A PET-CT study on neuroinflammation in Huntington’s disease patients participating in a randomized trial with laquinimod

Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington's disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, 11C-PBR28 PET-CT imaging can be used to assess the state of regional gliosis in vivo and explore the effects of laquinimod treatment. This study relates to the LEGATO-HD, multi-centre, double-blinded, Phase 2 clinical trial with laquinimod (US National Registration: NCT02215616). Fifteen patients of the UK LEGATO-HD cohort (mean age: 45.2 ± 7.4 years; disease duration: 5.6 ± 3.0 years) were treated with laquinimod (0.5 mg, N = 4; 1.0 mg, N = 6) or placebo (N = 5) daily. All participants had one 11C-PBR28 PET-CT and one brain MRI scan before laquinimod (or placebo) and at the end of treatment (12 months apart). PET imaging data were quantified to produce 11C-PBR28 distribution volume ratios. These ratios were calculated for the caudate and putamen using the reference Logan plot with the corpus callosum as the reference region. Partial volume effect corrections (Müller-Gartner algorithm) were applied. Differences were sought in Unified Huntington's Disease Rating Scale scores and regional distribution volume ratios between baseline and follow-up and between the two treatment groups (laquinimod versus placebo). No significant change in 11C-PBR28 distribution volume ratios was found post treatment in the caudate and putamen for both those treated with laquinimod (N = 10) and those treated with placebo (N = 5). Over time, the patients treated with laquinimod did not show a significant clinical improvement. Data from the 11C-PBR28 PET-CT study indicate that laquinimod may not have affected regional translocator protein expression and clinical performance over the studied period

Complement Inhibition Promotes Endogenous Neurogenesis and Sustained Anti-Inflammatory Neuroprotection following Reperfused Stroke

The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points.To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA).Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point.Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke

Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI): A Prospective Longitudinal Observational Study

BACKGROUND: Current classification of traumatic brain injury (TBI) is suboptimal, and management is based on weak evidence, with little attempt to personalize treatment. A need exists for new precision medicine and stratified management approaches that incorporate emerging technologies. OBJECTIVE: To improve characterization and classification of TBI and to identify best clinical care, using comparative effectiveness research approaches. METHODS: This multicenter, longitudinal, prospective, observational study in 22 countries across Europe and Israel will collect detailed data from 5400 consenting patients, presenting within 24 hours of injury, with a clinical diagnosis of TBI and an indication for computed tomography. Broader registry-level data collection in approximately 20 000 patients will assess generalizability. Cross sectional comprehensive outcome assessments, including quality of life and neuropsychological testing, will be performed at 6 months. Longitudinal assessments will continue up to 24 months post TBI in patient subsets. Advanced neuroimaging and genomic and biomarker data will be used to improve characterization, and analyses will include neuroinformatics approaches to address variations in process and clinical care. Results will be integrated with living systematic reviews in a process of knowledge transfer. The study initiation was from October to December 2014, and the recruitment period was for 18 to 24 months. EXPECTED OUTCOMES: Collaborative European NeuroTrauma Effectiveness Research in TBI should provide novel multidimensional approaches to TBI characterization and classification, evidence to support treatment recommendations, and benchmarks for quality of care. Data and sample repositories will ensure opportunities for legacy research. DISCUSSION: Comparative effectiveness research provides an alternative to reductionistic clinical trials in restricted patient populations by exploiting differences in biology, care, and outcome to support optimal personalized patient management

Modelling of temperature field in cold bridge by means of boundary element method

W artykule przedstawiono numeryczne modelowanie pól temperatury wybranych przykładów mostków cieplnych przy wykorzystaniu metody elementów brzegowych. W artykule pokazano, że obszary wielospójne, jakimi są rozpatrywane przegrody złożone w postaci mostków cieplnych mogą być skutecznie analizowane przy wykorzystaniu metody, która bardzo szybko się rozwija na świecie – metody elementów brzegowych. Artykuł jest próbą zaprezentowania, że do tego typu zagadnień metoda ta może być metodą konkurencyjną w stosunku do metod siatkowych takich jak metoda różnic skończonych, metoda elementów skończonych oraz metoda objętości skończonych.In the paper the model of temperature field in cold bridge is discussed using Boundary Element Method. The equations describing the steady heat conduction problem in cold bridge have been solved. Presented examples show efficiency of Boundary Element Method modelling in cold bridge in comparison with mesh method as Finite Difference Method, Finite Element Method or Finite Volume Method

Modeling and simulation of Boundary Element Method to temperature field in cold bridge

In the paper the model of temperature field in cold bridge is discussed using Boundary Element Method. The equations describing the steady heat conduction problem in cold bridge have been solved. Presented examples show efficiency of Boundary Element Method modeling in cold bridge in comparison with mesh method as Finite Difference Method, Finite Element Method or Finite Volume Method

Application Boundary Element Method to the analysis of groundwater flow

W pracy przedstawiono zastosowanie metody elementów brzegowych (MEB) w płaskim ruchu filtracyjnym wód gruntowych. W celu wykonania symulacji napisano autorski program obliczeniowy „Ground Flow 2D”. Walidacja zaimplementowanego algorytmu została przeprowadzona w oparciu o równomierną filtrację ciśnieniową. W publikacji przedstawiono przykłady obliczeniowe ruchu wód gruntowych, dla których nie są znane rozwiązania analityczne.The paper deals with modeling of groundwater flow using Boundary Element Method. This algorithm can be used to simulation laminar flow in ground with constant hydraulic conductivity. The efficiency and the credibility of proposed algorithm were verified by numerical tests and were compared with analytical solution. Results of numerical examples are presented. Computer program „Ground Flow 2D” was written in Fortran programming languages

Simulation of the streamlines of Stokes flow using Boundary Integral Equation Method

Opracowanie zawiera zaproponowany algorytm wyznaczania linii prądu w przepływach Stokes’a metodą brzegowych równań całkowych. W celu walidacji metody elementów brzegowych porównano rozwiązania metodą brzegowych równań całkowych ze znanym eksperymentem. Przedstawiony algorytm może być wykorzystany do wyznaczania linii prądu w płaskich przepływach Stokes’a w różnych dziedzinach techniki. W prezentowanej pracy przedstawiono przykładowe graficzne rezultaty obliczeń dla wybranych przykładów, dla których nie są znane rozwiązania analityczne. Algorytm został zaimplementowany w autorskim programie obliczeniowym napisanym w języku Fortran.In this article it has been introduced the way to calculate streamlines of Stokes flow using Boundary Integral Equation Method. The algorithm was verified using a known experiment S. Taneda. The computer program was written in Fortran programming language. The algorithm BEM enables very effective solving of test and practical problems in engineering and can be alternative to mesh methods like Finite Difference Method, Finite Volume Method or Finite Element Method. A numerical examples were presented

Computer simulation of heat transfer in walls with hot water installations using Boundary Element Method

W artykule omówiono modelowanie przenikania ciepła w przegrodach budowlanych, przez które przechodzą przewody ciepłej wody użytkowej. Algorytm został oparty na metodzie brzegowych równań całkowych. W publikacji przedstawiono praktyczny przykład zastosowania metody, w którym obliczono pole temperatury oraz rozkład gęstości strumienia ciepła dla przewodu c.w.u. izolowanego termicznie oraz dla przewodu bez izolacji termicznej. W pracy wyznaczono błąd metody brzegowych równań całkowych. Do analiz opracowano oprogramowanie w języku Fortran.The paper presents the numerical simulation of heat transfer in walls with hot water installations using Boundary Element Method in two dimensional problem. The efficiency and the credibility of proposed algorithm were verified by numerical tests and were compared with thermogram. This algorithm can be used to project increase efficiency a hot water transport in system pipe. A numerical examples are presented. Computer programs are written in Fortran programming languages

Estimation of risk of surface condensation at staircase wall with BEM

W pracy przeprowadzono symulację rozkładu temperatury w miejscu połączenia ściany klatki schodowej ze stropem w wariancie z izolacją i bez izolacji w celu określenia ryzyka wystąpienia powierzchniowej kondensacji pary wodnej i określenia zasadności izolacji ścian pomiędzy klatką schodową a lokalem mieszkalnym. Przyjęto różne wartości temperatury oraz wilgotności względnej powietrza wewnętrznego. Obliczenia wykonano za pomocą autorskiego programu komputerowego wykorzystującego algorytm MEB do rozwiązania ustalonego procesu przewodzenia ciepła w obszarach wielospójnych.In the paper, the temperature distribution in staircase wall – floor junction is determined in order to estimate the risk of surface condensation both with the necessity of insulation of staircase wall. The results were achieved for wall with and without insulation and for various conditions of inner temperature and relative humidity. The simulation was performed with the use of authoring program, assigned for solving the steady heat transfer problems in multi-regions