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PubMed2003

Influence of controllable lifestyle on recent trends in specialty choice by US medical students.

CONTEXT: Recent specialty choices of graduating US medical students suggest that lifestyle may be an increasingly important factor in their career decision making. OBJECTIVE: To determine whether and to what degree controllable lifestyle and other specialty-related characteristics are associated with recent (1996-2002) changes in the specialty preferences of US senior medical students. DESIGN AND SETTING: Specialty preference was based on analysis of results from the National Resident Matching Program, the San Francisco Matching Program, and the American Urological Association Matching Program from 1996 to 2002. Specialty lifestyle (controllable vs uncontrollable) was classified using earlier research. Log-linear models were developed that examined specialty preference and the specialty's controllability, income, work hours, and years of graduate medical education required. MAIN OUTCOME MEASURE: Proportion of variability in specialty preference from 1996 to 2002 explained by controllable lifestyle. RESULTS: The specialty preferences of US senior medical students, as determined by the distribution of applicants across selected specialties, changed significantly from 1996 to 2002 (P<.001). In the log-linear model, controllable lifestyle explained 55% of the variability in specialty preference from 1996 to 2002 after controlling for income, work hours, and years of graduate medical education required (P<.001). CONCLUSION: Perception of controllable lifestyle accounts for most of the variability in recent changing patterns in the specialty choices of graduating US medical students.

Career Choice↗

PubMed1992

Prediction of sotalol-induced maximum steady-state QTc prolongation from single-dose administration in healthy volunteers.

The relationship between racemic sotalol plasma concentrations and QTc interval prolongation after both single-dose and repeated administration of three sotalol oral doses was studied in a randomized crossover protocol performed in 10 healthy volunteers. QTc interval increase was significant after the three single-dose sotalol administrations and was significantly related to the administered dose (p < 0.0001). In 21 of 30 analyses, QTc interval was linearly correlated with sotalol plasma concentrations. After the 320 mg dose, the linear model was a best fit for 90% of the cases, and no hysteresis was observed. After repeated sotalol administration, 69 of 87 QTc interval measurements at steady state could be predicted from the plasma concentration versus effect relationship established after single-dose 320 mg administration. Seventeen of 18 errors (94%) corresponded to QTc intervals that were significantly lower than predicted. These findings suggest that a short-term individual linear model determined after a 320 mg test dose of sotalol allows a good prediction of expected maximal increase in QTc duration in healthy subjects.

Administration, Oral↗

PubMed1999

Seroprevalence of Trypanosoma cruzi infection in three rural communities in Guatemala.

A systematic, house-based serological survey for Trypanosoma cruzi seroreactivity was conducted in three contiguous communities in Olopa municipality, Chiquimula Department, Guatemala. Blood samples from a total of 292 individuals in 63 households were examined by enzyme-linked immunosorbent assay. The seropositive rate ranged from 0% to 20.8% for the three communities, with a mean of 15.1%. Log-linear models showed that seroprevalence was significantly related to age (P < 0.005) but not to sex. However, when the age group with the lowest prevalence (1-9 years) was excluded from the analysis, age was not a significant factor (P = 0.55). Data from a stratified sample collected at the same time were combined with those of the systematic sample to analyze the relationship between seropositivity and possible explanatory variables. Log-linear models, based on 586 individuals in 129 households from the two surveys, revealed a significant positive association between seropositivity and thatched roofs (P = 0.01).

Animals↗

PubMed1991

Local control in T3 laryngeal cancer treated with radical radiotherapy, time dose relationship: the concept of nominal standard dose and linear quadratic model.

In a retrospective study of the Dutch cooperative head and neck group 104 evaluable patients with T3NxMO squamous cell carcinoma of the larynx were treated primarily with a full course of radiotherapy. The results of treatment are presented in terms of locoregional control. The actuarial 3-year local control rate was 53%. Regional control was 77% for node positive patients and 96% for N0 patients (p = 0.01). Surgical salvage was successful in 53% of cases with a local recurrence and in 3/8 regional recurrences, resulting in an ultimate locoregional control rate of 83% for N0 patients and 68% for N+ patients. A uni- and multivariate analysis of local control rate versus total dose, nominal standard dose, and extrapolated response dose has been done. To calculate extrapolated response dose the linear quadratic equation was used, assuming an a/b of 10 and a potential doubling time of clonogenic cells of 3, 5, and 7 days. In multivariate analysis the extrapolated response dose with a potential doubling time of 5 days was the only independent prognostic factor for local control (p = 0.069) and ultimate locoregional control (p = 0.0015). Nominal standard dose showed no dose-response relationship. Based on the S-shaped dose response curve, using the LQ model, several therapeutical options are discussed.

Aged↗

PubMed2000

Dedifferentiation of human hepatocellular carcinoma up-regulates telomerase and Ki-67 expression.

HYPOTHESIS: Dedifferentiation of human hepatocellular carcinoma (HCC) may influence telomerase activation and Ki-67 expression. DESIGN: Laboratory study using human HCC specimens. SETTING: University hospital. PATIENTS: Twelve patients with HCC with specific morphologic patterns (nodule-in-nodule [n = 4] or confluent multinodular [n = 8] type) and histological heterogeneity and who had undergone curative hepatectomy were studied. Of these, 8 patients had 2 different histological grades of HCC cells distributed at various nodules but within the same tumor; 3 patients, 3 different histological grades; and 1 patient, all 4 different histological grades. INTERVENTION: Tissue samples were retrieved from each nodule of the tumor and not mixed with one another. A total of 42 cancerous tissues from different distinctive nodules of the 12 patients were taken for telomerase and Ki-67 study, and corresponding noncancerous counterparts (n = 12) served as healthy control samples. Telomerase activity was assayed by the telomerase repeat amplification protocol. Expression of messenger RNA (mRNA) by the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) was determined using reverse transcription polymerase chain reaction. The relative telomerase activity and hTERT mRNA in each tissue sample was quantified using densitometry and expressed as a percentage of the standardized HeLa cell line. Immunostaining with anti-Ki-67 antibody was used to detect Ki-67 and was expressed as Ki-67 labeling index. MAIN OUTCOME MEASURES: Telomerase activity, hTERT mRNA, and Ki-67 labeling index stratified by different histological gradings in each patient was analyzed. The correlations between telomerase activity and hTERT mRNA and between telomerase activity and expression of Ki-67 were plotted. RESULTS: Telomerase activity increased from more to less differentiated foci of HCC cells in each case (generalized linear model, P<.001). Mean +/- SD expression of hTERT mRNA in 43 cancerous tissue samples, even those 4 with negative telomerase activity, was distinguishable from that of the noncancerous controls (0.84 + 0.23 vs 0.41 + 0.11; t test, P =.008). Telomerase activity was correlated to hTERT mRNA expression (Pearson correlation, r(2) = 0.56; P<.001). The Ki-67 labeling index increased from more to less differentiated foci of HCC in each case (generalized linear model, P<.001). Expression of Ki-67 correlated with telomerase activity within differently graded areas within individual tumors (Pearson correlation, r(2) = 0.38; P<. 001). CONCLUSION: Using the model of human HCC with histological heterogeneity, we determined that dedifferentiation of human HCC induces telomerase activation and Ki-67 expression.

Carcinoma, Hepatocellular↗

PubMed2000

A new approach to adjust for multivariate confounders in small randomized studies applied to dendritic cell vaccination data.

In small studies, randomization alone is unlikely to eliminate confounding. In linear models, confounding can be addressed by including additional dependent variables, adding covariates, or stratifying the data for the analysis. When the functional relation between observed variables and underlying (latent) factors is unknown, however, methods based on ranks may be more appropriate than ANOVA. It is demonstrated, how the marginal likelihood principle can be used to provide objective and intrinsically valid procedures to adjust for (multiple) confounders when the assumptions of the linear model cannot be justified.

Cancer Vaccines↗

PubMed2006

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI.

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Adult↗

PubMed2006

The relationship between prevalence and duration of weight loss strategies and weight loss among overweight managed care organization members enrolled in a weight loss trial.

BACKGROUND: Many adults in the United States report engaging in weight loss behaviors. The current study examined weight loss strategies among managed care organization members, to determine the prevalence and impact of weight loss behaviors in this population. We hypothesized that greater engagement in weight loss strategies would be associated with greater weight loss success. METHODS: Data were taken from Weigh-to-Be (WTB), a two-year weight loss trial (N = 1801, 72% female, mean age = 50.7 years, mean weight = 95.9 kg, mean BMI = 34.2 kg/m2). Every six months, participants completed a questionnaire assessing frequency and duration of weight loss strategies (calorie reduction, fat reduction, increased fruit/vegetable intake, increased exercise, elimination of sweets, consumption of less food). General linear models and structural equation methods were used to examine associations between weight loss strategy use and weight change over time. RESULTS: Weight loss strategy prevalence rates ranged from 68% to 76% over two years. For all dietary strategies, any use of the strategy between baseline and 24 months was associated with weight loss at 24 months; those who did not engage in the strategy showed weight gains during that period. Results of general linear models and structural equation models indicated that increased use of weight loss strategies was significantly associated with greater 24-month weight loss. CONCLUSION: The prevalence of weight loss strategies in this obese adult managed care population was quite high, and use of these strategies was associated in dose-response fashion with better weight loss. Future interventions may benefit from emphasis on persistence of similar strategies to achieve more successful outcomes.

Journal Article↗

PubMed1994

A computer aided venous occlusion plethysmography.

A computer aided set of equipment for impedance plethysmographic research has been presented. A simple linear model of blood circulation in a limb has been used. A comparative analysis of blood circulation parameters in lower extremities has been carried out manually as well as calculated automatically. Parameters such as the limb blood flow Qo, the tissue blood flow qo, maximum volume change (venous capacitance, VC), the venous outflow time constant Tv and the venous outflow index were automatically and traditionally calculated on the basis of curve lines recorded on thermal recorder. A high linear correlation has been observed between parameters calculated manually and with computer-aided techniques. The results obtained confirm the usefulness of the linear model of blood circulation in a limb for pressures occurring under the conditions of vein occlusion.

Adolescent↗

PubMed2004

A neural network based prediction of octanol-water partition coefficients using atomic5 fragmental descriptors.

An artificial neural network based approach using Atomic5 fragmental descriptors has been developed to predict the octanol-water partition coefficient (logP). We used a pre-selected set of organic molecules from PHYSPROP database as training and test sets for a feedforward neural network. Results demonstrate the superiority of our non-linear model over the traditional linear method.

Models, Chemical↗

PubMed2002

Evaluation of the parameters of 1:1 charge transfer complexes from spectrophotometric data by non-linear numerical method.

The non-linear numerical method for evaluation of equilibrium constants and molar extinction coefficients of molecular complexes from a spectrophotometric experiment is described, which in contrast to linear models has no limitations with respect to concentrations of the components. The proposed procedure is applied to donor-acceptor interaction in solution between N-ethyl carbazole (EtCz) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) or n-hexyl 2,5,7-trinitro-9-dicyanomethylenefluorene-4-carboxylate (HexDTFC) to evaluate the method and to obtain the parameters of charge transfer complexes (CTCs) formation. Association constants (K) and molar extinction coefficients (epsilon) of CTCs derived from non-linear approach (EtCz-TCNQ: K = 2.49+0.19 M(-1); epsilon = 2950 +/- 160 M(-1) cm(-1). EtCz-HexDTFC: K = 12.1 +/- 0.3 M(-1); epsilon = 1335 +/- 24 M(-1) cm(-1)) are close to that from linear models but show lower standard errors in parameter estimations.

Chlorobenzenes↗

PubMed2006

Bayesian inference of hemodynamic changes in functional arterial spin labeling data.

The study of brain function using MRI relies on acquisition techniques that are sensitive to different aspects of the hemodynamic response contiguous to areas of neuronal activity. For this purpose different contrasts such as arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional MRI techniques have been developed to investigate cerebral blood flow (CBF) and blood oxygenation, respectively. Analysis of such data typically proceeds by separate, linear modeling of the appropriate CBF or BOLD time courses. In this work an approach is developed that provides simultaneous inference on hemodynamic changes via a nonlinear physiological model of ASL data acquired at multiple echo times. Importantly, this includes a significant contribution by changes in the static magnetization, M, to the ASL signal. Inference is carried out in a Bayesian framework. This is able to extract, from dual-echo ASL data, probabilistic estimates of percentage changes of CBF, R(2) (*), and the static magnetization, M. This approach provides increased sensitivity in inferring CBF changes and reduced contamination in inferring BOLD changes when compared with general linear model approaches on single-echo ASL data. We also consider how the static magnetization, M, might be related to changes in CBV by assuming the same mechanism for water exchange as in vascular space occupancy.

Bayes Theorem↗

PubMed2000

Derivation of low-dose extrapolation factors from analysis of curvature in the cancer incidence dose response in Japanese atomic bomb survivors.

PURPOSES: To assess the degree of overestimation in low-dose cancer risk when models linear in dose are fitted to cancer data. MATERIALS AND METHODS: Examination of the quadratic and the linear coefficients (in dose) in the Japanese atomic bomb survivor cancer incidence data, based on follow-up to 1987 and taking separate account of random errors in DS86 neutron and DS86 gamma dose estimates and systematic errors in Hiroshima DS86 neutron dose estimates. RESULTS: When the 0-4Gy dose range is used, the low-dose extrapolation factor for all solid tumours, assessing the degree to which low-dose cancer risks are overestimated by fitting a model linear in dose, is 1.06 (95% CI 0.78, 1.62) and so is not significantly different from 1; the associated ratio of the quadratic to the linear coefficients is 0.06 Sv(-1) (95% CI -0.22, 0.67). The best estimate of the low-dose extrapolation factor for leukaemia is 2.47 (95% CI 1.24, > 1,000). The ratio of the quadratic to the linear coefficients is 1.81 Sv(-1) (95% CI 0.21, > 1,000). When various types and groupings of solid tumours are considered there is not generally any strong evidence for upward curvature; for only two out of the six solid tumour groupings are there indications of appreciable upward curvature in the dose response, and in no instance is this statistically significant. Consideration of a lower dose range (0-2Gy rather than 0-4 Gy) results in the low-dose extrapolation factor for solid tumours increasing to 1.21 (95% CI 0.81, 2.45), with corresponding increases for solid tumour subtypes; the corresponding quantity for leukaemia decreases to 1.73 (95% CI 0.79, 147.67). Three out of the six solid tumour subtypes now show appreciable upward curvature. If there is additional adjustment of the Hiroshima neutron dose estimates over the 0-2 Gy dose range, the low-dose extrapolation factor for all solid tumours increases still further, to 1.43 (95% CI 0.97, 2.72), whereas for leukaemia this quantity is further reduced, to 1.58 (95% CI 0.90, 10.58). CONCLUSIONS: There is marked upward curvature in the dose response for leukaemia. For solid tumours there is little indication of upward curvature in the dose response over the 0-4 Gy dose range, although over the 0-2 Gy dose range and after adjustment of Hiroshima DS86 neutron dose estimates the upward curvature is more pronounced. Uncertainties in the likely adjustments to the Hiroshima DS86 neutron dose estimates imply that these findings should be treated with caution.

Dose-Response Relationship, Radiation↗

PubMed1996

Respiratory mechanics in patients ventilated for critical lung disease.

Respiratory mechanics, using flow interruption, was previously studied during the complete breath in healthy ventilated man, numerical techniques relieving constraints regarding flow pattern. The classical linear model of non-Newtonian behaviour was found to be valid. The present study was extended to subjects with critical lung disease. Subjects with acute lung injury (ALI; n = 2), acute respiratory distress syndrome (ARDS; n = 4), and chronic obstructive pulmonary disease (COPD; n = 3) were studied with and without positive end-expiratory pressure (PEEP). Functional residual capacity (FRC) was measured with sulphur hexafluoride (SF6) wash-out. The static pressure-volume (P-V) curve was linear at zero end-expiratory pressure (ZEEP), but nonlinear at PEEP. Its hysteresis was nonsignificant. In ALI/ARDS, PEEP increased lung volume by distension and recruitment, but only by distension in COPD. In ALI/ARDS, resistance was increased, at ZEEP. In COPD, resistance became extremely high during expiration at ZEEP. In ALI/ARDS at ZEEP, non-Newtonian behaviour, representing tissue stress relaxation and pendel-luft, complied with the classical linear model. At PEEP, the non-Newtonian compliance became volume-dependent to an extent correlated to the nonlinearity of the static P-V curve. In COPD, non-Newtonian behaviour was adequately explained only with a model with different inspiratory and expiratory behaviour. The classical model of the respiratory system is valid in ALI/ARDS at ZEEP. More advanced models are needed at PEEP and in COPD.

Adult↗

PubMed1995

A comparative study of trends in mortality rates of the ageing population in Norway, Sweden, Denmark, and Finland, 1966-1986.

The populations of Finland and the three Scandinavian countries (Denmark, Norway and Sweden) have experienced relatively marked differences regarding trends in mortality rates since the Second World War. To assess factors that might contribute to these differences, a cohort analysis was performed based upon vital statistics for the age category 45 years to 89 years, from the four countries, for the period 1966-86. The results of log-linear modelling, which included the effects of age, period, and cohort, on mortality rates, revealed differences in the effect of age parameters on mortality between Finland and the three Scandinavian countries. These differences may be related to a genetic component. Differences in patterns of mortality rates over time relating to period and cohort effects indicate a differential development in lifestyle-related risk factors associated with the major causes of death. Based on differences in goodness-of-fit of the log-linear models, it is suggested that the Finnish population has experienced a more heterogeneous development in mortality over time than has the Scandinavian. This may be related to the greater social inequities that have existed in Finland than in Scandinavia during the decades under study.

Aged↗

PubMed2002

Linear modes of gene expression determined by independent component analysis.

MOTIVATION: The expression of genes is controlled by specific combinations of cellular variables. We applied Independent Component Analysis (ICA) to gene expression data, deriving a linear model based on hidden variables, which we term 'expression modes'. The expression of each gene is a linear function of the expression modes, where, according to the ICA model, the linear influences of different modes show a minimal statistical dependence, and their distributions deviate sharply from the normal distribution. RESULTS: Studying cell cycle-related gene expression in yeast, we found that the dominant expression modes could be related to distinct biological functions, such as phases of the cell cycle or the mating response. Analysis of human lymphocytes revealed modes that were related to characteristic differences between cell types. With both data sets, the linear influences of the dominant modes showed distributions with large tails, indicating the existence of specifically up- and downregulated target genes. The expression modes and their influences can be used to visualize the samples and genes in low-dimensional spaces. A projection to expression modes helps to highlight particular biological functions, to reduce noise, and to compress the data in a biologically sensible way.

Algorithms↗

PubMed1998

Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed graft function.

The pharmacokinetics of mycophenolic acid (MPA), the immunosuppressant form of the prodrug mycophenolate mofetil (MMF), and the primary glucuronide metabolite, MPAG, were characterized in renal transplant patients with delayed graft function using random effects piecewise linear models. Eight patients were evaluated after receiving their first and subsequent daily oral doses of 1.5 g mycophenolate mofetil twice daily on study days 1 (n = 8), 7 (n = 8), 14 (n = 5), 21 (n = 2), and 28 (n = 7). The area under the concentration-time curve from zero to 12 hours (AUC0-12) for MPA, MPAG, MPA free fraction, and free MPA were analyzed in serial plasma samples using validated high-performance liquid chromatography and ultrafiltration procedures. Random effects piecewise linear models, fit by maximum likelihood methods, were applied to AUC0-12 of MPA and MPAG, MPA free fraction, AUC0-12 of free MPA, and serum creatinine concentration, the index of renal function used in this study. Two hemodialysis sessions did not lower MPA plasma concentration, although some MPAG was removed. The AUC0-12 of MPA increased as a function of time, although it was not possible to fit a statistical model to the data due to considerable among-patient variation in the pattern of increase with time. The AUC0-12 of MPAG, MPA free fraction, and AUC0-12 of free MPA reached maximal values on day 7; each of these parameters had unique day 1 to 7 positive slope values and unique day 7 to 28 negative slope values. The average creatinine concentration was maximal at day 1 and a unique negative slope was obtained between days 7 and 28. Thus, this study provides statistical models for the alteration of AUC0-12 of MPAG, MPA free fraction, AUC0-12 of free MPA, and serum creatinine in renal transplant patients with delayed graft function. These results provide evidence that renal dysfunction is associated with altered pharmacokinetics of MPA, particularly increased AUC0-12 of MPAG, MPA free fraction, and AUC0-12 of free MPA. The perturbed pharmacokinetics normalized with improving renal function.

Adult↗

PubMed1999

Associations of the angiotensinogen gene (M235T, T174M) and the angiotensin I-converting enzyme gene (I/D) with blood pressure in Japanese workers.

Blood pressure may be influenced by several polymorphisms associated with hypertension, such as the angiotensinogen gene (M235T, T174M) and the angiotensin I-converting enzyme gene (I/D). We investigated the associations of these polymorphisms with blood pressure and components of the renin-angiotensin system in Japanese workers. Additionally, we examined whether the polymorphisms were independently associated with blood pressure when other factors were taken into consideration in a general linear model. The study population, which was entirely Japanese, consisted of 196 male subjects. Subjects were selected from workers who received a company health examination. Systolic blood pressure of the M235T MM genotype was significantly higher than that of the MT genotype. Diastolic blood pressure of the M235T MM genotype was significantly higher than that of the MT or TT genotypes. Serum ACE activity of the ACE II genotype was significantly lower than that of the ID or DD genotypes. Multivariate analysis using a general linear model, including age and body mass index, demonstrated that the M235T MM genotype was one of the independent factors affecting blood pressure. The present study demonstrated that the M235T MM genotype was independently associated with systolic blood pressure and diastolic blood pressure in Japanese male workers.

Adult↗