METHODS: A population-based cohort study was conducted of 1.67 million children who were younger than 5 years during 1980 to 2001 and were followed up for 6.66 million person-years. The Danish National Patient Registry was used to identify cases of intussusception in the cohort. Age-specific incidence rates were main outcome measure. RESULTS: A total of 1814 cases of intussusception among children who were younger than 5 years were reported from 1980 to 2001. The incidence rate remained fairly constant during 1980 to 1990 but decreased by 55% (95% confidence interval: 43%-65%) from 1990 to 2001. The reduction was most pronounced among children aged 3 to 5 months. CONCLUSIONS: The incidence of intussusception among Danish children declined significantly during the 1990s, particularly among infants 3 to 5 months of age.

Age Distribution↗
PubMed1995

Incidence of prostate cancer diagnosis in the eras before and after serum prostate-specific antigen testing.

OBJECTIVE: To estimate the incidence of prostate cancer in Olmsted County, Minnesota, from 1983 through 1992 to describe the secular changes that have occurred since the introduction of serum prostate-specific antigen (PSA) testing to the community medical practice in 1987. DESIGN: Population-based, descriptive epidemiological study with ecological and individual level comparisons over time. STUDY SETTING: Olmsted County, Minnesota, where the Rochester Epidemiology Project provides passive surveillance of the population for health outcomes. SUBJECTS: All 511 biopsy-proven incident cases of adenocarcinoma of the prostate diagnosed from 1983 through 1992. The community inpatient and outpatient medical records of all incident cases were reviewed to evaluate the presenting characteristics of men at the time of diagnosis. RESULTS: The age-adjusted incidence of biopsy-proven prostate cancer increased from 64 per 100,000 person-years in 1983 to 216 per 100,000 person-years in 1992. The increase occurred primarily between 1987 and 1988 and was predominately for organ-confined tumors. The age-specific incidence increased dramatically in this same period among men aged 50 years and older. Among men aged 70 years and older, however, prostate carcinoma incidence rates declined after 1990 following the initial increase. This decline among older men contrasted with community-based estimates of PSA utilization rates, which demonstrated consistent increases since 1987 to nearly 50% of the older population in 1992. CONCLUSION: These results support the premise that the recent increase in prostate cancer is due in part to the increased utilization of serum PSA testing. Further, the increased incidence appears to be a transient phenomenon due to the depletion of previously undiagnosed cases from the previous pool. Finally, these data suggest that, in terms of stage at diagnosis, early detection efforts may be effective in identifying more early stage (smaller) cancers.

Adenocarcinoma↗
PubMed1994

Sample size calculation for clinical trials in which entry criteria and outcomes are counts of events. ACIP Investigators. Asymptomatic Cardiac Ischemia Pilot.

In many chronic diseases, therapy aims to prevent or reduce the frequency of episodes of a disease manifestation, for example cardiac ischaemic episodes or epileptic seizures. Entry criteria for clinical trials typically include a minimum number of episodes within a baseline period, and regression to the mean should be anticipated. The distribution of the number of episodes at follow-up, the statistical power for treatment comparisons, and the difficulty of recruitment will depend on the entry criterion chosen. A gamma-Poisson mixture model is employed to describe the regression to the mean when the entry criterion and outcome measure are counts of discrete events. Sample size formulae which take account of the entry criterion are derived for comparison of mean number of events at follow-up and the proportion of patients with zero events at follow-up. Application of these formulae to screening data from the Asymptomatic Cardiac Ischemia Pilot (ACIP) Study is presented as an example.

Clinical Trials as Topic↗
PubMed2000

Stochastic host-parasite interaction models.

We contribute to the discussion of causes and effects of aggregation (overdispersion) of macroparasite counts, focussing particularly upon the effects of clumped infections and parasite-induced host mortality. The simple nonlinear stochastic model for the evolution of the parasite load of a single host, investigated in Isham (1995), is extended to allow three parasite stages (larval, mature and offspring), and to allow durations of these stages to be non-exponentially distributed. As in the earlier work, exact algebraic results are possible, providing insight into the aggregation mechanisms, as long as the only source of interaction between host and parasites is an excess host mortality linearly related to the parasite load. Results are obtained on the distribution of parasite load and on host survival. In particular, although parasite-induced host mortality is usually thought of as a process that reduces parasite aggregation (Anderson and Gordon 1982), it is shown that, for this model, parasite-induced host mortality cannot cause the index of dispersion to fall below unity. Host heterogeneity and disease control are also discussed. An approximation based on moment assumptions appropriate to a specially-constructed multivariate negative binomial distribution is proposed. This approximation, which is applicable to other processes, and an alternative based on the multivariate normal distribution are compared with exact results.

Animals↗
PubMedDate not supplied

Amlodipine reduces blood pressure and headache frequency in cocaine-dependent outpatients.

Blood pressure and headache frequency were evaluated in normotensive male and female cocaine-dependent patients (N=43) participating in a placebo-controlled, double-blind trial of amlodipine for the treatment of cocaine dependence. Amlodipine produced a significant reduction in both systolic (p=0.04) and diastolic (p=0.01) blood pressures without producing dizziness or faintness. Placebo subjects had about three times the frequency of headaches compared to the amlodipine-treated subjects (p=0.004). The high frequency of headaches reported by cocaine-dependent individuals was significantly reduced by amlodipine and may reflect improved cerebrovascular tone.

Adult↗
PubMed1996

Seasonality in the clinical onset of insulin-dependent diabetes mellitus in Finnish children. Childhood Diabetes in Finland (DiMe) Study Group.

Seasonal patterns in the incidence of insulin-dependent diabetes based on 2,062 cases diagnosed at age 14 years or under in Finland are described for the years 1987-1992. Seasonal patterns were estimated presenting the data as short Fourier series up to three harmonics together with a possible linear trend. This method allows an arbitrary shape for the seasonal effect. Likelihood ratio tests and Akaike's information criterion were used to determine the number of harmonics necessary to model the seasonal pattern and to test differences among age- and sex-specific subgroups in the population. Seasonal patterns in incidence were compared between sexes and between the three 5-year age groups with each controlling for the other's effect. A significant seasonal pattern in the incidence of insulin-dependent diabetes was found for the sexes combined and for two age groups (0-9 and 10-14 years). A statistically significant seasonal pattern could be confirmed for males, but not for females. During a calendar year, one cycle with a decreased incidence of insulin-dependent diabetes in June was found among younger boys. Among older boys, there were two distinct cycles with a decreased incidence, the first in June and the second during November-December. The most visible seasonal pattern was a lower number of cases diagnosed in June, while during the rest of the year the incidence remained relatively stable and high. The average annual incidence was 35.6 per 100,000 persons without any upward peaks.

Adolescent↗
PubMed2003

Causes of low vision and blindness in rural Indonesia.

AIM: To determine the prevalence rates and major contributing causes of low vision and blindness in adults in a rural setting in Indonesia METHODS: A population based prevalence survey of adults 21 years or older (n=989) was conducted in five rural villages and one provincial town in Sumatra, Indonesia. One stage household cluster sampling procedure was employed where 100 households were randomly selected from each village or town. Bilateral low vision was defined as habitual VA (measured using tumbling "E" logMAR charts) in the better eye worse than 6/18 and 3/60 or better, based on the WHO criteria. Bilateral blindness was defined as habitual VA worse than 3/60 in the better eye. The anterior segment and lens of subjects with low vision or blindness (both unilateral and bilateral) (n=66) were examined using a portable slit lamp and fundus examination was performed using indirect ophthalmoscopy. RESULTS: The overall age adjusted (adjusted to the 1990 Indonesia census population) prevalence rate of bilateral low vision was 5.8% (95% confidence interval (CI) 4.2 to 7.4) and bilateral blindness was 2.2% (95% CI 1.1 to 3.2). The rates of low vision and blindness increased with age. The major contributing causes for bilateral low vision were cataract (61.3%), uncorrected refractive error (12.9%), and amblyopia (12.9%), and the major cause of bilateral blindness was cataract (62.5%). The major causes of unilateral low vision were cataract (48.0%) and uncorrected refractive error (12.0%), and major causes of unilateral blindness were amblyopia (50.0%) and trauma (50.0%). CONCLUSIONS: The rates of habitual low vision and blindness in provincial Sumatra, Indonesia, are similar to other developing rural countries in Asia. Blindness is largely preventable, as the major contributing causes (cataract and uncorrected refractive error) are amenable to treatment.

Adult↗
PubMed2000

Invasive group A streptococcal disease in children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group.

OBJECTIVES: To describe the incidence and clinical features of invasive group A streptococcal (GAS) disease in children in Ontario and determine the risk of invasive GAS infection following chickenpox. METHODS: During 1992-1996, we conducted prospective, active, population-based surveillance for pediatric invasive GAS disease in Ontario, Canada (population: 11 million; 2.5 million children) and reviewed clinical and laboratory records. RESULTS: There were 1.9 cases of invasive GAS disease per 100,000 children per year. Streptococcal toxic shock syndrome (STSS) occurred in 7% of cases and necrotizing fasciitis (NF) in 4% for incidences of.08 and.13 per 100,000 per year, respectively. Case-fatality rates were 56% for STSS, 10% for NF, and 4% overall. The presence of chronic underlying illness other than asthma was associated with death (relative risk [RR]: 11; 95% confidence interval [CI]: 2.4-45). Fifteen percent of children identified had preceding chickenpox infection, which significantly increased the risk for acquisition of invasive GAS disease (RR: 58; 95% CI: 40-85). Children with invasive GAS and recent chickenpox were more likely to have NF (RR: 6.3; 95% CI: 1.8-22.3). CONCLUSIONS: Childhood invasive GAS disease occurs at an incidence similar to the adult population but has a lower rate of STSS and case-fatality. Chickenpox dramatically increases the risk for acquiring invasive GAS disease, and universal chickenpox vaccination could potentially prevent up to 15% of all pediatric invasive GAS disease.

Adolescent↗
PubMed2003

[Prevalence of overweight and obesity and associated factors among adolescents in the Northeast and Southeast regions of Brazil, 1996 to 1997].

The purpose of this study was to assess the prevalence and factors associated with overweight and obesity (OW/O) among Brazilian adolescents, based on the Living Standards Survey conducted in 1996 and 1997 (IBGE, 1998a). The sample included 1,027 and 854 adolescents aged 15 to 19 years from the Northeast and Southeast regions, respectively. Body Mass Index (w/h2) was calculated. Statistical analysis considered expansion factors and sample design. Prevalence of OW/O was 8.45% in the Northeast and 11.53% in the Southeast. In the Northeast there was a higher risk of OW/O for girls (PR = 3.00), with the same situation in both urban (PR = 3.21) and rural areas (PR = 2.27). In the Southeast, the risk of OW/O was lower among girls (PR = 0.58). The same situation occurred in girls from urban areas (PR = 0.51), but in rural areas there was an increased risk among girls (PR = 1.86). Per capita monthly income was associated with the risk of OW/O among boys in both regions. Programs to prevent OW/O should incorporate nutritional reeducation and encourage physical exercise, besides considering socioeconomic, cultural, and regional differences and the location of the target population.

Adolescent↗
PubMed1990

Further studies in the variability of pock counts.

The problem of estimating viral activity from pock counts that exhibit a substantial degree of overdispersion is revisited from the viewpoint of quasilikelihood with unknown parameters in the variance function. Score statistics are developed for tests and interval estimates of both mean and variance parameters. These yield somewhat different conclusions than do methods based exclusively on point estimates and standard errors, especially for the variance parameters. A Monte Carlo study confirms that, in the absence of strong prior information about the shape of the error distribution, inferences on variances are highly unstable in small to moderate samples.

Animals↗
PubMed1997

On the EM algorithm for overdispersed count data.

In this paper, we consider the use of the EM algorithm for the fitting of distributions by maximum likelihood to overdispersed count data. In the course of this, we also provide a review of various approaches that have been proposed for the analysis of such data. As the Poisson and binomial regression models, which are often adopted in the first instance for these analyses, are particular examples of a generalized linear model (GLM), the focus of the account is on the modifications and extensions to GLMs for the handling of overdispersed count data.

Algorithms↗
PubMed1995

Risk of subsequent malignant neoplasms among 470,000 cancer patients in Finland, 1953-1991.

Because of increasing numbers of incident cancers and improving survival rates, more and more cancer patients are at risk of subsequent primary malignant neoplasms. The potential carcinogenicity of cancer therapies raises further concern regarding this unwanted long-term side effect. The objective of this cancer-registry-based study was to assess the trends in the risk of subsequent primary malignancies among cancer patients on a nationwide public-health level. The 470,000 cancer patients registered between 1953 and 1991 in Finland were followed up for subsequent primary neoplasms, and 19,800 subsequent malignant neoplasms were observed, yielding an overall standardized incidence ratio (SIR) of 1.00 for men and 1.25 for women. Substantial variation was observed in the SIR by the site of subsequent malignancy. The adjusted relative risk derived from multiple regression analyses showed only a slight increase by follow-up interval. Overall, the excess relative risk of subsequent malignancies was low, since the majority of cancer patients are old and at low relative risk. Patients under the age of 50 years, however, were at 70% increased risk, and the overall relative risk increased by 50% from the 1950s to the 1980s. Subsequent neoplasms among cancer patients do not pose a major public-health problem, but the possibility of subsequent cancers must be borne in mind in decisions concerning therapy and in clinical follow-up.

Adolescent↗
PubMed2001

Cancer risk in the reindeer breeding Saami population of Sweden, 1961-1997.

The Saami people are the natives of northern Scandinavia and the Kola Peninsula. In a cohort of 2033 Swedish reindeer breeding Saamis, the cancer risks between 1961 and 1997 were studied. In total, 193 cases of cancer were observed versus 322 expected in the general Swedish population and 249 in a geographically matched reference population of non-Saamis. In comparison to non-Saamis living in the same area, the reindeer breeding Saamis showed a statistically significant lower risk of developing cancer of the prostate and of malignant lymphoma, whereas the risk of stomach cancer was significantly higher. Although there were no statistically significant changes of cancer risks over time, temporal trends were indicated towards a decreased risk of cancer in the stomach and the prostate. The results suggest that the explanations of the low cancer risk of the reindeer breeding Saamis, in relation to the non-Saamis in the same environment, are to be found among lifestyle and/or genetic factors.

Age Distribution↗
PubMed1998

Mental retardation in Norway: prevalence and sub-classification in a cohort of 30037 children born between 1980 and 1985.

OBJECTIVES: We wanted to determine the prevalence and subcategories of mental retardation (MR) defined as IQ < or = 70 in Akershus county, which rated by average yearly income, had the second highest socioeconomic status (SES) in Norway. METHODS: The study population consisted of 30 037 children born between 1980 and 1985. Cases were ascertained from multiple sources and psychometrically assessed, predominantly with the Wechsler tests, which were standardized in Norway in 1978. The cases were divided into four groups: profound (IQ < 20), severe (IQ 20-34), moderate (IQ 35-49), and mild (IQ 50-70) MR, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). The median age was 10.8 y. The frequency and degree of parental consanguinity were registered, and the average inbreeding coefficient was calculated. RESULTS: Altogether, 185 had IQ < or = 70, giving a prevalence of MR of 6.2/1000. Prevalences for profound, severe, moderate, and mild MR were 0.8, 0.4, 1.5 and 3.5/1000, respectively. In two, possibly three, cases the parents were second cousins, giving an average inbreeding coefficient of 20-30 x 10(-5). CONCLUSIONS: The low prevalence of MR, particularly mild MR, could partly be explained by high SES, old standardization of IQ-test, and low inbreeding coefficient. The proportion of profound MR was considerably higher than estimated by DSM-IV.

Adolescent↗
PubMed2001

Per capita alcohol consumption and all-cause mortality in 14 European countries.

AIMS: (1) To estimate the relationship between per capita alcohol consumption and male all-cause mortality in 14 European countries. (2) To compare the estimates with predictions from the U-shaped curve at the aggregate level. DATA AND METHOD: The outcome measures comprised annual data, after 1950, on male mortality (all-cause mortality and mortality from diseases) for the following age groups: 15+, 15-29, 30-49, 50-69 and 70+ years. Female mortality was included as a control variable. Alcohol sales were used as proxy for per capita consumption. The data were analysed using the Box-Jenkins technique. The estimated alcohol effects were pooled within low-, medium- and high-consumption countries. RESULTS: For all-cause mortality (15+), the effect estimates were significantly positive in eight of the 14 countries. The effect on mortality of a 1-litre increase in consumption tended to be stronger in low-consumption countries (3% per litre) than in medium- and high-consumption countries (1%). This pattern deviates from that predicted from the U-shaped curve. No significant impact of alcohol was found in the youngest age group when mortality from diseases was used as the outcome. CONCLUSIONS: Increases in overall consumption seem to be associated with increases in total mortality. Differences in drinking patterns are discussed as a possible explanation for the variation between country groups in alcohol effect.

Adolescent↗