Event-related potential analyses via single-subject topographic classification.

Introduction: Responses to external stimuli are typically investigated by averaging peri-stimulus electroencephalography (EEG) epochs in order to derive event-related potentials (ERPs) across the electrode montage, under the assumption that signals that are related to the external stimulus are fixed in time across trials. We demonstrate the applicability of a single-trial model based on patterns of scalp topographies (De Lucia et al, 2007) that can be used for ERP analysis at the single-subject level. The model is able to classify new trials (or groups of trials) with minimal a priori hypotheses, using information derived from a training dataset. The features used for the classification (the topography of responses and their latency) can be neurophysiologically interpreted, because a difference in scalp topography indicates a different configuration of brain generators. An above chance classification accuracy on test datasets implicitly demonstrates the suitability of this model for EEG data. Methods: The data analyzed in this study were acquired from two separate visual evoked potential (VEP) experiments. The first entailed passive presentation of checkerboard stimuli to each of the four visual quadrants (hereafter, "Checkerboard Experiment") (Plomp et al, submitted). The second entailed active discrimination of novel versus repeated line drawings of common objects (hereafter, "Priming Experiment") (Murray et al, 2004). Four subjects per experiment were analyzed, using approx. 200 trials per experimental condition. These trials were randomly separated in training (90%) and testing (10%) datasets in 10 independent shuffles. In order to perform the ERP analysis we estimated the statistical distribution of voltage topographies by a Mixture of Gaussians (MofGs), which reduces our original dataset to a small number of representative voltage topographies. We then evaluated statistically the degree of presence of these template maps across trials and whether and when this was different across experimental conditions. Based on these differences, single-trials or sets of a few single-trials were classified as belonging to one or the other experimental condition. Classification performance was assessed using the Receiver Operating Characteristic (ROC) curve. Results: For the Checkerboard Experiment contrasts entailed left vs. right visual field presentations for upper and lower quadrants, separately. The average posterior probabilities, indicating the presence of the computed template maps in time and across trials revealed significant differences starting at ~60-70 ms post-stimulus. The average ROC curve area across all four subjects was 0.80 and 0.85 for upper and lower quadrants, respectively and was in all cases significantly higher than chance (unpaired t-test, p<0.0001). In the Priming Experiment, we contrasted initial versus repeated presentations of visual object stimuli. Their posterior probabilities revealed significant differences, which started at 250ms post-stimulus onset. The classification accuracy rates with single-trial test data were at chance level. We therefore considered sub-averages based on five single trials. We found that for three out of four subjects' classification rates were significantly above chance level (unpaired t-test, p<0.0001). Conclusions: The main advantage of the present approach is that it is based on topographic features that are readily interpretable along neurophysiologic lines. As these maps were previously normalized by the overall strength of the field potential on the scalp, a change in their presence across trials and between conditions forcibly reflects a change in the underlying generator configurations. The temporal periods of statistical difference between conditions were estimated for each training dataset for ten shuffles of the data. Across the ten shuffles and in both experiments, we observed a high level of consistency in the temporal periods over which the two conditions differed. With this method we are able to analyze ERPs at the single-subject level providing a novel tool to compare normal electrophysiological responses versus single cases that cannot be considered part of any cohort of subjects. This aspect promises to have a strong impact on both basic and clinical research.

Quality of life transformations before and after kidney transplantation: A prospective qualitative study.

The aim of this IRB-approved study was to analyze prospectively quality of life (QOL) and psychological changes in 30 ESRD patients before and after kidney transplantation (KT). Semi-structured interviews were conducted after inclusion on the waiting list (A). Follow-up interviews were performed 6 months later with patients still awaiting KT (B6, n= 15), and with transplant recipients 6, 12 and 24 months after KT (C6, n=15; C12, n=15; C24, n=14). Qualitative thematic analysis was performed. A: All patients reported loss of freedom, 87% tried to maintain normality; 57% modified medical directives. All mentioned emotional fragility, negative thoughts (43%), and suicidal thoughts (20%) related to loss of QOL from dialysis (D), and professional tension (26%). B6: 40% reported no change compared to baseline, while 60% mentioned increase of illness intrusiveness, 46% D side effects, 40% communication problems, and 33% concerns about the waiting list handling. Fear of emotional breakdown (40%), couple problems (47%), and worsened professional difficulties (20%) were reported. C6: All patients reported recovery of QOL and concerns about acute rejection. 73% were anxious about laboratory results. 93% felt dependent on immunosuppressants (IS), 47% reported difficulties coping with their regimen, and 47% were concerned about side effects; 67% had resumed work, but medical constraints led 40% to professional stigmatization. C12: All enjoyed good QOL. Adherence to IS was mandatory (100%). All were aware of the limited long-term graft survival and 47% anxious about a possible return to D. 60% underlined positive life value; 47% resumed a full time job; 40% were on social security. C24: Good QOL was underlined (86%). Patients stated they would prefer re-TX to resuming D (71%). Post-TX health problems were mentioned (64%); increase of creatinine levels induced fear (36%). 79% complained about side effects. 64% reported changes in life values. This study reveals positive QOL and psychological transformations after KT, which are associated with positive changes related to graft survival and freedom from D. Psychological follow-up should be offered to patients who face relapsing ESRD or post-TX co-morbidities.

Aspects professionnels associés à des symptômes de détresse psychique chez des spécialistes des urgences pré-hospitalières

Il y a relativement peu d'études portant sur la santé au travail des professionnels des urgences préhospitalières. Toutefois, quelques études suggèrent que les problèmes de santé mentale sont particulièrement fréquents et graves pour cette population de travailleurs et travailleuses. Notre étude visait d'une part à identifier certains facteurs professionnels associés à différents symptômes chez des professionnels des urgences pré-hospitalières. D'autre part, cette étude visait à identifier et à documenter diverses stratégies de préservation de la santé utiliséespar ces professionnels dans le cadre de leur travailDans un premier temps, une phase qualitative centrée sur l'observation du travail réel a été effectuée. Au cours de cette phase, les chercheurs ont accompagné des équipages de professionnels des urgences pré-hospitalières pour la durée entière de la journée de travail et pour une moyenne d'environ une semaine (4 X 12 heures) par équipage. Les analyses des données d'observation ont été réalisées en équipe multidisciplinaire. Certaines interventions ont été filmées et utilisées dans le cadre d'entretiens en auto-confrontation. Les observations ont été effectuées dans 11 services pour un total de 416 heures d'observation et 70 interventions. L'analyse de l'activité réelle de travail a été effectuée à travers diverses thématiques comme par exemple le travail d'équipe, l'organisation, ou la charge physique. Dans un second temps, un questionnaire a été développé et administré à l'ensemble des ambulanciers (N=669) en Suisse francophone. Cette démarche visait 1-à documenter l'état de santé de ces professionnels et 2- à mettre en évidence des associations entre certains facteurs liés au travail et des indicateurs de santé.Au total, 374 questionnaires ont été retournés. Cette démarche a permis de constater que les professionnels des urgences pré-hospitalières sont nombreux (14 %) à avoir un score élevé (associé à un risque augmenté de troubles psychiques) pour le General Health Questionnaire (GHQ). Des associations ont été observées entre le fait d'avoir un score élevé pour le GHQ et certaines caractéristiques du travail (le type d'intervention, le ratio efforts-récompenses de Siegrist, de même que certains aspects organisationnels ou liés à la supervision). 20 % des participants mentionnentaussi souffrir de séquelles psychiques attribuables à des interventions particulièrement diffi ciles sur le plan émotionnel. Les stratégies observées concernent par exemple l'utilisation des ressources disponibles (médecin conseil, collègues, psychologues), différentes stratégies de coping psychologique, des aménagements spontanés des rôles entre collègues, diverses modalités visant à développer/maintenir les compétences.Notre étude confi rme l'importance des problèmes de santé psychique pour des collectifs de professionnels des urgences pré-hospitalières. Notre démarche a aussi permis de constater que ces professionnels ont recours à diverses stratégies pour réguler leur activité de travail. Ces stratégies comportent un potentiel pour la préservation de la santé mentale.

Characterization of cocoa butter and cocoa butter equivalents by bulk and molecular carbon isotope analyses: Implications for vegetable fat quantification in chocolate

The fatty acids from cocoa butters of different origins, varieties, and suppliers and a number of cocoa butter equivalents (Illexao 30-61, Illexao 30-71, Illexao 30-96, Choclin, Coberine, Chocosine-Illipe, Chocosine-Shea, Shokao, Akomax, Akonord, and Ertina) were investigated by bulk stable carbon isotope analysis and compound specific isotope analysis. The interpretation is based on principal component analysis combining the fatty acid concentrations and the bulk and molecular isotopic data. The scatterplot of the two first principal components allowed detection of the addition of vegetable fats to cocoa butters. Enrichment in heavy carbon isotope (C-13) of the bulk cocoa butter and of the individual fatty acids is related to mixing with other vegetable fats and possibly to thermally or oxidatively induced degradation during processing (e.g., drying and roasting of the cocoa beans or deodorization of the pressed fat) or storage. The feasibility of the analytical approach for authenticity assessment is discussed.

Analyses critiques de ľ expression génétique

La question du filtrage de ľinformation génétique dans la cellule est fondamentale. Comment la cellule sélectionne-t-elle, avant de les transformer en RNA puis en protéines, certaines parties bien déterminées de son information génétique? Il ne sera probablement pas possible de donner une explication cohérente du développement embryonnaire, de la différentiation cellulaire et du maintien de ľétat différencie tant que nous n'aurons pas repondu de manière satis-faisante à cette question. Dans un premier chapitre, quelques notions de base concernant ľexpression génétique sont préséntées. Le dogme de flux de ľinformation génétique dans la cellule, DNARNA protéine est valable à la fois pour les procaryotes et les eucaryotes malgré des différences significatives au niveau de la structure et de la régulation des gènes. Contrairement aux génes procaryotes, la plu-part des gènes eucaryotes sont morcelés. Le DNA codant pour une protéine est interrompu par des régions non-codantes dont les transcrits sont éliminés par excision pendant la maturation du RNA messager ultérieurement traduit en protéine. Une grande variété de mécanismes interviennent dans la régulation de ľactivité de ces gènes. Le pouvoir et les limites des méthodes modernes de ľanalyse structurale et fonctionnelle des génes sont discutés dans la deuxième partie de ľarticle. Ľhybridation moléculaire reposant sur la complémentarité des bases azotées des acides nucléiques joue un rôle déterminant dans ľétude de la complexity des génomes et de leur expression. Récemment, ľapplication de la technologie du DNA recombinant et des techniques annexes a permis ľisolement ainsi que la caractérisation de plusieurs génes eucaryotes. La question de ľexpression différentielle de ces génes est actuellement intensément étudiée dans plusieurs systèmes de transcription ayant chacun ses points forts et ses faiblesses. En guise de conclusion, quelques implications de ľessor prodigieux que connaît la génétique moléculaire sont discutées.

An investigation of the potential of DIP-STR markers for DNA mixture analyses

The genetic characterization of unbalanced mixed stains remains an important area where improvement is imperative. In fact, using the standard tools of forensic DNA profiling (i.e., STR markers), the profile of the minor contributor in mixed DNA stains cannot be successfully detected if its quantitative share of DNA is less than 10% of the mixed trace. This is due to the fact that the major contributor's profile "masks" that of the minor contributor. Besides known remedies to this problem, such as Y-STR analysis, a new compound genetic marker that consists of a Deletion/Insertion Polymorphism (DIP) linked to a Short Tandem Repeat (STR) polymorphism, has recently been developed and proposed [1]. These novel markers are called DIP-STR markers. This paper compares, from a statistical and forensic perspective, the potential usefulness of these novel DIP-STR markers (i) with traditional STR markers in cases of moderately unbalanced mixtures, and (ii) with Y-STR markers in cases of female-male mixtures. This is done through a comparison of the distribution of 100,000 likelihood ratio values obtained using each method on simulated mixtures. This procedure is performed assuming, in turn, the prosecution's and the defence's point of view.

Qualitative and Hierarchical Analysis of Protective Factors against Illicit Use of Doping Substances in Athletes Calling a National Anti-Doping Phone-Help Service

Evidence of a sport-specific hierarchy of protective factors against doping would thus be a powerful aid in adapting information and prevention campaigns to target the characteristics of specific athlete groups, and especially those athletes most vulnerable for doping control. The contents of phone calls to a free and anonymous national anti-doping service called 'ecoute dopage' were analysed (192 bodybuilders, 124 cyclists and 44 footballers). The results showed that the protective factors that emerged from analysis could be categorised into two groups. The first comprised 'Health concerns', 'Respect for the law' and 'Doping controls from the environment' and the second comprised 'Doubts about the effectiveness of illicit products, 'Thinking skills' and 'Doubts about doctors'. The ranking of the factors for the cyclists differed from that of the other athletes. The ordering of factors was 1) respect for the law, 2) doping controls from the environment, 3) health concerns 4) doubts about doctors, and 5) doubts about the effectiveness illicit products. The results are analysed in terms of the ranking in each athlete group and the consequences on the athletes' experience and relationship to doping. Specific prevention campaigns are proposed to limit doping behaviour in general and for each sport.

Psychological transformations in kidney transplantation: A prospective qualitative study

The aim of this IRB-approved study was to prospectively analyze psychological transformations in ESRD patients before and after transplantation (KT). Semi-structured interviews were conducted in 30 patients (mean age = 53±10) after their inclusion on the waiting-list (Gr. A). Follow-up interviews were performed 6 months later in 15 patients still awaiting KT (Gr. B6), and in 15 patients 6 months (Gr. C6) and 12 months (Gr. C12) after KT. Qualitative analysis was performed. Gr: A:All patients underlined loss of freedom, 87% devoted much energy to maintain normality, 57% modified medical directives. All reported emotional fragility related to dialysis and loss of quality of life (QOL), negative (43%) or suicidal thoughts (20%). Professional stigma was underlined (26%). Gr: B6:40% reported no change, 60% mentioned increase of illness intrusiveness, 46% dialysis side-effects, 40% communication problems, 33% tension with medical staff and waiting list handling. Fear of emotional breakdown (40%), couple problems (47%) and worsened professional difficulties (20%) were reported. Gr: C6:All patients mentioned improved QOL and freedom recovery (87%). All expressed concerns about possible acute rejection, 73% were anxious about laboratory results, 93% experienced dependence to immunosuppressants, 47% reported difficulties in handling medication, 21% feared to forget them, 47% were concerned about side-effects, 67% had resumed work but medical constraints led to professional tension (40%). Gr: C12:All mentioned recovered QOL. Medical controls were accepted as a routine (87%) and adherence to medication was mandatory (100%). All mentioned the limited long-term graft survival and 47% were anxious about possible return to dialysis, especially younger patients (27%). Positive identity and existential changes were reported (60%). This prospective qualitative study identifies psychological modifications in the course of KT. It provides a basis to adequately address concerns, but it shows also that KT is clearly associated with positive psychological transformations.

Clinical, polysomnographic and genome-wide association analyses of narcolepsy with cataplexy: a European Narcolepsy Network study.

The aim of this study was to describe the clinical and PSG characteristics of narcolepsy with cataplexy and their genetic predisposition by using the retrospective patient database of the European Narcolepsy Network (EU-NN). We have analysed retrospective data of 1099 patients with narcolepsy diagnosed according to International Classification of Sleep Disorders-2. Demographic and clinical characteristics, polysomnography and multiple sleep latency test data, hypocretin-1 levels, and genome-wide genotypes were available. We found a significantly lower age at sleepiness onset (men versus women: 23.74 ± 12.43 versus 21.49 ± 11.83, P = 0.003) and longer diagnostic delay in women (men versus women: 13.82 ± 13.79 versus 15.62 ± 14.94, P = 0.044). The mean diagnostic delay was 14.63 ± 14.31 years, and longer delay was associated with higher body mass index. The best predictors of short diagnostic delay were young age at diagnosis, cataplexy as the first symptom and higher frequency of cataplexy attacks. The mean multiple sleep latency negatively correlated with Epworth Sleepiness Scale (ESS) and with the number of sleep-onset rapid eye movement periods (SOREMPs), but none of the polysomnographic variables was associated with subjective or objective measures of sleepiness. Variant rs2859998 in UBXN2B gene showed a strong association (P = 1.28E-07) with the age at onset of excessive daytime sleepiness, and rs12425451 near the transcription factor TEAD4 (P = 1.97E-07) with the age at onset of cataplexy. Altogether, our results indicate that the diagnostic delay remains extremely long, age and gender substantially affect symptoms, and that a genetic predisposition affects the age at onset of symptoms.

Effect of age on intraoperative cerebrovascular autoregulation and near-infrared spectroscopy-derived cerebral oxygenation.

Background. Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension.Methods. We monitored intraoperative cerebral perfusion in 50 patients aged 18-40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO(2), O(2), and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium).Results. Autoregulation was less efficient in patients aged >65 yr [by 0.10 (SE 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO2, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (SE 0.04; P=0.028)] and increasing MAP [by 0.11 (SE 0.05; P=0.043)].Conclusions. Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.

Staphylococcal biofilm formation on the surface of three different calcium phosphate bone grafts: a qualitative and quantitative in vivo analysis.

Differences in physico-chemical characteristics of bone grafts to fill bone defects have been demonstrated to influence in vitro bacterial biofilm formation. Aim of the study was to investigate in vivo staphylococcal biofilm formation on different calcium phosphate bone substitutes. A foreign-body guinea-pig infection model was used. Teflon cages prefilled with β-tricalcium phosphate, calcium-deficient hydroxyapatite, or dicalcium phosphate (DCP) scaffold were implanted subcutaneously. Scaffolds were infected with 2 × 10(3) colony-forming unit of Staphylococcus aureus (two strains) or S. epidermidis and explanted after 3, 24 or 72 h of biofilm formation. Quantitative and qualitative biofilm analysis was performed by sonication followed by viable counts, and microcalorimetry, respectively. Independently of the material, S. aureus formed increasing amounts of biofilm on the surface of all scaffolds over time as determined by both methods. For S. epidermidis, the biofilm amount decreased over time, and no biofilm was detected by microcalorimetry on the DCP scaffolds after 72 h of infection. However, when using a higher S. epidermidis inoculum, increasing amounts of biofilm were formed on all scaffolds as determined by microcalorimetry. No significant variation in staphylococcal in vivo biofilm formation was observed between the different materials tested. This study highlights the importance of in vivo studies, in addition to in vitro studies, when investigating biofilm formation of bone grafts.

The investigation of deaths in custody: a qualitative analysis of problems and prospects.

The right to be treated humanely when detained is universally recognized. Deficiencies in detention conditions and violence, however, subvert this right. When this occurs, proper medico-legal investigations are critical irrespective of the nature of death. Unfortunately, the very context of custody raises serious concerns over the effectiveness and fairness of medico-legal examinations. The aim of this manuscript is to identify and discuss the practical and ethical difficulties encountered in the medico-legal investigation following deaths in custody. Data for this manuscript come from a larger project on Death in Custody that examined the causes of deaths in custody and the conditions under which these deaths should be investigated and prevented. A total of 33 stakeholders from forensic medicine, law, prison administration or national human rights administration were interviewed. Data obtained were analyzed qualitatively. Forensic experts are an essential part of the criminal justice process as they offer evidence for subsequent indictment and eventual punishment of perpetrators. Their independence when investigating a death in custody was deemed critical and lack thereof, problematic. When experts were not independent, concerns arose in relation to conflicts of interest, biased perspectives, and low-quality forensic reports. The solutions to ensure independent forensic investigations of deaths in custody must be structural and simple: setting binding standards of practice rather than detailed procedures and relying on preexisting national practices as opposed to encouraging new practices that are unattainable for countries with limited resources.