The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

Objective To examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia. Study design Prospective experimental blinded cross-over study. Animals Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg and age 25 +/- 16 months. Methods Anaesthesia was induced with propofol and maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 mug kg(-1) IV) followed by a continuous rate infusion (1 mug kg(-1) hour(-1) ) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data. Results The AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0. Conclusions During isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation. Clinical relevance This experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.

Sideband-Ratio and Harmonic Response of Sub-Millimeter Wave Mixers measured with a Martin Puplett Interferometer

Heterodyne receivers at millimeter and submillimeter wavelength are widely used for radiometric spectral line observations for atmospheric remote sensing or radio astronomy. The quantitative analysis of such observations requires an accurate knowledge of the mixers's sideband ratio. In addition, its potential sensitivity to spurious harmonics needs to be well understood. In this paper, we discuss a measurement technique for these receiver characteristics, which is based on a scanning Martin Puplett Interferometer used in conjunction with a wide band digital autocorrelation spectrometer for the analysis of the intermediate frequency band. We present measurement results of different double sideband and sideband separating mixers, which were developed for the proposed 340GHz multi-beam limb sounder STEAMR.

Influence of inspiration to expiration ratio on cyclic recruitment and derecruitment of atelectasis in a saline lavage model of acute respiratory distress syndrome*

OBJECTIVE Cyclic recruitment and derecruitment of atelectasis can occur during mechanical ventilation, especially in injured lungs. Experimentally, cyclic recruitment and derecruitment can be quantified by respiration-dependent changes in PaO2 (ΔPaO2), reflecting the varying intrapulmonary shunt fraction within the respiratory cycle. This study investigated the effect of inspiration to expiration ratio upon ΔPaO2 and Horowitz index. DESIGN Prospective randomized study. SETTING Laboratory investigation. SUBJECTS Piglets, average weight 30 ± 2 kg. INTERVENTIONS At respiratory rate 6 breaths/min, end-inspiratory pressure (Pendinsp) 40 cm H2O, positive end-expiratory pressure 5 cm H2O, and FIO2 1.0, measurements were performed at randomly set inspiration to expiration ratios during baseline healthy and mild surfactant depletion injury. Lung damage was titrated by repetitive surfactant washout to induce maximal cyclic recruitment and derecruitment as measured by multifrequency phase fluorimetry. Regional ventilation distribution was evaluated by electrical impedance tomography. Step changes in airway pressure from 5 to 40 cm H2O and vice versa were performed after lavage to calculate PO2-based recruitment and derecruitment time constants (TAU). MEASUREMENTS AND MAIN RESULTS In baseline healthy, cyclic recruitment and derecruitment could not be provoked, whereas in model acute respiratory distress syndrome, the highest ΔPaO2 were routinely detected at an inspiration to expiration ratio of 1:4 (range, 52-277 torr [6.9-36.9 kPa]). Shorter expiration time reduced cyclic recruitment and derecruitment significantly (158 ± 85 torr [21.1 ± 11.3 kPa] [inspiration to expiration ratio, 1:4]; 25 ± 12 torr [3.3 ± 1.6 kPa] [inspiration to expiration ratio, 4:1]; p < 0.0001), whereas the PaO2/FIO2 ratio increased (267 ± 50 [inspiration to expiration ratio, 1:4]; 424 ± 53 [inspiration to expiration ratio, 4:1]; p < 0.0001). Correspondingly, regional ventilation redistributed toward dependent lung regions (p < 0.0001). Recruitment was much faster (TAU: fast 1.6 s [78%]; slow 9.2 s) than derecruitment (TAU: fast 3.1 s [87%]; slow 17.7 s) (p = 0.0078). CONCLUSIONS Inverse ratio ventilation minimizes cyclic recruitment and derecruitment of atelectasis in an experimental model of surfactant-depleted pigs. Time constants for recruitment and derecruitment, and regional ventilation distribution, reflect these findings and highlight the time dependency of cyclic recruitment and derecruitment.

Feasible Dose Reduction in Routine Chest Computed Tomography Maintaining Constant Image Quality Using the Last Three Scanner Generations: From Filtered Back Projection to Sinogram-affirmed Iterative Reconstruction and Impact of the Novel Fully Integrated Detector Design Minimizing Electronic Noise

OBJECTIVE The aim of the present study was to evaluate a dose reduction in contrast-enhanced chest computed tomography (CT) by comparing the three latest generations of Siemens CT scanners used in clinical practice. We analyzed the amount of radiation used with filtered back projection (FBP) and an iterative reconstruction (IR) algorithm to yield the same image quality. Furthermore, the influence on the radiation dose of the most recent integrated circuit detector (ICD; Stellar detector, Siemens Healthcare, Erlangen, Germany) was investigated. MATERIALS AND METHODS 136 Patients were included. Scan parameters were set to a thorax routine: SOMATOM Sensation 64 (FBP), SOMATOM Definition Flash (IR), and SOMATOM Definition Edge (ICD and IR). Tube current was set constantly to the reference level of 100 mA automated tube current modulation using reference milliamperes. Care kV was used on the Flash and Edge scanner, while tube potential was individually selected between 100 and 140 kVp by the medical technologists at the SOMATOM Sensation. Quality assessment was performed on soft-tissue kernel reconstruction. Dose was represented by the dose length product. RESULTS Dose-length product (DLP) with FBP for the average chest CT was 308 mGy*cm ± 99.6. In contrast, the DLP for the chest CT with IR algorithm was 196.8 mGy*cm ± 68.8 (P = 0.0001). Further decline in dose can be noted with IR and the ICD: DLP: 166.4 mGy*cm ± 54.5 (P = 0.033). The dose reduction compared to FBP was 36.1% with IR and 45.6% with IR/ICD. Signal-to-noise ratio (SNR) was favorable in the aorta, bone, and soft tissue for IR/ICD in combination compared to FBP (the P values ranged from 0.003 to 0.048). Overall contrast-to-noise ratio (CNR) improved with declining DLP. CONCLUSION The most recent technical developments, namely IR in combination with integrated circuit detectors, can significantly lower radiation dose in chest CT examinations.

Multinomial goodness-of-fit: large sample tests with survey design correction and exact tests for small samples

I introduce the new mgof command to compute distributional tests for discrete (categorical, multinomial) variables. The command supports largesample tests for complex survey designs and exact tests for small samples as well as classic large-sample x2-approximation tests based on Pearson’s X2, the likelihood ratio, or any other statistic from the power-divergence family (Cressie and Read, 1984, Journal of the Royal Statistical Society, Series B (Methodological) 46: 440–464). The complex survey correction is based on the approach by Rao and Scott (1981, Journal of the American Statistical Association 76: 221–230) and parallels the survey design correction used for independence tests in svy: tabulate. mgof computes the exact tests by using Monte Carlo methods or exhaustive enumeration. mgof also provides an exact one-sample Kolmogorov–Smirnov test for discrete data.

Hygroscopic growth of atmospheric aerosol particles based on active remote sensing and radiosounding measurements: selected cases in southeastern Spain

A new methodology based on combining active and passive remote sensing and simultaneous and collocated radiosounding data to study the aerosol hygroscopic growth effects on the particle optical and microphysical properties is presented. The identification of hygroscopic growth situations combines the analysis of multispectral aerosol particle backscatter coefficient and particle linear depolarization ratio with thermodynamic profiling of the atmospheric column. We analyzed the hygroscopic growth effects on aerosol properties, namely the aerosol particle backscatter coefficient and the volume concentration profiles, using data gathered at Granada EARLINET station. Two study cases, corresponding to different aerosol loads and different aerosol types, are used for illustrating the potential of this methodology. Values of the aerosol particle backscatter coefficient enhancement factors range from 2.1 ± 0.8 to 3.9 ± 1.5, in the ranges of relative humidity 60–90 and 40–83%, being similar to those previously reported in the literature. Differences in the enhancement factor are directly linked to the composition of the atmospheric aerosol. The largest value of the aerosol particle backscatter coefficient enhancement factor corresponds to the presence of sulphate and marine particles that are more affected by hygroscopic growth. On the contrary, the lowest value of the enhancement factor corresponds to an aerosol mixture containing sulphates and slight traces of mineral dust. The Hänel parameterization is applied to these case studies, obtaining results within the range of values reported in previous studies, with values of the γ exponent of 0.56 ± 0.01 (for anthropogenic particles slightly influenced by mineral dust) and 1.07 ± 0.01 (for the situation dominated by anthropogenic particles), showing the convenience of this remote sensing approach for the study of hygroscopic effects of the atmospheric aerosol under ambient unperturbed conditions. For the first time, the retrieval of the volume concentration profiles for these cases using the Lidar Radiometer Inversion Code (LIRIC) allows us to analyze the aerosol hygroscopic growth effects on aerosol volume concentration, observing a stronger increase of the fine mode volume concentration with increasing relative humidity.

Long-term ticagrelor monotherapy versus standard dual antiplatelet therapy followed by aspirin monotherapy in patients undergoing biolimus-eluting stent implantation: rationale and design of the GLOBAL LEADERS trial

AIMS The GLOBAL LEADERS trial is a superiority study in patients undergoing percutaneous coronary intervention, with a uniform use of Biolimus A9-eluting stents (BES) and bivalirudin. GLOBAL LEADERS was designed to assess whether a 24-month antithrombotic regimen with ticagrelor and one month of acetylsalicylic acid (ASA), compared to conventional dual antiplatelet therapy (DAPT), improves outcomes. METHODS AND RESULTS Patients (n >16,000) are randomised (1:1 ratio) to ticagrelor 90 mg twice daily for 24 months plus ASA ≤100 mg for one month versus DAPT with either ticagrelor (acute coronary syndrome) or clopidogrel (stable coronary artery disease) for 12 months plus ASA ≤100 mg for 24 months. The primary outcome is a composite of all-cause mortality or non-fatal, new Q-wave myocardial infarction at 24 months. The key safety endpoint is investigator-reported class 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions. Sensitivity analysis will be carried out to explore potential differences in outcome across geographic regions and according to specific angiographic and clinical risk estimates. CONCLUSIONS The GLOBAL LEADERS trial aims to assess the role of ticagrelor as a single antiplatelet agent after a short course of DAPT for the long-term prevention of cardiac adverse events, across a wide spectrum of patients, following BES implantation.

Life style habits such as alcohol consumption and physical activity in relation to serum apoB / apoA-I ratio amongst 64-year-old women with varying degrees of glucose tolerance.

OBJECTIVES To investigate how life style factors such as alcohol consumption and physical activity relate to the serum apoB / apoA-I ratio in a cohort of middle-aged women with varying degrees of glucose tolerance. DESIGN Observational, cross-sectional cohort study. SETTING Research laboratory at a University Hospital. SUBJECTS A screened cohort of 64-year-old postmenopausal women with varying degrees of glucose tolerance, ranging from diabetes (n = 232), impaired (n = 212) and normal (n = 191) glucose tolerance. MAIN OUTCOME MEASURE ApoB / apoA-I ratio in relation to alcohol consumption and physical activity as assessed by questionnaires. RESULTS Alcohol consumption and regular physical activity at high levels were inversely associated with the serum apoB / apoA-I ratio independently of confounding factors such as obesity, lipid-lowering treatment, degree of glucose tolerance and hormone replacement therapy. Alcohol seemed related to the apoB / apoA-I ratio mainly through increasing apoA-I, whereas physical activity seemed mainly related to lowering of apoB. Alcohol consumption above a daily intake of 8.9 g, i.e. less than a glass of wine was accompanied by a decrease in apoB / apoA-I ratio. CONCLUSIONS Amongst these 64-year-old women with varying degrees of glucose tolerance, a moderate alcohol intake and regular physical exercise leading to sweating were associated with lower apoB / apoA-I ratio and these effects seem to be additive.

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

Background: Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective: To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods: A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results: All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions: In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

Peri-implant bone loss of dental implants with platform-switching design after 5 years of loading: a cross-sectional study

OBJECTIVE The aim of this cross-sectional study was to estimate bone loss of implants with platform-switching design and analyze possible risk indicators after 5 years of loading in a multi-centered private practice network. METHOD AND MATERIALS Peri-implant bone loss was measured radiographically as the distance from the implant shoulder to the mesial and distal alveolar crest, respectively. Risk factor analysis for marginal bone loss included type of implant prosthetic treatment concept and dental status of the opposite arch. RESULTS A total of 316 implants in 98 study patients after 5 years of loading were examined. The overall mean value for radiographic bone loss was 1.02 mm (SD ± 1.25 mm, 95% CI 0.90- 1.14). Correlation analyses indicated a strong association of peri-implant bone loss > 2 mm for removable implant-retained prostheses with an odds ratio of 53.8. CONCLUSION The 5-year-results of the study show clinically acceptable values of mean bone loss after 5 years of loading. Implant-supported removable prostheses seem to be a strong co-factor for extensive bone level changes compared to fixed reconstructions. However, these results have to be considered for evaluation of the included special cohort under private dental office conditions.

Temporal association between childhood leukaemia and population growth in Swiss municipalities.

The population mixing hypothesis proposes that childhood leukaemia (CL) might be a rare complication of a yet unidentified subclinical infection. Large population influxes into previously isolated rural areas may foster localised epidemics of the postulated infection causing a subsequent increase of CL. While marked population growth after a period of stability was central to the formulation of the hypothesis and to the early studies on population mixing, there is a lack of objective criteria to define such growth patterns. We aimed to determine whether periods of marked population growth coincided with increases in the risk of CL in Swiss municipalities. We identified incident cases of CL aged 0-15 years for the period 1985-2010 from the Swiss Childhood Cancer Registry. Annual data on population counts in Swiss municipalities were obtained for 1980-2010. As exposures, we defined (1) cumulative population growth during a 5-year moving time window centred on each year (1985-2010) and (2) periods of 'take-off growth' identified by segmented linear regression. We compared CL incidence across exposure categories using Poisson regression and tested for effect modification by degree of urbanisation. Our study included 1500 incident cases and 2561 municipalities. The incident rate ratio (IRR) comparing the highest to the lowest quintile of 5-year population growth was 1.18 (95 % CI 0.96, 1.46) in all municipalities and 1.33 (95 % CI 0.93, 1.92) in rural municipalities (p value interaction 0.36). In municipalities with take-off growth, the IRR comparing the take-off period (>6 % annual population growth) with the initial period of low or negative growth (<2 %) was 2.07 (95 % CI 0.95, 4.51) overall and 2.99 (1.11, 8.05) in rural areas (p interaction 0.52). Our study provides further support for the population mixing hypothesis and underlines the need to distinguish take-off growth from other growth patterns in future research.

Multinomial goodness-of-fit: large sample tests with survey design correction and exact tests for small samples

A new Stata command called -mgof- is introduced. The command is used to compute distributional tests for discrete (categorical, multinomial) variables. Apart from classic large sample $\chi^2$-approximation tests based on Pearson's $X^2$, the likelihood ratio, or any other statistic from the power-divergence family (Cressie and Read 1984), large sample tests for complex survey designs and exact tests for small samples are supported. The complex survey correction is based on the approach by Rao and Scott (1981) and parallels the survey design correction used for independence tests in -svy:tabulate-. The exact tests are computed using Monte Carlo methods or exhaustive enumeration. An exact Kolmogorov-Smirnov test for discrete data is also provided.