Critical illness polyneuropathy in ICU patients is related to reduced motor nerve excitability caused by reduced sodium permeability

Background: Reduced motor and sensory nerve amplitudes in critical illness polyneuropathy (CIP) are characteristic features described in electrophysiological studies and due to dysfunction of voltage-gated sodium channels. Yet, faulty membrane depolarization as reported in various tissues of critically ill patients may cause reduced membrane excitability as well. The aim of this study was to compare the pathophysiological differences in motor nerve membrane polarization and voltage-gated sodium channel function between CIP patients and critically ill patients not developing CIP during their ICU stay (ICU controls). Methods: ICU patients underwent electrophysiological nerve conduction studies and were categorized as either ICU controls or CIP patients. Subsequently, excitability parameters were recorded as current-threshold relationship, stimulus-response behavior, threshold electrotonus, and recovery of excitability from the abductor pollicis brevis following median nerve stimulation. Results: Twenty-six critically ill patients were enrolled and categorized as 12 ICU controls and 14 CIP patients. When compared to 31 healthy subjects, the ICU controls exhibited signs of membrane depolarization as shown by reduced superexcitability (p = 0.003), depolarized threshold electrotonus (p = 0.007), increased current-threshold relationship (p = 0.03), and slightly prolonged strength-duration time constant. In contrast, the CIP patients displayed a significantly reduced strength-duration time constant (p < 0.0001), which indicates an increased inactivation of voltage-gated sodium channels. Conclusions: Abnormal motor nerve membrane depolarization is a general finding in critically ill patients whereas voltage-gated sodium channel dysfunction is a characteristic of CIP patients

Evaluation of fatigue damage in steel structural components by magnetoelastic Barkhausen signal analysis

This paper is concerned with using a magnetic technique for the evaluation of fatigue damage in steel structural components. It is shown that Barkhausen effect measurements can be used to indicate impending failure due to fatigue under certain conditions. The Barkhausen signal amplitude is known to be highly sensitive to changes in density and distribution of dislocations in materials. The sensitivity of Barkhausen signal amplitude to fatigue damage has been studied in the low‐cycle fatigue regime using smooth tensile specimens of a medium strength steel. The Barkhausen measurements were taken at depths of penetration of 0.02, 0.07, and 0.2 mm. It was found that changes in magnetic properties are sensitive to microstructural changes taking place at the surface of the material throughout the fatigue life. The changes in the Barkhausen signals have been attributed to distribution of dislocations in stage I and stage II of fatigue life and the formation of a macrocrack in the final stage of fatigue

Primary Hepatosplenic Large B-Cell Lymphoma: A Rare Aggressive Tumor

Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment

DEvIANT: Discovering Significant Exceptional (Dis-)Agreement Within Groups

We strive to find contexts (i.e., subgroups of entities) under which exceptional (dis-)agreement occurs among a group of individuals , in any type of data featuring individuals (e.g., parliamentarians , customers) performing observable actions (e.g., votes, ratings) on entities (e.g., legislative procedures, movies). To this end, we introduce the problem of discovering statistically significant exceptional contextual intra-group agreement patterns. To handle the sparsity inherent to voting and rating data, we use Krippendorff's Alpha measure for assessing the agreement among individuals. We devise a branch-and-bound algorithm , named DEvIANT, to discover such patterns. DEvIANT exploits both closure operators and tight optimistic estimates. We derive analytic approximations for the confidence intervals (CIs) associated with patterns for a computationally efficient significance assessment. We prove that these approximate CIs are nested along specialization of patterns. This allows to incorporate pruning properties in DEvIANT to quickly discard non-significant patterns. Empirical study on several datasets demonstrates the efficiency and the usefulness of DEvIANT. Technical Report Associated with the ECML/PKDD 2019 Paper entitled: "DEvIANT: Discovering Significant Exceptional (Dis-)Agreement Within Groups"

Atrial myxoma presenting with orthostatic hypotension in an 84-year-old Hispanic man: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

G-CSF Prevents the Progression of Structural Disintegration of White Matter Tracts in Amyotrophic Lateral Sclerosis: A Pilot Trial

Background: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF) has neuroprotective and regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS). The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible.Methods: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 mu g/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS), a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days). The total number of adverse events (AE) and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI), brain volumetry, and voxel-based morphometry.Results: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA) encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF.Conclusions: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of clinical data showed no significant effect, DTI measurements suggest that the widespread and progressive microstructural neural damage in ALS can be modulated by G-CSF treatment. These findings may carry significant implications for further clinical trials on ALS using growth factors

Assessment of the reliability of the motor unit size index (MUSIX) in single subject “round-robin” and multi-centre settings

Objective The motor unit size index (MUSIX) is incorporated into the motor unit number index (MUNIX). Our objective was to assess the intra-/inter-rater reliability of MUSIX in healthy volunteers across single subject “round robin” and multi-centre settings. Methods Data were obtained from i). a round-robin assessment in which 12 raters (6 with prior experience and 6 without) assessed six muscles (abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, extensor digitorum brevis and abductor hallucis) and ii). a multi-centre study with 6 centres studying the same muscles in 66 healthy volunteers. Intra/inter-rater data were provided by 5 centres, 1 centre provided only intra-rater data. Intra/inter-rater variability was assessed using the coefficient of variation (COV), Bland-Altman plots, bias and 95% limits of agreement. Results In the round-robin assessment intra-rater COVs for MUSIX ranged from 7.8% to 28.4%. Inter-rater variability was between 7.8% and 16.2%. Prior experience did not impact on MUSIX values. In the multi-centre study MUSIX was more consistent than the MUNIX. Abductor hallucis was the least reliable muscle. Conclusions The MUSIX is a reliable neurophysiological biomarker of reinnervation. Significance MUSIX could provide insights into the pathophysiology of a range of neuromuscular disorders, providing a quantitative biomarker of reinnervation

Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria

A proline-to-serine substitution at position 56 in the gene encoding vesicle-associated membrane protein-associated protein B (VAPB; VAPBP56S) causes some dominantly inherited familial forms of motor neuron disease, including amyotrophic lateral sclerosis (ALS) type-8. Here, we show that expression of ALS mutant VAPBP56S but not wild-type VAPB in neurons selectively disrupts anterograde axonal transport of mitochondria. VAPBP56S-induced disruption of mitochondrial transport involved reductions in the frequency, velocity and persistence of anterograde mitochondrial movement. Anterograde axonal transport of mitochondria is mediated by the microtubule-based molecular motor kinesin-1. Attachment of kinesin-1 to mitochondria involves the outer mitochondrial membrane protein mitochondrial Rho GTPase-1 (Miro1) which acts as a sensor for cytosolic calcium levels ([Ca2+]c); elevated [Ca2+]c disrupts mitochondrial transport via an effect on Miro1. To gain insight into the mechanisms underlying the VAPBP56S effect on mitochondrial transport, we monitored [Ca2+]c levels in VAPBP56S-expressing neurons. Expression of VAPBP56S but not VAPB increased resting [Ca2+]c and this was associated with a reduction in the amounts of tubulin but not kinesin-1 that were associated with Miro1. Moreover, expression of a Ca2+ insensitive mutant of Miro1 rescued defective mitochondrial axonal transport and restored the amounts of tubulin associated with the Miro1/kinesin-1 complex to normal in VAPBP56S-expressing cells. Our results suggest that ALS mutant VAPBP56S perturbs anterograde mitochondrial axonal transport by disrupting Ca2+ homeostasis and effecting the Miro1/kinesin-1 interaction with tubulin

Logic, Probability and Action: A Situation Calculus Perspective

The unification of logic and probability is a long-standing concern in AI, and more generally, in the philosophy of science. In essence, logic provides an easy way to specify properties that must hold in every possible world, and probability allows us to further quantify the weight and ratio of the worlds that must satisfy a property. To that end, numerous developments have been undertaken, culminating in proposals such as probabilistic relational models. While this progress has been notable, a general-purpose first-order knowledge representation language to reason about probabilities and dynamics, including in continuous settings, is still to emerge. In this paper, we survey recent results pertaining to the integration of logic, probability and actions in the situation calculus, which is arguably one of the oldest and most well-known formalisms. We then explore reduction theorems and programming interfaces for the language. These results are motivated in the context of cognitive robotics (as envisioned by Reiter and his colleagues) for the sake of concreteness. Overall, the advantage of proving results for such a general language is that it becomes possible to adapt them to any special-purpose fragment, including but not limited to popular probabilistic relational models