A photometric study of Be stars located in the seismology fields of COROT

Context. In preparation for the COROT mission, an exhaustive photometric study of Be stars located in the seismology fields of the mission has been performed. The very precise and long-time-spanned photometric observations gathered by the COROT satellite will give important clues on the origin of the Be phenomenon. Aims. The aim of this work is to find short-period variable Be stars located in the seismology fields of COROT, and to study and characterise their pulsational properties. Methods. Light curves obtained at the Observatorio de Sierra Nevada, together with data from Hipparcos and ASAS-3 for a total of 84 Be stars, were analysed in order to search for short-term variations. We applied standard Fourier techniques and non-linear least-square fitting to the time series. Results. We found 7 multiperiodic, 21 mono-periodic and 26 non-variable Be stars. Short-term variability was detected in 74% of early-type Be stars and in 31% of mid- to late-type Be stars. We show that non-radial pulsations are more frequent among Be stars than in slow-rotating B stars of the same spectral [email protected]; [email protected]

New Vesicle-polymer Hybrids: the parachute architecture

The influence of organized media on polymerization reactions results in many cases in interesting morphologies of the polymeric material. In the present study, vesicle bilayers were used as ordered medium for the free radical polymerization of styrene. Cryo-electron microscopy gives evidence that the polymerization induces phase-separation phenomena leading to parachute-like morphologies. On the basis of general knowledge about vesicles and polymerizations in heterogeneous media, explanations for the observed phenomena are given. Bearing in mind that vesicles are outstanding models for membrane mimetic chemistry, it becomes evident that these findings can be relevant to the investigation of, for example, membrane−protein interactions

Neurodegenerative and functional signatures of the cerebellar cortex in m.3243A \u3e G patients

Mutations of the mitochondrial DNA are an important cause of inherited diseases that can severely affect the tissue\u27s homeostasis and integrity. The m.3243A \u3e G mutation is the most commonly observed across mitochondrial disorders and is linked to multisystemic complications, including cognitive deficits. In line with in vitro experiments demonstrating the m.3243A \u3e G\u27s negative impact on neuronal energy production and integrity, m.3243A \u3e G patients show cerebral grey matter tissue changes. However, its impact on the most neuron dense, and therefore energy-consuming brain structure - the cerebellum - remains elusive. In this work, we used high-resolution structural and functional data acquired using 7 T MRI to characterize the neurodegenerative and functional signatures of the cerebellar cortex in m.3243A \u3e G patients. Our results reveal altered tissue integrity within distinct clusters across the cerebellar cortex, apparent by their significantly reduced volume and longitudinal relaxation rate compared with healthy controls, indicating macroscopic atrophy and microstructural pathology. Spatial characterization reveals that these changes occur especially in regions related to the frontoparietal brain network that is involved in information processing and selective attention. In addition, based on resting-state functional MRI data, these clusters exhibit reduced functional connectivity to frontal and parietal cortical regions, especially in patients characterized by (i) a severe disease phenotype and (ii) reduced information-processing speed and attention control. Combined with our previous work, these results provide insight into the neuropathological changes and a solid base to guide longitudinal studies aimed to track disease progression

Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study

One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N = 22) and healthy controls (N = 15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T1, T2* and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T1, T2* and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes

Technical design and performance of the NEMO3 detector

The development of the NEMO3 detector, which is now running in the Frejus Underground Laboratory (L.S.M. Laboratoire Souterrain de Modane), was begun more than ten years ago. The NEMO3 detector uses a tracking-calorimeter technique in order to investigate double beta decay processes for several isotopes. The technical description of the detector is followed by the presentation of its performance.Comment: Preprint submitted to Nucl. Instrum. Methods A Corresponding author: Corinne Augier ([email protected]

Phase I/II Clinical Trial-Based Early Economic Evaluation of Acalabrutinib for Relapsed Chronic Lymphocytic Leukaemia

Objectives: The objective of this study was to construct an early economic evaluation for acalabrutinib for relapsed chronic lymphocytic leukaemia (CLL) to assist early reimbursement decision making. Scenarios were assessed to find the relative impact of critical parameters on incremental costs and quality-adjusted life-years (QALYs). Methods: A partitioned survival model was constructed comparing acalabrutinib and ibrutinib from a UK national health service perspective. This model included states for progression-free survival (PFS), post-progression survival (PPS) and death. PFS and overall survival (OS) were parametrically extrapolated from ibrutinib publications and a preliminary hazard ratio based on phase I/II data was applied for acalabrutinib. Deterministic and probabilistic sensitivity analyses were performed, and 1296 scenarios were assessed. Results: The base-case inc

Reporting of quality attributes in scientific publications presenting biosimilarity assessments of (intended) biosimilars: a systematic literature review

Last years, more than 46 unique biosimilars were approved by EMA and/or US-FDA following patent expiration of reference products. Biosimilars are not identical like generics, but highly similar versions where demonstrating biosimilarity of quality attributes (QAs) to a reference product is the basis of development and regulatory approval. Information on QAs assessed to establish biosimilarity may not always be publicly available, although this information is imperative to understand better the science behind biosimilars approval. This study aims to identify QA types reported in publications presenting biosimilarity assessments of (intended) biosimilars over time. English full-text publications presenting biosimilarity assessments of QAs for (intended) biosimilars between 2000 and 2019 identified from PubMed and EMBASE. Publication characteristics and QAs classified into: structural (physicochemical properties, primary structure, higher-order structures (HOSs), post-translational modifications (PTMs), and purity and impurities) and functional (biological and immunochemical activities) were extracted from publications. Seventy-nine publications were identified (79% open-access, 75% industry-sponsored, 62% including unapproved biosimilars, and 66% involving antibodies). Reporting frequencies varied for QA types: biological activity (94%), physicochemical properties (81%), PTMs (79%), primary structure (77%) purity and impurities (73%), HOSs (58%), and immunochemical activity (41%). The number of publications increased from 6 (7%) during 2009–2011 to 62 (79%) during 2015–2019. Eighteen (28%) publications reported all QA types relevant to an active-biological-substance. Reporting of most QA types increased over time that most evidenced by immunochemical activity (from 0% to 47%) which occured after EMA monoclona