Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Enhanced Dispersion of TiO2 Nanoparticles in a TiO2/PEDOT:PSS Hybrid Nanocomposite via Plasma-Liquid Interactions

A facile method to synthesize a TiO2/PEDOT:PSS hybrid nanocomposite material in aqueous solution through direct current (DC) plasma processing at atmospheric pressure and room temperature has been demonstrated. The dispersion of the TiO2 nanoparticles is enhanced and TiO2/polymer hybrid nanoparticles with a distinct core shell structure have been obtained. Increased electrical conductivity was observed for the plasma treated TiO2/PEDOT:PSS nanocomposite. The improvement in nanocomposite properties is due to the enhanced dispersion and stability in liquid polymer of microplasma treated TiO2 nanoparticles. Both plasma induced surface charge and nanoparticle surface termination with specific plasma chemical species are proposed to provide an enhanced barrier to nanoparticle agglomeration and promote nanoparticle-polymer binding

Altered Dendritic Morphology of Purkinje cells in Dyt1 ΔGAG Knock-In and Purkinje Cell-Specific Dyt1 Conditional Knockout Mice

BACKGROUND: DYT1 early-onset generalized dystonia is a neurological movement disorder characterized by involuntary muscle contractions. It is caused by a trinucleotide deletion of a GAG (ΔGAG) in the DYT1 (TOR1A) gene encoding torsinA; the mouse homolog of this gene is Dyt1 (Tor1a). Although structural and functional alterations in the cerebellum have been reported in DYT1 dystonia, neuronal morphology has not been examined in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined the morphology of the cerebellum in Dyt1 ΔGAG knock-in (KI) mice. Golgi staining of the cerebellum revealed a reduction in the length of primary dendrites and a decrease in the number of spines on the distal dendrites of Purkinje cells. To determine if this phenomenon was cell autonomous and mediated by a loss of torsinA function in Purkinje cells, we created a knockout of the Dyt1 gene only in Purkinje cells of mice. We found the Purkinje-cell specific Dyt1 conditional knockout (Dyt1 pKO) mice have similar alterations in Purkinje cell morphology, with shortened primary dendrites and decreased spines on the distal dendrites. CONCLUSION/SIGNIFICANCE: These results suggest that the torsinA is important for the proper development of the cerebellum and a loss of this function in the Purkinje cells results in an alteration in dendritic structure

Plasma–liquid interactions: a review and roadmap

Plasma–liquid interactions represent a growing interdisciplinary area of research involving plasma science, fluid dynamics, heat and mass transfer, photolysis, multiphase chemistry and aerosol science. This review provides an assessment of the state-of-the-art of this multidisciplinary area and identifies the key research challenges. The developments in diagnostics, modeling and further extensions of cross section and reaction rate databases that are necessary to address these challenges are discussed. The review focusses on non-equilibrium plasmas

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

Post-disaster social recovery: disaster governance lessons learnt from Tropical Cyclone Yasi

Post-disaster social recovery remains the least understood of the disaster phases despite increased risks of extreme events leading to disasters due to climate change. This paper contributes to advance this knowledge by focusing on the disaster recovery process of the Australian coastal town of Cardwell which was affected by category 4/5 Tropical Cyclone Yasi in 2011. Drawing on empirical data collected through semi-structured interviews with Cardwell residents post-Yasi, it examines issues related to social recovery in the first year of the disaster and 2 years later. Key findings discuss the role played by community members, volunteers and state actors in Cardwell’s post-disaster social recovery, especially with respect to how current disaster risk management trends based on self-reliance and shared responsibility unfolded in the recovery phase. Lessons learnt concerning disaster recovery governance are then extracted to inform policy implementation for disaster risk management to support social recovery and enhance disaster resilience in the light of climate change

Influence of inhalation injury on incidence, clinical profile and recovery pattern of dysphagia following burn injury

Inhalation injury is predictive of dysphagia post burns; however, the nature of dysphagia associated with inhalation burns is not well understood. This study describes the clinical profile and recovery pattern of swallowing following inhalation burn injury. All patients admitted 2008–2017 with confirmed inhalation burns on laryngoscopy and managed by speech-language pathology (SLP) were included. Initial dysphagia presentation and dysphagia recovery pattern were documented using the FOIS. Co-presence of dysphonia was determined clinically and rated present/absent. Persistent laryngeal/pharyngeal injury at 6\ua0months was documented using laryngoscopy. Data were compared to published data from a large adult burn cohort. All patients with confirmed inhalation burns during the study period received SLP input, enabling review of 38 patients (68% male; m = 40.8\ua0years). Percent Total Body Surface Area burn ranged 1–90%, 100% had head and neck burns, 97% required mechanical ventilation (mean 9.4\ua0days), 18% required tracheostomy and 100% had dysphonia. Comparing to non-inhalation burn patients, the inhalation cohort had significantly (p < 0.01) higher dysphagia incidence (89.47% vs 5.6%); more with severe dysphagia at presentation (78.9% vs 1.7%); increased duration to initiate oral intake (m = 24.69 vs 0.089\ua0days); longer duration of enteral feeding (m = 45.03 vs 1.96\ua0days); and longer duration to resolution of dysphagia (m = 29.79 vs 1.67\ua0days). Persistent laryngeal pathology was present in 47.37% at 6\ua0months. This study shows dysphagia incidence in burn patients with inhalation injury is 16 times greater than for those without inhalation injury. Laryngeal pathology due to inhalation injury increases dysphagia severity and duration to dysphagia recovery

Polygenic risk of spasmodic dysphonia is associated with vulnerable sensorimotor connectivity

Spasmodic dysphonia (SD), or laryngeal dystonia, is an isolated task-specific dystonia of unknown causes and pathophysiology that selectively affects speech production. Using next-generation whole-exome sequencing in SD patients, we computed polygenic risk score from 1804 genetic markers based on a genome-wide association study in another form of similar task-specific focal dystonia, musician's dystonia. We further examined the associations between the polygenic risk score, resting-state functional connectivity abnormalities within the sensorimotor network, and SD clinical characteristics. We found that the polygenic risk of dystonia was significantly associated with decreased functional connectivity in the left premotor/primary sensorimotor and inferior parietal cortices in SD patients. Reduced connectivity of the inferior parietal cortex was correlated with the age of SD onset. The polygenic risk score contained a significant number of genetic variants lying near genes related to synaptic transmission and neural development. Our study identified a polygenic contribution to the overall genetic risk of dystonia in the cohort of SD patients. Associations between the polygenic risk and reduced functional connectivity of the sensorimotor and inferior parietal cortices likely represent an endophenotypic imaging marker of SD, while genes involved in synaptic transmission and neuron development may be linked to the molecular pathophysiology of this disorder

Decoupling Interfacial Reactions between Plasmas and Liquids: Charge Transfer vs Plasma Neutral Reactions

Plasmas (gas discharges) formed at the surface of liquids can promote a complex mixture of reactions in solution. Here, we decouple two classes of reactions, those initiated by electrons (electrolysis) and those initiated by gaseous neutral species, by examining an atmospheric-pressure microplasma formed in different ambients at the surface of aqueous saline (NaCl) solutions. Electrolytic reactions between plasma electrons and aqueous ions yield an excess of hydroxide ions (OH^–), making the solution more basic, while reactions between reactive neutral species formed in the plasma phase and the solution lead to nitrous acid (HNO₂), nitric acid (HNO₃), and hydrogen peroxide (H₂O₂), making the solution more acidic. The relative importance of either reaction path is quantified by pH measurements, and we find that it depends directly on the composition of the ambient background gas. With a background gas of oxygen or argon, electron transfer reactions yielding excess OH^– dominate, while HNO₂ and HNO₃ formed in the plasma and by the dissolution of nitrogen oxide (NO_<i>x</i>) species dominate in the case of air and nitrogen. For pure nitrogen (N₂) gas, we observe a unique coupling between both reactions, where oxygen (O₂) gas formed via water electrolysis reacts in the bulk of the plasma to form NO_<i>x</i>, HNO₂, and HNO₃