919 resultados para electrophoretic profiles


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Research has shown that chance events affect careers but has not established the nature of their effects. Moreover, the relationship between chance and career decidedness is not well understood. The present study used a person-centered approach with latent profile analysis to examine 312 Swiss adolescents in their first year of vocational training. We identified five qualitatively differing profiles according to levels of perceived chance events and career decidedness: balanced scorers, undecided with mean chance, undecided with high chance, decided with chance, and decided without chance. The groups differed significantly in work motivation (i.e., occupational self-efficacy beliefs, perceived person-job fit, and work engagement). Decided adolescents reported more favorable work motivation regardless of their level of perceived chance events. The results imply that promoting decidedness remains a valuable goal in career counseling despite the occurrence of unpredicted events.

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The Joint Commission of the Swiss Medical Schools (SMIFK/CIMS) decided in 2000 to establish a Swiss Catalogue of Learning Objectives (SCLO) for undergraduate medical training, which was adapted from a similar Dutch blueprint. A second version of the SCLO was developed and launched in 2008. The catalogue is a prerequisite for the accreditation of the curricula of the six Swiss medical faculties and defines the contents of the Federal Licensing Examination (FLE). Given the evolution of the field of medicine and of medical education, the SMIFK/CIMS has decided to embark on a total revision of the SCLO. This article presents the proposed structure and content of Profiles, a new document which, in the future, will direct the format of undergraduate studies and of the FLE. Profiles stands for the Principal Relevant Objectives for Integrative Learning and Education in Switzerland. It is currently being developed by a group of experts from the six Swiss faculties as well as representatives of other institutions involved in these developments. The foundations of Profiles are grounded in the evolution of medical practice and of public health and are based on up-to-date teaching concepts, such as EPAs (entrustable professional activities). An introduction will cover the concepts and a tutorial will be displayed. Three main chapters will provide a description of the seven 2015 CanMEDS roles, a list of core EPAs and a series of ≈250 situations embracing the most frequent and current conditions affecting health. As Profiles is still a work in progress, it is hoped that this paper will attract the interest of all individuals involved in the training of medical students.

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BACKGROUND: Lack of adaptive and enhanced maladaptive coping with stress and negative emotions are implicated in many psychopathological disorders. We describe the development of a new scale to investigate the relative contribution of different coping styles to psychopathology in a large population sample. We hypothesized that the magnitude of the supposed positive correlation between maladaptive coping and psychopathology would be stronger than the supposed negative correlation between adaptive coping and psychopathology. We also examined whether distinct coping style patterns emerge for different psychopathological syndromes. METHODS: A total of 2200 individuals from the general population participated in an online survey. The Patient Health Questionnaire-9 (PHQ-9), the Obsessive-Compulsive Inventory revised (OCI-R) and the Paranoia Checklist were administered along with a novel instrument called Maladaptive and Adaptive Coping Styles (MAX) questionnaire. Participants were reassessed six months later. RESULTS: MAX consists of three dimensions representing adaptive coping, maladaptive coping and avoidance. Across all psychopathological syndromes, similar response patterns emerged. Maladaptive coping was more strongly related to psychopathology than adaptive coping both cross-sectionally and longitudinally. The overall number of coping styles adopted by an individual predicted greater psychopathology. Mediation analysis suggests that a mild positive relationship between adaptive and certain maladaptive styles (emotional suppression) partially accounts for the attenuated relationship between adaptive coping and depressive symptoms. LIMITATIONS: Results should be replicated in a clinical population. CONCLUSIONS: Results suggest that maladaptive and adaptive coping styles are not reciprocal. Reducing maladaptive coping seems to be more important for outcome than enhancing adaptive coping. The study supports transdiagnostic approaches advocating that maladaptive coping is a common factor across different psychopathologies.

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Pharmacokinetic and pharmacodynamic properties of a chiral drug can significantly differ between application of the racemate and single enantiomers. During drug development, the characteristics of candidate compounds have to be assessed prior to clinical testing. Since biotransformation significantly influences drug actions in an organism, metabolism studies represent a crucial part of such tests. Hence, an optimized and economical capillary electrophoretic method for on-line studies of the enantioselective drug metabolism mediated by cytochrome P450 enzymes was developed. It comprises a diffusion-based procedure, which enables mixing of the enzyme with virtually any compound inside the nanoliter-scale capillary reactor and without the need of additional optimization of mixing conditions. For CYP3A4, ketamine as probe substrate and highly sulfated γ-cyclodextrin as chiral selector, improved separation conditions for ketamine and norketamine enantiomers compared to a previously published electrophoretically mediated microanalysis method were elucidated. The new approach was thoroughly validated for the CYP3A4-mediated N-demethylation pathway of ketamine and applied to the determination of its kinetic parameters and the inhibition characteristics in presence of ketoconazole and dexmedetomidine. The determined parameters were found to be comparable to literature data obtained with different techniques. The presented method constitutes a miniaturized and cost-effective tool, which should be suitable for the assessment of the stereoselective aspects of kinetic and inhibition studies of cytochrome P450-mediated metabolic steps within early stages of the development of a new drug.

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A computer simulation study describing the electrophoretic separation and migration of methadone enantiomers in presence of free and immobilized (2-hydroxypropyl)-β-CD is presented. The 1:1 interaction of methadone with the neutral CD was simulated by using experimentally determined mobilities and complexation constants for the complexes in a low-pH BGE comprising phosphoric acid and KOH. The use of complex mobilities represents free solution conditions with the chiral selector being a buffer additive, whereas complex mobilities set to zero provide data that mimic migration and separation with the chiral selector being immobilized, that is CEC conditions in absence of unspecific interaction between analytes and the chiral stationary phase. Simulation data reveal that separations are quicker, electrophoretic displacement rates are reduced, and sensitivity is enhanced in CEC with on-column detection in comparison to free solution conditions. Simulation is used to study electrophoretic analyte behavior at the interface between sample and the CEC column with the chiral selector (analyte stacking) and at the rear end when analytes leave the environment with complexation (analyte destacking). The latter aspect is relevant for off-column analyte detection in CEC and is described here for the first time via the dynamics of migrating analyte zones. Simulation provides insight into means to counteract analyte dilution at the column end via use of a BGE with higher conductivity. Furthermore, the impact of EOF on analyte migration, separation, and detection for configurations with the selector zone being displaced or remaining immobilized under buffer flow is simulated. In all cases, the data reveal that detection should occur within or immediately after the selector zone.

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There is a growing concern by regulatory authorities for the selection of antibiotic resistance caused by the use of biocidal products. We aimed to complete the detailed information on large surveys by investigating the relationship between biocide and antibiotic susceptibility profiles of a large number of Staphylococcus aureus isolates using four biocides and antibiotics commonly used in clinical practice. The minimal inhibitory concentration (MIC) for most clinically-relevant antibiotics was determined according to the standardized methodology for over 1600 clinical S. aureus isolates and compared to susceptibility profiles of benzalkonium chloride, chlorhexidine, triclosan, and sodium hypochlorite. The relationship between antibiotic and biocide susceptibility profiles was evaluated using non-linear correlations. The main outcome evidenced was an absence of any strong or moderate statistically significant correlation when susceptibilities of either triclosan or sodium hypochlorite were compared for any of the tested antibiotics. On the other hand, correlation coefficients for MICs of benzalkonium chloride and chlorhexidine were calculated above 0.4 for susceptibility to quinolones, beta-lactams, and also macrolides. Our data do not support any selective pressure for association between biocides and antibiotics resistance and furthermore do not allow for a defined risk evaluation for some of the compounds. Importantly, our data clearly indicate that there does not involve any risk of selection for antibiotic resistance for the compounds triclosan and sodium hypochlorite. These data hence infer that biocide selection for antibiotic resistance has had so far a less significant impact than feared.

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Dua and Miller (1996) created leading and coincident employment indexes for the state of Connecticut, following Moore's (1981) work at the national level. The performance of the Dua-Miller indexes following the recession of the early 1990s fell short of expectations. This paper performs two tasks. First, it describes the process of revising the Connecticut Coincident and Leading Employment Indexes. Second, it analyzes the statistical properties and performance of the new indexes by comparing the lead profiles of the new and old indexes as well as their out-of-sample forecasting performance, using the Bayesian Vector Autoregressive (BVAR) method. The new indexes show improved performance in dating employment cycle chronologies. The lead profile test demonstrates that superiority in a rigorous, non-parametric statistic fashion. The mixed evidence on the BVAR forecasting experiments illustrates the truth in the Granger and Newbold (1986) caution that leading indexes properly predict cycle turning points and do not necessarily provide accurate forecasts except at turning points, a view that our results support.

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Cardiovascular disease (CVD) is this nation's leading source of morbidity and mortality, with health disparities evident. Despite inconsistencies in the literature, there is a growing body of evidence that links anger and CV reactivity (CVR) to future CVD. Because CVD is a life-long process with beginnings in childhood, and because adolescents experience and express anger frequently, the need to understand the role that anger has in future CV profiles is important. If identifiable patterns are found, nursing interventions can be implemented at the most beneficial point in the lifespan. This study examined data collected as part of The Heartfelt Study (N = 374), which investigated anger in relation to 24-hour ambulatory blood pressure (BP) and CVR in a multi-ethnic (African, Hispanic, and European American) sample of adolescents (Time 1). This investigator conducted a follow-up for all The Heartfelt Study participants, 11 to 13 years old at the beginning of study, still in attendance at the middle school (N = 44) one year later (Time 2) to determine: (1) changes in anger over time were associated with changes in ambulatory CV profiles: systolic (SBP), diastolic (DBP), heart rate (HR), and pulse pressure (PP) over time; and (2) the extent to which CVR, initiated by talking about a recent anger-producing event, related to future ambulatory CV profiles. A mixed-effects regression for repeated measures was used to analyze the data and found that SBP reactivity at Time 1 was significantly (β = 0.2341, t = 5.91, p < 0.0001) associated with ambulatory SBP at Time 2 and PP reactivity at Time 1 was significantly (β = 0.1530, t = 5.70, p < 0.0001) associated with ambulatory PP at Time 2. Changes in anger over time were not associated with changes in ambulatory BP measures over time. Further research on anger and CVR among adolescents over longer periods of time is recommended. ^

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The purpose of this study, based on secondary data from attendees at a substance abuse clinic for the Kickapoo Healing Grounds in Eagle Pass, Texas, is two fold: (1) to elucidate neuro-behavioral performance of volatile substance abusers in the Kickapoo tribe and (2) to determine factors associated with their treatment completion and rehabilitation as measured by their employment at follow-up. Volatile substance abuse (VSA) is associated with a host of neurological manifestations, and secondary prevention or clinical treatment and rehabilitation remains the mainstay of control efforts. Very little is known about VSA in general, and especially among Native American populations. It is anticipated that the results will help determine and assist other tribes and non-tribal substance abuse centers with treatment planning for volatile substance abusers among Native American populations. ^

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Triglyceride levels are a component of plasma lipids that are thought to be an important risk factor for coronary heart disease and are influenced by genetic and environmental factors, such as single nucleotide polymorphisms (SNPs), alcohol intake, and smoking. This study used longitudinal data from the Bogalusa Heart Study, a biracial community-based survey of cardiovascular disease risk factors. A sample of 1191 individuals, 4 to 38 years of age, was measured multiple times from 1973 to 2000. The study sample consisted of 730 white and 461 African American participants. Individual growth models were developed in order to assess gene-environment interactions affecting plasma triglycerides over time. After testing for inclusion of significant covariates and interactions, final models, each accounting for the effects of a different SNP, were assessed for fit and normality. After adjustment for all other covariates and interactions, LIPC -514C/T was found to interact with age3, age2, and age and a non-significant interaction of CETP -971G/A genotype with smoking status was found (p = 0.0812). Ever-smokers had higher triglyceride levels than never smokers, but persons heterozygous at this locus, about half of both races, had higher triglyceride levels after smoking cessation compared to current smokers. Since tobacco products increase free fatty acids circulating in the bloodstream, smoking cessation programs have the potential to ultimately reduce triglyceride levels for many persons. However, due to the effect of smoking cessation on the triglyceride levels of CETP -971G/A heterozygotes, the need for smoking prevention programs is also demonstrated. Both smoking cessation and prevention programs would have a great public health impact on minimizing triglyceride levels and ultimately reducing heart disease. ^

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Objective: To explore the natural trajectory of core body temperature (CBT) and cortisol (CORT) circadian rhythms in mechanically ventilated intensive care unit (MV ICU) patients. ^ Design: Prospective, observational, time-series pilot study. ^ Setting: Medical-surgical and pulmonary ICUs in a tertiary care hospital. ^ Sample: Nine (F = 3, M = 6) adults who were mechanically ventilated within 12 hrs of ICU admission with mean ± SD age of 65.2 ± 14 years old. ^ Measurements: Core body temperature and environmental measures of light, sound, temperature, and relative humidity were logged in 1-min intervals. Hourly urine specimens and 2-hr interval blood specimens were collected for up to 7 consecutive days for CORT assay. Mechanical ventilation days, ICU length of stay, and ICU mortality were documented. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were computed for each study day. The data of each biologic and environmental variable were analyzed using single cosinor analysis of 24-hr serial segments. One patient did not complete the study because mortality occurred within 8 hrs of enrollment. Nine ICU patients completed the study in 1.6 to 7.0 days. ^ Results: No normal circadian rhythm pattern was found when the cosinor-derived parameters of amplitude (one-half the peak-trough variability) and acrophase (peak time) were compared with cosinor-derived parameter reference ranges of healthy, diurnally active humans, although 83% of patient-day CBT segments showed statistically significant (p ≤ .05) and biologically meaningful (R2≥ 0.30) 24-hr rhythms with abnormal cosinor parameters. Cosinor parameters of the environmental temporal profiles showed 27% of light, 76% of ambient temperature, and 78% of relative humidity serial segments had a significant and meaningful 24-hr diurnal pattern. Average daily light intensity varied from 34 to 187 lx with a maximum light exposure of 1877 lx. No sound measurement segment had a statistically significant cosine pattern, and numerous 1-minute interval peaks ≥ 60 dB occurred around the clock. Average daily ambient temperature and relative humidity varied from 19 to 24°C and from 25% to 61%, respectively. There was no statistically significant association between CBT or clinical outcomes and cosinor-derived parameters of the environmental variables. Circadian rhythms of urine and plasma CORT were deferred for later analysis. ^ Conclusions: The natural trajectory of the CBT circadian rhythm in MV ICU patients demonstrated persistent cosinor parameter alteration, even when a significant and meaningful 24-hr rhythm was present. The ICU environmental measures showed erratic light and sound exposures. Room temperature and relative humidity data produced the highest rate of significant and meaningful diurnal 24-hr patterns. Additional research is needed to clarify relations among the CBT biomarker of the circadian clock and environmental variables of MV ICU patients. ^

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Children who experience early pubertal development have an increased risk of developing cancer (breast, ovarian, and testicular), osteoporosis, insulin resistance, and obesity as adults. Early pubertal development has been associated with depression, aggressiveness, and increased sexual prowess. Possible explanations for the decline in age of pubertal onset include genetics, exposure to environmental toxins, better nutrition, and a reduction in childhood infections. In this study we (1) evaluated the association between 415 single nucleotide polymorphisms (SNPs) from hormonal pathways and early puberty, defined as menarche prior to age 12 in females and Tanner Stage 2 development prior to age 11 in males, and (2) measured endocrine hormone trajectories (estradiol, testosterone, and DHEAS) in relation to age, race, and Tanner Stage in a cohort of children from Project HeartBeat! At the end of the 4-year study, 193 females had onset of menarche and 121 males had pubertal staging at age 11. African American females had a younger mean age at menarche than Non-Hispanic White females. African American females and males had a lower mean age at each pubertal stage (1-5) than Non-Hispanic White females and males. African American females had higher mean BMI measures at each pubertal stage than Non-Hispanic White females. Of the 415 SNPs evaluated in females, 22 SNPs were associated with early menarche, when adjusted for race ( p<0.05), but none remained significant after adjusting for multiple testing by False Discovery Rate (p<0.00017). In males, 17 SNPs were associated with early pubertal development when adjusted for race (p<0.05), but none remained significant when adjusted for multiple testing (p<0.00017). ^ There were 4955 hormone measurements taken during the 4-year study period from 632 African American and Non-Hispanic White males and females. On average, African American females started and ended the pubertal process at a younger age than Non-Hispanic White females. The mean age of Tanner Stage 2 breast development in African American and Non-Hispanic White females was 9.7 (S.D.=0.8) and 10.2 (S.D.=1.1) years, respectively. There was a significant difference by race in mean age for each pubertal stage, except Tanner Stage 1 for pubic hair development. Both Estradiol and DHEAS levels in females varied significantly with age, but not by race. Estradiol and DHEAS levels increased from Tanner Stage 1 to Tanner Stage 5.^ African American males had a lower mean age at each Tanner Stage of development than Non-Hispanic White males. The mean age of Tanner Stage 2 genital development in African American and Non-Hispanic White males was 10.5 (S.D.=1.1) and 10.8 (S.D.=1.1) years, respectively, but this difference was not significant (p=0.11). Testosterone levels varied significantly with age and race. Non-Hispanic White males had higher levels of testosterone than African American males from Tanner Stage 1-4. Testosterone levels increased for both races from Tanner Stage 1 to Tanner Stage 5. Testosterone levels had the steepest increase from ages 11-15 for both races. DHEAS levels in males varied significantly with age, but not by race. DHEAS levels had the steepest increase from ages 14-17. ^ In conclusion, African American males and females experience pubertal onset at a younger age than Non-Hispanic White males and females, but in this study, we could not find a specific gene that explained the observed variation in age of pubertal onset. Future studies with larger study populations may provide a better understanding of the contribution of genes in early pubertal onset.^

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Purpose: To explore the natural trajectory of circadian rhythms of sedation requirement, core body temperature (CBT), pulmonary mechanics (PM), and gas exchange (GE) in mechanically ventilated swine, as these variables affect the duration of mechanical ventilation. ^ Design: A secondary analysis to describe and compare circadian rhythms of study variables in swine mechanically ventilated for ≤ 7 days. ^ Setting: Porcine Intensive Care Unit (ICU).^ Sample: Six male swine. ^ Methods: Sedation requirements were recorded hourly and the CBT, PM and GE variables were sampled every 1 s – 1 min for ≤ 7 days. The data sets for each pig with > 5 days ICU length of stay were divided into one section representing the first 3 days and one section representing subsequent days. The Lomb periodogram was used to estimate the circadian time period for each variable, and cosinor analysis with the estimated time period to obtain amplitude and mesor. Circadian to ultradian bandpower ratio to assess rhythm quality and stability over time and goodness-of-fit index to describe biological significance of a rhythm were used. Together, these two parameters were used to define rhythm robustness over time. The masking effect of sedation as a potential confounder of the circadian rhythms of CBT, PM, and GE was explored, and circadian rhythm profiles of CBT of pigs in the ICU setting were compared with those of the same pigs in the ambulatory setting. ^ Results: All pigs had significant rhythms in CBT, respiratory rate, and peripheral oxygen saturation across ICU data sets. Healthier pigs had more robust rhythms of study variables over time. Sedation did not appear to mask the circadian rhythms of CBT, PM, and GE. The circadian rhythm of CBT was less robust in the ICU setting than in the ambulatory setting. ^ Conclusions: Individual subject observations provided preliminary evidence that robustness of rhythms varies with subject acuity. Comparison of profiles of circadian rhythms among ICU subjects with similar acuity and disease processes is warranted to determine if the profiles in the present study are reproducible. Identification of consistent patterns may provide insight into subject morbidity and timing of such therapeutic interventions as weaning from mechanical ventilation. ^