Antiferromagnetic Order in MnO Spherical Nanoparticles

We have performed unpolarized and polarized neutron diffraction experiments on monodisperse 8 nm and 13 nm antiferromagnetic MnO nanoparticles. For the 8 nm sample, the antiferromagnetic transition temperature $T_N$ (114 K) is suppressed compared to the bulk material (119 K) while for the 13 nm sample $T_N$ (120 K) is comparable to the bulk. The neutron diffraction data of the nanoparticles is well described using the bulk MnO magnetic structure but with a substantially reduced average magnetic moment of 4.2$\pm$0.3 $\mu_B$/Mn for the 8 nm sample and 3.9$\pm$0.2 $\mu_B$/Mn for the 13 nm sample. An analysis of the polarized neutron data on both samples shows that in an individual MnO nanoparticle about 80$$ of Mn ions order. These results can be explained by a structure in which the monodisperse nanoparticles studied here have a core that behaves similar to the bulk with a surface layer which does not contribute significantly to the magnetic order.Comment: 7 pages, 5 figure

Chinese herbal medicine granules (PTQX) for children with moderate to severe atopic eczema: Study protocol for a randomised controlled trial

Background: Atopic eczema or atopic dermatitis is a chronic inflammatory skin disease. Current conventional medical treatment for moderate and severe atopic eczema is not satisfactory. There is promising evidence derived from randomised clinical trials to support the clinical use of Chinese herbal medicine in the management of atopic eczema. However, the available evidence is compromised by the high risk of bias associated with most of the included trials. Therefore, well-designed and adequately powered randomised clinical trials are needed. The primary aim of this trial is to evaluate the efficacy and safety of oral ingestion of an oral Chinese herbal formula (Pei Tu Qing Xin granules; PTQX) in children aged between 6 and 16 years with moderate to severe atopic eczema. Methods/Design: We have designed a randomised, double-blind, placebo-controlled, two-arm, parallel clinical trial with 12 weeks of treatment and a 4-week follow-up period. A pilot study with 30 participants will be conducted at the RMIT University in Australia to determine the feasibility of the full-scale randomised clinical trial (N = 124). Eczema Area and Severity Index score will be the primary outcome. Secondary outcome measures include change in symptoms using the Patient-Oriented Eczema Measure, the Children's Dermatology Life Quality Index and the use of concomitant medicines. Safety parameters include report of adverse events and pathology tests during the trial period. Discussion: Key elements for conducting a high-quality randomised clinical trial have been addressed in this protocol. Findings from the proposed trial will provide critical evidence regarding Chinese herbal medicine treatment for atopic eczema

Using hydraulic head, chloride and electrical conductivity data to distinguish between mountain-front and mountain-block recharge to basin aquifers

This work is distributed under the Creative Commons Attribution 4.0 License.Numerous basin aquifers in arid and semi-arid regions of the world derive a significant portion of their recharge from adjacent mountains. Such recharge can effectively occur through either stream infiltration in the mountain-front zone (mountain-front recharge, MFR) or subsurface flow from the mountain (mountain-block recharge, MBR). While a thorough understanding of recharge mechanisms is critical for conceptualizing and managing groundwater systems, distinguishing between MFR and MBR is difficult. We present an approach that uses hydraulic head, chloride and electrical conductivity (EC) data to distinguish between MFR and MBR. These variables are inexpensive to measure, and may be readily available from hydrogeological databases in many cases. Hydraulic heads can provide information on groundwater flow directions and stream–aquifer interactions, while chloride concentrations and EC values can be used to distinguish between different water sources if these have a distinct signature. Such information can provide evidence for the occurrence or absence of MFR and MBR. This approach is tested through application to the Adelaide Plains basin, South Australia. The recharge mechanisms of this basin have long been debated, in part due to difficulties in understanding the hydraulic role of faults. Both hydraulic head and chloride (equivalently, EC) data consistently suggest that streams are gaining in the adjacent Mount Lofty Ranges and losing when entering the basin. Moreover, the data indicate that not only the Quaternary aquifers but also the deeper Tertiary aquifers are recharged through MFR and not MBR. It is expected that this finding will have a significant impact on the management of water resources in the region. This study demonstrates the relevance of using hydraulic head, chloride and EC data to distinguish between MFR and MBR

Size matters: the value of small populations for wintering waterbirds

Protecting systematically selected areas of land is a major step towards biodiversity conservation worldwide. Indeed, the identification and designation of protected areas more often than not forms a core component of both national and international conservation policies. In this paper we provide an overview of those Special Protection Areas and Ramsar Sites that have been classified in Great Britain as of 1998/99 for a selection of wintering waterbird species, using bird count data from the Wetland Bird Survey. The performance of this network of sites is remarkable, particularly in comparison with published analyses of networks elsewhere in the world. Nevertheless, the current site-based approach, whilst having the great benefit of simplicity, is deliberately biased towards aggregating species at the expense of the more dispersed distribution species. To ensure that the network continues successfully to protect nationally and internationally important waterbird populations, efforts now need to concentrate on the derivation of species-specific representation targets and, in particular, the ways in which these can be incorporated into the site selection process. Although these analyses concern the performance of protected areas for waterbirds in Great Britain, the results have wide-ranging importance for conservation planning in general and the design of protected area networks

LPMLE3 : a novel 1-D approach to study water flow in streambeds using heat as a tracer

We introduce LPMLE3, a new 1-D approach to quantify vertical water flow components at streambeds using temperature data collected in different depths. LPMLE3 solves the partial differential equation for coupled water flow and heat transport in the frequency domain. Unlike other 1-D approaches it does not assume a semi-infinite halfspace with the location of the lower boundary condition approaching infinity. Instead, it uses local upper and lower boundary conditions. As such, the streambed can be divided into finite subdomains bound at the top and bottom by a temperature-time series. Information from a third temperature sensor within each subdomain is then used for parameter estimation. LPMLE3 applies a low order local polynomial to separate periodic and transient parts (including the noise contributions) of a temperature-time series and calculates the frequency response of each subdomain to a known temperature input at the streambed top. A maximum-likelihood estimator is used to estimate the vertical component of water flow, thermal diffusivity, and their uncertainties for each streambed subdomain and provides information regarding model quality. We tested the method on synthetic temperature data generated with the numerical model STRIVE and demonstrate how the vertical flow component can be quantified for field data collected in a Belgian stream. We show that by using the results in additional analyses, nonvertical flow components could be identified and by making certain assumptions they could be quantified for each subdomain. LPMLE3 performed well on both simulated and field data and can be considered a valuable addition to the existing 1-D methods

Amiloride, fluoxetine or riluzole to reduce brain volume loss in secondary progressive multiple sclerosis: the MS-SMART four-arm RCT

Background: Neuroprotective drugs are needed to slow or prevent neurodegeneration and disability accrual in secondary progressive multiple sclerosis. Amiloride, fluoxetine and riluzole are repurposed drugs with potential neuroprotective effects. Objectives: To assess whether or not amiloride, fluoxetine and riluzole can reduce the rate of brain volume loss in people with secondary progressive multiple sclerosis over 96 weeks. The secondary objectives that were assessed were feasibility of a multiarm trial design approach, evaluation of anti-inflammatory effects, clinician- and patient-reported efficacy and three mechanistic substudies. Design: A multicentre, multiarm, randomised, double-blind, placebo-controlled, parallel-group Phase IIb trial with follow-up at 4, 8, 12, 24, 36, 48, 72 and 96 weeks. Patients, investigators (including magnetic resonance imaging analysts), and treating and independent assessing neurologists were blinded to the treatment allocation. The target sample size was 440 patients. Setting: Thirteen UK clinical neuroscience centres. Participants: Participants were aged 25–65 years, had secondary progressive multiple sclerosis with evidence of disease progression independent of relapses in the previous 2 years, and had an Expanded Disability Status Scale score of 4.0–6.5. Patients were ineligible if they could not have a magnetic resonance imaging scan; had a relapse or steroids in the previous 3 months; or had epilepsy, depression, bipolar disorder, glaucoma, bleeding disorders or significant organ comorbidities. Exclusion criteria were concurrent disease-modified treatments, immunosuppressants or selective serotonin reuptake inhibitors. Interventions: Participants received amiloride (5 mg), fluoxetine (20 mg), riluzole (50 mg) or placebo (randomised 1 : 1 : 1 : 1) twice daily. Main outcome measures: The primary end point was magnetic resonance imaging-derived percentage brain volume change at 96 weeks. Secondary end points were new/enlarging T2 lesions, pseudoatrophy, and clinician- and patient-reported measures (including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Symbol Digit Modalities Test, low-contrast letter visual acuity, Multiple Sclerosis Impact Scale 29 items, version 2, Multiple Sclerosis Walking Scale, version 2, and questionnaires addressing pain and fatigue). The exploratory end points included measures of persistent new T1 hypointensities and grey matter volume changes. The substudies were advanced magnetic resonance imaging, optical coherence tomography and cerebrospinal fluid analyses. Results: Between December 2014 and June 2016, 445 patients were randomised (analysed) to amiloride [n = 111 (99)], fluoxetine [n = 111 (96)], riluzole [n = 111 (99)] or placebo [n = 112 (99)]. A total of 206 randomised patients consented to the advanced magnetic resonance imaging substudy, 260 consented to the optical coherence tomography substudy and 70 consented to the cerebrospinal fluid substudy. No significant difference was seen between the active drugs and placebo in percentage brain volume change at week 96 as follows (where negative values mean more atrophy than placebo): amiloride minus placebo 0.0% (Dunnett-adjusted 95% confidence interval –0.4% to 0.5%), fluoxetine minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.5% to 0.3%); riluzole minus placebo –0.1% (Dunnett-adjusted 95% confidence interval –0.6% to 0.3%). There was good adherence to study drugs. The proportion of patients experiencing adverse events was similar in the treatment and placebo groups. There were no emergent safety issues. Limitations: There was a lower than expected uptake in the cerebrospinal fluid substudy. Conclusions: A multiarm Phase II paradigm is efficient in determining which neuroprotective agents to take through to Phase III trials. Amiloride, fluoxetine and riluzole were not effective in reducing the brain atrophy rate in people with secondary progressive multiple sclerosis. Mechanistic pathobiological insight was gained. Future work: To use the information gained from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) to inform future trial design as new candidate agents are identified. Trial registration: Current Controlled Trials ISRCTN28440672, NCT01910259 and EudraCT 2012-005394-31. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 3. See the NIHR Journals Library website for further project information. This trial also received funding from the UK MS Society and the US National Multiple Sclerosis Society

Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART):a phase 2b, multiarm, double-blind, randomised placebo-controlled trial

Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource. Methods: We did a phase 2b, multiarm, parallel group, double-blind, randomised placebo-controlled trial at 13 clinical neuroscience centres in the UK. We recruited patients (aged 25-65 years) with secondary progressive multiple sclerosis who were not on disease-modifying treatment and who had an Expanded Disability Status Scale (EDSS) score of 4·0-6·5. Participants were randomly assigned (1:1:1:1) at baseline, by a research nurse using a centralised web-based service, to receive twice-daily oral treatment of either amiloride 5 mg, fluoxetine 20 mg, riluzole 50 mg, or placebo for 96 weeks. The randomisation procedure included minimisation based on sex, age, EDSS score at randomisation, and trial site. Capsules were identical in appearance to achieve masking. Patients, investigators, and MRI readers were unaware of treatment allocation. The primary outcome measure was volumetric MRI percentage brain volume change (PBVC) from baseline to 96 weeks, analysed using multiple regression, adjusting for baseline normalised brain volume and minimisation criteria. The primary analysis was a complete-case analysis based on the intention-to-treat population (all patients with data at week 96). This trial is registered with ClinicalTrials.gov, NCT01910259