Myogenic transcranial motor evoked potentials monitoring cannot always predict neurologic outcome after spinal cord ischemia in rats

AbstractObjectivesA day after undergoing an operation of the thoracic aorta, a patient showed signs of spastic paraplegia, but on myogenic transcranial motor evoked potential monitoring, the myogenic transcranial motor evoked potentials recorded from the left anterior tibial muscle appeared normal. We sought to confirm these observations by using a rat spinal ischemia model to define the possibility of false-negative results in myogenic transcranial motor evoked potential monitoring by motor function behavior and spinal histopathology.MethodsSpinal ischemia was induced for 6 minutes (group A, n = 6) or 10 minutes (group B, n = 6) with an intra-aortic balloon. After ischemia, motor function was assessed periodically by using the motor deficit index (0, complete recovery; 6, complete paraplegia). Myogenic transcranial motor evoked potentials were recorded from the right soleus muscle before ischemia, 2 and 6 minutes after the start of spinal ischemia, and at 30 minutes, 24 hours, and 72 hours of reperfusion.ResultsAll group A rats showed normal motor function at 72 hours of reperfusion, whereas all group B rats displayed complete spastic paraplegia (motor deficit index = 6) at 72 hours of reperfusion. However, transcranial motor evoked potential was preserved in both group B and group A. Histopathologic analysis in group B revealed the presence of extensive necrotic changes of the gray matter distributed between laminae V through VII in the L3 to L5 segments but normal appearance of α motor neurons.ConclusionAccording to our data, in using myogenic transcranial motor evoked potential monitoring during thoracic or thoracoabdominal aneurysm repair, we should be aware that transcranial motor evoked potentials cannot always be used to predict neurologic outcome after the operation

On Eigenvalues of the sum of two random projections

We study the behavior of eigenvalues of matrix P_N + Q_N where P_N and Q_N are two N -by-N random orthogonal projections. We relate the joint eigenvalue distribution of this matrix to the Jacobi matrix ensemble and establish the universal behavior of eigenvalues for large N. The limiting local behavior of eigenvalues is governed by the sine kernel in the bulk and by either the Bessel or the Airy kernel at the edge depending on parameters. We also study an exceptional case when the local behavior of eigenvalues of P_N + Q_N is not universal in the usual sense.Comment: 14 page

Determinantal process starting from an orthogonal symmetry is a Pfaffian process

When the number of particles $N$ is finite, the noncolliding Brownian motion (BM) and the noncolliding squared Bessel process with index $\nu > -1$ (BESQ$^{(\nu)}$) are determinantal processes for arbitrary fixed initial configurations. In the present paper we prove that, if initial configurations are distributed with orthogonal symmetry, they are Pfaffian processes in the sense that any multitime correlation functions are expressed by Pfaffians. The $2 \times 2$ skew-symmetric matrix-valued correlation kernels of the Pfaffians processes are explicitly obtained by the equivalence between the noncolliding BM and an appropriate dilatation of a time reversal of the temporally inhomogeneous version of noncolliding BM with finite duration in which all particles start from the origin, $N \delta_0$, and by the equivalence between the noncolliding BESQ$^{(\nu)}$ and that of the noncolliding squared generalized meander starting from $N \delta_0$.Comment: v2: AMS-LaTeX, 17 pages, no figure, corrections made for publication in J.Stat.Phy

Noncolliding Squared Bessel Processes

We consider a particle system of the squared Bessel processes with index $\nu > -1$ conditioned never to collide with each other, in which if $-1 < \nu < 0$ the origin is assumed to be reflecting. When the number of particles is finite, we prove for any fixed initial configuration that this noncolliding diffusion process is determinantal in the sense that any multitime correlation function is given by a determinant with a continuous kernel called the correlation kernel. When the number of particles is infinite, we give sufficient conditions for initial configurations so that the system is well defined. There the process with an infinite number of particles is determinantal and the correlation kernel is expressed using an entire function represented by the Weierstrass canonical product, whose zeros on the positive part of the real axis are given by the particle-positions in the initial configuration. From the class of infinite-particle initial configurations satisfying our conditions, we report one example in detail, which is a fixed configuration such that every point of the square of positive zero of the Bessel function $J_{\nu}$ is occupied by one particle. The process starting from this initial configuration shows a relaxation phenomenon converging to the stationary process, which is determinantal with the extended Bessel kernel, in the long-term limit.Comment: v3: LaTeX2e, 26 pages, no figure, corrections made for publication in J. Stat. Phy

Excessive adventitial stress drives inflammation-mediated fibrosis in hypertensive aortic remodelling in mice

Hypertension induces significant aortic remodeling, often adaptive but sometimes not. To identify immuno-mechanical mechanisms responsible for differential remodeling, we studied thoracic aortas from 129S6/SvEvTac and C57BL/6J mice before and after continuous 14-day angiotensin II infusion, which elevated blood pressure similarly in both strains. Histological and biomechanical assessments of excised vessels were similar at baseline, suggesting a common homeostatic set-point for mean wall stress. Histology further revealed near mechano-adaptive remodeling of the hypertensive 129S6/SvEvTac aortas, but grossly maladaptive remodeling of C57BL/6J aortas. Bulk RNA sequencing suggested that increased smooth muscle contractile processes promoted mechano-adaptation of 129S6/SvEvTac aortas while immune processes prevented adaptation of C57BL/6J aortas. Functional studies confirmed an increased vasoconstrictive capacity of the former while immunohistochemistry demonstrated marked increases in inflammatory cells in the latter. We then used multiple computational biomechanical models to test the hypothesis that excessive adventitial wall stress correlates with inflammatory cell infiltration. These models consistently predicted that increased vasoconstriction against an increased pressure coupled with modest deposition of new matrix thickens the wall appropriately, restoring wall stress toward homeostatic consistent with adaptive remodeling. In contrast, insufficient vasoconstriction permits high wall stresses and exuberant inflammation-driven matrix deposition, especially in the adventitia, reflecting compromised homeostasis and gross maladaptation

Moderate deviations via cumulants

The purpose of the present paper is to establish moderate deviation principles for a rather general class of random variables fulfilling certain bounds of the cumulants. We apply a celebrated lemma of the theory of large deviations probabilities due to Rudzkis, Saulis and Statulevicius. The examples of random objects we treat include dependency graphs, subgraph-counting statistics in Erd\H{o}s-R\'enyi random graphs and $U$-statistics. Moreover, we prove moderate deviation principles for certain statistics appearing in random matrix theory, namely characteristic polynomials of random unitary matrices as well as the number of particles in a growing box of random determinantal point processes like the number of eigenvalues in the GUE or the number of points in Airy, Bessel, and $\sin$ random point fields.Comment: 24 page

Assessment of plasma lyso-Gb(3)for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease

Purpose To assess the utility of globotriaosylsphingosine (lyso-Gb(3)) for clinical monitoring of treatment response in patients with Fabry disease receiving migalastat. Methods A post hoc analysis evaluated data from 97 treatment-naive and enzyme replacement therapy (ERT)-experienced patients with migalastat-amenableGLAvariants from FACETS (NCT00925301) and ATTRACT (NCT01218659) and subsequent open-label extension studies. The relationship between plasma lyso-Gb(3)and measures of Fabry disease progression (left ventricular mass index [LVMi], estimated glomerular filtration rate [eGFR], and pain) and the relationship between lyso-Gb(3)and incidence of Fabry-associated clinical events (FACEs) were assessed in both groups. The relationship between changes in lyso-Gb(3)and kidney interstitial capillary (KIC) globotriaosylceramide (Gb(3)) inclusions was assessed in treatment-naive patients. Results No significant correlations were identified between changes in lyso-Gb(3)and changes in LVMi, eGFR, or pain. Neither baseline lyso-Gb(3)levels nor the rate of change in lyso-Gb(3)levels during treatment predicted FACE occurrences in all patients or those receiving migalastat for >= 24 months. Changes in lyso-Gb(3)correlated with changes in KIC Gb(3)inclusions in treatment-naive patients. Conclusions Although used as a pharmacodynamic biomarker in research and clinical studies, plasma lyso-Gb(3)may not be a suitable biomarker for monitoring treatment response in migalastat-treated patients.Medical Biochemistr

Two-Dimensional Unoriented Strings And Matrix Models

We investigate unoriented strings and superstrings in two dimensions and their dual matrix quantum mechanics. Most of the models we study have a tachyon tadpole coming from the RP^2 worldsheet which needs to be cancelled by a renormalization of the worldsheet theory. We find evidence that the dual matrix models describe the renormalized theory. The singlet sector of the matrix models is integrable and can be formulated in terms of fermions moving in an external potential and interacting via the Calogero-Moser potential. We show that in the double-scaling limit the latter system exhibits particle-hole duality and interpret it in terms of the dual string theory. We also show that oriented string theories in two dimensions can be continuously deformed into unoriented ones by turning on non-local interactions on the worldsheet. We find two unoriented superstring models for which only oriented worldsheets contribute to the S-matrix. A simple explanation for this is found in the dual matrix model.Comment: 36 pages, harvmac, 2 eps figure

Psoriasis and mental health workshop report : Exploring the links between psychosocial factors, psoriasis, neuroinflammation and cardiovascular disease risk

Psoriasis is a systemic, relapsing, inflammatory disease associated with serious comorbidities including mood problems and/or unhealthy lifestyle behaviours. Cutaneous and systemic abnormalities in innate and acquired immunity play a role in its pathogenesis. The exact pathogenetic mechanism remains elusive. Evidence is accumulating that TNF-alpha, IL-17 and IL-23 signalling are highly relevant as targeting these pathways reduces disease activity. Evidence suggests a strong link between psoriasis and depression in adults. The International Psoriasis Council (IPC) held a roundtable event, "Psoriasis and Mental Health", in Barcelona, Spain which focused on the presence of depression and suicidality, plus the role of neuroinflammation in psoriasis, sleep disruption and the impact of depression on cardiovascular disease outcomes. We summarize here the expert presentations to provide additional insight into the understanding of psychiatric comorbidities of psoriasis and of the impact of chronic, systemic inflammation on neuro-and cardiovascular outcomes. the associations between psoriasis and other psychiatric comorbidities are still controversial and warrant further attention

Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: A Children's Oncology Group study

Background: Most patients with juvenile myelomonocytic leukemia (JMML) are curable only with allogeneic hematopoietic cell transplantation (HCT). However, the current standard conditioning regimen, busulfan-cyclophosphamide-melphalan (Bu-Cy-Mel), may be associated with higher risks of morbidity and mortality. ASCT1221 was designed to test whether the potentially less-toxic myeloablative conditioning regimen containing busulfan-fludarabine (Bu-Flu) would be associated with equivalent outcomes. Procedure: Twenty-seven patients were enrolled on ASCT1221 from 2013 to 2015. Pre- and post-HCT (starting Day +30) mutant allele burden was measured in all and pre-HCT therapy was administered according to physician discretion. Results: Fifteen patients were randomized (six to Bu-Cy-Mel and nine to Bu-Flu) after meeting diagnostic criteria for JMML. Pre-HCT low-dose chemotherapy did not appear to reduce pre-HCT disease burden. Two patients, however, received aggressive chemotherapy pre-HCT and achieved low disease-burden state; both are long-term survivors. All four patients with detectable mutant allele burden at Day +30 post-HCT eventually progressed compared to two of nine patients with unmeasurable allele burden (P = 0.04). The 18-month event-free survival of the entire cohort was 47% (95% CI, 21–69%), and was 83% (95% CI, 27–97%) and 22% (95% CI, 03–51%) for Bu-Cy-Mel and Bu-Flu, respectively (P = 0.04). ASCT1221 was terminated early due to concerns that the Bu-Flu arm had inferior outcomes. Conclusions: The regimen of Bu-Flu is inadequate to provide disease control in patients with JMML who present to HCT with large burdens of disease. Advances in molecular testing may allow better characterization of biologic risk, pre-HCT responses to chemotherapy, and post-HCT management