Fatal tolperisone poisoning: Autopsy and toxicology findings in three suicide cases.

Tolperisone (Mydocalm(®)) is a centrally acting muscle relaxant with few sedative side effects that is used for the treatment of chronic pain conditions. We describe three cases of suicidal tolperisone poisoning in three healthy young subjects in the years 2006, 2008 and 2009. In all cases, macroscopic and microscopic autopsy findings did not reveal the cause of death. Systematic toxicological analysis (STA) including immunological tests, screening for volatile substances and blood, urine and gastric content screening by GC-MS and HPLC-DAD demonstrated the presence of tolperisone in all cases. In addition to tolperisone, only the analgesics paracetamol (acetaminophen), ibuprofen and naproxen could be detected. The blood ethanol concentrations were all lower than 0.10g/kg. Tolperisone was extracted by liquid-liquid extraction using n-chlorobutane as the extraction solvent. The quantification was performed by GC-NPD analysis of blood, urine and gastric content. Tolperisone concentrations of 7.0mg/l, 14mg/l and 19mg/l were found in the blood of the deceased. In the absence of other autopsy findings, the deaths in these three cases were finally explained as a result of lethal tolperisone ingestion. To the best of our knowledge, these three cases are the first reported cases of suicidal tolperisone poisonings.

Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. METHODS: Planar and SPECT data were available for a patient examined with (111)In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., (111)In, (90)Y and (177)Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. RESULTS: Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for (90)Y and (177)Lu. Nevertheless, for (111)In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated treatment planning are compatible with real activities administered to patients in PRRT. CONCLUSIONS: The 3D-RD treatment planning approach based on the fixed BED was found to be the method of choice for clinical implementation in PRRT by providing realistic activity to administer and number of cycles. While dividing the activity in several cycles is important to reduce renal toxicity, the clinical outcome of fractionated PRRT should be investigated in the future.

ZHARP: three-dimensional motion tracking from a single image plane.

Three-dimensional imaging and quantification of myocardial function are essential steps in the evaluation of cardiac disease. We propose a tagged magnetic resonance imaging methodology called zHARP that encodes and automatically tracks myocardial displacement in three dimensions. Unlike other motion encoding techniques, zHARP encodes both in-plane and through-plane motion in a single image plane without affecting the acquisition speed. Postprocessing unravels this encoding in order to directly track the 3-D displacement of every point within the image plane throughout an entire image sequence. Experimental results include a phantom validation experiment, which compares zHARP to phase contrast imaging, and an in vivo study of a normal human volunteer. Results demonstrate that the simultaneous extraction of in-plane and through-plane displacements from tagged images is feasible.

Three-dimensional black-blood cardiac magnetic resonance coronary vessel wall imaging detects positive arterial remodeling in patients with nonsignificant coronary artery disease.

BACKGROUND: Direct noninvasive visualization of the coronary vessel wall may enhance risk stratification by quantifying subclinical coronary atherosclerotic plaque burden. We sought to evaluate high-resolution black-blood 3D cardiovascular magnetic resonance (CMR) imaging for in vivo visualization of the proximal coronary artery vessel wall. METHODS AND RESULTS: Twelve adult subjects, including 6 clinically healthy subjects and 6 patients with nonsignificant coronary artery disease (10% to 50% x-ray angiographic diameter reduction) were studied with the use of a commercial 1.5 Tesla CMR scanner. Free-breathing 3D coronary vessel wall imaging was performed along the major axis of the right coronary artery with isotropic spatial resolution (1.0x1.0x1.0 mm(3)) with the use of a black-blood spiral image acquisition. The proximal vessel wall thickness and luminal diameter were objectively determined with an automated edge detection tool. The 3D CMR vessel wall scans allowed for visualization of the contiguous proximal right coronary artery in all subjects. Both mean vessel wall thickness (1.7+/-0.3 versus 1.0+/-0.2 mm) and wall area (25.4+/-6.9 versus 11.5+/-5.2 mm(2)) were significantly increased in the patients compared with the healthy subjects (both P<0.01). The lumen diameter (3.6+/-0.7 versus 3.4+/-0.5 mm, P=0.47) and lumen area (8.9+/-3.4 versus 7.9+/-3.5 mm(2), P=0.47) were similar in both groups. CONCLUSIONS: Free-breathing 3D black-blood coronary CMR with isotropic resolution identified an increased coronary vessel wall thickness with preservation of lumen size in patients with nonsignificant coronary artery disease, consistent with a "Glagov-type" outward arterial remodeling. This novel approach has the potential to quantify subclinical disease.

A Three-Dimensional Framework to Analyse the Governance of Population Registers

In June 2006, the Swiss Parliament made two important decisions with regards to public registers' governance and individuals' identification. It adopted a new law on the harmonisation of population registers in order to simplify statistical data collection and data exchange from around 4'000 decentralized registers, and it also approved the introduction of a Unique Person Identifier (UPI). The law is rather vague about the implementation of this harmonisation and even though many projects are currently being undertaken in this domain, most of them are quite technical. We believe there is a need for analysis tools and therefore we propose a conceptual framework based on three pillars (Privacy, Identity and Governance) to analyse the requirements in terms of data management for population registers.

Leadership at the upper echelons : three essays

"IT'S THE ECONOMY STUPID", BUT CHARISMA MATTERS TOO: A DUAL PROCESS MODEL OF PRESIDENTIAL ELECTION OUTCOMES. ABSTRACT Because charisma is assumed to be an important determinant of effective leadership, the extent to which a presidential nominee is more charismatic than his opponent should be an important determinant of voter choices. We computed a composite measure of the rhetorical richness of acceptances speeches given by U.S. presidential candidates at their national party convention. We added this marker of charisma to Ray C. Fair's presidential vote-share equation (1978; 2009). We theorized that voters decide using psychological attribution (i.e., due to macroeconomics and incumbency) as well as inferential processes (i.e., due to leader charismatic behavior) when voting. Controlling for the macro-level variables and incumbency in the Fair model, our results indicated that difference between nominees' charisma is a significant determinant of electoral success, particularly in close elections. This extended model significantly improves the precision of the Fair model and correctly predicts 23 out of the last 24 U.S. presidential elections. Paper 2: IT CEO LEADERSHIP, CORPORATE SOCIAL AND FINANCIAL PERFORMANCE. ABSTRACT We investigated whether CEO leadership predicted corporate financial performance (CFP) and corporate social performance (CSP). Using longitudinal data on 258 CEOs from 117 firms across 19 countries and 10 industry sectors, we found that determinants of CEO leadership (i.e., implicit motives) significantly predicted both CFP and CSP. As expected, the most consistent positive predictor was Responsibility Disposition when interacting with n (need for) Power. n Achievement and n Affiliation were generally negatively related or unrelated to outcomes. CSP was positively related to accounting measures of CFP. Our findings suggest that executive leader characteristics have important consequences for corporate level outcomes. Paper 3. PUNISHING THE POWERFUL: ATTRIBUTIONS OF BLAME AND LEADERSHIP ABSTRACT We propose that individuals are more lenient in attributing blame to leaders than to nonleaders. We advance a motivational explanation building on the perspective of punishment and on system justification theory. We conducted two scenario experiments which supported our proposition. In study 1, wrongdoer leader status was negatively related to blame and the perceived seriousness of the wrongdoing. In study 2, controlling for the Big-Five personality factor and individual differences in moral evaluation (i.e., moral foundations), wrongdoer leader status was negatively related with desired severity of punishment, and fair punishments were perceived as more just for non-leaders than for leaders.

Hierarchy of interactive functions in father-mother-baby three-way games

In developmental research, the family has mainly been studied through dyadic interaction. Three-way interactions have received less attention, partly because of their complexity. This difficulty may be overcome by distinguishing between four hierarchically embedded functions in three-way interactions: (1) participation (inclusion of all participants), (2) organization (partners keeping to their roles), (3) focalization (sharing a common focus) and (4) affective contact (being in tune). We document this hierarchical model on a sample of 80 families observed in the Lausanne Trilogue Play situation across four different sites. Hierarchy between functions was demonstrated by means of Guttman scalability coefficient. Given the importance of the child's development in a threesome, the pertinence of this model for family assessment is discussed.

Psychometrics of the Dyadic Coping Inventory in three language groups

This article introduces the Dyadic Coping Inventory (DCI; Bodenmann, 2008) and aims (1) to investigate the reliability and aspects of the validity of the Italian and French versions of the DCI, and (2) to replicate its factor structure and reliabilities using a new Swiss German sample. Based on 216 German-, 378 Italian-, and 198 French-speaking participants, the factor structure of the original German inventory was able to be replicated by using principal components analysis in all three groups after excluding two items in the Italian and French versions. The latter were shown to be as reliable as the German version with the exception of the low reliabilities of negative dyadic coping in the French group. Confirmatory factor analyses provided additional support for delegated dyadic coping and evaluation of dyadic coping. Intercorrelations among scales were similar across all three languages groups with a few exceptions. Previous findings could be replicated in all three groups, showing that aspects of dyadic coping were more strongly related to marital quality than to dyadic communication. The use of the dyadic coping scales in the actor-partner interdependence model, the common fate model, and the mutual influence model is discussed.

Importance of a three-dimensional measure of humeral head subluxation in osteoarthritic shoulders.

HYPOTHESIS: During total shoulder arthroplasty (TSA), humeral head subluxation may be difficult to manage. Furthermore, there is a risk for postoperative recurrence of subluxation, affecting the outcome of TSA. An accurate evaluation of the subluxation is necessary to evaluate this risk. Currently, subluxation is measured in 2 dimensions (2D), usually relative to the glenoid face. The goal of this study was to extend this measure to 3 dimensions (3D) to compare glenohumeral and scapulohumeral subluxation and to evaluate the association of subluxation with the glenoid version. MATERIALS AND METHODS: The study analyzed 112 computed tomography scans of osteoarthritic shoulders. We extended the usual 2D definition of glenohumeral subluxation, scapulohumeral subluxation, and glenoid version by measuring their orientation in 3D relative to the scapular plane and the scapular axis. We evaluated statistical associations between subluxation and version in 2D and 3D. RESULTS: Orientation of subluxation and version covered all sectors of the glenoid surface. Scapulohumeral subluxation and glenoid version were highly correlated in amplitude (R(2) = 0.71; P < .01) and in orientation (R(2) = 0.86; P < .01). Approximately every degree of glenoid version induced 1% of scapulohumeral subluxation in the same orientation of the version. Conversely, glenohumeral subluxation was not correlated to glenoid version in 2D or in 3D. CONCLUSIONS: Orientation of the humeral subluxation is rarely within the arbitrary computed tomography plane and should therefore be measured in 3D to detect out-of-plane subluxation. Scapulohumeral subluxation and glenoid version measured in 3D could bring valuable information for decision making during TSA.

A comparison of three methods of Mendelian randomization when the genetic instrument, the risk factor and the outcome are all binary.

The method of instrumental variable (referred to as Mendelian randomization when the instrument is a genetic variant) has been initially developed to infer on a causal effect of a risk factor on some outcome of interest in a linear model. Adapting this method to nonlinear models, however, is known to be problematic. In this paper, we consider the simple case when the genetic instrument, the risk factor, and the outcome are all binary. We compare via simulations the usual two-stages estimate of a causal odds-ratio and its adjusted version with a recently proposed estimate in the context of a clinical trial with noncompliance. In contrast to the former two, we confirm that the latter is (under some conditions) a valid estimate of a causal odds-ratio defined in the subpopulation of compliers, and we propose its use in the context of Mendelian randomization. By analogy with a clinical trial with noncompliance, compliers are those individuals for whom the presence/absence of the risk factor X is determined by the presence/absence of the genetic variant Z (i.e., for whom we would observe X = Z whatever the alleles randomly received at conception). We also recall and illustrate the huge variability of instrumental variable estimates when the instrument is weak (i.e., with a low percentage of compliers, as is typically the case with genetic instruments for which this proportion is frequently smaller than 10%) where the inter-quartile range of our simulated estimates was up to 18 times higher compared to a conventional (e.g., intention-to-treat) approach. We thus conclude that the need to find stronger instruments is probably as important as the need to develop a methodology allowing to consistently estimate a causal odds-ratio.

Sandwich enzyme immunoassay using three monoclonal antibodies against different epitopes of carcinoembryonic antigen (CEA).

Purified monoclonal antibodies (Mab) produced by 3 hybridomas and reacting with 3 different epitopes of carcinoembryonic antigen (CEA) were used in a solid phase enzyme immunoassay. Two Mabs were physically adsorbed to polystyrene balls and the third Mab was coupled to alkaline phosphatase using the bifunctional reagent N-succinimidyl-3-(2-pyridyldithio)-propionate. During a first incubation, CEA from heat-extracted serum samples was immunoadsorbed to the antibody coated balls. After washing of the balls, bound CEA was detected by a second incubation with the enzyme coupled Mab. The sensitivity of the assay was 0.6 ng per ml of serum. A total of 196 serum samples from patients with various types of carcinoma, with liver cirrhosis, or from healthy blood donors with or without smoking habits, were tested. The results obtained with the monoclonal enzyme immunoassay (M-EIA) were compared with those obtained with perchloric acid extracts of the same serum samples tested by an inhibition radioimmunoassay using conventional goat anti-CEA antiserum. There was an excellent correlation between the two assays. In particular, the new M-EIA gave good results for the detection of tumor recurrences in the follow-up of colon carcinoma patients. However, despite the use of exclusively monoclonal antibodies the new assay detected a similar percentage of slightly elevated CEA values as the conventional assay in patients with non-malignant disease, suggesting that the CEA associated with non-malignant diseases is immunologically identical to the CEA released by colon carcinoma.