Prognostic Implication of Preoperative Behavior Changes in Patients with Primary High-Grade Meningiomas

High-grade meningiomas are rare extra-axial tumors, frequently causing brain invasion and prominent brain edema. Patients harboring high-grade meningiomas occasionally present with behavior changes. Data about frequency and prognostic importance of preoperative behavior changes in patients with high-grade meningiomas is missing. 86 patients with primary high-grade meningiomas were analyzed. Statistical analysis was performed to determine correlation of preoperative behavior changes with tumor location, preoperative brain edema, tumor cleavability, tumor grade, Ki67 proliferation index, and microscopic brain invasion. Survival analysis was performed. 30 (34.9%) patients presented with preoperative behavior changes. These changes were more frequent with male patients (P=0.066) and patients older than 55 years (P=0.018). They correlated with frontal location (P=0.013), tumor size (P=0.023), microscopic brain invasion (P=0.015), and brain edema (P=0.006). Preoperative behavior changes did not correlate with duration of symptoms, tumor cleavability, tumor malignancy grade, and Ki67 proliferation index. They were not significantly related to overall survival or recurrence-free survival of patients with primary high-grade meningiomas. Preoperative behavior changes are frequent in patients harboring primary high-grade meningiomas. They correlate with tumor size, microscopic brain invasion, and brain edema. Preoperative behavior changes do not predict prognosis in patients with primary high-grade meningiomas

Sociology of low expectations: Recalibration as innovation work in biomedicine

"This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm). "Social scientists have drawn attention to the role of hype and optimistic visions of the future in providing momentum to biomedical innovation projects by encouraging innovation alliances. In this article, we show how less optimistic, uncertain, and modest visions of the future can also provide innovation projects with momentum. Scholars have highlighted the need for clinicians to carefully manage the expectations of their prospective patients. Using the example of a pioneering clinical team providing deep brain stimulation to children and young people with movement disorders, we show how clinicians confront this requirement by drawing on their professional knowledge and clinical expertise to construct visions of the future with their prospective patients; visions which are personalized, modest, and tainted with uncertainty. We refer to this vision-constructing work as recalibration, and we argue that recalibration enables clinicians to manage the tension between the highly optimistic and hyped visions of the future that surround novel biomedical interventions, and the exigencies of delivering those interventions in a clinical setting. Drawing on work from science and technology studies, we suggest that recalibration enrolls patients in an innovation alliance by creating a shared understanding of how the “effectiveness” of an innovation shall be judged.This project was funded by the Wellcome Trust (Wellcome Trust Biomedical Strategic Award 086034)

Fluorescence lifetime endoscopy using TCSPC for the measurement of FRET in live cells

Development of remote imaging for diagnostic purposes has progressed dramatically since endoscopy began in the 1960’s. The recent advent of a clinically licensed intensity-based fluorescence micro-endoscopic instrument has offered the prospect of real-time cellular resolution imaging. However, interrogating protein-protein interactions deep inside living tissue requires precise fluorescence lifetime measurements to derive the Förster resonance energy transfer between two tagged fluorescent markers. We developed a new instrument combining remote fiber endoscopic cellular-resolution imaging with TCSPC-FLIM technology to interrogate and discriminate mixed fluorochrome labeled beads and expressible GFP/TagRFP tags within live cells. Endoscopic-FLIM (e-FLIM) data was validated by comparison with data acquired via conventional FLIM and e-FLIM was found to be accurate for both bright bead and dim live cell samples. The fiber based micro-endoscope allowed remote imaging of 4 µm and 10 µm beads within a thick Matrigel matrix with confident fluorophore discrimination using lifetime information. More importantly, this new technique enabled us to reliably measure protein-protein interactions in live cells embedded in a 3D matrix, as demonstrated by the dimerization of the fluorescent protein-tagged membrane receptor CXCR4. This cell-based application successfully demonstrated the suitability and great potential of this new technique for in vivo pre-clinical biomedical and possibly human clinical applications

Identification of Immunogenic Proteins of Waddlia chondrophila

Evidence is growing for a role of Waddlia chondrophila as an agent of adverse pregnancy outcomes in both humans and ruminants. This emerging pathogen, member of the order Chlamydiales, is also implicated in bronchiolitis and lower respiratory tract infections. Until now, the serological diagnosis of W. chondrophila infection has mainly relied on manually intensive tests including micro-immunofluorescence and Western blotting. Thus, there is an urgent need to establish reliable high throughput serological assays. Using a combined genomic and proteomic approach, we detected 57 immunogenic proteins of W. chondrophila, of which 17 were analysed by mass spectrometry. Two novel hypothetical proteins, Wim3 and Wim4, were expressed as recombinant proteins in Escherichia coli, purified and used as antigens in an ELISA test. Both proteins were recognized by sera of rabbits immunized with W. chondrophila as well as by human W. chondrophila positive sera but not by rabbit pre-immune sera nor human W. chondrophila negative sera. These results demonstrated that the approach chosen is suitable to identify immunogenic proteins that can be used to develop a serological test. This latter will be a valuable tool to further clarify the pathogenic potential of W. chondrophila

HAT-P-9b: A Low Density Planet Transiting a Moderately Faint F star

We report the discovery of a planet transiting a moderately faint (V=12.3 mag) late F star, with an orbital period of 3.92289 +/- 0.00004 days. From the transit light curve and radial velocity measurements we determine that the radius of the planet is R_p = 1.40 +/- 0.06 R_Jup and that the mass is M_p = 0.78 +/- 0.09 M_Jup. The density of the new planet, rho = 0.35 +/- 0.06 g cm^{-3}, fits to the low-density tail of the currently known transiting planets. We find that the center of transit is at T_c = 2454417.9077 +/- 0.0003 (HJD), and the total transit duration is 0.143 +/- 0.004 days. The host star has M_s = 1.28 +/- 0.13 M_Sun and R_s = 1.32 +/- 0.07 R_Sun.Comment: Submitted to ApJ; V2: Replaced with accepted versio

Photometric Follow-up Observations of the Transiting Neptune-Mass Planet GJ 436b

This paper presents multi-band photometric follow-up observations of the Neptune-mass transiting planet GJ 436b, consisting of 5 new ground-based transit light curves obtained in May 2007. Together with one already published light curve we have at hand a total of 6 light curves, spanning 29 days. The analysis of the data yields an orbital period P = 2.64386+-0.00003 days, mid-transit time T_c [HJD] =2454235.8355+-0.0001, planet mass M_p = 23.1+-0.9 M_{\earth} = 0.073+-0.003 M_{Jup}, planet radius R_p = 4.2+-0.2 R_{\earth} = 0.37+-0.01 R_{Jup} and stellar radius R_s = 0.45+-0.02 R_{\sun}. Our typical precision for the mid transit timing for each transit is about 30 seconds. We searched the data for a possible signature of a second planet in the system through transit timing variations (TTV) and variation of the impact parameter. The analysis could not rule out a small, of the order of a minute, TTV and a long-term modulation of the impact parameter, of the order of +0.2 year^{-1}.Comment: V2: Replaced with accepted versio

A Family of variable metric proximal methods

An updated version of this paper has appeared in Mathematical Programming, no 68 (1995), pp. 15-47, DOI 10.1007/BF01585756Nous considérons des méthodes conceptuelles d'optimisation combinant deux idéees : La régularisation de Moreau-Yosida en analyse convexe et les approximations quasi-Newtoniennes des fonctions régulières

Definition of implanted neurological device abandonment: a systematic review and consensus statement

Importance Establishing a formal definition for neurological device abandonment has the potential to reduce or to prevent the occurrence of this abandonment. Objective To perform a systematic review of the literature and develop an expert consensus definition for neurological device abandonment. Evidence Review After a Royal Society Summit on Neural Interfaces (September 13-14, 2023), a systematic English language review using PubMed was undertaken to investigate extant definitions of neurological device abandonment. Articles were reviewed for relevance to neurological device abandonment in the setting of deep brain, vagal nerve, and spinal cord stimulation. This review was followed by the convening of an expert consensus group of physicians, scientists, ethicists, and stakeholders. The group summarized findings, added subject matter experience, and applied relevant ethics concepts to propose a current operational definition of neurological device abandonment. Data collection, study, and consensus development were done between September 13, 2023, and February 1, 2024. Findings The PubMed search revealed 734 total articles, and after review, 7 articles were found to address neurological device abandonment. The expert consensus group addressed findings as germane to neurological device abandonment and added personal experience and additional relevant peer-reviewed articles, addressed stakeholders’ respective responsibilities, and operationally defined abandonment in the context of implantable neurotechnological devices. The group further addressed whether clinical trial failure or shelving of devices would constitute or be associated with abandonment as defined. Referential to these domains and dimensions, the group proposed a standardized definition for abandonment of active implantable neurotechnological devices. Conclusions and Relevance This study’s consensus statement suggests that the definition for neurological device abandonment should entail failure to provide fundamental aspects of patient consent; fulfill reasonable responsibility for medical, technical, or financial support prior to the end of the device’s labeled lifetime; and address any or all immediate needs that may result in safety concerns or device ineffectiveness and that the definition of abandonment associated with the failure of a research trial should be contingent on specific circumstances

Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor

Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma. Their in vivo expansion is often observed with advanced disease. In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen. Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma. Interestingly, this population is oligoclonal and displays a clear memory phenotype. However, a detailed study of these cells indicated that they are unlikely to be directly specific for melanoma, so that their in vivo expansion may have been driven by an exogenous antigen. Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen. Finally, we discuss potential perspectives regarding the role of such cells in heterologous immunity, by influencing the balance between protective immunity and pathology, e.g. in the case of melanoma developmen

Persistence of Monopoly and Research Specialization

We examine the persistence of monopolies in markets with innovations when the outcome of research is uncertain. We show that for low success probabilities of research, the incumbent can seldom preempt the potential entrant. Then the efficiency effect outweighs the replacement effect. It is vice versa for high probabilities. Moreover, the incumbent specializes in safe research and the potential entrant in risky research. We also show that the probability of entry has an inverted U-shape in the success probability. Since even at the peak entry is rather unlikely, the persistence of the monopoly is high