A pitfall in the reconstruction of fibre ODFs using spherical deconvolution of diffusion MRI data

Diffusion weighted ( DW ) MRI facilitates non-invasive quantification of tissue microstructure and, in combination with appropriate signal processing, three-dimensional estimates of fibrous orientation. In recent years, attention has shifted from the diffusion tensor model, which assumes a unimodal Gaussian diffusion displacement profile to recover fibre orientation ( with various well-documented limitations ), towards more complex high angular resolution diffusion imaging ( HARDI ) analysis techniques. Spherical deconvolution ( SD ) approaches assume that the fibre orientation density function ( fODF ) within a voxel can be obtained by deconvolving a ‘common’ single fibre response function from the observed set of DW signals. In practice, this common response function is not known a priori and thus an estimated fibre response must be used. Here the establishment of this single-fibre response function is referred to as ‘calibration’. This work examines the vulnerability of two different SD approaches to inappropriate response function calibration: ( 1 ) constrained spherical harmonic deconvolution ( CSHD )—a technique that exploits spherical harmonic basis sets and ( 2 ) damped Richardson–Lucy ( dRL ) deconvolution—a technique based on the standard Richardson–Lucy deconvolution. Through simulations, the impact of a discrepancy between the calibrated diffusion profiles and the observed ( ‘Target’ ) DW-signals in both single and crossing-fibre configurations was investigated. The results show that CSHD produces spurious fODF peaks ( consistent with well known ringing artefacts ) as the discrepancy between calibration and target response increases, while dRL demonstrates a lower over-all sensitivity to miscalibration ( with a calibration response function for a highly anisotropic fibre being optimal ). However, dRL demonstrates a reduced ability to resolve low anisotropy crossing-fibres compared to CSHD. It is concluded that the range and spatial-distribution of expected single-fibre anisotropies within an image must be carefully considered to ensure selection of the appropriate algorithm, parameters and calibration. Failure to choose the calibration response function carefully may severely impact the quality of any resultant tractography

Expression and Differential Responsiveness of Central Nervous System Glial Cell Populations to the Acute Phase Protein Serum Amyloid A

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-\u3b1 and lipopolysaccaride (LPS). TNF-\u3b1 time-dependently increased Saa1 (but not Saa3) mRNA expression in purified microglia, enriched astrocytes, and OPCs (as did LPS for microglia and astrocytes). Astrocytes depleted of microglia were markedly less responsive to TNF-\u3b1 and LPS, even after re-addition of microglia. Microglia and enriched astrocytes showed complementary Saa1 expression profiles following TNF-\u3b1 or LPS challenge, being higher in microglia with TNF-\u3b1 and higher in astrocytes with LPS. Recombinant human apo-SAA stimulated production of both inflammatory mediators and its own mRNA in microglia and enriched, but not microglia-depleted astrocytes. Co-ultramicronized palmitoylethanolamide/luteolin, an established anti-inflammatory/neuroprotective agent, reduced Saa1 expression in OPCs subjected to TNF-\u3b1 treatment. These last data, together with past findings suggest that co-ultramicronized palmitoylethanolamide/luteolin may be a novel approach in the treatment of inflammatory demyelinating disorders like MS

Значение экспрессии рАКТ1 при диффузной В-крупноклеточной лимфоме

Aim. To evaluate the prognostic value of pAKT1 expression by tumor cells in patients with diffuse large B-cell lymphoma.Materials and methods. The study included 90 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), who were treated at the clinic of Kirov Research Institute of Hematology and Blood Transfusion from 2014 to 2017 and received standard first-line polychemotherapy according to the R-CHOP regimen. Using immunohistochemical and morphometric methods, the relative number of tumor cells expressing pAKT1 was determined. Using the two-sided Fisher’s exact test, the relationship of different levels of marker expression with clinical and laboratory parameters of patients and long-term treatment results was analyzed. The impact of pAKT1 on the risk of an adverse event was assessed using the Cox regression analysis.Results. Overexpression of pAKT1 is associated with unfavorable clinical characteristics of patients with DLBCL, excessive expression of the BCL2 and c-Myc oncoproteins, as well as with low rates of overall and progressive survival. Overexpression of pAKT1 is an independent prognostic factor and statistically significantly affects the risk of an adverse outcome in DLBCL.Conclusion. The degree of pAKT1 expression is an informative criterion that allows to predict the course of diffuse large B-cell lymphoma. It is advisable to use the indicated marker when stratifying patients into risk groups.Цель – оценить прогностическое значение экспрессии рАКТ1 опухолевыми клетками у больных диффузной В-крупноклеточной лимфомой.Материалы и методы. В исследование включены 90 пациентов с впервые диагностированной диффузной В-крупноклеточной лимфомой (ДВККЛ), наблюдавшиеся в клинике института с 2014 по 2017 г. и получавшие стандартную полихимиотерапию первой линии по схеме R-CHOP. С помощью иммуногистохимического и морфометрического методов определено относительное количество экспрессирующих рАКТ1 опухолевых клеток. С помощью точного двухстороннего критерия Фишера проанализирована взаимосвязь различных уровней экспрессии маркера с клинико-лабораторными показателями пациентов и отдаленными результатами лечения. Оценку влияния рАКТ1 на риск наступления неблагоприятного события проводили с помощью регрессионного анализа Кокса.Результаты. Гиперэкспрессия рАКТ1 ассоциирована с неблагоприятными клиническими характеристиками больных диффузной В-крупноклеточной лимфомой, избыточной экспрессией онкобелков BCL2, cMyc, а также низкими показателями общей и беспрогрессивной выживаемости. Гиперэкспрессия рАКТ1 является независимым фактором прогноза и статистически значимо влияет на риск возникновения неблагоприятного исхода при ДВККЛ.Заключение. Степень экспрессии рАКТ1 является информативным критерием, позволяющим прогнозировать течение диффузной В-крупноклеточной лимфомы. Указанный маркер целесообразно использовать при стратификации пациентов на группы риска

Automatic Annotation and Retrieval of Images

Although a variety of techniques have been developed for content-based image retrieval (CBIR), automatic image retrieval by semantics still remains a challenging problem. We propose a novel approach for semantics-based image annotation and retrieval. Our approach is based on the monotonic tree model. The branches of the monotonic tree of an image, termed as structural elements , are classified and clustered based on their low level features such as color, spatial location, coarseness, and shape. Each cluster corresponds to some semantic feature. The category keywords indicating the semantic features are automatically annotated to the images. Based on the semantic features extracted from images, high-level (semantics-based) querying and browsing of images can be achieved. We apply our scheme to analyze scenery features. Experiments show that semantic features, such as sky, building, trees, water wave, placid water, and ground, can be effectively retrieved and located in images.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41397/1/11280_2004_Article_5122908.pd

Key Modulatory Role of Presynaptic Adenosine A 2A

Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1 and D2 receptors, respectively. Adenosine A2A receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2A receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2A receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

Analysis of adverse events and clinical risks of intensive care for critically ill patients

The article is devoted to analysis of adverse events and clinical risks for patients in the department of intensive care and intensive care. It has been shown that the presence of two or more adverse events can be an independent risk factor for mortality (OR = 3,09; 95% DI 1,30 – 7,36; р = 0,039). Risk criticality assessment showed the significance of prolongation of diagnostic measures in patients with sepsis (r = 0,798; р< 0,001) and overload by infusion media (r = 0,672; р = 0,03). A promising method of monitoring and managing clinical risks may be clinical supervision aimed at analyzing incidents.Статья посвящена анализу неблагоприятных событий и клинических рисков для пациентов в отделении реанимации и интенсивной терапии. Показано, что наличие двух или более неблагоприятных событий может являться независимым фактором риска смертности (OR = 3,09; 95% ДИ 1,30 – 7,36; р = 0,039). Оценка критичности рисков показала значимость пролонгирования диагностических мероприятий у пациентов с сепсисом (r = 0,798; р < 0,001) и перегрузки инфузионными средами (r = 0,672; р = 0,03). Перспективным методом контроля и управления клиническими рисками может являться клинический надзор, направленный на анализ инцидентов

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; &lt;4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Electron-beam Calibration of Aerogel Tiles for the HELIX RICH Detector

The HELIX cosmic-ray detector is a balloon-borne instrument designed to measure the flux of light isotopes in the energy range from 0.2 GeV/n to beyond 3 GeV/n. It will rely on a ring-imaging Cherenkov (RICH) detector for particle identification at energies greater than 1 GeV/n and will use aerogel tiles with refractive index near 1.15 as the radiator. To achieve the performance goals of the experiment it is necessary to know the refractive index and its position dependence over the lateral extent of the tiles to a precision of O(10$^{-4}). In this paper we describe the apparatus and methods developed to calibrate the HELIX tiles in an electron beam, in order to meet this requirement.Comment: 27 pages and 16 figures. Accepted for publication in Nuclear Instruments and Methods