Scale invariance in coarsening of binary and ternary fluids

Phase separation in binary and ternary fluids is studied using a two dimensional Lattice Gas Automata. The lengths, given by the the first zero crossing point of the correlation function and the total interface length is shown to exhibit power law dependence on time. In binary mixtures, our data clearly indicate the existence of a regime having more than one length scale where the coarsening process proceeds through the rupture and reassociation of domains. In ternary fluids; in the case of symmetric mixtures there exists a regime with a single length scale having dynamic exponent 1/2, while in asymmetric mixtures our data establish the break down of scale invariance.Comment: 20 pages, 13 figure

T-cell activation marker sCD27 is associated with clinically definite multiple sclerosis in childhood-acquired demyelinating syndromes

Background: Cerebrospinal fluid (CSF) levels of T-cell activation marker soluble CD27 (sCD27) are associated with subsequent disease activity after a first attack of suspected MS in adults. The predictive value for disease course in children with acquired demyelinating syndromes (ADS) is unknown. Objectives: To assess the predictive value of sCD27 levels for clinically definite multiple sclerosis (CDMS) diagnosis in childhood ADS. Methods: Children <18 years with a first demyelinating event were prospectively included and followed. Soluble CD27 was determined in CSF using an enzyme-linked immunosorbent assay (ELISA). Cox regression analyses were used to calculate hazard ratios (HRs) for CDMS. Results: A total of 94 ADS children were included (ADS with encephalopathy (ADS+) n = 33 and ADS without encephalopathy (ADS–) n = 61). Of the 61 ADS– children, 21 (48%) were diagnosed with CDMS during follow-up. At baseline, sCD27 levels were higher in patients with a future CDMS diagnosis (n = 29) than in monophasic ADS+ (n = 30), monophasic ADS– (n = 28) and relapsing non-MS patients (n = 7; p < 0.001). In ADS– patients, sCD27 was associated with CDMS (HR = 1.8 per 100 U/mL increase in sCD27 levels, p = 0.031), after adjustments for age, oligoclonal bands and the presence of dissemination in space on baseline magnetic resonance imaging (MRI). Conclusion: CSF sCD27 levels at first attack of demyelination were associated with CDMS diagnosis in children. This makes sCD27 a potential clinically relevant quantitative marker when performing routine CSF diagnostics

HLA association in MOG-IgG- and AQP4-IgG-related disorders of the CNS in the Dutch population

OBJECTIVE: To investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases. METHODS: Blood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG-seropositive and 42 AQP4-IgG-seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors. RESULTS: No significant HLA association was found in MOG-IgG-seropositive patients. The AQP4-IgG-seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707-5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513-8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495-5.042, pc = 0.0199) compared with controls. CONCLUSIONS: The present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG-positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG-positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders

Betacellulin drives therapy resistance in glioblastoma

Background: The transcription factor signal transducer and activator of transcription 3 (STAT3) drives progression in glioblastoma (GBM), suggesting STAT3 as a therapeutic target. Surprisingly however, GBM cells generally show primary resistance to STAT3 blockade. Methods: Human glioblastoma cell lines LN229, U87, SF767, and U373, and patient-derived xenografts (PDXs) GBM8 and GBM43 were used to evaluate epidermal growth factor receptor (EGFR) activation during STAT3 inhibition. Protein and gene expression experiments, protein stability assays, cytokine arrays, phospho-tyrosine arrays and EGFR-ligand protein arrays were performed on STAT3 inhibitor-treated cells. To evaluate antitumor activity, we administered a betacellulin (BTC)-neutralizing antibody alone and in combination with STAT3 inhibition. BTC is an EGFR ligand. We therefore treated mice with orthotopic xenografts using the third-generation EGFR inhibitor osimertinib, with or without STAT3 knockdown. Results: We demonstrate that both small-molecule inhibitors and knockdown of STAT3 led to expression and secretion of the EGFR ligand BTC, resulting in activation of EGFR and subsequent downstream phosphorylation of nuclear factor-kappaB (NF-κB). Neutralizing antibody against BTC abrogated activation of both EGFR and NF-κB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in GBM cells. Blocking EGFR and STAT3 together inhibited tumor growth, improving survival in mice bearing orthotopic GBM PDXs in vivo. Conclusion: These data reveal a feedback loop among STAT3, EGFR, and NF-κB that mediates primary resistance to STAT3 blockade and suggest strategies for therapeutic intervention

Prognostic factors for relapse and outcome in pediatric acute transverse myelitis

Objective: It may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM. Methods: This prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5–16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18–75). Results: In total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02). Conclusion: Pediatric ATM patients presenting with clinical

Siberian Snake Overcomes "Overlapping" Depolarizing Resonances

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Real-world validation of the 2017 McDonald criteria for pediatric MS

Objective To compare the diagnostic accuracy of the McDonald 2017 vs the McDonald 2010 criteria to predict a second attack of MS (clinically definite MS [CDMS]) at the first attack of acquired demyelinating syndromes (ADS). Methods One hundred sixty-four children (aged <18 years) with an incident attack of ADS were included in a prospective multicenter study between June 2006 and December 2016. Brain (and spinal if available) MRI was performed ≤3 months after symptom onset. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were compared at baseline between the 2010 and 2017 criteria. Results Among the 164 patients, 110 patients (67%) presented without encephalopathy (ADS–, female 63%; median age 14.8 years, IQR 11.3–16.1years) and 54 (33%) with encephalopathy (acute disseminated encephalomyelitis [ADEM], female 52%; median age 4.0 years, IQR 2.6–6.1 years). Of the 110 ADS– patients, 52 (47%) were diagnosed with CDMS within a median follow-up of 4.5 years (IQR 2.6–6.7 years). The sensitivity was higher for the 2017 criteria than for the 2010 criteria (83%; 95% CI 67–92, vs 49%; 95% CI 33–65; p < 0.001), but the specificity was lower (73%; 95% CI 59–84 vs 87%; 95% CI 74–94, p = 0.02). At baseline, 48 patients fulfilled the 2017 criteria compared with 27 patients when using the 2010 criteria. The results for children aged <12 years without encephalopathy were similar. In patients with ADEM, 8% fulfilled the 2010 criteria and 10% the 2017 criteria at baseline but no patient fulfilled the criteria for CDMS. Conclusions The McDonald 2017 criteria are more sensitive than the McDonald 2010 criteria for predicting CDMS at baseline. These criteria can also be applied in children aged <12 years without encephalopathy but not in children with ADEM. Classification of evidence This study provides Class II evidence that in children with ADS, the 2017 McDonald criteria are more sensitive but less specific than the 2010 McDonald criteria for predicting CDMS

RF Induced Depolarizing Resonanaces, Spin Flip, and Partial Siberian Snakes

This research was sponsored by the National Science Foundation Grant NSF PHY-931478

Toward an internally consistent astronomical distance scale

Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted