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PubMed1992

A new computer program for detailed off-line analysis of swimming navigation in the Morris water maze.

The program TRACK-ANALYZER runs on AT-compatible microcomputers and performs off-line analysis of data recorded from Morris water-maze experiments by means of a video tracking system or digitizing tablet. Raw data must be available on disk as ASCII-files listing position coordinates sampled at a constant frequency. Automatic recognition and correction of artifacts and missing data is a key feature of the program, as well as the option to combine commands to user-defined macros. TRACK-ANALYZER offers maximal flexibility regarding experimental schedule, maze geometry and recording parameters and may also be used to analyze open-field activity. In addition to calculating basic parameters of the swim path, such as path length and time, the program counts crossings and hits of goal platform and four virtual reference annuli, calculates search times in five different maze fields, determines directionality, tortuosity and turning preferences of swimming behavior and allows the viewing of any number of trials simultaneously on screen. ASCII-formated data output may easily be exported to commercial statistics and graphics software.

Animals↗

PubMed1985

The nominative technique: a new method of estimating heroin prevalence.

Over the years, nominative estimates of heroin prevalence have been consistently higher than self-reports of heroin use. During this time, nominative data have generally followed mainstream patterns of drug use: nominative estimates for young adults and for males are higher than nominative estimates for older persons, youth, and females; moreover, the recent downward trends in drug use have been replicated by the nominative heroin data. Thus, the overall picture presented by the nominative data--similar patterns but higher levels of prevalence--seems to support the validity of the new approach. Nevertheless, considerable caution should be exercised in interpreting nominative data. This is chiefly because a substantial minority of nominators cannot report the number of other close friends of the heroin user who also "know." While missing data has been handled by a conservative imputation rule, the fact that so many persons are unable to provide an answer to this key question casts doubt on the accuracy of the answers that were given. In fact, the nominative approach might tend to produce over-estimates, because of the potential for undercounts of the numbers of others who "know." Additional tests of validity should be performed, such as application of the nominative approach to nonsensitive behaviors or minimally sensitive behaviors, such as marijuana use or perhaps cocaine use. Certainly, the overall validity of the nominative heroin data would be supported if in future surveys new nominative heroin estimates for relatively unstigmatized forms of drug use proved to be similar to self-reported levels of use, thus pointing to the unique difference in estimates that might be observed for heroin. Finally, in interpreting the heroin estimates presented here, it should be remembered that both the nominative and self-report estimates refer to heroin use in the household population of the United States. Thus, many heroin addicts and other users who reside in various unconventional living arrangements would not be included in the counts presented here. Among the excluded groups are transients residing in rooming houses or "crashing" in the home of one "friend" after another or who are incarcerated in jails or confined to residential drug treatment centers. This is a caution for interpreting the estimates presented in this paper, not a criticism of the nominative technique itself.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1976

Data attrition in follow-up studies of alcoholics.

Alcoholics who responded to posttreatment follow-up evaluation showed more improvement than those wh did not respond. Thus nonresponders may bias follow-up research tht does not account for missing data. Several procedures are outlined to increase follow-up return.

Adult↗

PubMed2025

Multimodal CustOmics: A unified and interpretable multi-task deep learning framework for multimodal integrative data analysis in oncology.

Characterizing cancer presents a delicate challenge as it involves deciphering complex biological interactions within the tumor's microenvironment. Clinical trials often provide histology images and molecular profiling of tumors, which can help understand these interactions. Despite recent advances in representing multimodal data for weakly supervised tasks in the medical domain, achieving a coherent and interpretable fusion of whole slide images and multi-omics data is still a challenge. Each modality operates at distinct biological levels, introducing substantial correlations between and within data sources. In response to these challenges, we propose a novel deep-learning-based approach designed to represent multi-omics & histopathology data for precision medicine in a readily interpretable manner. While our approach demonstrates superior performance compared to state-of-the-art methods across multiple test cases, it also deals with incomplete and missing data in a robust manner. It extracts various scores characterizing the activity of each modality and their interactions at the pathway and gene levels. The strength of our method lies in its capacity to unravel pathway activation through multimodal relationships and to extend enrichment analysis to spatial data for supervised tasks. We showcase its predictive capacity and interpretation scores by extensively exploring multiple TCGA datasets and validation cohorts. The method opens new perspectives in understanding the complex relationships between multimodal pathological genomic data in different cancer types and is publicly available on Github.

Deep Learning↗

PubMed1989

RECPAM: a computer program for recursive partition amalgamation for censored survival data and other situations frequently occurring in biostatistics. II. Applications to data on small cell carcinoma of the lung (SCCL).

The RECPAM methodology previously presented in part I (A. Ciampi et al., Comput. Methods Programs Biomed. 26 (1988) 239-256) is applied to the analysis of survival data on small cell carcinoma of the lung (SCCL). It is shown how RECPAM can help answer the following questions which occur frequently in the analysis of clinical data: Is it possible to find a classification of patients with a certain disease into distinct prognostic groups? Given a covariate of special interest, does it have an independent prognostic significance even after confounding is taken into account? Does the prognostic significance of a covariate of special interest vary across patient subgroups? For the SCCL data, a prognostic classification is obtained and the tumor marker LDH is treated as a variable of special interest. Many features of RECPAM are illustrated, including, among others, Forward and Backward (Pruning) Stopping Rules, treatment of missing data, and use of several dissimilarity measures.

Biomarkers, Tumor↗

PubMed1989

Repeated-measures model for the investigation of temporal trends using longitudinal family studies: application to systolic blood pressure.

A contemporary path model for the analysis of familial resemblance is extended to incorporate repeated measurements on the entire pedigree over time, in order to assess age-related changes in familiality. The parameters of the model can be defined as arbitrary functions of the ages, age differences, or cohabitation times of the family members at the exact time of measurement. Tracking of the phenotypes is decomposed into a familial and a nonfamilial component, which varies with both the time span between measurements and the ages at measurement. Some of the family members may have data missing on one or more visits, and the visits may be unequally spaced both within and across families. The method incorporates all measurements available from all visits into a single model. The model is applied to longitudinal data on systolic blood pressure in 490 East Boston families measured two times at 3-year intervals. Evidence for some nonfamilial tracking is found. Additionally, significant temporal trends are demonstrated in the familiality as a function of age, t2(A), which appears to be near zero at birth, grow to a maximum of about 40% at around age 30, and then appears to monotonically decrease again. No evidence was found for temporal trends in marital resemblance or residual sibling environmental effects. This model provides an objective method of investigating developmental changes in the correlational structure of families over time using repeated-measures and of estimating continuous changes in familiality with age.

Age Factors↗

PubMed1989

Comparison of questionnaire and diary methods in acute childhood respiratory illness surveillance.

We compared two prospective survey methods, an interviewer-administered questionnaire and a daily diary, used concurrently to record acute respiratory illness experience over a 2-yr period in 422 children 5 to 11 yr of age from East Boston, Massachusetts. Respondents contributed more months of data with the questionnaire than with the diary method. Respiratory symptom and illness rates, as determined for the first year by each of the methods, were compared for 277 children who had less than 4 months of missing data. Respondents from families with more children tended to report a lower total respiratory illness rate by the diary than by the questionnaire method (p = 0.006). Although upper respiratory illness rates did not differ by method, lower respiratory illnesses were reported more frequently (p = 0.0001) by questionnaire than by diary. In the group of 49 children who were identified as having had greater than one lower respiratory illness, 25% of the illnesses reported as having been lower respiratory by questionnaire were reported as having been another form of respiratory illness by diary. For this group the ratio of 3:1 of boys to girls for the diary as compared with 1.5:1 for the questionnaire suggests the presence of reporting bias and no comparability of methods. Standardization of an acute respiratory illness questionnaire would provide greater opportunity than use of diaries for synthesis of prospective data from different epidemiologic studies.

Acute Disease↗

PubMed1986

Problems in setting up an executing large-scale psychiatric epidemiological studies.

This paper focuses on problems that can be encountered in conceptualizing, executing and writing up large-scale psychiatric epidemiological studies. It makes no attempt to cover fundamental issues of design and analysis, rather it centers on problems associated with projects of considerable size. In the conceptual area, it discusses the prerequisites to be considered before deciding to launch such a study. It notes the administrative and scientific uses of epidemiological studies and considers the strengths and weaknesses of large-scale studies to address those concerns. Issues in carrying out such studies are discussed including decisions about study design, sampling method and instrumentation. All are dependent on the central purpose of the study but trade-offs between feasibility and scientific rigor are always present. Data collection and analysis problems highlighted in large-scale studies are examined. They include the difficulty, in the former, of adequately motivating and supervising field personnel and, in the latter, of dealing with problems that accompany missing data and complicated sampling strategies. Potential problems in data access and use and writing up the results are seen as arising from the presence of a large investigative team with diverse interests. Lastly, the comparative worth of these studies is considered.

Data Collection↗

PubMed1992

A longitudinal analysis of factors related to survival in old age.

Data from a longitudinal study of the elderly in rural North Wales are used in an exploratory study of the relationships between very broadly defined social circumstances and longevity. A statistical modeling approach is adopted and has some nonroutine features necessitated by missing data on dates of death. A variety of demographic, socioeconomic, social network, quality-of-life, dependence, and health variables are found, individually, to be related to survival. Multivariate analysis demonstrated that many of these relationships are spurious and, in particular, there is no prima facie evidence that survival is affected by social networks or quality-of-life factors. However, socioeconomic factors emerge as important for the old elderly.

Aged↗

PubMed1989

Temporal trends of human immunodeficiency virus type 1 (HIV-1) infection among inmates entering a statewide prison system, 1985-1987.

Acquired immune deficiency syndrome (AIDS) became the leading cause of death among Maryland State prisoners in 1985. To identify the prevalence, risk factors, and temporal trends for infection with the human immunodeficiency virus type 1 (HIV-1) in the statewide prison system, excess sera were obtained from incoming male inmates during specified periods between April and June 1985, 1986, and 1987. Correctional medical personnel also provided demographic variables of age, race, offense category, sentence, jurisidiction, and an indicator of intravenous drug use. Once rendered anonymous, specimens were assayed for antibody to HIV-1, using ELISA and Western blot techniques. For data from April to June 1985, 1986, and 1987, the crude prevalence of anti-HIV-1 was 7.1, 7.7, and 7.0%, respectively. Although one-third of incoming inmates were identified as intravenous drug users (IVDUs), the drug use variable was missing for 70% of the 1985 sample, and 40% of the 1986 sample. Several strategies were used to examined temporal trends in the context of missing data. Univariate analyses suggested no substantial change over time for either HIV-1 seroprevalence or risk of infection among IVDUs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Familial aggregation in the presence of temporal trends.

Models for assessing temporal trends in familial aggregation are described for both cross-sectional and longitudinal family data. Simultaneous linear structural equations on latent variables are used to model the dependence among family members. The coefficients of the equations are assumed to be parametric functions of time, so that quite complex temporal trends in familial aggregations can be accommodated. Variable family sizes and missing data values pose no problem as the parameters of the models are estimated via maximum likelihood techniques. One of the models is applied to systolic blood pressure data in 542 Japanese-American nuclear families. The results indicate limited evidence for temporal variation in the genetic expression, but that there is substantial temporal variation in environmental influences, which appear to peak at middle age.

Age Factors↗

PubMed2026

Suggestive genome-wide associations with inflammatory biomarkers in an admixed population, including a missense variant in the OR6K6 olfactory receptor gene associated with MCP-1.

BACKGROUND: Chronic low-grade inflammation drives cardiometabolic diseases and has a strong genetic basis. Most genome-wide association studies (GWAS) have focused on European populations, limiting knowledge of the genetic influences on inflammation in admixed populations such as those in Brazil. METHODS: This study is part of the cross-sectional ISA Capital Health Survey. It uses data from the 2015 ISA Nutrition cohort, which measured biochemical, genetic, anthropometric, and lifestyle factors in a probabilistic sample of São Paulo residents. Genomic DNA was extracted from 841 individuals. Genotyping was performed using the Axiom 2.0 Precision Medicine Research Array. After quality control and missing data exclusion, 244,338 SNPs from 638 individuals remained for GWAS-based association analysis with eight inflammatory biomarkers. Models were adjusted for sex, age, age2, overweight, and the first two principal components of ancestry. RESULTS: Most participants were male (53%) and not overweight (55%). The median age was 49, and 38% were older adults. In the genome-wide analysis of TNF-α, IL-10, IL-1β, monocyte chemoattractant protein-1 (MCP-1), and adiponectin, 12 SNPs were significantly associated, most of which were intronic. Notably, one signal mapped to the missense variant rs16841009 in the olfactory receptor gene OR6K6. This variant was associated with MCP-1, suggesting a possible involvement in inflammatory responses. CONCLUSIONS: We identified new SNPs linked to inflammatory biomarkers in a highly admixed Brazilian population, including a missense variant in an olfactory receptor gene linked to MCP-1. This association may be biologically important for inflammation and could affect the risk of cardiometabolic diseases.

Humans↗

PubMed1991

An indicator of adverse pregnancy outcome in France: not receiving maternity benefits.

STUDY OBJECTIVE: The aim was to compare the social characteristics, the pregnancy outcome, and the antenatal care of women in France who did not receive maternity benefits to women who did. These benefits (860 FF, approx 86 pounds per month) are given to every pregnant woman, starting in the second trimester. Payments are made on the condition that at least three antenatal visits are made, the first being before the end of the first trimester. DESIGN: The study involved a random sample of women who were interviewed after delivery during their stay in hospital. Data on pregnancy outcome were collected from medical records. SETTING: The study was carried out in four public maternity units in different regions of France. PARTICIPANTS: 1692 women were included in the analysis (86.8% of the selected sample). Of 257 exclusions, 40 had multiple pregnancies, 189 had missing data, and 28 did not answer the question concerning maternity benefits. MEASUREMENTS AND MAIN RESULTS: 4.3% of the women did not receive any maternity benefits. These women lived in poorer social conditions than the women who received the benefits. They had a higher preterm delivery rate, after controlling for risk factors in a logistic regression. Women without maternity benefits were characterised by a lower level of care, yet the majority began their antenatal care during the first trimester or had more than six visits. CONCLUSIONS: Not receiving maternity benefits during pregnancy is an index of an underprivileged situation and a risk factor for pregnancy outcome.

Age Factors↗

PubMed1989

A cautionary note on the use of autoregressive models in analysis of longitudinal data.

Rosner et al. presented a simple, easily implemented modelling method for retaining time order relationships in analyses of longitudinal data when successive measures are correlated. Evaluation of time order is particularly useful in epidemiologic studies concerned with exposure to potentially toxic substances and subsequent outcome, but may also have use in more traditional growth studies that relate intake to subsequent development. The analysis allows for unequally spaced measures and missing data. The estimation method permits varying numbers of observations per subject and, with measures equally spaced, one can fit the model with use of ordinary least squares regression software. We report on a potential false association that can result when both exposure and outcome are related to time. We illustrate this problem with a small scale simulation and example. We also note a more serious problem with Rosner's approach in interpreting parameters. Although the model may be useful for prediction, parameters depend on the autocorrelation and are not readily interpretable. We recommend alternative modelling strategies be used when autocorrelation of errors is suspected.

Age Factors↗

PubMed1991

Running average analysis of clinical trial ambulatory blood pressure data.

A method is presented for analyzing ambulatory blood pressure monitoring (ABPM) time series data obtained from well-controlled clinical trials. The method uses running averages based on fixed time-of-day intervals (rather than a fixed number of neighboring measurements). These "interval running averages" effectively estimate average blood pressure during the specified time intervals, adjusting for unequal spacing between measurements, embedded missing data, varying measurement times-of-day, and doses of study medication taken during ABP monitoring. Blood pressure changes from baseline may be computed using the interval running averages in order to separate treatment effects from patients' normal daily blood pressure cycles. To ensure valid estimation of treatment effects over time, study medication dosing times should be rigorously controlled in the trial design and conduct. Interval running average curves may be presented graphically, and from them summary statistics may be computed for purposes of statistical analysis. By allowing for the inherent complications of ABP data collection, the effect of antihypertensive treatment in well-controlled clinical trials can be discerned.

Ambulatory Care↗

PubMed2026

Cardiometabolic Multimorbidity Increases the Risk of Hip Fracture: A Longitudinal Cohort Study Based on CHARLS.

BACKGROUND: Cardiometabolic Multimorbidity (CMM) is defined as the co-occurrence of two or more conditions among heart disease, diabetes mellitus, stroke, and hypertension. Previous studies have shown associations between cardiometabolic diseases and fragility fractures; however, the relationship between CMM and hip fractures remains unclear in the Chinese population. This study therefore aims to investigate this association in a Chinese cohort to inform fracture prevention strategies. METHODS: This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) collected from 2011 to 2020. Participants from the 2011 baseline survey cohort were initially included. Subsequently, individuals were sequentially excluded if they were under 45 years of age, had incomplete baseline CMM information, had a history of hip fracture, lost to follow-up, or had missing data on confounders. Kaplan-Meier survival analysis, Cox proportional hazards regression, subgroup analyses, and sensitivity analyses were performed to evaluate the association between CMM and the risk of hip fracture. RESULTS: A total of 6314 participants aged 45 years and older were included, of whom 544 had CMM. Over a 9-year follow-up period, 287 incident hip fractures (4.55%) were identified. Among these, 36 participants had been diagnosed with CMM at baseline, whereas 251 had not. The incidence of hip fracture was significantly higher in participants with CMM than in those without CMM (13% vs. 8%, p = 0.015). After full adjustment for confounders, multivariable Cox regression showed that CMM was associated with a 70% increased risk of hip fracture (HR = 1.70, 95% CI: 1.318-2.47; p = 0.005). Subgroup analyses indicated that age and history of falls were significant effect modifiers. The association between CMM and hip fracture was more pronounced in participants under 60 years old (P for interaction = 0.048) and those with a history of falls (P for interaction = 0.014). CONCLUSION: These findings suggest that CMM increases the risk of hip fracture, particularly among relatively younger individuals and those with a history of falls.

Humans↗

PubMed1991

Practice databases and their uses in clinical research.

A few large clinical information databases have been established within larger medical information systems. Although they are smaller than claims databases, these clinical databases offer several advantages: accurate and timely data, rich clinical detail, and continuous parameters (for example, vital signs and laboratory results). However, the nature of the data vary considerably, which affects the kinds of secondary analyses that can be performed. These databases have been used to investigate clinical epidemiology, risk assessment, post-marketing surveillance of drugs, practice variation, resource use, quality assurance, and decision analysis. In addition, practice databases can be used to identify subjects for prospective studies. Further methodologic developments are necessary to deal with the prevalent problems of missing data and various forms of bias if such databases are to grow and contribute valuable clinical information.

Clinical Medicine↗

PubMed1988

[Reduction of cerebral hemorrhage and respiratory distress syndrome in premature infants by avoiding perinatal asphyxia].

Intra- and periventricular haemorrhage (IVH/PVH) and, under certain conditions, the respiratory distress syndrome (RDS) seem to be typical sequelae of perinatal asphyxia in preterm born infants. Therefore, an association of IVH/PVH and RDS can be expected. We have retrospectively analyzed the data of 118 premature infants born between 1982 and 1986, weighing between 750 and 1499 g. 11 of these had experienced a severe IVH/PVH and a severe RDS at the same time, whereas 75 infants did not develop either of those. (2 of the 118 showed a severe IVH/PVH without evidence of severe RDS whereas 29 developed severe RDS without signs of serious IVH/PVH. 1 could not be evaluated due to missing data). This association of severe intracerebral haemorrhage and severe respiratory distress syndrome was statistically significant (p less than 0.005). The number of severe IVH/PVH has decreased during 1984-1986 in comparison to 1982/83 (4/76 vs. 9/42; p less than 0.05); the incidence of severe RDS has slightly declined. Comparing the perinatal conditions we found that the infants of the years 1984-1986 were more rarely delivered after an interval exceeding 24 h after premature rupture of the membranes (p less than 0.05), were more often delivered by caesarean section (p less than 0.005), and were nearly always primarily cared for by an experienced paediatrician (p less than 0.01). There were no significant differences between these two groups as far as dexamethasone-prophylaxis, mean birth weight, percentage of small-for-gestational-age infants and mean Apgar scores were concerned.(ABSTRACT TRUNCATED AT 250 WORDS)

Asphyxia Neonatorum↗