Predicting the outcome of post-anoxic comatose patients based on single-trial EEG analysis

Les maladies cardio-vasculaires représentent la première cause de mortalité en Suisse. Après un arrêt cardio-respiratoire, une minorité des patients survit sans ou avec peu de séquelles fonctionnelles. L'évaluation du pronostic se fait classiquement selon des critères établis par l'Académie Américaine de Neurologie (AAN) en 2006, soit précédant l'introduction de l'hypothermie thérapeutique. Depuis, ces critères semblent insuffisants, et de nouveaux examens para-cliniques sont nécessaires afin d'identifier les patients ayant un pronostic favorable. La détection d'irrégularités auditives, et plus particulièrement l'évolution de cette détection sur plusieurs jours, pourrait être un indicateur du pronostic de patients comateux suite à une anoxie cérébrale. En effet, lors d'une violation de la régularité établie par des séries de sons identiques, deux signaux sont détectables à l'électro- encéphalographie (EEG). Le premier, dénommé «Mismatch negativity» (MMN), peut être enregistré après une violation locale d'une régularité établie au niveau de chaque son. Il reflète un processus inconscient et ne demandant pas de ressources attentionnelles. Le deuxième, dénommé « complexe P300 » survient par contre après une violation globale d'une régularité établie au niveau de groupes de sons. La littérature actuelle indique que ce deuxième phénomène requerrait la présence de capacités attentionnelles. Dans notre étude, nous avons testé l'existence de cette détection d'irrégularités auditives globales chez des patients dans une phase précoce de coma post-anoxique, sous hypothermie thérapeutique. Nous avons enregistré la réponse électro-encéphalographique lors de violations de régularités auditives globales, à l'aide d'un protocole expérimental qui intégrait en plus un paradigme de MMN classique, afin de tester la détection d'irrégularités auditives locales également. Notre analyse finale inclut 24 patients comateux ayant subi un arrêt cardio-respiratoire, et bénéficié du protocole hypothermie du Centre Hospitalier Universitaire Vaudois (CHUV) à Lausanne. Après une analyse multivariée des réponses électro-encéphalographiques de chaque tracé individuellement (« single-trial »), nous avons trouvé que 8 patients sur 24 pouvaient discriminer une irrégularité globale, alors qu'étant définis comateux selon l'échelle de Glasgow (GCS). De plus, l'amélioration de la détection d' irrégularités auditives entre deux EEG consécutifs (en hypo- puis normothermie), était un facteur de bon pronostic. Notre test pourrait ainsi être un complément para-clinique dans l'évaluation du pronostic de patients en coma post- anoxique.

Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes.

Myc controls the metabolic reprogramming that supports effector T cell differentiation. The expression of Myc is regulated by the T cell antigen receptor (TCR) and pro-inflammatory cytokines such as interleukin-2 (IL-2). We now show that the TCR is a digital switch for Myc mRNA and protein expression that allows the strength of the antigen stimulus to determine the frequency of T cells that express Myc. IL-2 signalling strength also directs Myc expression but in an analogue process that fine-tunes Myc quantity in individual cells via post-transcriptional control of Myc protein. Fine-tuning Myc matters and is possible as Myc protein has a very short half-life in T cells due to its constant phosphorylation by glycogen synthase kinase 3 (GSK3) and subsequent proteasomal degradation. We show that Myc only accumulates in T cells exhibiting high levels of amino acid uptake allowing T cells to match Myc expression to biosynthetic demands. The combination of digital and analogue processes allows tight control of Myc expression at the population and single cell level during immune responses.

Tailoring the surface density of silicon nanocrystals embedded in SiOx single layers

In this article, we explore the possibility of modifying the silicon nanocrystal areal density in SiOx single layers, while keeping constant their size. For this purpose, a set of SiOx monolayers with controlled thickness between two thick SiO2 layers has been fabricated, for four different compositions (x=1, 1.25, 1.5, or 1.75). The structural properties of the SiO x single layers have been analyzed by transmission electron microscopy (TEM) in planar view geometry. Energy-filtered TEM images revealed an almost constant Si-cluster size and a slight increase in the cluster areal density as the silicon content increases in the layers, while high resolution TEM images show that the size of the Si crystalline precipitates largely decreases as the SiO x stoichiometry approaches that of SiO2. The crystalline fraction was evaluated by combining the results from both techniques, finding a crystallinity reduction from 75% to 40%, for x = 1 and 1.75, respectively. Complementary photoluminescence measurements corroborate the precipitation of Si-nanocrystals with excellent emission properties for layers with the largest amount of excess silicon. The integrated emission from the nanoaggregates perfectly scales with their crystalline state, with no detectable emission for crystalline fractions below 40%. The combination of the structural and luminescence observations suggests that small Si precipitates are submitted to a higher compressive local stress applied by the SiO2 matrix that could inhibit the phase separation and, in turn, promotes the creation of nonradiative paths.

Spatial mapping of exciton lifetimes in single ZnO nanowires

We investigate the spatial dependence of the exciton lifetimes in single ZnO nanowires. We have found that the free exciton and bound exciton lifetimes exhibit a maximum at the center of nanowires, while they decrease by 30% towards the tips. This dependence is explained by considering the cavity-like properties of the nanowires in combination with the Purcell effect. We show that the lifetime of the bound-excitons scales with the localization energy to the power of 3/2, which validates the model of Rashba and Gurgenishvili at the nanoscale.

Dynamic single cell measurements of kinase activity by synthetic kinase activity relocation sensors.

BACKGROUND: Mitogen activated protein kinases (MAPK) play an essential role in integrating extra-cellular signals and intra-cellular cues to allow cells to grow, adapt to stresses, or undergo apoptosis. Budding yeast serves as a powerful system to understand the fundamental regulatory mechanisms that allow these pathways to combine multiple signals and deliver an appropriate response. To fully comprehend the variability and dynamics of these signaling cascades, dynamic and quantitative single cell measurements are required. Microscopy is an ideal technique to obtain these data; however, novel assays have to be developed to measure the activity of these cascades. RESULTS: We have generated fluorescent biosensors that allow the real-time measurement of kinase activity at the single cell level. Here, synthetic MAPK substrates were engineered to undergo nuclear-to-cytoplasmic relocation upon phosphorylation of a nuclear localization sequence. Combination of fluorescence microscopy and automated image analysis allows the quantification of the dynamics of kinase activity in hundreds of single cells. A large heterogeneity in the dynamics of MAPK activity between individual cells was measured. The variability in the mating pathway can be accounted for by differences in cell cycle stage, while, in the cell wall integrity pathway, the response to cell wall stress is independent of cell cycle stage. CONCLUSIONS: These synthetic kinase activity relocation sensors allow the quantification of kinase activity in live single cells. The modularity of the architecture of these reporters will allow their application in many other signaling cascades. These measurements will allow to uncover new dynamic behaviour that previously could not be observed in population level measurements.

Regression-based techniques for statistical decision making in single-case designs

The present study evaluates the performance of four methods for estimating regression coefficients used to make statistical decisions regarding intervention effectiveness in single-case designs. Ordinary least squares estimation is compared to two correction techniques dealing with general trend and one eliminating autocorrelation whenever it is present. Type I error rates and statistical power are studied for experimental conditions defined by the presence or absence of treatment effect (change in level or in slope), general trend, and serial dependence. The results show that empirical Type I error rates do not approximate the nominal ones in presence of autocorrelation or general trend when ordinary and generalized least squares are applied. The techniques controlling trend show lower false alarm rates, but prove to be insufficiently sensitive to existing treatment effects. Consequently, the use of the statistical significance of the regression coefficients for detecting treatment effects is not recommended for short data series.

Correcting surface coil excitation inhomogeneities in single-shot SPEN MRI.

Given their high sensitivity and ability to limit the field of view (FOV), surface coils are often used in magnetic resonance spectroscopy (MRS) and imaging (MRI). A major downside of surface coils is their inherent radiofrequency (RF) B1 heterogeneity across the FOV, decreasing with increasing distance from the coil and giving rise to image distortions due to non-uniform spatial responses. A robust way to compensate for B1 inhomogeneities is to employ adiabatic inversion pulses, yet these are not well adapted to all imaging sequences - including to single-shot approaches like echo planar imaging (EPI). Hybrid spatiotemporal encoding (SPEN) sequences relying on frequency-swept pulses provide another ultrafast MRI alternative, that could help solve this problem thanks to their built-in heterogeneous spatial manipulations. This study explores how this intrinsic SPEN-based spatial discrimination, could be used to compensate for the B1 inhomogeneities inherent to surface coils. Experiments carried out in both phantoms and in vivo rat brains demonstrate that, by suitably modulating the amplitude of a SPEN chirp pulse that progressively excites the spins in a direction normal to the coil, it is possible to compensate for the RF transmit inhomogeneities and thus improve sensitivity and image fidelity.

Elastic properties and secondary structure formation of single-stranded DNA at monovalent and divalent salt conditions

Single-stranded DNA (ssDNA) plays a major role in several biological processes. It is therefore of fundamental interest to understand how the elastic response and the formation of secondary structures are modulated by the interplay between base pairing and electrostatic interactions. Here we measure force-extension curves (FECs) of ssDNA molecules in optical tweezers set up over two orders of magnitude of monovalent and divalent salt conditions, and obtain its elastic parameters by fitting the FECs to semiflexible models of polymers. For both monovalent and divalent salts, we find that the electrostatic contribution to the persistence length is proportional to the Debye screening length, varying as the inverse of the square root of cation concentration. The intrinsic persistence length is equal to 0.7 nm for both types of salts, and the effectivity of divalent cations in screening electrostatic interactions appears to be 100-fold as compared with monovalent salt, in line with what has been recently reported for single-stranded RNA. Finally, we propose an analysis of the FECs using a model that accounts for the effective thickness of the filament at low salt condition and a simple phenomenological description that quantifies the formation of non-specific secondary structure at low forces.

Single centre experience of the application of self navigated 3D whole heart cardiovascular magnetic resonance for the assessment of cardiac anatomy in congenital heart disease.

BACKGROUND: For free-breathing cardiovascular magnetic resonance (CMR), the self-navigation technique recently emerged, which is expected to deliver high-quality data with a high success rate. The purpose of this study was to test the hypothesis that self-navigated 3D-CMR enables the reliable assessment of cardiovascular anatomy in patients with congenital heart disease (CHD) and to define factors that affect image quality. METHODS: CHD patients ≥2 years-old and referred for CMR for initial assessment or for a follow-up study were included to undergo a free-breathing self-navigated 3D CMR at 1.5T. Performance criteria were: correct description of cardiac segmental anatomy, overall image quality, coronary artery visibility, and reproducibility of great vessels diameter measurements. Factors associated with insufficient image quality were identified using multivariate logistic regression. RESULTS: Self-navigated CMR was performed in 105 patients (55% male, 23 ± 12y). Correct segmental description was achieved in 93% and 96% for observer 1 and 2, respectively. Diagnostic quality was obtained in 90% of examinations, and it increased to 94% if contrast-enhanced. Left anterior descending, circumflex, and right coronary arteries were visualized in 93%, 87% and 98%, respectively. Younger age, higher heart rate, lower ejection fraction, and lack of contrast medium were independently associated with reduced image quality. However, a similar rate of diagnostic image quality was obtained in children and adults. CONCLUSION: In patients with CHD, self-navigated free-breathing CMR provides high-resolution 3D visualization of the heart and great vessels with excellent robustness.

CTP in Transient Global Amnesia: A Single-Center Experience of 30 Patients.

BACKGROUND AND PURPOSE: Medial temporal lobe abnormalities on DWI and functional imaging are occasionally observed in patients with transient global amnesia. We used CTP to study these patients during or briefly after resolution of their amnesic syndrome. MATERIALS AND METHODS: From 2002 onward, patients satisfying clinical criteria for transient global amnesia who underwent CTP were included. Patients with additional clinical features suggesting transient ischemic attack or stroke and those with an ischemic lesion on subsequent DWI were excluded. If deemed necessary by the clinician, DWI was performed within 10 days. RESULTS: Thirty patients with transient global amnesia underwent CTP at a median latency of 5.9 hours (interquartile range, 4.3-9.7 hours) after symptom onset. All findings, except for those in 1 patient, were normal, including those in the 14 patients with well-imaged hippocampi. In the patient with abnormal findings, CTP and PWI showed hypoperfusion in both lentiform nuclei extending into the insulae, with normalization on the repeat CTP 6 days later. In 10 patients, DWI was performed at a median latency of 2 days (interquartile range, 0-9 days). Of these, 2 showed punctate hippocampal lesions, often seen in transient global amnesia. In 2 patients excluded because of mildly atypical transient global amnesia and ischemic lesions on subsequent DWI, acute CTP findings were also normal. CONCLUSIONS: Patients with transient global amnesia had normal CTP findings in the acute phase with the exception of 1 patient with transient hypoperfusion in both basal ganglia. If imaging is performed for typical and atypical transient global amnesia, DWI should be the preferred method.

1.84 micron emission of Tm3+ sensitized by Yb3+ ions in monoclinic KGd(WO4)2 single crystals

By exciting at 940 nm, we have characterized the 1.84 m near infrared emission of trivalent thulium ions in Yb3+, Tm3+:KGd WO4 2 single crystals as a function of the dopant concentration and temperature, from 10 K to room temperature. An overall 3H6 Stark splitting of 470 cm−1 for the Tm3+ ions in the Yb3+, Tm3+:KGd WO4 2 was obtained. We also studied the blue emission at 476 nm Tm3+ and the near infrared emissions at 1.48 m Tm3+ and 1 m Yb3+ as a function of the dopant concentration. Experimental decay times of the 1G4, 3H4, and 3F4 Tm3+ and 2F5/2 Yb3+ excited states have been measured as a function of Yb3+ and Tm3+ ion concentrations. For the 3F4 →3H6 transition of Tm3+ ions, we used the reciprocity method to calculate the maximum emission cross section of 3.07 10−20 cm2 at 1.84 m for the polarization parallel to the Nm principal optical direction.

Clinical utility of a molecular test in adjuvant treatment decision making in women with endocrine-sensitive early stage breast cancer: a retrospective, single center one year experience

Background. Molecular tests for breast cancer (BC) risk assessment are reimbursed by health insurances in Switzerland since the beginning of year 2015. The main current role of these tests is to help oncologists to decide about the usefulness of adjuvant chemotherapy in patients with early stage endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)-negative BC. These gene expression signatures aim at predicting the risk of recurrence in this subgroup. One of them (OncotypeDx/OT) also predicts distant metastases rate with or without the addition of cytotoxic chemotherapy to endocrine therapy. The clinical utility of these tests -in addition to existing so-called "clinico-pathological" prognostic and predictive criteria (e.g. stage, grade, biomarkers status)-is still debated. We report a single center one year experience of the use of one molecular test (OT) in clinical decision making. Methods. We extracted from the CHUV Breast Cancer Center data base the total number of BC cases with estrogen-receptor positive (ER+), HER2-negative early breast cancer (node negative (pN0) disease or micrometastases in up to 3 lymph nodes) operated between September 2014 and August 2015. For the cases from this group in which a molecular test had been decided by the tumor board, we collected the clinicopathologic parameters, the initial tumor board decision, and the final adjuvant systemic therapy decision. Results. A molecular test (OT) was done in 12.2% of patients with ER + HER2 negative early BC. The median age was 57.4 years and the median invasive tumor size was 1.7 cm. These patients were classified by ODX testing (Recurrence Score) into low-, intermediate-, and high risk groups, respectively in 27.2%, 63.6% and 9% of cases. Treatment recommendations changed in 18.2%, predominantly from chemotherapyendocrine therapy to endocrine treatment alone. Of 8 patients originally recommended chemotherapy, 25% were recommended endocrine treatment alone after receiving the Recurrence Score result. Conclusions. Though reimbursed by health insurances since January 2015, molecular tests are used moderately in our institution as per the decision of the multidisciplinary tumor board. It's mainly used to obtain a complementary confirmation supporting the decision of no chemotherapy. The OncotypeDx Recurrence Score results were in the intermediate group in 66% of the 9 tested cases but contributed to avoid chemotherapy in 2 patients during the last 12 months.