Background: Efgartigimod, a human immunoglobulin G (IgG)1 antibody Fc fragment, blocks the neonatal Fc receptor, decreasing IgG recycling and reducing pathogenic IgG autoantibody levels. ADHERE assessed the efficacy and safety of efgartigimod PH20 subcutaneous (SC; co-formulated with recombinant human hyaluronidase PH20) in chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: ADHERE enrolled participants with CIDP (treatment naive or on standard treatments withdrawn during run-in period) and consisted of open-label Stage A (efgartigimod PH20 SC once weekly [QW]), and randomized (1:1) Stage B (efgartigimod or placebo QW). Primary outcomes were clinical improvement (assessed with aINCAT, I-RODS, or mean grip strength; Stage A) and time to first aINCAT score deterioration (relapse; Stage B). Secondary outcomes included treatment-emergent adverse events (TEAEs) incidence. Results: 322 participants entered Stage A. 214 (66.5%) were considered responders, randomized, and treated in Stage B. Efgartigimod significantly reduced the risk of relapse (HR: 0.394; 95% CI: 0.25–0.61) versus placebo (p=0.000039). Reduced risk of relapse occurred in participants receiving corticosteroids, intravenous or SC immunoglobulin, or no treatment before study entry. Most TEAEs were mild to moderate; 3 deaths occurred, none related to efgartigimod. Conclusions: Participants treated with efgartigimod PH20 SC maintained a clinical response and remained relapse-free longer than those treated with placebo.

We present the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY) Pilot Phase I Hi kinematic models. This first data release consists of Hi observations of three fields in the direction of the Hydra and Norma clusters, and the NGC 4636 galaxy group. In this paper, we describe how we generate and publicly release flat-disk tilted-ring kinematic models for 109/592 unique Hi detections in these fields. The modelling method adopted here—which we call the WALLABY Kinematic Analysis Proto-Pipeline (WKAPP) and for which the corresponding scripts are also publicly available—consists of combining results from the homogeneous application of the FAT and 3DBarolo algorithms to the subset of 209 detections with sufficient resolution and $S/N$ in order to generate optimised model parameters and uncertainties. The 109 models presented here tend to be gas rich detections resolved by at least 3–4 synthesised beams across their major axes, but there is no obvious environmental bias in the modelling. The data release described here is the first step towards the derivation of similar products for thousands of spatially resolved WALLABY detections via a dedicated kinematic pipeline. Such a large publicly available and homogeneously analysed dataset will be a powerful legacy product that that will enable a wide range of scientific studies.

We present WALLABY pilot data release 1, the first public release of H i pilot survey data from the Wide-field ASKAP L-band Legacy All-sky Blind Survey (WALLABY) on the Australian Square Kilometre Array Pathfinder. Phase 1 of the WALLABY pilot survey targeted three $60\,\mathrm{deg}^{2}$ regions on the sky in the direction of the Hydra and Norma galaxy clusters and the NGC 4636 galaxy group, covering the redshift range of $z \lesssim 0.08$ . The source catalogue, images and spectra of nearly 600 extragalactic H i detections and kinematic models for 109 spatially resolved galaxies are available. As the pilot survey targeted regions containing nearby group and cluster environments, the median redshift of the sample of $z \approx 0.014$ is relatively low compared to the full WALLABY survey. The median galaxy H i mass is $2.3 \times 10^{9}\,{\rm M}_{{\odot}}$ . The target noise level of $1.6\,\mathrm{mJy}$ per 30′′ beam and $18.5\,\mathrm{kHz}$ channel translates into a $5 \sigma$ H i mass sensitivity for point sources of about $5.2 \times 10^{8} \, (D_{\rm L} / \mathrm{100\,Mpc})^{2} \, {\rm M}_{{\odot}}$ across 50 spectral channels ( ${\approx} 200\,\mathrm{km \, s}^{-1}$ ) and a $5 \sigma$ H i column density sensitivity of about $8.6 \times 10^{19} \, (1 + z)^{4}\,\mathrm{cm}^{-2}$ across 5 channels ( ${\approx} 20\,\mathrm{km \, s}^{-1}$ ) for emission filling the 30′′ beam. As expected for a pilot survey, several technical issues and artefacts are still affecting the data quality. Most notably, there are systematic flux errors of up to several 10% caused by uncertainties about the exact size and shape of each of the primary beams as well as the presence of sidelobes due to the finite deconvolution threshold. In addition, artefacts such as residual continuum emission and bandpass ripples have affected some of the data. The pilot survey has been highly successful in uncovering such technical problems, most of which are expected to be addressed and rectified before the start of the full WALLABY survey.

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.

During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.

We present an indentation-scope that interfaces with confocal microscopy, enabling direct observation of the three-dimensional (3D) microstructural response of coatings on substrates. Using this method, we compared microns-thick polymer coatings on glass with and without silica nanoparticle filler. Bulk force data confirmed the >30% modulus difference, while microstructural data further revealed slip at the glass-coating interface. Filled coatings slipped more and about two times faster, as reflected in 3D displacement and von Mises strain fields. Overall, these data indicate that silica-doping of coatings can dramatically alter adhesion. Moreover, this method compliments existing theoretical and modeling approaches for studying indentation in layered systems.

Introduction: High-quality cardiopulmonary resuscitation (CPR) is essential for patient survival. Typically, CPR quality is only measured during the first 10 minutes of resuscitation. There is limited research examining the quality of CPR over the entire duration of resuscitation.Objective: To examine the quality of CPR over the entire duration of resuscitation and correlate the quality of CPR to patient survival. Methods: This was a retrospective observational study using data from the Toronto RescuNET Epistry-Cardiac Arrest database. We included consecutive, adult (>18) OHCA treated by EMS between January 1, 2014 and September 30, 2015. High-quality CPR was defined, in accordance with 2015 AHA Guidelines, as a chest compression rate of 100-120/min, depth of 5.0-6.0 cm and chest compression fraction (ccf) of >0.80. We further categorized high-quality resuscitation as meeting benchmarks >80% of the time, moderate-quality between 50-80% and low-quality meeting benchmarks <50% of the resuscitation. We used multivariable logistic regression to determine association between variables of interest, including CPR quality metrics, and survival to hospital discharge. Results: A total of 5,208 OHCA met our inclusion criteria with a survival rate of 8%. The median (IQR) duration of resuscitation was 23.0 min (15.0,32.7). Overall CPR quality was considered high-quality for ccf in 81% of resuscitation episodes, 41% for rate, and 7% for depth. The percentage of resuscitations meeting the quality benchmarks differed between survivors and non-survivors for both depth (15% vs 6%) and ccf (61% vs 83%) (P value <0.001). After controlling for Utstein variables maintaining a chest compression depth within recommendations for >80% showed a trend towards improved survival (OR 1.68, 95% CI 0.96, 2.92). Other variables associated with survival were public location, initial CPR by EMS providers or bystanders, witnessed cardiac arrest (EMS or bystander), and initial shockable rhythm. Increasing age and longer duration of resuscitation were associated with decreased survival. Conclusion: Overall, EMS providers were not able to maintain rate or depth within guideline recommendations for the majority of the duration of resuscitation. Maintaining chest compression depth for greater than 80% of the resuscitation showed a trend towards increased survival from OHCA.

The monocyte–lymphocyte ratio (MLR) is a useful biomarker for disease development, but little is known about the extent to which genetic and environmental factors influence MLR variation. Here, we study the genetic architecture of MLR and determine the influence of demographic and lifestyle factors on MLR in data from a Dutch non-patient twin-family population. Data were obtained in 9,501 individuals from the Netherlands Twin Register. We used regression analyses to determine the effects of age, sex, smoking, and body mass index (BMI) on MLR and its subcomponents. Data on twins, siblings and parents (N = 7,513) were analyzed by genetic structural equation modeling to establish heritability and genome wide single nucleotide polymorphism (SNP) data from a genotyped subsample (N = 5,892) and used to estimate heritability explained by SNPs. SNP and phenotype data were also analyzed in a genome-wide association study to identify the genes involved in MLR. Linkage disequilibrium (LD) score regression and expression quantitative trait loci (eQTL) analyses were performed to further explore the genetic findings. Results showed that age, sex, and age × sex interaction effects were present for MLR and its subcomponents. Variation in MLR was not related to BMI, but smoking was positively associated with MLR. Heritability was estimated at 40% for MLR, 58% for monocyte, and 58% for lymphocyte count. The Genome-wide association study (GWAS) identified a locus on ITGA4 that was associated with MLR and only marginally significantly associated with monocyte count. For monocyte count, additional genetic variants were identified on ITPR3, LPAP1, and IRF8. For lymphocyte count, GWAS provided no significant findings. Taking all measured SNPs together, their effects accounted for 13% of the heritability of MLR, while all known and identified genetic loci explained 1.3% of variation in MLR. eQTL analyses showed that these genetic variants were unlikely to be eQTLs. In conclusion, variation in MLR level in the general population is heritable and influenced by age, sex, and smoking. We identified gene variants in the ITGA4 gene associated with variation in MLR. The significant SNP-heritability indicates that more genetic variants are likely to be involved.

U-Th isochron ages of tufas formed on shorelines suggest that the last pluvial event in Lake Lahontan and Searles Lake was synchronous at about 16,500 cal yr B.P. (equivalent to a radiocarbon age of between 14,000 and 13,500 yr B.P.), whereas the timing of this pluvial event determined by radiocarbon dating is on the order of 1000 yr younger. The timing of seven distinct periods of near desiccation in Searles Lake during late-glacial time has been reinvestigated for U-Th age determination by mass spectrometry. U-Th dating of evaporite layers in the interbedded mud and salt unit called the Lower Salt in Searles Lake was hampered by the uncertainty in assessing the initial 230Th/232Th of the samples. The resulting ages, corrected by a conservative range of initial 230Th/232Th ratios, suggest close correlation of the abrupt changes recorded in Greenland ice cores (Dansgaard-Oeschger events) and wet–dry conditions in Searles Lake between 35,000 and 24,000 cal yr B.P.

The increasing demand for energy storage devices has propelled research for developing efficient super-capacitors (SC) with long cycle life and ultrahigh energy density. Carbon-based materials are commonly used as electrode materials for SC. Herein, we report a new approach to improve the SC performance utilizing a Porous Carbon/Cerium Oxide nanoparticle (PC-CON) hybrid as electrode material synthesized via a low temperature hydrothermal method. Through this approach, charges can be stored not only via electrochemical double layer capacitance (EDLC) from PC but also through pseudo-capacitive effect from CeO2 nanoparticles (NPs). The electrode-electrolyte interaction due to the electrochemical properties of the electrolyte provides an enhanced voltage window for the SC. Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectroscopy (XPS), and X-Ray Diffraction (XRD) measurements were used for the characterization of this PC/CeO2 hybrid material system. The testing results have shown that a maximum of 500% higher specific capacitance could be obtained using PC/CeO2 instead of using PC only.

Malaysia introduced graphic health warning labels (GHWLs) on all tobacco packages in 2009. We aimed to examine if implementing GHWLs led to stronger warning reactions (e.g., thinking about the health risks of smoking) and an increase in subsequent quitting activities; and to examine how reactions changed over time since the implementation of the GHWLs in Malaysia and Thailand where GHWL size increased from 50–55% in 2010. Data came from six waves (2005–2014) of the International Tobacco Control Southeast Asia Survey. Between 3,706 and 4,422 smokers were interviewed across these two countries at each survey wave. Measures included salience of warnings, cognitive responses (i.e., thinking about the health risks and being more likely to quit smoking), forgoing cigarettes, and avoiding warnings. The main outcome was subsequent quit attempts. Following the implementation of GHWLs in Malaysia, reactions increased, in some cases to levels similar to the larger Thai warnings, but declined over time. In Thailand, reactions increased following implementation, with no decline for several years, and no clear effect of the small increase in warning size. Reactions, mainly cognitive responses, were consistently predictive of quit attempts in Thailand, but this was only consistently so in Malaysia after the change to GHWLs. In conclusion, GHWLs are responded to more frequently, and generate more quit attempts, but warning wear-out is not consistent in these two countries, perhaps due to differences in other tobacco control efforts.

The phenomena of surface instabilities in a thin power-law fluid during spin coating are investigated. The set of Navier-Stokes equations with non-Newtonian behavior in the region of low Reynolds number serves as a mathematical description of the physical systems. Long-wave perturbation analysis is proposed to derive an evolution equation of the Ostwald de-Waele type fluid to govern the propagation of surface waves. Weakly nonlinear dynamics of film flow is studied by the multiple scales method. The amplitude of instability is determined by a Ginzburg-Landau equation. The study reveals that the degree of power-law index plays a vital role in stabilizing the film flow. The shear-thinning fluid is more unstable than the shear-thickening fluid in the stability analysis. Further, the nonlinear wave speed in the supercritical stability region decreases with increasing values of power-law index.