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PubMed2003

Central obesity and breast cancer risk: a systematic review.

The specific effect of central rather than general obesity on breast cancer risk is not clear. This review examines the relationship between waist and waist-hip ratio (WHR) and risk of breast cancer in pre- and post-menopausal women using all available cohort and case-control data. The databases of the Cochrane Library, Medline, Cancer Lit and Embase were searched until October 2002. Relevant cohort and case-control studies with separate analyses in pre- and/or post-menopausal women were included. Random effects meta-analyses were carried out, subgrouped by pre- or post-menopausal status and cohort or case-control design. Sensitivity analyses were also performed. Five cohort studies with 72,1705 person years of observation (453 pre-menopausal and 2684 post-menopausal cases), and three case-control studies comprising 276 pre-menopausal cases with 758 pre-menopausal controls and 390 post-menopausal cases with 1071 post-menopausal controls were included. Pooled results from cohort studies using the most adjusted data [but without adjustment for weight or body mass index (BMI)] suggest a 39% lower risk of breast cancer in post-menopausal women with the smallest waist (compared with the largest) and a 24% lower risk in women with the smallest WHR. In pre-menopausal women, however, pooled results suggest that measurement of waist or WHR have little effect on risk of breast cancer. Adjustment for BMI abolished the relationship between waist or WHR and risk of post-menopausal breast cancer, but introduced such a relationship amongst pre-menopausal women. The relationship between a smaller measurement of waist or WHR and lower risk of post-menopausal breast cancer appears to result from the associated correlation with BMI. Amongst pre-menopausal women, central (not general) obesity may be specifically associated with an increased risk of breast cancer.

Anthropometry↗
PubMed1998

Adjusting for missing data due to culling before testing in genetic evaluations of swine.

The aim of this study was to evaluate data augmentation in genetic evaluations as a method of adjusting for missing data due to culling of pigs before testing. A stochastic simulation was used to generate 10 yr of data for age at test (AGE) and fat thickness (FAT) in a breeding unit with 100 sows and 15 boars. Culling was performed at random (C-RAND), within litters (C-W/IN) or over litters (C-OVER), by deleting two-thirds of the records from the simulated data sets. The culling variate (CVAR) used had genetic and phenotypic correlations of 1.00, .75, .50, and .25 with AGE [r(CVAR, AGE)], whereas culling was uncorrelated with AGE in C-RAND. Missing records for AGE were replaced with their expectations (dummy records), based on the phenotypic average of the tested animals and selection intensities applied. With missing records, predictions were seriously biased for AGE in C-W/IN and especially in C-OVER, when r(CVAR, AGE) exceeded .50 and .25, respectively. The ranking of the animals was more affected in C-OVER than in C-W/IN. With dummy records, bias was removed effectively in cases with a high r(CVAR, AGE) in C-W/IN and C-OVER, whereas a larger bias was created in the opposite direction when r(CVAR, AGE) was less than .50 and for C-RAND. In conclusion, this method was beneficial for adjusting missing data owing to culling, when the correlation between CVAR and AGE was .50 or greater.

Animals↗
PubMed1981

A statistical model and analysis for genetic and environmental effects in responses from twin-family studies.

A statistical model and analysis for genetic and environmental effects in twin-family data are presented. The model is used to derive expressions for phenotypic correlations of 22 essential pair relationships in twin-family units. The analysis proceeds in two steps. First, differential effects of sex, generation, and sex-zygosity of twin-family units and correlations due to cluster sampling are eliminated from correlation data. Then, estimates and tests of model parameters are calculated from the adjusted data. The theory and methods were developed for a Swedish twin-family study of many behaviors possibly related to the smoking habit. There, it is important to screen for behaviors that clearly are under genetic control and to assess relative influences of various biological and social environments on the development of all behaviors. Height data from the Swedish study are used to illustrate concepts and methods presented in this paper.

Body Height↗
PubMed1969

Continuous infusion indicator dilution measurement of limb blood flow and vascular response to magnesium sulfate in normotensive and hypotensive men.

A constant infusion, indicator dilution technique for blood flow measurements in the forearm and hand of man was tested and validated in vitro and in vivo. This technique employs jet injection to improve mixing of indicator with arterial blood. The mixing characteristics of the jet injection system were studied in vitro in tubing simulating the brachial artery of man. In addition, actual blood flows in the isolated pump-perfused forelimbs of five dogs were compared with constant infusion, indicator dilution calculated flows. Measurements were also made of mixing and of blood flow in the forearm and hand of man. The technique was used to compare forearm and hand vascular responses with constant intrabrachial arterial infusions of magnesium sulfate in 13 normotensive and 13 essential hypertensive men. In vitro and in vivo the jet injection system significantly improved mixing of indicator with blood, as compared with mixing produced by standard infusion techniques, without causing hemolysis. In 30 measurements in isolated, perfused dog forelimbs the correlation coefficient between actual and calculated blood flow was 0.992. Resting limb vascular resistance in the hypertensive group was significantly higher than in the normotensive group. Limb vascular resistance in all 26 men decreased in response to intrabrachial-arterial infusion of 0.25% magnesium sulfate (8 ml/min). Rate of infusion of Mg(++) was 0.162 mEq/min. There was a significant positive linear correlation between level of initial limb vascular resistance and magnitude of response to magnesium sulfate. Vascular response data adjusted for this source of variation were similar in hypertensives and normotensives.The data suggest that this constant infusion, indicator dilution technique allows accurate calculation of total limb blood flow in man, provided that anomalous bifurcation of the brachial artery is not present. The data also suggest that the jet injection system improves mixing of substances with arterial blood. Thus, use of this system should especially aid reliability of studies of limb vascular responses to vasoactive agents infused into the brachial artery.

Adult↗
PubMed2004

Three-parameter lognormal distribution ubiquitously found in cDNA microarray data and its application to parametric data treatment.

BACKGROUND: To cancel experimental variations, microarray data must be normalized prior to analysis. Where an appropriate model for statistical data distribution is available, a parametric method can normalize a group of data sets that have common distributions. Although such models have been proposed for microarray data, they have not always fit the distribution of real data and thus have been inappropriate for normalization. Consequently, microarray data in most cases have been normalized with non-parametric methods that adjust data in a pair-wise manner. However, data analysis and the integration of resultant knowledge among experiments have been difficult, since such normalization concepts lack a universal standard. RESULTS: A three-parameter lognormal distribution model was tested on over 300 sets of microarray data. The model treats the hybridization background, which is difficult to identify from images of hybridization, as one of the parameters. A rigorous coincidence of the model to data sets was found, proving the model's appropriateness for microarray data. In fact, a closer fitting to Northern analysis was obtained. The model showed inconsistency only at very strong or weak data intensities. Measurement of z-scores as well as calculated ratios was reproducible only among data in the model-consistent intensity range; also, the ratios were independent of signal intensity at the corresponding range. CONCLUSION: The model could provide a universal standard for data, simplifying data analysis and knowledge integration. It was deduced that the ranges of inconsistency were caused by experimental errors or additive noise in the data; therefore, excluding the data corresponding to those marginal ranges will prevent misleading analytical conclusions.

Blotting, Northern↗
PubMed2002

BioDataServer: a SQL-based service for the online integration of life science data.

Regarding molecular biology, we see an exponential growth of data and knowledge. Among others, this fact is reflected in more than 300 molecular databases which are readily available on the Internet. The usage of these data requires integration tools capable of complex information fusion processes. This paper will present a novel concept for user specific integration of life science data. Our approach is based on a mediator architecture in conjunction with freely adjustable data schemes. The implemented prototype is called BioDataServer and can be accessed on the Internet: http://integration.genophen.de. To realize a comfortable usage of the resulted data sets of the integration process, a SQL-based query language and a XML data format were developed and implemented.

Computational Biology↗
PubMed1993

The "Toward Excellence in Care" program: a statewide indicator project.

BACKGROUND: The "Toward Excellence in Care" program was launched by Connecticut hospitals and physicians in 1988 to develop and use quality-of-care indicators for use in quality improvement. METHODOLOGY: Data came primarily from the Connecticut Health Information Management and Exchange (CHIME) database, which contains discharge abstract information, UB (uniform billing)-82 information, and additional data elements, for all of Connecticut's 34 acute care hospitals. Linkages also occur with the state mortality database, the trauma registry, and with admission/discharge data within and across Connecticut hospitals. The "Toward Excellence in Care" program staff help the hospital use the data on indicator reports for quality improvement. EXAMPLE: On receiving a report on care for patients with acute myocardial infarction (AMI) a program representative summarized opportunities for improvement. The data were then disseminated to both the cardiology and the hospitalwide quality improvement staffs. Cardiologists conducted chart review on 100% of patients included in the last time-frame on the report (for example, fiscal year 1991). The quality improvement professional documented the system of care for an AMI patient. Recommended actions included adoption of a policy for emergency department administration of thrombolytic therapy before a cardiology consultation, and modification of the postcoronary care program. CONCLUSIONS: Progress in addressing four challenges-easing the burden of data collection on the hospitals, maximizing acceptance of information by hospitals and physicians, risk adjusting data to permit comparison of outcomes, and facilitating understanding of reports--is reflected in expanding use of the "Toward Excellence in Care" program.

Confidentiality↗
PubMed1990

Use of adjustment factors with a brief food frequency questionnaire to obtain nutrient values.

The 100-item National Cancer Institute (Block) Food Frequency Questionnaire was created to measure an individual's relative nutrient intake as well as absolute nutrient values. A 60-item, brief questionnaire was then developed; its results correlate well with results from the 100-item questionnaire and with food record data. Adjustment factors, presented here, were developed that allow investigators to use the shorter questionnaire while obtaining nutrient values nearer the correct absolute values than those from the brief questionnaire alone. Data from the National Health and Nutrition Examination Survey II (1976-1980) and the first quarter of the National Health Interview Survey (1987) were used in developing the adjustment factors. The brief questionnaire was administered to approximately 22,000 subjects in the National Health Interview Survey. When the adjustment factors were applied to data from the second, third, and fourth quarters of the National Health Interview Survey, the adjusted values of 17 micro- and macronutrients were on average within 0.51% and 1.17% of estimates obtained by 24-hour recall in the National Health and Nutrition Examination Survey II, for men and women, respectively. Correlations between the adjusted nutrient values and absolute nutrient consumption, as measured by diet diaries in three smaller studies, were nearly the same or somewhat better than correlations with the unadjusted brief questionnaire.

Adolescent↗
PubMed2001

Towards a national system for monitoring the quality of hospital-based stroke services.

BACKGROUND AND PURPOSE: We sought to evaluate a system for monitoring the quality of hospital-based stroke services that uses routinely collected case fatality data, adjusted for case mix, as well as simple measures of the process of stroke care. METHODS: We compared the process of care and case fatality after stroke between 5 Scottish hospitals (A through E) during 1995-1997. We retrospectively identified 2724 patients with acute stroke using routine discharge data and obtained case mix and process of care data from the medical record. We ascertained case fatality by record linkage and adjusted for case mix using a simple, externally validated regression model. RESULTS: Crude case fatality varied by 21 deaths per 100 admissions between the 5 hospitals. After adjustment, case fatality still differed significantly (P=0.047), with 5 to 7 more deaths per 100 admissions at Hospital A than at Hospitals B through E. There were major shortcomings in the specialization and organization of care, the use of CT scanning, and the completeness of documentation at Hospital A compared with the other hospitals. There were smaller, but clinically important, differences in care between Hospitals B through E but no significant differences in adjusted case fatality. CONCLUSIONS: Once adjusted for important prognostic variables, routinely collected case fatality data might identify hospitals with major shortcomings in the processes of stroke care. More moderate, but still clinically important, variations in stroke care can only be identified by monitoring the process of care directly.

Aged↗
PubMed1989

Genetic determination of plasma apolipoprotein AI in a population-based sample.

Apolipoprotein AI (apo AI) is the major protein of high-density lipoprotein (HDL). Using radioimmunoassay, we measured plasma apo AI levels in 1,880 individuals in 283 pedigrees randomly selected from the population with respect to disease status and risk factors for coronary artery disease. Apo AI levels were first adjusted for date of assay (6.8% of apo AI variation) and then adjusted for variability in age and body mass index (an additional 6.6%, 20.4%, and 23.0% of apo AI variations for males, females not using exogenous hormones, and females using exogenous hormones, respectively). A mixture of two normal distributions fit the adjusted data better than did a single normal distribution. Genetic and environmental models that could explain the mixture of normal distributions were investigated using complex segregation analysis. Heterogeneous etiologies for individual differences in adjusted apo AI levels were suggested by the data in the 283 pedigrees. In a subset of 126 pedigrees, there is evidence for the major effect of a nontransmitted environmental factor that explains the mixture of distributions as well as polygenic loci that influence apo AI levels within each distribution. The environmental factor and polygenic loci account for 32% and 65% of the adjusted variation, respectively. In the other 157 pedigrees there is strong support for a single locus with a major effect that accounts for 27% of the adjusted variation. The effect of the polygenic loci is not different from zero in these 157 pedigrees. This is the first study to present evidence for the segregation of a single unmeasured locus with a major effect on levels of apo AI in a population-based sample of pedigrees.

Adolescent↗
PubMed2006

Dehydration of risedronate hemi-pentahydrate: analytical and physical characterization.

Dehydration of hydrates of pharmaceutical active ingredients (pharmaceutical hydrates) may easily occur during storage or manufacturing. Loss of water may have little effect on the crystal lattice, produce less hydrated forms or possibly amorphous forms. Characterizing the effects of water loss on crystal hydrate forms is important for understanding the behavior of pharmaceutical hydrates throughout the manufacturing and storage processes. This study shows that exposure of the hemi-pentahydrate form of risedronate monosodium to gentle heating (60 degrees C) or conditions of low relative humidity (<10% RH) results in the loss of 1 mole of channel-type water. Upon removal of the channel-type water, the crystal lattice adjusts producing a distinct phase characterized by X-ray, thermal, IR, Raman, and NMR data. Adjustment of the crystal lattice appears to compromise crystal integrity and can result in reduced crystallite and particle sizes.

Bone Density Conservation Agents↗
PubMed2006

The use of soil survey data to determine the magnitude and extent of historic metal deposition related to atmospheric smelter emissions across Humberside, UK.

When a smelter has ceased operation, and in the absence of historical emission data, high-resolution geochemical surveys of the soil can reveal historical loads to the surrounding land. We use measurements of lead and tin in the soil at two depths to estimate the total quantities of these metals deposited on 286 km(2) of land around the former Capper Pass smelter (north-east England). We subtracted median background concentrations for three parent material types outside the region of deposition from the data within it. We then constructed a statistical model of metal deposition based on the adjusted data. The data were from irregularly spaced sites and were strongly skewed with a spatial trend. We mapped the concentrations of the metals by lognormal universal kriging with the parameters for the trend and residuals modelled simultaneously by residual maximum likelihood (REML). The maps suggest that metal was deposited up to 24 km to the north-east of the smelter by the prevailing wind. We estimated total excess metal in the soil over the area of deposition to be 2500 t of lead and 830 t of tin.

Air Pollutants↗
PubMed1991

Method and effect of adjustment for heterogeneous variance.

Lactation records were standardized for differing genetic and error variances across herds and over time based on phenotypic variance for each herd-year-parity group. Each herd-year-parity phenotypic variance estimate was combined with those of adjacent years and regressed toward a region-year-parity variance. Heritability was assumed to be .25 at mean variance within year and to range from .2 for herds with smallest phenotypic SD to .3 for herds with largest phenotypic SD. Lactation deviations from management group mean were adjusted by ratio of base genetic SD to genetic SD estimated from heritability and phenotypic SD. The base was defined as 1987 calvings for first parity and 1988 calvings for later parities. Records were weighted according to heritability by multiplying lactation length weight by herd error weight defined as ratio of base error variance to error variance in the adjusted record. Estimated genetic trend for milk increased by nearly 5 kg/yr for Holsteins with this adjustment, which caused predicted breeding values of oldest animals to be lower by about 100 kg. Most correlations of parent and progeny information were slightly higher with adjusted data. Cows in high variance herds were most likely to have large reductions in their evaluations. Adjustment for heterogeneous variance was implemented in July 1991 for national evaluations for yield traits.

Animals↗
PubMed2004

Low-cost 7-channel magnetocardiographic system for unshielded environment.

The purpose of this work was to develop a low-cost magnetocardiography (MCG) system for use at cardiology clinics, without any magnetic shielding. The device consists of seven channels: four signal and three reference channels. The signal channels are based on relaxation-oscillation SQUIDs. The reference channels are assembled into an orthogonal reference vector magnetometer (RVM). The 11-litre magnetotransparent helium cryostat allows operation for 5 days without refilling. With the 4-channel device, it is possible to perform measurements of magnetic maps in a standard 36-point grid so that only 9 spatial positions of the multichannel magnetometer are used; acquiring 30 s of data for each observation point takes about 10-15 minutes. Software was developed for the device adjustment, data acquisition, and data processing, including preliminary processing, MCG-mapping, and medical analysis. Digital filtering, adaptive noise compensation, and averaging are used to suppress magnetic noises. Cardiac sources were modelled with effective magnetic dipoles, and with estimated 2D current density distributions at a frontal plane.

Costs and Cost Analysis↗
PubMed1977

Refining physician manpower data.

Many conclusions about trends in physician manpower are based on the physician data set of the American Medical Association. Comparisons of specialty and activity status of physicians over time are hampered by changes in the AMA classification procedure in 1968 and growth in the "not classified" category since 1970. A method of adjusting data on physician manpower, taking into account these changes, is presented. The adjustments suggest that movements in the total physician supply away from patient care and primary care practice are overstated by use of unadjusted AMA data, and the percentage of physicians engaged in patient care has increased rather than decreased over the past decade.

American Medical Association↗
PubMed2003

Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors.

BACKGROUND: Adiponectin (ADPN), the gene product of apM1, is the most abundant secretory protein of the adipose tissue in human plasma. Altered regulation (reduced synthesis) of this substance may be relevant to endothelial dysfunction and cardiovascular complications in patients with ESRD. METHODS: We investigated the relationship between plasma ADPN, glomerular filtration rate (GFR) (plasma iohexol clearance), and metabolic risk factors in 16 patients with nephrotic syndrome, in 25 patients with chronic nephropathies without nephrotic syndrome, and in 31 healthy subjects. RESULTS: Plasma ADPN was much higher (P < 0.01) in patients with nephrotic syndrome (24.4 +/- 14.9 microg/mL) than in patients with chronic nephropathies without nephrotic syndrome (12.3 +/- 7.2 microg/mL) and healthy subjects (5.9 +/- 2.6 microg/mL). In the aggregate 24-hour, proteinuria (r = 0.53, P < 0.01) and serum cholesterol (r = 0.53, P < 0.01) were strong and direct correlates of plasma ADPN, while serum albumin correlated inversely (r = -0.46, P < 0.01) with this protein. Proteinuria appeared to be an important confounder of the relationship between ADPN and the GFR because in the whole patient population (with and without nephrotic syndrome), this relationship emerged only after data adjustment for 24-hour proteinuria (partial r = -0.31, P = 0.05), while no such relationship was demonstrable on crude data analysis (r = 0.03, P = 0.87). CONCLUSIONS: ADPN is markedly increased in patients with nephrotic syndrome, and proteinuria is strongly related to circulating ADPN in patients with nephrotic and non-nephrotic renal diseases. The relationships between plasma ADPN, serum cholesterol, and serum albumin suggest that this adipocyte protein may serve to mitigate endothelial damage triggered by dyslipidemia and other risk factors in patients with chronic renal diseases.

Adiponectin↗
PubMedDate not supplied

New quinolones: pharmacology, pharmacokinetics, and dosing in patients with renal insufficiency.

Despite similarities in their chemical structures, the new fluoroquinolones differ greatly in the extent to which renal clearance contributes to their elimination. On the opposite ends of this spectrum are ofloxacin, which is almost entirely eliminated by the kidney as unmodified drug, and pefloxacin, which undergoes extensive biotransformation. Dosage adjustments in patients with renal insufficiency therefore are recommended for ofloxacin, but, on the basis of currently available data, adjustments do not appear to be required for pefloxacin. Both renal clearance of unmodified drug and metabolic transformation contribute substantially to the elimination of norfloxacin and ciprofloxacin. Because of the great antimicrobial potency of the new fluoroquinolones, it should be possible to employ them in the treatment of urinary tract infections caused by highly susceptible bacteria even in patients with marked impairment of renal function.

Administration, Oral↗
PubMed1990

Intrathoracic current flow during transthoracic defibrillation in dogs. Transcardiac current fraction.

To achieve transcardiac threshold current during transthoracic defibrillation, a considerably larger current must be delivered to the thorax to compensate for the shunting effect of the lungs, the thoracic cage, and other elements of the torso. This shunting effect is thus an important determinant of transthoracic defibrillation threshold and can be quantified by the transcardiac current fraction (FC, the ratio of transcardiac to transthoracic threshold currents). Previous estimates of FC have ranged from as low as 3% to as high as 45%. The purpose of of this study was to quantify both FC and the major intrathoracic current pathways. Transthoracic and intrathoracic voltages and currents were simultaneously measured during high-voltage transthoracic shocks in 20 dogs. With correction factors determined from another set of 12 dogs, these raw data were corrected to compensate for field distortion caused by the presence of the intrathoracic electrodes, and the adjusted data were fit to a resistive network model. The results showed that 82% of the transthoracic current was shunted by the thoracic cage, while 14% was shunted by the lungs. The remaining 4% (FC) is the portion that passed through the heart. There was good agreement between the two independent methods used to calculate FC. Analysis based on the model indicated that FC was 3.7%, whereas FC determined by direct measurement with calibrated electrodes was 4.2%. Therefore, the results of this study, in contrast to earlier estimates of FC, show that defibrillation in dogs is achieved by only 4% of the total transthoracic current.

Animals↗