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PubMed2006

Parental effort and reproductive skew in coalitions of brood rearing female common eiders.

Members of breeding groups face conflicts over parental effort when balancing antipredatory vigilance and feeding. Empirical evidence has shown disparate responses to manipulations of parental effort. We develop a model in which we determine the evolutionarily stable effort of partners given their body conditions, allowing the benefits of shared care to be unevenly divided, and we test this model's predictions with data on common eiders (Somateria mollissima). Eiders show uniparental female care; females may share brood rearing, or they may tend alone, and their body condition at hatching of the young shows large environmentally induced variation. The model predicts that parental effort (vigilance) in a coalition is lower than when tending alone, controlling for parental condition; this prediction is supported by the data. The parental effort in a coalition should be positively correlated with body condition, and this prediction is also supported. Finally, parental effort should increase when partner condition decreases and vice versa; this prediction is partially supported. The Nash bargaining game may provide promising avenues by which to determine the precise settlement of reproductive skew and effort between coalition partners in the future.

Animals↗

PubMedDate not supplied

Predicting the cause of common bile duct obstruction with sonographic data: analysis of binary variables.

A retrospective analysis of 71 patients with proven common bile duct obstruction, who had not undergone previous biliary surgery, was performed. To determine optimal criteria for differentiating stone from nonstone obstruction by ultrasonography, five sonographic signs were analyzed as binary variables. These signs are the demonstration of (1) common duct stones, (2) mass at the site of the common bile duct, (3) gallbladder stones, (4) gallbladder volume greater than a critical value, and (5) common duct diameter greater than a critical value. Maximum expected accuracy was 85% achieved by prediction based on a set of three variables: common duct stone, common duct mass, and gallbladder stones. This was not significantly better than the accuracy (82%) achieved by prediction on the basis of gallbladder stones alone. Three signs in combination, ie, demonstration of gallbladder stones, gallbladder volume less than 52 ml, and common duct diameter less than 14 mm, had predictive value equal to demonstration of a common duct stone as an indicator that common bile duct obstruction is the result of a stone.

Adolescent↗

PubMed1993

MULCOX2: a general computer program for the Cox regression analysis of multivariate failure time data.

Multivariate failure time data is commonly encountered in biomedicine, because each study subject may experience multiple events or because there exists clustering of subjects such that failure times within the same cluster are correlated. MULCOX2 implements a general statistical methodology for analyzing such data. This approach formulates the marginal distributions of multivariate failure times by Cox proportional hazards models without specifying the nature of dependence among related failure times. The baseline hazard functions for the marginal models may be identical or different. A variety of statistical inference can be made regarding the effects of (possibly time-dependent) covariates on the failure rates. Although designed primarily for the marginal approach, MULCOX2 is general enough to implement several alternative methods. The program runs on any computer with a FORTRAN compiler. The running time is minimal. Two illustrative examples are provided.

Age Factors↗

PubMed1997

Local estimation of smooth curves for longitudinal data.

Longitudinal data are commonly analysed using mixed-effects models in which the population growth curve and individual subjects' growth curves are assumed to be known functions of time. Frequently, polynomial functions are assumed. In practice, however, polynomials may not fit the data and a mechanistic model that could suggest a non-linear function might not be known. Recent, more flexible approaches to these data approximate the underlying population mean curve or the individual subjects' curves using smoothing splines or kernel-based functions. I apply the local likelihood estimation method of Tibshirani and Hastie and estimate smooth population and individual growth curves by assuming that they are approximately linear or quadratic functions of time within overlapping neighbourhoods. This method requires neither complete data, nor that measurements are made at the same time points for each individual. For descriptive purposes, this approach is easy to implement with standard software. Inference for the resulting curve is facilitated by the theory of estimating equations. I illustrate the methods with data sets containing longitudinal measurements of serum neopterin in an AIDS clinical trial, measurements of ultrafiltration rates of high flux membrane dialysers for haemodialysis, and measurements of the volume of air expelled by individuals.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Median-of-subsets normalization of intensities for cDNA array data.

cDNA arrays allow quantitative measurement of expression levels for thousands of genes simultaneously. The measurements are affected by many sources of variation, and substantial improvements in the precision of estimated effects accompany adjustments for these effects. Two generic nuisance variations, one associated with the magnitude of expression and the other associated with array location, are common in data from filter arrays. Procedures, like normalization using lowess regression, are effective at reducing variation associated with magnitude, and they have been widely adopted. However, variation associated with location has received less attention. Here, a simple, but effective method based on localized median is expounded for dealing with these nuisance effects, and its properties are discussed. The proposed methodology handles location-dependent variation ("splotches") and magnitude-dependent variation (background and/or saturation) effectively. The procedure is related to lowess when implemented to adjust magnitude-dependent variation, and it performs similarly. The proposed methodology is illustrated with data from the National Center for Toxicological Research (NCTR), where treatment differences in levels of mRNA from rat hepatocytes were assessed using 33P-labeled samples hybridized to cDNA spotted arrays. Normalizing intensities by the median-of-subsets removes systematic variation associated with the location of a gene on the array and/or the level of its expression. This procedure is easy to implement using iteratively reweighted least-squares algorithms. Although less sophisticated than lowess, this procedure works nearly as well for normalizing intensities based upon their magnitude. Unlike lowess, it can adjust for location-dependent effects.

DNA, Complementary↗

PubMed1991

PC-based molecular modeling in the classroom: applications to medicinal chemistry and biochemistry.

Among the most difficult aspects of medicinal chemistry and biochemistry for the student to master are the three-dimensional (3D) nature of drugs and bio-organic substances and the interaction of these substances with 3D targets. Compounding this problem is the fact that such relationships are very difficult to illustrate in a lecture or discussion format. While skeletal molecular models serve a useful role in the learning process, the techniques of PC-based desktop molecular visualization provide a more powerful and effective alternative to the lecture format. These techniques can be implemented on standard MS-DOS PC hardware using one of the commonly available data projection systems. The approach has found considerable use in several areas, including the generation of computer-based lecture aids, the illustration of the molecular shapes of drugs and biochemical structures, the superposition and comparison of drug substances with common pharmacophores, and the illustration of enzyme-substrate interactions. Another related technique, molecular animation, has proven to be quite successful at illustrating the essentials of enzyme mechanisms in the classroom. The "film clips" resulting from this technique may have use beyond the classroom, and further work in this area is underway.

Audiovisual Aids↗

PubMed2003

CERR: a computational environment for radiotherapy research.

A software environment is described, called the computational environment for radiotherapy research (CERR, pronounced "sir"). CERR partially addresses four broad needs in treatment planning research: (a) it provides a convenient and powerful software environment to develop and prototype treatment planning concepts, (b) it serves as a software integration environment to combine treatment planning software written in multiple languages (MATLAB, FORTRAN, C/C++, JAVA, etc.), together with treatment plan information (computed tomography scans, outlined structures, dose distributions, digital films, etc.), (c) it provides the ability to extract treatment plans from disparate planning systems using the widely available AAPM/RTOG archiving mechanism, and (d) it provides a convenient and powerful tool for sharing and reproducing treatment planning research results. The functional components currently being distributed, including source code, include: (1) an import program which converts the widely available AAPM/RTOG treatment planning format into a MATLAB cell-array data object, facilitating manipulation; (2) viewers which display axial, coronal, and sagittal computed tomography images, structure contours, digital films, and isodose lines or dose colorwash, (3) a suite of contouring tools to edit and/or create anatomical structures, (4) dose-volume and dose-surface histogram calculation and display tools, and (5) various predefined commands. CERR allows the user to retrieve any AAPM/RTOG key word information about the treatment plan archive. The code is relatively self-describing, because it relies on MATLAB structure field name definitions based on the AAPM/RTOG standard. New structure field names can be added dynamically or permanently. New components of arbitrary data type can be stored and accessed without disturbing system operation. CERR has been applied to aid research in dose-volume-outcome modeling, Monte Carlo dose calculation, and treatment planning optimization. In summary, CERR provides a powerful, convenient, and common framework which allows researchers to use common patient data sets, and compare and share research results.

Biomedical Research↗

PubMed1994

Cox regression analysis of multivariate failure time data: the marginal approach.

Multivariate failure time data are commonly encountered in scientific investigations because each study subject may experience multiple events or because there exists clustering of subjects such that failure times within the same cluster are correlated. In this paper, I present a general methodology for analysing such data, which is analogous to that of Liang and Zeger for longitudinal data analysis. This approach formulates the marginal distributions of multivariate failure times with the familiar Cox proportional hazards models while leaving the nature of dependence among related failure times completely unspecified. The baseline hazard functions for the marginal models may be identical or different. Simple estimating equations for the regression parameters are developed which yield consistent and asymptotically normal estimators, and robust variance-covariance estimators are constructed to account for the intra-class correlation. Simulation results demonstrate that the large-sample approximations are adequate for practical use and that ignoring the intra-class correlation could yield rather misleading variance estimators. The proposed methodology has been fully implemented in a simple computer program which also incorporates several alternative approaches. Detailed illustrations with data from four clinical or epidemiologic studies are provided.

Adolescent↗

PubMed2002

Geography and geographic information systems in family medicine research.

Understanding spatial relationships between determinants and outcomes of health care is important as the concept of population-based health care gains acceptance. A wide range of tools for understanding these spatial relationships is available to the family medicine researcher through the use of Geographic Information Systems (GIS). The power of GIS lies in its ability to display the spatial distribution of a health-related predictor or outcome. These maps can then be used to either generate or test hypotheses that would not have otherwise occurred to the investigator without visualizing the spatial relationships. The type of GIS application used is dependent on the type of data the researcher has and the research question. The three most common types of data are point or event data, lattice data, and geostatistical data. Point or event data can be displayed using a technique known as geocoding. Lattice data is most commonly displayed as shaded or colored areas where the shading represents rates or counts. Geostatistical data provides counts or numbers at a given location. The analytic techniques used for analyzing spatial data depend on the type of data. Maps tell powerful stories and display relationships that may not be obvious using other techniques.

Environmental Exposure↗

PubMed2000

Vitamin C for preventing and treating the common cold.

BACKGROUND: The role of oral ascorbic acid (vitamin C) in the prevention and treatment of colds remains controversial despite many controlled trials. There have also been a number of efforts to synthesize and/or overview the results of these trials, and controversy over what these overviews tell us. OBJECTIVES: The objective of this review was to answer the following two questions: (1) Does regular high dosage supplementation with vitamin C reduce the incidence of colds? (2) Does taking vitamin C in high doses at the onset of a cold have a therapeutic effect? SEARCH STRATEGY: This review currently deals only with published trials from two previously published reviews by Kleijnen 1989 and Hemila 1992. SELECTION CRITERIA: Randomised and non-randomised trials of vitamin C taken to prevent or treat the common cold. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Thirty trials were included. The quality of the included trials was variable. Vitamin C in doses as high as one gram daily for several winter months, had no consistent beneficial effect on incidence of the common cold. For both preventive and therapeutic trials, there was a consistently beneficial but generally modest therapeutic effect on duration of cold symptoms. This effect was variable, ranging from -0.07% to a 39% reduction in symptom days. The weighted difference across all of the studies revealed a reduction of a little less than half a symptom day per cold episode, representing an 8% to 9% reduction in symptom days. There was no clear indication of the relative benefits of different regimes or vitamin C doses. However in trials that tested vitamin C after cold symptoms occurred, there was some evidence that a large dose produced greater benefits than lower doses. REVIEWER'S CONCLUSIONS: Long term daily supplementation with vitamin C in large doses daily does not appear to prevent colds. There appears to be a modest benefit in reducing duration of cold symptoms from ingestion of relatively high doses of vitamin C. The relation of dose to therapeutic benefit needs further exploration.

Administration, Oral↗

PubMed1993

Peptic ulcer in the elderly--a double-blind, short-term study comparing nizatidine 300 mg with ranitidine 300 mg. GISU (Interdisciplinary Ulcer Study Group).

UNLABELLED: This was a randomized, double-blind, multicentre, short-term study comparing ranitidine and nizatidine at the standard dosages of 300 mg at bedtime. In 49 centres in Italy, all peptic ulcer patients aged over 65 years and with endoscopically documented acute disease were considered eligible for the study. Clinical check-ups were repeated every 3 weeks, while the endoscopic and biochemical assessments were scheduled at 6 and (in unhealed patients) 12 weeks. STATISTICS: chi-squared test, Fisher's exact test, Student t-test for unpaired data. The study included 170 duodenal ulcer and 75 gastric ulcer patients. Of these, 83/170 duodenal ulcer and 38/75 gastric ulcer patients were treated with nizatidine 300 mg and the remainder with ranitidine 300 mg. The groups were well-matched for common clinical data. Eight patients dropped out. Healing rates at 6 and 12 weeks were 81.9% and 91.5% for nizatidine-treated duodenal ulcer patients versus 78.1% and 94.2% for ranitidine-treated duodenal ulcer cases (P: N.S.); 6 and 12-week healing rates were 76.3% and 89.5% for nizatidine-treated gastric ulcer patients versus 67.6% and 83.8% for ranitidine-treated gastric ulcer patients (P: N.S.). No slow healing risk factors were found. Only minor adverse events were registered. IN CONCLUSION: ranitidine 300 mg and nizatidine 300 mg both proved effective and safe in the treatment of acute peptic ulceration in the elderly.

Aged↗

PubMed2006

A method for multitask fMRI data fusion applied to schizophrenia.

It is becoming common to collect data from multiple functional magnetic resonance imaging (fMRI) paradigms on a single individual. The data from these experiments are typically analyzed separately and sometimes directly subtracted from one another on a voxel-by-voxel basis. These comparative approaches, although useful, do not directly attempt to examine potential commonalities between tasks and between voxels. To remedy this we propose a method to extract maximally spatially independent maps for each task that are "coupled" together by a shared loading parameter. We first compute an activation map for each task and each individual as "features," which are then used to perform joint independent component analysis (jICA) on the group data. We demonstrate our approach on a data set derived from healthy controls and schizophrenia patients, each of which carried out an auditory oddball task and a Sternberg working memory task. Our analysis approach revealed two interesting findings in the data that were missed with traditional analyses. First, consistent with our hypotheses, schizophrenia patients demonstrate "decreased" connectivity in a joint network including portions of regions implicated in two prevalent models of schizophrenia. A second finding is that for the voxels identified by the jICA analysis, the correlation between the two tasks was significantly higher in patients than in controls. This finding suggests that schizophrenia patients activate "more similarly" for both tasks than do controls. A possible synthesis of both findings is that patients are activating less, but also activating with a less-unique set of regions for these very different tasks. Both of the findings described support the claim that examination of joint activation across multiple tasks can enable new questions to be posed about fMRI data. Our approach can also be applied to data using more than two tasks. It thus provides a way to integrate and probe brain networks using a variety of tasks and may increase our understanding of coordinated brain networks and the impact of pathology upon them.

Adult↗

PubMed2005

A qualitative review of studies of diabetes preventive care among minority patients in the United States, 1993-2003.

OBJECTIVE: To review existing data to determine whether ethnic disparities exist for diabetes-related preventive care among adults in the United States. STUDY DESIGN: Literature review. METHODS: We identified diabetes-related studies published between 1993 and 2003, using a reproducible search strategy. Studies were selected for review if there were ethnic comparisons or if data on a specific ethnic minority were reported. From these studies, we extracted data on commonly accepted diabetes-related preventive-care measures (testing for glycemia, eye examinations, foot examinations, lipid profile, influenza vaccination, nephropathy assessment, smoking-cessation counseling). The sources were US healthcare facilities, national survey samples, Veterans Affairs facilities, Medicare databases, and managed care data. RESULTS: Thirty-six studies met our search criteria. Data were extracted on glycemia testing (15 studies), eye examination rates (27 studies), foot examination rates (18 studies), lipid-profile assessment (15 studies), percentage of patients receiving influenza vaccinations (8 studies), nephropathy assessment (7 studies), and counseling referrals for smoking cessation (4 studies). The majority of the data indicated that the rates of diabetes monitoring are generally low regardless of the population being studied. The major ethnic differences reported were lower rates of eye examination, influenza vaccination, and lipid-profile testing among Hispanics and African Americans than among non-Hispanic whites. CONCLUSIONS: Despite the availability of evidence-based guidelines, rates of diabetes preventive care are low, particularly for some measures in ethnic minority groups. Additional data are needed to further elucidate these disparities.

Adolescent↗

PubMed1998

Gonadal function in men with testicular cancer.

This article reviews current knowledge on the effect of testicular germ cell cancer (TGCC) on gonadal function and of the cancer treatment on spermatogenesis and Leydig cell function. It seems likely that development of TGCC shares common etiological factors with development other types of testicular dysfunction. This suggestion is supported by the observation that men with various types of gonadal dysfunction such as testicular dysgenesis, androgen insensitivity syndrome, and cryptorchidism have increased risk of testicular cancer. Epidemiological and clinical data indicate common etiology between testicular germ cell cancer and other abnormalities in male reproductive health such as infertility and cryptorchidism. These observations are in agreement with the suggestions of hormonal involvement in the etiology of testicular cancer. It is well documented that testicular cancer is associated with impaired spermatogenic function and some patients have impairment of Leydig's cell function already before orchidectomy. The degree of spermatogenic dysfunction is higher than what can be explained by local tumor effect and by a general cancer effect. These observations are supported by histological investigations, which have shown a high prevalence of abnormalities of spermatogenesis in the contralateral testis in patients with unilateral TGCC. The spermatogenetic function is still severely impaired after orchidectomy and radiotherapy as well as chemotherapy induce further dose-dependent impairment of spermatogenesis. Recovery of spermatogenesis after treatment may be long, in some patients lasting more than 5 years. Sufficient androgen production is seen in the majority of the patients but some patients do suffer from testosterone deficiency. The effect of chemotherapy on Leydig's cell function seems to be dose dependent. Trials on protection of spermatogenetic function against the harmful effects of radiotherapy and chemotherapy by suppression of spermatogenesis has not been successful. The only way to maintain fertility is to limit gonadal exposure to harmful agents. Moreover cryopreservation of semen should be done before treatment. The optimal time for cryopreservation is before orchiectomy at least in some patients. Generally men with TGCC need counselling about their reproductive function, with respect to semen cryopreservation, chance for recovery of spermatogenesis, fertility, and the possibility of need for androgen replacement.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

From peptidoglycan to glycoproteins: common features of lipid-linked oligosaccharide biosynthesis.

The peptidoglycan layer of bacterial cell walls is biosynthesised using a lipid carrier undecaprenyl phosphate to assemble and transport the MurNAc(GlcNAc)-pentapeptide precursor. Similar lipid-linked cycles are involved in the biosynthesis of other bacterial exopolysaccharides and eukaryotic asparagine-linked glycoproteins, the latter involving the structurally related dolichyl phosphate as a lipid carrier. Recent protein sequence data and common inhibitors of the bacterial and eukaryotic systems have revealed functional similarities between the two systems. Biological and physical studies on the lipid carriers themselves have provided clues to their role in oligosaccharide translocation, but have not revealed significant differences in function between undecaprenyl phosphate and dolichyl phosphate. The presence of dolichyl phosphate and a family of saturated isoprenoid lipids in Archaebacteria suggests a possible evolutionary link between the two systems.

Amino Acid Sequence↗

PubMed1979

Biocomputational methodology an adjunct to theory and applications.

The role of "methodology", as distinguished from "theory" and "application", is discussed and illustrated. It is argued that research in the biomedical sciences is moving towards a degree of complexity different in both kind and extent from that usually encountered in other disciplines. Certain biocomputational methodology can be viewed as a bridge between the data forms commonly encountered in biomedicine, and the statistical and computational machinery which had previously been developed to deal with physical science information. Examples are given of three promising research subareas, all of which concern methods for dealing with highly complex forms of health and medical data.

Computers↗

PubMed1989

The generation of spatial population distributions from census centroid data.

"Census data are commonly used in geographical analysis and to inform planning purposes, though at the disaggregate level the basis of enumeration poses difficulties. In this paper an approach to surface generation is described that offers the prospect of revealing an underlying population distribution from centroid-based data which is independent of zonal geography. It is suggested that this can serve a wide variety of analytical, cartographic, and policy purposes, including the creation of spatial indicators of economic and social conditions and enhancing the value of census data. The approach is illustrated by reference to an analysis of part of the valleys of South Wales, in the United Kingdom."

Censuses↗

PubMed1980

Clinical assessment of renal function in the dog with a reduction in nephron number.

The viewpoint presented is that, because compensatory functional adjustment of the residual nephrons occurs in chronic renal disease, reduction in nephron number usually exceeds 70% before a diagnosis is made. The case that earlier diagnoses are likely if laboratory medicine values are measured and interpreted with a maximum of efficiency is then made. The laboratory data more commonly used in practice for the clinical assessment of renal function in the dog are presented and some comparisons with findings in man are made. The information originates from clinical and experimental observations of the authors, as well as from a literature review. The laboratory data presented and discussed includes glomerular filtration rate and the clearance of nitrogenous waste (urea and creatinine), plasma protein concentration, plasma osmolality, renal concentrating capacity, and urinary constituents, particularly its protein concentration and sediment (centrifuge deposit). All parameters recommended for the clinical assessment of chronic renal failure are considered qualitatively, and some are also dealt with quantitatively.

Animals↗