Man Made Black Holes and Big Bangs: Diffusion and Integration of Scientific Information into Everyday Thinking

Drawing on Social Representations Theory, this study investigates focalisation and anchoring during the diffusion of information concerning the Large Hadron Collider (LHC), the particle accelerator at the European Organisation for Nuclear Research (CERN). We hypothesised that people focus on striking elements of the message, abandoning others, that the nature of the initial information affects diffusion of information, and that information is anchored in prior attitudes toward CERN and science. A serial reproduction experiment with two generations and four chains of reproduction diffusing controversial versus descriptive information about the LHC shows a reduction of information through generations, the persistence of terminology regarding the controversy and a decrease of other elements for participants exposed to polemical information. Concerning anchoring, positive attitudes toward CERN and science increase the use of expert terminology unrelated to the controversy. This research highlights the relevance of a social representational approach in the public understanding of science.

Undetectable serum anti-Müllerian hormone levels and occurrence of ongoing pregnancy.

OBJECTIVE: To discuss, on the basis of the experience of two clinical cases and extensive literature review, the significance of extremely low levels of anti-Müllerian hormone (AMH), also known as Müllerian-inhibiting substance, in infertile women. DESIGN: Case report. SETTING: University-based infertility clinic at a medical center in Switzerland. PATIENT(S): Two women, 29 and 41 years of age and with a 2- and 4-year history of secondary infertility, respectively. INTERVENTION(S): Clinical, radiological, and biological investigation of infertility, including repeated measurements of the serum AMH with serial ELISA assays. MAIN OUTCOME MEASURE(S): Levels of AMH and development of ongoing pregnancy. RESULT(S): Both women had a spontaneous ongoing pregnancy despite undetectable AMH levels. CONCLUSION(S): Although it is helpful for day-to-day management of infertile patients, the predictive value of AMH for the occurrence of a spontaneous ongoing pregnancy has limits.

Retinal Dystrophy In The Oculo-auricular Syndrome Due to HMX1 Mutation.

Purpose: To report on the clinical and electrophysiological findings in a patient with oculo-auricular syndrome due to HMX1 mutation, with a follow-up of 12 years. Background: Oculo-auricular syndrome (MIM: 612109) is a rare developmental recessive condition affecting the eye and external ear that results from a mutation in the HMX1 gene. Previously described ocular abnormalities include bilateral microcornea, posterior synechiae, cataract, chorioretinal colobomas and rod-cone dystrophy. Methods: Retrospective chart review of an affected boy followed over a period of 12 years who had serial complete ophthalmologic examinations, fundus photographs, Goldmann perimetry and full-field electroretinograms (ERG). Results: Initial ERG tracings revealed generalized rod more than cone dysfunction. Thereafter, a rapid deterioration in rod and cone function was detected on follow up ERGs. Conclusion: The retinal degeneration in the recessively inherited oculo-auricular syndrome is a progressive rod-cone dystrophy. Visual prognosis is guarded considering the progressive nature of the retinal dystrophy in early infancy.

Noninvasive coronary vessel wall and plaque imaging with magnetic resonance imaging.

BACKGROUND: Conventional x-ray angiography frequently underestimates the true burden of atherosclerosis. Although intravascular ultrasound allows for imaging of coronary plaque, this invasive technique is inappropriate for screening or serial examinations. We therefore sought to develop a noninvasive free-breathing MR technique for coronary vessel wall imaging. We hypothesized that such an approach would allow for in vivo imaging of coronary atherosclerosis. METHODS AND RESULTS: Ten subjects, including 5 healthy adult volunteers (aged 35+/-17 years, range 19 to 56 years) and 5 patients (aged 60+/-4 years, range 56 to 66 years) with x-ray-confirmed coronary artery disease (CAD), were studied with a T2-weighted, dual-inversion, fast spin-echo MR sequence. Multiple adjacent 5-mm cross-sectional images of the proximal right coronary artery were obtained with an in-plane resolution of 0.5x1.0 mm. A right hemidiaphragmatic navigator was used to facilitate free-breathing MR acquisition. Coronary vessel wall images were readily acquired in all subjects. Both coronary vessel wall thickness (1.5+/-0.2 versus 1.0+/-0.2 mm) and wall area (21.2+/-3.1 versus 13.7+/-4.2 mm(2)) were greater in patients with CAD (both P:<0.02 versus healthy adults). CONCLUSIONS: In vivo free-breathing coronary vessel wall and plaque imaging with MR has been successfully implemented in humans. Coronary wall thickness and wall area were significantly greater in patients with angiographic CAD. The presented technique may have potential applications in patients with known or suspected atherosclerotic CAD or for serial evaluation after pharmacological intervention.

Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic.

BACKGROUND: Hepatitis C virus (HCV) infection has a growing impact on morbidity and mortality in patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS). METHODS: HCV infection incidence was assessed from 1998, when routine serial HCV screening was introduced in the SHCS, until 2011. All HCV-seronegative patients with at least 1 follow-up serology were included. Incidence rates (IRs) of HCV infections were compared between men who have sex with men (MSM), injection drug users (IDU), and heterosexuals (HET). RESULTS: HCV incidence was assessed in 3333 MSM, 123 IDU, and 3078 HET with a negative HCV serology at baseline. Over 23 707 person-years (py) for MSM, 733 py for IDU, and 20 752 py for HET, 101 (3%), 41 (33%), and 25 (1%) of patients seroconverted, respectively. The IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py in 1998 to 4.09 (95% CrI, 2.57-6.18) in 2011. The IR decreased in IDU and remained <1 per 100 py in HET. In MSM, history of inconsistent condom use (adjusted hazard ratio [HR], 2.09; 95% CI, 1.33-3.29) and past syphilis (adjusted HR, 2.11; 95% confidence interval [CI], 1.39-3.20) predicted HCV seroconversion. CONCLUSIONS: In the SHCS, HCV infection incidence decreased in IDU, remained stable in HET, and increased 18-fold in MSM in the last 13 years. These observations underscore the need for improved HCV surveillance and prevention among HIV-infected MSM.

Patterns of calcium-binding proteins support parallel and hierarchical organization of human auditory areas.

The human primary auditory cortex (AI) is surrounded by several other auditory areas, which can be identified by cyto-, myelo- and chemoarchitectonic criteria. We report here on the pattern of calcium-binding protein immunoreactivity within these areas. The supratemporal regions of four normal human brains (eight hemispheres) were processed histologically, and serial sections were stained for parvalbumin, calretinin or calbindin. Each calcium-binding protein yielded a specific pattern of labelling, which differed between auditory areas. In AI, defined as area TC [see C. von Economo and L. Horn (1930) Z. Ges. Neurol. Psychiatr.,130, 678-757], parvalbumin labelling was dark in layer IV; several parvalbumin-positive multipolar neurons were distributed in layers III and IV. Calbindin yielded dark labelling in layers I-III and V; it revealed numerous multipolar and pyramidal neurons in layers II and III. Calretinin labelling was lighter than that of parvalbumin or calbindin in AI; calretinin-positive bipolar and bitufted neurons were present in supragranular layers. In non-primary auditory areas, the intensity of labelling tended to become progressively lighter while moving away from AI, with qualitative differences between the cytoarchitectonically defined areas. In analogy to non-human primates, our results suggest differences in intrinsic organization between auditory areas that are compatible with parallel and hierarchical processing of auditory information.

Development and use of a high-fidelity simulator for fetal endotracheal balloon occlusion (FETO) insertion and removal.

Objectives The objective of this article is to describe the development of an anatomically accurate simulator in order to aid the training of a perinatal team in the insertion and removal of a fetal endoscopic tracheal occlusion (FETO) balloon in the management of prenatally diagnosed congenital diaphragmatic hernia. Methods An experienced perinatal team collaborated with a medical sculptor to design a fetal model for the FETO procedure. Measurements derived from 28-week fetal magnetic resonance imaging were used in the development of an anatomically precise simulated airway within a silicone rubber preterm fetal model. Clinician feedback was then used to guide multiple iterations of the model with serial improvements in the anatomic accuracy of the simulator airway. Results An appropriately sized preterm fetal mannequin with a high-fidelity airway was developed. The team used this model to develop surgical skills with balloon insertion, and removal, and to prepare the team for an integrated response to unanticipated delivery with the FETO balloon still in situ. Conclusions This fetal mannequin aided in the ability of a fetal therapy unit to offer the FETO procedure at their center for the first time. This model may be of benefit to other perinatal centers planning to offer this procedure.

Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the photocoagulation site and around it. Confocal microscopy demonstrates that the vessels throughout the path lesion are located within the neuroretina while in the choroid (after separation of the neural retina) only GFAP-positive but no lectin-positive cells can be seen. The involvement of infiltrating inflammatory cells in these remodeling and healing processes remained minimal throughout the study period. During the 4 weeks following krypton laser photocoagulation in the mouse eye, processes of wound healing and remodeling appear to be driven by cells (and vessels) originating from the retina.

Harnessing epithelial stem cell potency

Increase in potency of adult stem/progenitor cells holds great expectations for regenerative medicine; reprogramming is achieved by manipulating the genome or indirectly by manipulating the microenvironment. However, the genetic approach, which can result in lineage conversion up to ground pluripotent embryonic state, will certainly face strict regulatory constraints and consequently translation to the clinic may be difficult. Manipulating stem cell fate without altering the genome of adult stem cells is a promising alternative. My laboratory has demonstrated that non hairy squamous epithelia e.g. the cornea, the oral cavity, the oesophagus, the vagina, contain clonogenic stem cells that can respond to skin morphogenetic signals and form epidermis, cycling hair follicles and sebaceous glands. This capacity is maintained in serial transplantation, crosses primary germ line boundaries and is intrinsic to the stem cells, as cells which have never been exposed to cell culture behave in a similar fashion. Even more surprising, the thymus contains a population of clonogenic epithelial cells of endodermal origin that maintain a thymic identity in culture and have the capacity to incorporate into a thymic network, but can acquire the functionality of bona fide multipotent stem cells of the skin when exposed to proper developmental signals. Thymic epithelial cells exposed to a skin microenvironment exhibit a down-regulation or silencing of transcription factors important for thymic function. Hence, it is possible to reveal unsuspected potency and even to robustly reprogram stem cells by solely manipulating the microenvironment.

In vivo characterization of sunitinib eluting beads

Purpose: To study the pharmacokinetics and potential toxicity of sunitinib eluting beads in an animal modelMaterials: Healthy New-Zealand white rabbits were used. 8 animals received 0.2ml of DC Beads loaded with 6mg of sunitinb intra arterially in the hepatic artery (group 1) and 4 animals received 6mg of sunitinib administered orally (group 2). In group 1, animals were sacrificed 6 hours (n=4) and 24 hours (n=4) after embolization. In group 2, animals were sacrificed 6 hours (n=2) and 24 hours (n=2) after oral administration of sunitinib. Liver enzymes were measured at 0, 6 and 24 hours in both groups. Plasmatic sunitinib concentration was measured by LC MS/MS tandem mass spectroscopy at 0, 1, 2, 3, 4, 5, 6 and 24 hours. At sacrifice, the livers were harvested and sunitinib concentration in liver tissue was assessed by LC MS/MS tandem mass spectroscopy.Results: After embolization we observed an expected elevation of AST and ALT. Serial plasmatic measurments after embolization showed a very low sunitinib concentration (<50ng/ml). Measurment of sunitinib in the embolized liver tissue showed a very high concentration at 6 hours (3870ng/ml) and 24 hours (4741.7ng/ml).Conclusions: Sunitinib eluting beads are well tolerated by rabbits when administered intra-arterially in the hepatic artery. No unexpected toxicity was observed. Very high drug concentration canbe obtained at the site of embolization with minimal systemic passage.

Quantitative Assessment of T1 Relaxation and Diffusion as a Prognostic Tool for Brain Development: A Longitudinal Preliminary Study on Preterm Babies

BACKGROUND: Despite major advances in care of premature infants, survivors exhibit mild cognitive deficits in around 40%. Beside severe intraventricular haemorrhages (IVH) and cystic periventricular leucomalacia (PVL), more subtle patterns such as grade I and II IVH, punctuate WM lesions and diffuse PVL might be linked to the cognitive deficits. Grey matter disease is also recognized to contribute to long-term cognitive impairment.¦OBJECTIVE: We intend to use novel MR techniques to study more precisely the different injury patterns. In particular MP2RAGE (magnetization prepared dual rapid echo gradient) produces high-resolution quantitative T1 relaxation maps. This contrast is known to reflect tissue anomalies such as white matter injury in general and dysmyelination in particular. We also used diffusion tensor imaging, a quantitative technique known to reflect white matter maturation and disease.¦DESIGN/METHODS: All preterm infants born under 30 weeks of GA were included. Serial 3T MR-imaging using a neonatal head-coil at DOL 3, 10 and at term equivalent age (TEA), using DTI and MP2RAGE sequences was performed. MP2RAGE generates a T1 map and allows calculating the relaxation time T1. Multiple measurements were performed for each exam in 12 defined white and grey matter ROIs.¦RESULTS: 16 patients were recruited: mean GA 27 2/7 w (191,2d SD±10,8), mean BW 999g (SD±265). 39 MRIs were realized (12 early: mean 4,83d±1,75, 13 late: mean 18,77d±8,05 and 14 at TEA: 88,91d±8,96). Measures of relaxation time T1 show a gradual and significant decrease over time (for ROI PLIC mean±SD in ms: 2100.53±102,75, 2116,5±41,55 and 1726,42±51,31 and for ROI central WM: 2302,25±79,02, 2315,02±115,02 and 1992,7±96,37 for early, late and TEA MR respectively). These trends are also observed in grey matter area, especially in thalamus. Measurements of ADC values show similar monotonous decrease over time.¦CONCLUSIONS: From these preliminary results, we conclude that quantitative MR imaging in very preterm infants is feasible. On the successive MP2RAGE and DTI sequences, we observe a gradual decrease over time in the described ROIs, representing the progressive maturation of the WM micro-structure and interestingly the same evolution is observed in the grey matter. We speculate that our study will provide normative values for T1map and ADC and might be a predictive factor for favourable or less favourable outcome.

Three essays on liquidity risk

Preface In this thesis we study several questions related to transaction data measured at an individual level. The questions are addressed in three essays that will constitute this thesis. In the first essay we use tick-by-tick data to estimate non-parametrically the jump process of 37 big stocks traded on the Paris Stock Exchange, and of the CAC 40 index. We separate the total daily returns in three components (trading continuous, trading jump, and overnight), and we characterize each one of them. We estimate at the individual and index levels the contribution of each return component to the total daily variability. For the index, the contribution of jumps is smaller and it is compensated by the larger contribution of overnight returns. We test formally that individual stocks jump more frequently than the index, and that they do not respond independently to the arrive of news. Finally, we find that daily jumps are larger when their arrival rates are larger. At the contemporaneous level there is a strong negative correlation between the jump frequency and the trading activity measures. The second essay study the general properties of the trade- and volume-duration processes for two stocks traded on the Paris Stock Exchange. These two stocks correspond to a very illiquid stock and to a relatively liquid stock. We estimate a class of autoregressive gamma process with conditional distribution from the family of non-central gamma (up to a scale factor). This process was introduced by Gouriéroux and Jasiak and it is known as Autoregressive gamma process. We also evaluate the ability of the process to fit the data. For this purpose we use the Diebold, Gunther and Tay (1998) test; and the capacity of the model to reproduce the moments of the observed data, and the empirical serial correlation and the partial serial correlation functions. We establish that the model describes correctly the trade duration process of illiquid stocks, but have problems to adjust correctly the trade duration process of liquid stocks which present long-memory characteristics. When the model is adjusted to volume duration, it successfully fit the data. In the third essay we study the economic relevance of optimal liquidation strategies by calibrating a recent and realistic microstructure model with data from the Paris Stock Exchange. We distinguish the case of parameters which are constant through the day from time-varying ones. An optimization problem incorporating this realistic microstructure model is presented and solved. Our model endogenizes the number of trades required before the position is liquidated. A comparative static exercise demonstrates the realism of our model. We find that a sell decision taken in the morning will be liquidated by the early afternoon. If price impacts increase over the day, the liquidation will take place more rapidly.