Stimulation induced variability of pulse plethysmography does not discriminate responsiveness to intubation

BACKGROUND: Hypnotic depth but not haemodynamic response to painful stimulation can be measured with various EEG-based anaesthesia monitors. We evaluated the variation of pulse plethysmography amplitude induced by an electrical tetanic stimulus (PPG variation) as a potential measure for analgesia and predictor of haemodynamic responsiveness during general anaesthesia. METHODS: Ninety-five patients, ASA I or II, were randomly assigned to five groups [Group 1: bispectral index (BIS) (range) 40-50, effect site remifentanil concentration 1 ng ml(-1);Group 2: BIS 40-50, remifentanil 2 ng ml(-1); Group 3: BIS 40-50, remifentanil 4 ng ml(-1); Group 4: BIS 25-35, remifentanil 2 ng ml(-1); Group 5: BIS 55-65, remifentanil 2 ng ml(-1)]. A 60 mA tetanic stimulus was applied for 5 s on the ulnar nerve. From the digitized pulse oximeter wave recorded on a laptop computer, linear and non-linear parameters of PPG variation during the 60 s period after stimulation were computed. The haemodynamic response to subsequent orotracheal intubation was recorded. The PPG variation was compared between groups and between responders and non-responders to intubation (anova). Variables independently predicting the response were determined by logistic regression. RESULTS: The probability of a response to tracheal intubation was 0.77, 0.47, 0.05, 0.18 and 0.52 in Groups 1-5, respectively (P<0.03). The PPG variability was significantly higher in responders than in non-responders but it did not improve the prediction of the response to tracheal intubation based on BIS level and effect site remifentanil concentration. CONCLUSION: Tetanic stimulation induced PPG variation does not reflect the analgesic state in a wide clinical range of surgical anaesthesia.

Application and comparison of classification algorithms for recognition of Alzheimer's disease in electrical brain activity (EEG)

The early detection of subjects with probable Alzheimer's disease (AD) is crucial for effective appliance of treatment strategies. Here we explored the ability of a multitude of linear and non-linear classification algorithms to discriminate between the electroencephalograms (EEGs) of patients with varying degree of AD and their age-matched control subjects. Absolute and relative spectral power, distribution of spectral power, and measures of spatial synchronization were calculated from recordings of resting eyes-closed continuous EEGs of 45 healthy controls, 116 patients with mild AD and 81 patients with moderate AD, recruited in two different centers (Stockholm, New York). The applied classification algorithms were: principal component linear discriminant analysis (PC LDA), partial least squares LDA (PLS LDA), principal component logistic regression (PC LR), partial least squares logistic regression (PLS LR), bagging, random forest, support vector machines (SVM) and feed-forward neural network. Based on 10-fold cross-validation runs it could be demonstrated that even tough modern computer-intensive classification algorithms such as random forests, SVM and neural networks show a slight superiority, more classical classification algorithms performed nearly equally well. Using random forests classification a considerable sensitivity of up to 85% and a specificity of 78%, respectively for the test of even only mild AD patients has been reached, whereas for the comparison of moderate AD vs. controls, using SVM and neural networks, values of 89% and 88% for sensitivity and specificity were achieved. Such a remarkable performance proves the value of these classification algorithms for clinical diagnostics.

On Time Series Analysis of Public Health and Biomedical Data

A time series is a sequence of observations made over time. Examples in public health include daily ozone concentrations, weekly admissions to an emergency department or annual expenditures on health care in the United States. Time series models are used to describe the dependence of the response at each time on predictor variables including covariates and possibly previous values in the series. Time series methods are necessary to account for the correlation among repeated responses over time. This paper gives an overview of time series ideas and methods used in public health research.

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration in Shetland ponies sedated with xylazine

The pharmacokinetics of ketamine and norketamine enantiomers after administration of intravenous (IV) racemic ketamine (R-/S-ketamine; 2.2mg/kg) or S-ketamine (1.1mg/kg) to five ponies sedated with IV xylazine (1.1mg/kg) were compared. The time intervals to assume sternal and standing positions were recorded. Arterial blood samples were collected before and 1, 2, 4, 6, 8 and 13min after ketamine administration. Arterial blood gases were evaluated 5min after ketamine injection. Plasma concentrations of ketamine and norketamine enantiomers were determined by capillary electrophoresis and were evaluated by non-linear least square regression analysis applying a monocompartmental model. The first-order elimination rate constant was significantly higher and elimination half-life and mean residence time were lower for S-ketamine after S-ketamine compared to R-/S-ketamine administration. The maximum concentration of S-norketamine was higher after S-ketamine administration. Time to standing position was significantly diminished after S-ketamine compared to R-/S-ketamine. Blood gases showed low-degree hypoxaemia and hypercarbia.

Stereoselective pharmacokinetics of ketamine and norketamine after racemic ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland ponies

BACKGROUND: The arterial pharmacokinetics of ketamine and norketamine enantiomers after racemic ketamine or S-ketamine i.v. administration were evaluated in seven gelding ponies in a crossover study (2-month interval). METHODS: Anaesthesia was induced with isoflurane in oxygen via a face-mask and then maintained at each pony's individual MAC. Racemic ketamine (2.2 mg kg(-1)) or S-ketamine (1.1 mg kg(-1)) was injected in the right jugular vein. Blood samples were collected from the right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after ketamine administration. Ketamine and norketamine enantiomer plasma concentrations were determined by capillary electrophoresis. Individual R-ketamine and S-ketamine concentration vs time curves were analysed by non-linear least square regression two-compartment model analysis using PCNonlin. Plasma disposition curves for R-norketamine and S-norketamine were described by estimating AUC, C(max), and T(max). Pulse rate (PR), respiratory rate (R(f)), tidal volume (V(T)), minute volume ventilation (V(E)), end-tidal partial pressure of carbon dioxide (PE'(CO(2))), and mean arterial blood pressure (MAP) were also evaluated. RESULTS: The pharmacokinetic parameters of S- and R-ketamine administered in the racemic mixture or S-ketamine administered separately did not differ significantly. Statistically significant higher AUC and C(max) were found for S-norketamine compared with R-norketamine in the racemic group. Overall, R(f), V(E), PE'(CO(2)), and MAP were significantly higher in the racemic group, whereas PR was higher in the S-ketamine group. CONCLUSIONS: Norketamine enantiomers showed different pharmacokinetic profiles after single i.v. administration of racemic ketamine in ponies anaesthetised with isoflurane in oxygen (1 MAC). Cardiopulmonary variables require further investigation.

Performance of a new, 3D-monitor based random-dot stereotest for children under 4 years of age

BACKGROUND: The aim of this study was to determine the performance of a new, 3D-monitor based, objective stereotest in children under the age of four. METHODS: Random-dot circles (diameter 10 cm, crossed, disparity of 0.34 degrees) randomly changing their position were presented on an 3D-monitor while eye movements were monitored by infrared photo-oculography. If > or = 3 consecutive stimuli were seen, a positive response was assumed. One hundred thirty-four normal children aged 2 months to 4 years (average 17+/-15.3 months) were examined. RESULTS: Below the age of 12 months, we were not able to obtain a response to the 3D stimulus. For older children the following rates of positive responses were found: 12-18 months 25%, 18-24 months 10%, 24-30 months 16%, 30-36 months 57%, 36-42 months 100%, and 42-48 months 91%. Multiple linear logistic regression showed a significant influence on stimulus recognition of the explanatory variables age (p<0.00001) and child cooperation (p<0.001), but not of gender (p>0.1). CONCLUSIONS: This 3D-monitor based stereotest allows an objective measurement of random-dot stereopsis in younger children. It might open new ways to screen children for visual abnormalities and to study the development of stereovision. However, the current experimental setting does not allow determining random-dot stereopsis in children younger than 12 months.

EVALUATION OF INTELLIGENT COMPACTION CONTROL IN THE M-189 RECONSTRUCTION PROJECT AT IRON RIVER, MICHIGAN

This research evaluated an Intelligent Compaction (IC) unit on the M-189 highway reconstruction project at Iron River, Michigan. The results from the IC unit were compared to several traditional compaction measurement devices including Nuclear Density Gauge (NDG), Geogauge, Light Weight Deflectometer (LWD), Dynamic Cone Penetrometer (DCP), and Modified Clegg Hammer (MCH). The research collected point measurements data on a test section in which 30 test locations on the final Class II sand base layer and the 22A gravel layer. These point measurements were compared with the IC measurements (ICMVs) on a point-to-point basis through a linear regression analysis. Poor correlations were obtained among different measurements points using simple regression analysis. When comparing the ICMV to the compaction measurements points. Factors attributing to the weak correlation include soil heterogeneity, variation in IC roller operation parameters, in-place moisture content, the narrow range of the compaction devices measurement ranges and support conditions of the support layers. After incorporating some of the affecting factors into a multiple regression analysis, the strength of correlation significantly improved, especially on the stiffer gravel layer. Measurements were also studied from an overall distribution perspective in terms of average, measurement range, standard deviation, and coefficient of variance. Based on data analysis, on-site project observation and literature review, conclusions were made on how IC performed in regards to compaction control on the M-189 reconstruction project.

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

Effects of gender and dementia severity on Alzheimer's disease caregivers' sleep and biomarkers of coagulation and inflammation

BACKGROUND: Being a caregiver for a spouse with Alzheimer's disease is associated with increased risk for cardiovascular illness, particularly for males. This study examined the effects of caregiver gender and severity of the spouse's dementia on sleep, coagulation, and inflammation in the caregiver. METHODS: Eighty-one male and female spousal caregivers and 41 non-caregivers participated (mean age of all participants 70.2 years). Full-night polysomnography (PSG) was recorded in each participants home. Severity of the Alzheimer's disease patient's dementia was determined by the Clinical Dementia Rating (CDR) scale. The Role Overload scale was completed as an assessment of caregiving stress. Blood was drawn to assess circulating levels of D-dimer and Interleukin-6 (IL-6). RESULTS: Male caregivers who were caring for a spouse with moderate to severe dementia spent significantly more time awake after sleep onset than female caregivers caring for spouses with moderate to severe dementia (p=.011), who spent a similar amount of time awake after sleep onset to caregivers of low dementia spouses and to non-caregivers. Similarly, male caregivers caring for spouses with worse dementia had significantly higher circulating levels of D-dimer (p=.034) than females caring for spouses with worse dementia. In multiple regression analysis (adjusted R(2)=.270, p<.001), elevated D-dimer levels were predicted by a combination of the CDR rating of the patient (p=.047) as well as greater time awake after sleep onset (p=.046). DISCUSSION: The findings suggest that males caring for spouses with more severe dementia experience more disturbed sleep and have greater coagulation, the latter being associated with the disturbed sleep. These findings may provide insight into why male caregivers of spouses with Alzheimer's disease are at increased risk for illness, particularly cardiovascular disease.

Sampling-Design Effects on Properties of Species-Area Relationships - A Case Study from Estonian Dry Grassland Communities

Despite widespread use of species-area relationships (SARs), dispute remains over the most representative SAR model. Using data of small-scale SARs of Estonian dry grassland communities, we address three questions: (1) Which model describes these SARs best when known artifacts are excluded? (2) How do deviating sampling procedures (marginal instead of central position of the smaller plots in relation to the largest plot; single values instead of average values; randomly located subplots instead of nested subplots) influence the properties of the SARs? (3) Are those effects likely to bias the selection of the best model? Our general dataset consisted of 16 series of nested-plots (1 cm(2)-100 m(2), any-part system), each of which comprised five series of subplots located in the four corners and the centre of the 100-m(2) plot. Data for the three pairs of compared sampling designs were generated from this dataset by subsampling. Five function types (power, quadratic power, logarithmic, Michaelis-Menten, Lomolino) were fitted with non-linear regression. In some of the communities, we found extremely high species densities (including bryophytes and lichens), namely up to eight species in 1 cm(2) and up to 140 species in 100 m(2), which appear to be the highest documented values on these scales. For SARs constructed from nested-plot average-value data, the regular power function generally was the best model, closely followed by the quadratic power function, while the logarithmic and Michaelis-Menten functions performed poorly throughout. However, the relative fit of the latter two models increased significantly relative to the respective best model when the single-value or random-sampling method was applied, however, the power function normally remained far superior. These results confirm the hypothesis that both single-value and random-sampling approaches cause artifacts by increasing stochasticity in the data, which can lead to the selection of inappropriate models.

The role of admission blood glucose in outcome prediction of surviving patients with multiple injuries

BACKGROUND: Recent literature demonstrates hyperglycemia to be common in patients with trauma and associated with poor outcome in patients with traumatic brain injury and critically ill patients. The goal of this study was to analyze the impact of admission blood glucose on the outcome of surviving patients with multiple injuries. METHODS: Patients' charts (age >16) admitted to the emergency room of the University Hospital of Berne, Switzerland, between January 1, 2002, and December 31, 2004, with an Injury Severity Score >or=17 and more than one severely injured organ system were reviewed retrospectively. Outcome measurements included morbidity, intensive care unit, and hospital length of stay. RESULTS: The inclusion criteria were met by 555 patients, of which 108 (19.5%) patients died. After multiple regression analysis, admission blood glucose proved to be an independent predictor of posttraumatic morbidity (p < 0.0001), intensive care unit, and hospital length of stay (p < 0.0001), despite intensified insulin therapy on the intensive care unit. CONCLUSIONS: In this population of patients with multiple injuries, hyperglycemia on admission was strongly associated with increased morbidity, especially infections, prolonged intensive care unit, and hospital length of stay independent of injury severity, gender, age, and various biochemical parameters.

Determinants of Experience of Discrimination in Minorities in Germany

This study examines perceived ethnic discrimination (as opposed to “objective” discrimination). It includes a discussion of definitions of discrimination and attempts to measure it, and a review of findings on the distribution of discrimination experiences among minorities. The aim of the study is to determine the influence of factors that increase the risk of exposure to situations in which discrimination can take place (exposure hypothesis), and those that sensitize perceptions and give rise to different frequencies of subjective feelings of discrimination (sensitization hypothesis). A standardized questionnaire was administered to a random sample of German-born persons of Turkish and Greek origin and Aussiedler (ethnic Germans born in the former Soviet Union) (total N = 301). Minorities of non-German, especially of Turkish origin reported significantly more discrimination than Aussiedler in a set of nineteen everyday situations. A bivariate correlation was found between number of incidents reported and employment status with homemakers reporting the fewest incidents. However, multiple regression analysis yielded no significant effect, thus lending no clear support to the exposure hypothesis. Frequency of contacts with German friends has no effect and seems not to entail an increase in exposure opportunities, but may lead to a desensitization to discrimination due to the erosion of the relevance of ethnic categories. On the other hand, an influence through intra-ethnic contacts clearly occurs, as frequency of contact with co-ethnic friends exerts a strong positive effect on experienced discrimination. A similar effect was found for ethnic self-awareness. The latter finding confirms the sensitization hypothesis.

On trend estimation under monotone Gaussian subordination with long-memory: application to fossil pollen series

Fossil pollen data from stratigraphic cores are irregularly spaced in time due to non-linear age-depth relations. Moreover, their marginal distributions may vary over time. We address these features in a nonparametric regression model with errors that are monotone transformations of a latent continuous-time Gaussian process Z(T). Although Z(T) is unobserved, due to monotonicity, under suitable regularity conditions, it can be recovered facilitating further computations such as estimation of the long-memory parameter and the Hermite coefficients. The estimation of Z(T) itself involves estimation of the marginal distribution function of the regression errors. These issues are considered in proposing a plug-in algorithm for optimal bandwidth selection and construction of confidence bands for the trend function. Some high-resolution time series of pollen records from Lago di Origlio in Switzerland, which go back ca. 20,000 years are used to illustrate the methods.

No evidence for an association of posttraumatic stress disorder with circulating levels of CRP and IL-18 in a population-based study.

Several studies have shown associations of posttraumatic stress disorder (PTSD) with the development of cardiometabolic diseases. The underlying psychopathological mechanisms, including potential links to inflammatory processes, have been discussed but remain elusive. Therefore, the aim of the present study was to evaluate the association of PTSD symptoms with the inflammatory biomarkers C-reactive protein (CRP) and interleukin-18 (IL-18). The study population consisted of 3012 participants aged 32-81years drawn from the population-based KORA F4 study conducted in 2006-08 in the Augsburg region (Southern Germany). PTSD symptoms were measured by the Impact of Event Scale, the Posttraumatic Diagnostic Scale and interview data and classified as no, partial or full PTSD. The associations of PTSD with CRP and IL-18 concentrations were estimated by multiple regression analyses with adjustments for age, sex and cardiometabolic risk factors. Linear regression analyses showed no significant association between PTSD and CRP or IL-18 concentration: adjusted for age and sex, the geometric mean concentrations in participants with full PTSD was for CRP 9% lower and for IL-18 1% higher than in participants with no PTSD (p values 0.53 and 0.89). However, further analyses indicated that individuals with partial PTSD had an increased chance of belonging to the highest quartile of the IL-18 concentration. No significant association was observed for any of the three subscales intrusion, avoidance or hyperarousal with CRP or IL-18 concentration. This large, population-based study could not find an association of full PTSD with CRP and IL-18 concentrations. Further research is needed to analyse these relationships.

THE RELATIONSHIP BETWEEN OBESITY AND PSYCHOLOGICAL GENERAL WELL-BEING IN UNITED STATES WOMEN

While clinical studies have shown a negative relationship between obesity and mental health in women, population studies have not shown a consistent association. However, many of these studies can be criticized regarding fatness level criteria, lack of control variables, and validity of the psychological variables.^ The purpose of this research was to elucidate the relationship between fatness level and mental health in United States women using data from the First National Health and Nutrition Examination Survey (NHANES I), which was conducted on a national probability sample from 1971 to 1974. Mental health was measured by the General Well-Being Schedule (GWB), and fatness level was determined by the sum of the triceps and subscapular skinfolds. Women were categorized as lean (15th percentile or less), normal (16th to 84th percentiles), or obese (85th percentile or greater).^ A conceptual framework was developed which identified the variables of age, race, marital status, socioeconomic status (education), employment status, number of births, physical health, weight history, and perception of body image as important to the fatness level-GWB relationship. Multiple regression analyses were performed separately for whites and blacks with GWB as the response variable, and fatness level, age, education, employment status, number of births, marital status, and health perception as predictor variables. In addition, 2- and 3-way interaction terms for leanness, obesity and age were included as predictor variables. Variables related to weight history and perception of body image were not collected in NHANES I, and thus were not included in this study.^ The results indicated that obesity was a statistically significant predictor of lower GWB in white women even when the other predictor variables were controlled. The full regression model identified the young, more educated, obese female as a subgroup with lower GWB, especially in blacks. These findings were not consistent with the previous non-clinical studies which found that obesity was associated with better mental health. The social stigma of being obese and the preoccupation of women with being lean may have contributed to the lower GWB in these women. ^