Signature and escape of highly fractionated plasma in an active region

Accurate forecasting of space weather requires knowledge of the source regions where solar energetic particles (SEP) and eruptive events originate. Recent work has linked several major SEP events in 2014, January, to specific features in the host active region (AR 11944). In particular, plasma composition measurements in and around the footpoints of hot, coronal loops in the core of the active region were able to explain the values later measured in situ by the Wind spacecraft. Due to important differences in elemental composition between SEPs and the solar wind, the magnitude of the Si/S elemental abundance ratio emerged as a key diagnostic of SEP seed population and solar wind source locations. We seek to understand if the results are typical of other active regions, even if they are not solar wind sources or SEP productive. In this paper, we use a novel composition analysis technique, together with an evolutionary magnetic field model, in a new approach to investigate a typical solar active region (AR 11150), and identify the locations of highly fractionated (high Si/S abundance ratio) plasma. Material confined near the footpoints of coronal loops, as in AR 11944, that in this case have expanded to the AR periphery, show the signature, and can be released from magnetic field opened by reconnection at the AR boundary. Since the fundamental characteristics of closed field loops being opened at the AR boundary is typical of active regions, this process is likely to be general

The source of the major solar energetic particle events from super active region 11944

Shock waves associated with fast coronal mass ejections (CMEs) accelerate solar energetic particles (SEPs) in the long duration, gradual events that pose hazards to crewed spaceflight and near-Earth technological assets, but the source of the CME shock-accelerated plasma is still debated. Here, we use multi-messenger observations from the Heliophysics System Observatory to identify plasma confined at the footpoints of the hot, core loops of active region 11944 as the source of major gradual SEP events in January 2014. We show that the elemental composition signature detected spectroscopically at the footpoints explains the measurements made by particle counting techniques near Earth. Our results localize the elemental fractionation process to the top of the chromosphere. The plasma confined closest to that region, where the coronal magnetic field strength is high (a few hundred Gauss), develops the SEP composition signature. This source material is continually released from magnetic confinement and accelerated as SEPs following M-, C-, and X-class flares

Activity of chitosan and its derivatives against Leishmania major and L. mexicana in vitro

There is an urgent need for safe, efficacious, affordable and field-adapted drugs for the treatment of cutaneous leishmaniasis which affects around 1.5 million new people worldwide annually. Chitosan, a biodegradable cationic polysaccharide, has previously been reported to have antimicrobial, anti-leishmanial and immunostimulatory activities. We investigated the in vitro activity of chitosan and several of its derivatives and showed that pH of the culture medium plays a critical role on anti-leishmanial activity of chitosan against both extracellular promastigotes and intracellular amastigotes of Leishmania major and Leishmania mexicana Chitosan and its derivatives were approximately 7-20 times more active at pH 6.5 than at pH 7.5 with high molecular weight chitosan being the most potent. High molecular weight chitosan stimulated the production of nitric oxide and reactive oxygen species by uninfected and Leishmania infected macrophages in a time and dose dependent manner at pH 6.5. Despite the in vitro activation of bone marrow macrophages by chitosan to produce nitric oxide and reactive oxygen species, we showed that the anti-leishmanial activity of chitosan was not mediated by these metabolites. Finally, we showed that rhodamine-labelled chitosan is taken up by pinocytosis and accumulates in the parasitophorous vacuole of Leishmania infected macrophages

Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

AmBisome® (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with Fungizone® (DAmB), the deoxycholate form of AmB, in murine models of Leishmania major CL. Drug levels at the target site (the localized lesion) 48 hours after single intravenous (IV) dosing of the individual AmB formulations (1 mg/kg of body weight) were similar, but were 3-fold higher for LAmB than for DAmB on day 10 after multiple administrations (1 mg/kg on days 0, 2, 4, 6 and 8). After single and multiple dosing, intralesional concentrations were respectively 5- and 20-fold higher compared to those in the healthy control skin of the same infected mice. We then evaluated how drug levels in the lesion after LAmB treatment relate to therapeutic outcomes. After five administrations of the drug at 0, 6.25 or 12.5 mg/kg (IV), there was a clear correlation between dose level, intralesional AmB concentration and relative reduction in parasite load and lesion size (R2 values > 0.9). This study confirms the improved efficacy of the liposomal over the deoxycholate AmB formulation in experimental CL, which is related to higher intralesional drug accumulation

Evolution of the magnetic field distribution of active regions

AIMS: Although the temporal evolution of active regions (ARs) is relatively well understood, the processes involved continue to be the subject of investigation. We study how the magnetic field of a series of ARs evolves with time to better characterise how ARs emerge and disperse. METHODS: We examined the temporal variation in the magnetic field distribution of 37 emerging ARs. A kernel density estimation plot of the field distribution was created on a log-log scale for each AR at each time step. We found that the central portion of the distribution is typically linear, and its slope was used to characterise the evolution of the magnetic field. RESULTS: The slopes were seen to evolve with time, becoming less steep as the fragmented emerging flux coalesces. The slopes reached a maximum value of ∼-1.5 just before the time of maximum flux before becoming steeper during the decay phase towards the quiet-Sun value of ∼-3. This behaviour differs significantly from a classical diffusion model, which produces a slope of -1. These results suggest that simple classical diffusion is not responsible for the observed changes in field distribution, but that other processes play a significant role in flux dispersion. CONCLUSIONS. We propose that the steep negative slope seen during the late-decay phase is due to magnetic flux reprocessing by (super)granular convective cells

Project evaluation “classroom of the future”

U uvjetima sve veće informatizacije društva, kada znanja postaju osnovni proizvodni resurs, od institucije škole očekuje se da zauzme ulogu predvodnika promjena. Obrazovni sustav mora biti osjetljiv i adaptabilan kako bi postao generator promjena i stalni pratitelj boljeg i kvalitetnijeg rada škole te obrazovanja kao cjeline. Danas se sve više naglašava potreba za obrazovanjem zasnovanom na metodama koje koriste informacijske i komunikacijske tehnologije zbog čega je naše istraživanje bilo usmjereno na procjenu stupnja iskorištenosti suvremenih nastavih sredstava i kvaliteta nastave u “Učionici budućnosti” gimnazije Frana Galovića u Koprivnici. Istraživanje je provedeno na 52 nastavnika navedene škole s ciljem ocjene trenutnog stanja u vezi sa stupnjem korištenja informacijskih tehnologija u nastavi te efektima njihove primjene. To je tek preliminarno istraživanje koje otvara mogućnosti za daljnja istraživanja o suvremenim metodama poučavanja baziranim na korištenju novih informacijskih tehnologija. Dobiveni rezultati upućuju na promišljanje o uspješnosti i kvaliteti korištenja informacijske i komunikacijske tehnologije, praćenje napretka te nude prijedloga od strane nastavnika za njihov daljnji razvoj.In terms of increasing computerization of society, where knowledge is becoming a basic production resource, it is expected that the school as an educational institution takes a leading role in these changes. The education system must be responsive and adaptive to become a generator of change and constant companion of a high quality school work and education as a whole. Today, the need for education based on methods that use information and communication technology is more and more emphasized, which is why our research was focused on evaluating the degree of utilization of modern means of teaching and the quality of teaching in the “classroom of the future” of the Gymnasium Fran Galović in Koprivnica. The study involved 52 teachers of the mentioned school in order to evaluate the current situation in relation to the degree of use of information technology in teaching and the effects of their use. It is only a preliminary study that opens up opportunities for further research in modern teaching methods based on the use of new information technologies. The results indicate reflection on the success and quality of the information and communication technology, tracking progress and offer suggestions from teachers for their further development

Evolution of Plasma Composition in an Eruptive Flux Rope

Magnetic flux ropes are bundles of twisted magnetic field enveloping a central axis. They harbor free magnetic energy and can be progenitors of coronal mass ejections (CMEs). However, identifying flux ropes on the Sun can be challenging. One of the key coronal observables that has been shown to indicate the presence of a flux rope is a peculiar bright coronal structure called a sigmoid. In this work, we show Hinode EUV Imaging Spectrometer observations of sigmoidal active region (AR) 10977. We analyze the coronal plasma composition in the AR and its evolution as a sigmoid (flux rope) forms and erupts as a CME. Plasma with photospheric composition was observed in coronal loops close to the main polarity inversion line during episodes of significant flux cancellation, suggestive of the injection of photospheric plasma into these loops driven by photospheric flux cancellation. Concurrently, the increasingly sheared core field contained plasma with coronal composition. As flux cancellation decreased and a sigmoid/flux rope formed, the plasma evolved to an intermediate composition in between photospheric and typical AR coronal compositions. Finally, the flux rope contained predominantly photospheric plasma during and after a failed eruption preceding the CME. Hence, plasma composition observations of AR 10977 strongly support models of flux rope formation by photospheric flux cancellation forcing magnetic reconnection first at the photospheric level then at the coronal level

Intervention planning and modification of the BUMP intervention: a digital intervention for the early detection of raised blood pressure in pregnancy

Background: Hypertensive disorders in pregnancy, particularly pre-eclampsia, pose a substantial health risk for both maternal and foetal outcomes. The BUMP (Blood Pressure Self-Monitoring in Pregnancy) interventions are being tested in a trial. They aim to facilitate the early detection of raised blood pressure through self-monitoring. This article outlines how the self-monitoring interventions in the BUMP trial were developed and modified using the person-based approach to promote engagement and adherence. Methods: Key behavioural challenges associated with blood pressure self-monitoring in pregnancy were identified through synthesising qualitative pilot data and existing evidence, which informed guiding principles for the development process. Social cognitive theory was identified as an appropriate theoretical framework. A testable logic model was developed to illustrate the hypothesised processes of change associated with the intervention. Iterative qualitative feedback from women and staff informed modifications to the participant materials. Results: The evidence synthesis suggested women face challenges integrating self-monitoring into their lives and that adherence is challenging at certain time points in pregnancy (for example, starting maternity leave). Intervention modification included strategies to address adherence but also focussed on modifying outcome expectancies, by providing messages explaining pre-eclampsia and outlining the potential benefits of self-monitoring. Conclusions: With an in-depth understanding of the target population, several methods and approaches to plan and develop interventions specifically relevant to pregnant women were successfully integrated, to address barriers to behaviour change while ensuring they are easy to engage with, persuasive and acceptable

Measurement properties of the Dizziness Handicap Inventory by cross-sectional and longitudinal designs

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

Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Donepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD), was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d.</p> <p>Method</p> <p>Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs) and their relationship to treatment initiation; changes in weight, electrocardiogram, vital signs, and laboratory parameters; and the incidence of premature study discontinuation. The analysis population (n = 1434) included all randomized patients who took at least 1 dose of study drug and had a postbaseline safety assessment. To further examine the effect of transition from a lower to a higher donepezil dose, a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed.</p> <p>Results</p> <p>The safety population comprised 1434 patients: donepezil 23 mg/d (n = 963); donepezil 10 mg/d (n = 471); completion rates were 71.1% and 84.7%, respectively. The most common AEs were nausea, vomiting, and diarrhea (donepezil 23 mg/d: 11.8%, 9.2%, 8.3%; donepezil 10 mg/d: 3.4%, 2.5%, 5.3%, respectively). AEs that contributed most to early discontinuations were vomiting (2.9% of patients in the 23 mg/d group and 0.4% in the 10 mg/d group), nausea (1.9% and 0.4%), diarrhea (1.7% and 0.4%), and dizziness (1.1% and 0.0%). The percentages of patients with AEs in the 23 mg/d group, as well as the timing, type, and severity of these AEs, were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d. Serious AEs were uncommon (23 mg/d, 8.3%; 10 mg/d, 9.6%).</p> <p>Discussion</p> <p>The 23 mg/d dose of donepezil was associated with typical cholinergic AEs, particularly gastrointestinal-related AEs, similar to those observed in studies with a dose increase from 5 to 10 mg/d.</p> <p>Conclusion</p> <p>The good safety and predictable tolerability profile for donepezil 23 mg/d supports its favorable risk/benefit ratio in patients with moderate to severe AD.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00478205">NCT00478205</a></p