Structural magnetic resonance imaging findings and histopathological correlations in motor neuron diseases—A systematic review and meta-analysis

OBJECTIVES The lack of systematic evidence on neuroimaging findings in motor neuron diseases (MND) hampers the diagnostic utility of magnetic resonance imaging (MRI). Thus, we aimed at performing a systematic review and meta-analysis of MRI features in MND including their histopathological correlation. METHODS In a comprehensive literature search, out of 5941 unique publications, 223 records assessing brain and spinal cord MRI findings in MND were eligible for a qualitative synthesis. 21 records were included in a random effect model meta-analysis. RESULTS Our meta-analysis shows that both T2-hyperintensities along the corticospinal tracts (CST) and motor cortex T2$^{*}$-hypointensitites, also called "motor band sign", are more prevalent in ALS patients compared to controls [OR 2.21 (95%-CI: 1.40-3.49) and 10.85 (95%-CI: 3.74-31.44), respectively]. These two imaging findings correlate to focal axonal degeneration/myelin pallor or glial iron deposition on histopathology, respectively. Additionally, certain clinical MND phenotypes such as amyotrophic lateral sclerosis (ALS) seem to present with distinct CNS atrophy patterns. CONCLUSIONS Although CST T2-hyperintensities and the "motor band sign" are non-specific imaging features, they can be leveraged for diagnostic workup of suspected MND cases, together with certain brain atrophy patterns. Collectively, this study provides high-grade evidence for the usefulness of MRI in the diagnostic workup of suspected MND cases. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020182682

Neural Networks for State Evaluation in General Game Playing

Abstract. Unlike traditional game playing, General Game Playing is concerned with agents capable of playing classes of games. Given the rules of an unknown game, the agent is supposed to play well without human intervention. For this purpose, agent systems that use deterministic game tree search need to automatically construct a state value function to guide search. Successful systems of this type use evaluation functions derived solely from the game rules, thus neglecting further improvements by experience. In addition, these functions are fixed in their form and do not necessarily capture the game’s real state value function. In this work we present an approach for obtaining evaluation functions on the basis of neural networks that overcomes the aforementioned problems. A network initialization extracted from the game rules ensures reasonable behavior without the need for prior training. Later training, however, can lead to significant improvements in evaluation quality, as our results indicate.

Imaging of adult leukodystrophies

Leukodystrophies are genetically determined white matter disorders. Even though leukodystrophies essentially affect children in early infancy and childhood, these disorders may affect adults. In adults, leukodystrophies may present a distinct clinical and imaging presentation other than those found in childhood. Clinical awareness of late-onset leukodystrophies should be increased as new therapies emerge. MRI is a useful tool to evaluate white matter disorders and some characteristics findings can help the diagnosis of leukodystrophies. This review article briefly describes the imaging characteristics of the most common adult leukodystrophies

Radiological studies of LMNB1-related autosomal dominant leukodystrophy and Marinesco-Sjögren syndrome

There are approximately 6000 to 8000 rare diseases, each with a prevalence of less than 1 / 10 000, but in aggregate affecting 6 to 8% of the population. It is important to evaluate disease development and progression to know the natural course of any disease. This information can be utilized in diagnostics and in assessing effects of therapeutic interventions as they become available. This thesis describes the natural clinical history and evolution of imaging findings of two rare diseases over approximately two decades. Papers I, II and III present clinical, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) findings in LMNB1-related autosomal dominant leukodystrophy (ADLD). MRI was found to be very sensitive in finding pathology in patients with LMNB1-related ADLD, even before the onset of clinical symptoms. However, even patients with widespread MRI changes can have a relatively mild symptomatology and present only slight disturbances in metabolic examinations such as MRS and FDG-PET. This is compatible with relatively intact axons, even as myelin impairment is widespread. Paper IV presents clinical and MRI findings in the brain and musculature in SIL1-positive Marinesco-Sjögren syndrome (MSS), and describes a new, mild phenotype of the disease with no intellectual disabilities and only slight motor disabilities. With a 19-year-long radiological follow-up, a slow progressive atrophic process in the cerebellum and brainstem could be demonstrated. MRI of the musculature shows early involvement of the quadriceps and gastrocnemii but not the tibialis anterior, progressing to widespread atrophy in the back and upper and lower limbs at the age of 20 years. In the mildest phenotype, the most severely affected muscles were the m gluteus maximus, m sartorius, m peroneus longus, and the lateral head of the m gastrocnemius

Stýrandi áhrif útdrátta úr sjávarhryggleysingjum á þroska angafrumna in vitro

Inngangur: Ónæmiskerfi mannslíkamans er flókið samspil margra þátta þar sem að angafrumur gegna mikilvægu hlutverki í stjórnun og sérhæfingu ónæmissvarsins. Þróað hefur verið in vitro angafrumulíkan til að rannsaka ónæmisstýrandi áhrif efna og hefur það verið notað í leit að lífvirkum efnum úr íslensku lífríki. Leit að lífvirkum efnum úr sjávarhryggleysingjum hefur borið talsverðan árangur en flest þessara efnasambanda hafa verið einangruð úr lífverum sem lifa í heitari höfum. Ísland er staðsett á einstökum stað í Norður-Atlantshafi og hefur líffræðilegur fjölbreytileiki í hafinu í kringum landið nánast ekkert verið rannsakaður m.t.t. efnainnihalds lífvera. Sérstaða íslenska hafsvæðisins felst í því að landið liggur á mótum hlýsjávar úr suðri og kaldsjávar úr norðri og auk jarðhitasvæða á hafsbotni. Þessar aðstæður geta því skapað skilyrði fyrir einstak lífríki í sjó sem síðan getur leitt til þess að lífverurnar sem þar lifa framleiða áhugaverð efnasambönd sér til varnar. Markmið: Markmið verkefnisins var að skima fyrir lífvirkni í útdráttum úr íslenskum sjávarhryggleysingjum í in vitro angafrumulíkani. Aðferðir: Ónæmisfræðileg áhrif 58 útdrátta voru könnuð í in vitro angafrumulíkaninu í einum styrk, 100 μg/mL. Sjö útdrættir sem sýndu mesta virkni voru valdir úr og prófaðir í fleiri styrkjum. Einn lífvirkur útdráttur var valinn úr, hann þáttaður og áhrif fraktionanna könnuð. Í in vitro angafrumulíkaninu voru óþroskaðar angafrumur þroskaðar í návist eða án útdrátta úr sjávarhryggleysingjum og áhrif útdráttanna metin með því að mæla yfirborðssameindirnar CD86, HLA-DR og CD14 með frumuflæðisjá og seytingu á boðefnunum IL-10 og IL-12p40 með ELISA aðferð. Niðurstöður: Þroskun angafrumna í návist sjö útdrátta í styrkjunum 50 og 100 μg/ml leiddu til lægra hlutfalls CD86+ og HLA-DR angafrumna, drógu úr meðaltalstjáningu þessara sameinda og úr seytingu boðefnanna IL-12p40 og IL-10 miðað við angafrumur þroskaðra án útdrátta. Þáttun á einum útdrættinum leiddi í ljós að mesta virknin var hjá óskautuðu fraktionunum og að IL-12p40 seytun því sem næst hvarf þegar angafrumur voru þroskaðar í návist einnar þeirra. Ekki náðist að halda áfram með lífvirknileidda þáttun þessara fraktiona. Umræður og ályktanir: Niðurstöður verkefnisins bentu til þess að lífvirk efni finnist í útdráttum af a.m.k. sjö íslenskum sjávarhryggleysingjum og að efni í einum þeirra geti hugsanlega haft veruleg áhrif á ræsingu Th1 og/eða Th17 frumur og þannig hugsanlega dregið úr sjálfsofnæmissjúkdómum. Því er mikilvægt að gera lífvirknileidda einangrun til að ákvarða hver virku efnin eru í þessum lífverum og kanna nánar ónæmisfræðileg áhrif hreinna innihaldsefna

Generalized Monte-Carlo Tree Search Extensions for General Game Playing

General Game Playing (GGP) agents must be capable of playing a wide variety of games skillfully. Monte-Carlo Tree Search (MCTS) has proven an effective reasoning mechanism for this challenge, as is reflected by its popularity among designers of GGP agents. Providing GGP agents with the knowledge relevant to the game at hand in real time is, however, a challenging task. In this paper we propose two enhancements for MCTS in the context of GGP, aimed at improving the effectiveness of the simulations in real time based on in-game statistical feedback. The first extension allows early termination of lengthy and uninformative simulations while the second improves the action-selection strategy when both explored and unexplored actions are available. The methods are empirically evaluated in a state-of-the-art GGP agent and shown to yield an overall significant improvement in playing strength

Unbonded Pre-tensioned Bridge Columns with Hybrid Fiber-Reinforced Concrete Shells

Thesis (Master's)--University of Washington, 2013Many bridges in the United States are getting old and will need to be replaced in the near future. If these bridges are constructed with conventional cast-in-place methods, this construction will cause traffic congestion, which is a costly problem. Furthermore, these cast-in-place systems are susceptible to earthquake-induced damage, such as bar buckling, bar fracture and residual displacements. A new pre-tensioned precast bent system has been developed to meet these challenges. The system consists of precast technology to accelerate the bridge construction, unbonded pre-tensioning to minimize residual displacements, and high-performance materials that extend the bridge durability. Davis et al. (2012) tested the new system using only conventional concrete. They found out that pre-tensioning improves system's re-centering capabilities, but it results in earlier bar buckling and bar fracture than in previously tested reinforced concrete columns (Pang et al. 2008, Haraldsson et al. 2012). Two columns were designed and tested in the University of Washington Structural Laboratory. In the plastic-hinge region of the columns a very ductile concrete shell was added. The shell was made of a hybrid fiber reinforced concrete (HyFRC, developed by Prof. Ostertag at U.C. Berkeley) containing both polymer and steel fibers. The main goal of adding the shell was to delay spalling and buckling of the longitudinal reinforcement bars. One of the columns was the same as one of the columns tested by Davis with only the addition of HyFRC shell. The other column had a HyFRC shell in the plastic hinge region and stainless steel reinforcement bars as longitudinal reinforcement instead of regular black steel rebars. The addition of the stainless steel rebar was expected to increase the ductility of the system and minimize the corrosion susceptibility. The tests showed that the HyFRC delayed the concrete spalling, and to a limited extent, the buckling of the longitudinal bars. The main benefits of having the HyFRC shell was that the columns kept 80% of its strength at 10% drift ratio, which was much higher than the conventional concrete specimens tested by Davis et al. (2012). The response of the stainless steel column was comparable to the black steel column, the main difference being that the stainless steel column was stronger, because the stainless steel was stronger than the black steel

Rehabiliteringscoacher : deras roll och betydelse för att få de långtidssjukskrivna TBAKS i arbete

Validerat; 20101217 (root