Cerebellar Motor Learning Deficits: Structural mapping, neuromodulation and training-related interventions

Movement allows us to interact with our direct environment, manipulate objects and communicate with each other. Moreover, we can adjust our movements to fit a remarkable range of situations and circumstances. The ability to adjust movements in response to changes in the environment and task demands is referred to as motor learning. The cerebellum is a key neural structure for motor learning. As such, disease of the cerebellum, in addition to the clinical symptom of ataxia, results in various motor learning deficits. There is a consensus that supportive therapy (e.g. physiotherapy, occupational therapy or speech therapy) can reduce ataxia symptoms of cerebellar patients, but little is known about the mechanisms underlying the improvements, and how patients can benefit most. Additionally, motor learning deficits are associated with reduced efficacy of supportive therapy. With the work described in this thesis, we sought to unravel the structural components of cerebellar disease and the relationship between cerebellar integrity and motor learning. Furthermore, we investigated whether motor learning deficits in cerebellar patients could be ameliorated with neuromodulation or training-related interventions, under experimental conditions, hoping to support the development of interventions relevant for application in a clinical setting

The effect of stellar feedback on a Milky Way-like galaxy and its gaseous halo

We present the study of a set of N-body+smoothed particle hydrodynamics simulations of a Milky Way-like system produced by the radiative cooling of hot gas embedded in a dark matter halo. The galaxy and its gaseous halo evolve for 10 Gyr in isolation, which allows us to study how internal processes affect the evolution of the system. We show how the morphology, the kinematics and the evolution of the galaxy are affected by the input supernova feedback energy ESN, and we compare its properties with those of the Milky Way. Different values of ESN do not significantly affect the star formation history of the system, but the disc of cold gas gets thicker and more turbulent as feedback increases. Our main result is that, for the highest value of ESN considered, the galaxy shows a prominent layer of extraplanar cold (log (T/K) < 4.3) gas extended up to a few kiloparsec above the disc at column densities of 1019 cm-2. The kinematics of this material is in agreement with that inferred for the H I haloes of our Galaxy and NGC 891, although its mass is lower. Also, the location, the kinematics and the typical column densities of the hot (5.3 < log (T/K) < 5.7) gas are in good agreement with those determined from the O VI absorption systems in the halo of the Milky Way and external galaxies. In contrast with the observations, however, gas at log (T/K) < 5.3 is lacking in the circumgalactic region of our systems

Deep sternal wound infection after open heart surgery: current treatment insights. A retrospective study of 36 cases

The aim of this study was to retrospectively evaluate the results of reconstructing infected post-sternotomy wounds, with either sternal plating and/or pectoralis major flap transposition or pedicled omentoplasty after previous vacuum-assisted closure (VAC) therapy. Between January 2005 and December 2010, 36 patients, suffering from deep sternal wound infection (DSWI) after coronary artery bypass grafting procedure, received (plastic) reconstructive surgery. All patients, treated in the Maastricht University Medical Centre (Departments of Plastic Surgery and Cardiothoracic Surgery), were selected for this study. For 22 patients, sternal refixation and reconstruction were obtained by sternal internal plate fixation combined with bilateral pectoralis major advancement flap. In 11 patients, a pedicled omentoplasty was performed, with or without split-skin graft and additional VAC therapy. Three patients only received a pectoralis plasty. We evaluated preoperative characteristics and post-operative course. Twenty-four patients (66.7%) had an uneventful post-operative course. Complications in the other patients included wound dehiscence, herniation of the donor site and infection of sternal plating material. Average sternal wound healing after sternal plating plus pectoralis plasty, pectoralis plasty and omentoplasty respectively accounted 7.7, 8.0 and 11.6 weeks. From our experience, we recommend VAC therapy plus delayed sternal plating and additional bilateral pectoralis major flap advancement as first repair option in case of DSWI. However, individual clinical conditions need to be taken into account when making a decision between the different available reconstructive options. Omentoplasty should be reserved for cases in which the sternum has recurrently fallen open after previous sternal plate refixation, or for cases in which the sternum defect is too extended

Impaired affective and cognitive theory of mind and behavioural change in amyotrophic lateral sclerosis

ObjectivesExecutive and behavioural changes are well-recognised in classical amyotrophic lateral sclerosis (ALS), indicating a subclinical behavioural-variant frontotemporal dementia (bvFTD) in some patients. Social cognitive deficits in ALS have been recently described and an impairment was identified on a simple Theory of Mind (ToM) test, which assesses the judgement of the preference of another through direction of eye gaze. The present study further delineated this deficit, by distinguishing between Affective and Cognitive subcomponents, and determining the relationship to behavioural change, levels of empathy and self-awareness.MethodsThe Cognitive–Affective Judgement of Preference Test was administered to 33 patients with ALS and 26 controls. Furthermore, a comprehensive neuropsychological battery and detailed behavioural assessment, with measures of empathy and awareness, were included.ResultsPatients with ALS showed a significant impairment in Affective ToM only when compared with healthy controls, with a deficit in 36% of patients; 12% showed an isolated Affective ToM deficit while 24% showed more generic ToM dysfunction. A Cognitive ToM deficit was found in 27% of patients, with 3% showing an isolated Cognitive ToM deficit. The patients with ALS showed reduced empathy (Fantasy scale) and increased behavioural dysfunction with high levels of apathy. In addition, patients with either an Affective and/or Cognitive ToM deficit exhibited poor self-awareness of their performance and abnormalities on verbal fluency, while those with an Affective ToM deficit also displayed higher levels of apathy and a naming deficit.ConclusionsDysfunctional ToM is a prominent feature of the cognitive profile of ALS. This specific difficulty in identifying and distinguishing the feelings and thoughts of another from a self-perspective may underpin the social behavioural abnormalities present in some patients with ALS, manifest as apathy and loss of awareness.</jats:sec

Glutamine for induction of remission in Crohn's disease.

BACKGROUND: Crohn's disease is a chronic relapsing condition of the alimentary tract with a high morbidity secondary to bowel inflammation. Glutamine plays a key role in maintaining the integrity of the intestinal mucosa and has been shown to reduce inflammation and disease activity in experimental models of Crohn's disease. OBJECTIVES: To evaluate the efficacy and safety of glutamine supplementation for induction of remission in Crohn's disease. SEARCH METHODS: We searched the following databases from inception to November 15, 2015: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialised Register. Study references were also searched for additional trials. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared glutamine supplementation administered by any route to a placebo, active comparator or no intervention in people with active Crohn's disease were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of the included studies. The Cochrane risk of bias tool was used to assess methodological quality. The primary outcome measure was clinical or endoscopic remission. Secondary outcomes included intestinal permeability, clinical response, quality of life, growth in children and adverse events. Risk ratios and 95% confidence intervals were calculated for dichotomous outcomes. The overall quality of the evidence supporting the primary outcome was evaluated using the GRADE criteria. MAIN RESULTS: Two small RCTs (total 42 patients) met the inclusion criteria and were included in the review. One study (18 patients) compared four weeks of treatment with a glutamine-enriched polymeric diet (42% amino acid composition) to a standard polymeric diet (4% amino acid composition) with low glutamine content in paediatric patients ( 18 years of age) with acute exacerbation of inflammatory bowel disease. The paediatric study was rated as low risk of bias. The study in adult patients was rated as unclear risk of bias for blinding and low risk of bias for all other items. It was not possible to pool data for meta-analysis because of significant differences in study populations, nature of interventions, and the way outcomes were assessed. Data from one study showed no statistically significant difference in clinical remission rates at four weeks. Forty-four per cent (4/9) of patients who received a glutamine-enriched polymeric diet achieved remission compared to 56% (5/9) of patients who received a standard low-glutamine polymeric diet (RR 0.80, 95% CI 0.31 to 2.04). A GRADE analysis indicated that the overall quality of evidence for this outcome was low due to serious imprecision (9 events). In both included studies, no statistically significant changes in intestinal permeability were found between patients who received glutamine supplementation and those who did not. Neither study reported on clinical response, quality of life or growth in children. Adverse event data were not well documented. There were no serious adverse events in the paediatric study. The study in adult patients reported three central catheter infections with positive blood cultures in the glutamine group compared to none in the control group (RR 7.00, 95% CI 0.40 to 122.44). AUTHORS' CONCLUSIONS: Currently there is insufficient evidence to allow firm conclusions regarding the efficacy and safety of glutamine for induction of remission in Crohn's disease. Data from two small studies suggest that glutamine supplementation may not be beneficial in active Crohn's disease but these results need to be interpreted with caution as they are based on small numbers of patients. This review highlights the need for adequately powered randomised controlled trials to investigate the efficacy and safety of glutamine for induction of remission in Crohn's diseas

HI in NGC 5433 and its Environment: High-Latitude Emission in a Small Galaxy Group

We present HI synthesis maps of the edge-on starburst NGC 5433 and its environment, obtained with the VLA in its C and D configurations. The observations and spectral model residuals of the main disc emission in NGC 5433 reveal 3 extraplanar features. We associate 2 of these features with coherent extraplanar extensions across multiple spectral channels in our data, including a complete loop in position-velocity space. Interpreting the latter as an expanding shell we derive a corresponding input energy of 2 x 10^54 ergs, comparable to that for the largest supershells found in the Galaxy and those in other edge-on systems. NGC 5433 is in a richer environment than previously thought. We confirm that KUG 1359+326 is a physical companion to NGC 5433 and find two new faint companions, both with Minnesota Automated Plate Scanner identifications, that we label SIS-1 and SIS-2. Including the more distant IC 4357, NGC 5433 is the dominant member of a group of at least 5 galaxies, spanning over 750 kpc in a filamentary structure. A variety of evidence suggests that interactions are occurring in this group. While a number of underlying mechanisms are consistent with the morphology of the high-latitude features in NGC 5433, we argue that environmental effects may play a role in their generation.Comment: 18 pages including 10 figures. Accepted for publication in MNRAS. For higher resolution Fig. 1, see http://www.astro.cornell.edu/~spekkens/papers/ v2: Proof-corrected cop

DNGR1-mediated deletion of A20/Tnfaip3 in dendritic cells alters T and B-cell homeostasis and promotes autoimmune liver pathology

Dendritic cells (DCs) are central regulators of tolerance versus immunity. The outcome depends amongst others on DC subset and activation status. Whereas CD11b+ type 2 conventional DCs (cDC2s) initiate proinflammatory helper T (Th)-cell responses, CD103+ cDC1s are crucial for regulatory T-cell (Treg) induction and CD8+ T-cell activation. DC activation is controlled by the transcription factor NF-κB. Ablation of A20/Tnfaip3, a critical regulator of NF-κB activation, in DCs leads to constitutive DC activation and development of systemic autoimmunity. We hypothesized that the activation status of cDCs controls the development of autoimmunity. To target cDCs, DNGR1(Clec9a)-cre-mediated excision of A20/Tnfaip3 was used through generation of Tnfaip3fl/flxClec9a+/cre (Tnfaip3DNGR1−KO) mice. Immune cell activation was evaluated at 31-weeks of age. We found that DNGR1-cre-mediated deletion of A20/Tnfaip3 resulted in liver pathology characterized by inflammatory infiltrates adjacent to the portal triads. Both cDC subsets as well as monocyte-derived DCs (moDCs) in Tnfaip3DNGR1−KO livers harbored an activated phenotype. Specifically, the costimulatory molecule CD40 in liver cDCs and moDCs was regulated by A20/Tnfaip3 expression. Livers from Tnfaip3DNGR1−KO mice had augmented prop

The Source of Three-minute Magneto-acoustic Oscillations in Coronal Fans

We use images of high spatial, spectral and temporal resolution, obtained using both ground- and space-based instrumentation, to investigate the coupling between wave phenomena observed at numerous heights in the solar atmosphere. Intensity oscillations of 3 minutes are observed to encompass photospheric umbral dot structures, with power at least three orders-of-magnitude higher than the surrounding umbra. Simultaneous chromospheric velocity and intensity time series reveal an 87 \pm 8 degree out-of-phase behavior, implying the presence of standing modes created as a result of partial wave reflection at the transition region boundary. An average blue-shifted Doppler velocity of ~1.5 km/s, in addition to a time lag between photospheric and chromospheric oscillatory phenomena, confirms the presence of upwardly-propagating slow-mode waves in the lower solar atmosphere. Propagating oscillations in EUV intensity are detected in simultaneous coronal fan structures, with a periodicity of 172 \pm 17 s and a propagation velocity of 45 \pm 7 km/s. Numerical simulations reveal that the damping of the magneto-acoustic wave trains is dominated by thermal conduction. The coronal fans are seen to anchor into the photosphere in locations where large-amplitude umbral dot oscillations manifest. Derived kinetic temperature and emission measure time-series display prominent out-of-phase characteristics, and when combined with the previously established sub-sonic wave speeds, we conclude that the observed EUV waves are the coronal counterparts of the upwardly-propagating magneto-acoustic slow-modes detected in the lower solar atmosphere. Thus, for the first time, we reveal how the propagation of 3 minute magneto-acoustic waves in solar coronal structures is a direct result of amplitude enhancements occurring in photospheric umbral dots.Comment: Accepted into ApJ (13 pages and 10 figures

Structure and dynamics of galaxies with a low surface-brightness disc - II. Stellar populations of bulges

The radial profiles of the Hb, Mg, and Fe line-strength indices are presented for a sample of eight spiral galaxies with a low surface-brightness stellar disc and a bulge. The correlations between the central values of the line-strength indices and velocity dispersion are consistent to those known for early-type galaxies and bulges of high surface-brightness galaxies. The age, metallicity, and alpha/Fe enhancement of the stellar populations in the bulge-dominated region are obtained using stellar population models with variable element abundance ratios. Almost all the sample bulges are characterized by a young stellar population, on-going star formation, and a solar alpha/Fe enhancement. Their metallicity spans from high to sub-solar values. No significant gradient in age and alpha/Fe enhancement is measured, whereas only in a few cases a negative metallicity gradient is found. These properties suggest that a pure dissipative collapse is not able to explain formation of all the sample bulges and that other phenomena, like mergers or acquisition events, need to be invoked. Such a picture is also supported by the lack of a correlation between the central value and gradient of the metallicity in bulges with very low metallicity. The stellar populations of the bulges hosted by low surface-brightness discs share many properties with those of high surface-brightness galaxies. Therefore, they are likely to have common formation scenarios and evolution histories. A strong interplay between bulges and discs is ruled out by the fact that in spite of being hosted by discs with extremely different properties, the bulges of low and high surface-brightness discs are remarkably similar.Comment: 24 pages, 12 figures, 7 tables, accepted for pubblication on MNRA

Exact results in modeling planetary atmospheres--I. Gray atmospheres

An exact model is proposed for a gray, isotropically scattering planetary atmosphere in radiative equilibrium. The slab is illuminated on one side by a collimated beam and is bounded on the other side by an emitting and partially reflecting ground. We provide expressions for the incident and reflected fluxes on both boundary surfaces, as well as the temperature of the ground and the temperature distribution in the atmosphere, assuming the latter to be in local thermodynamic equilibrium. Tables and curves of the temperature distribution are included for various values of the optical thickness. Finally, semi-infinite atmospheres illuminated from the outside or by sources at infinity will be dealt with.Comment: 29 pages, 1 figure, Journal of Quantitative Spectroscopy and Radiative Transfer (www.elsevier.com/locate/jqsrt), accepted 11 September 200