IgG and IgA autoantibodies against L1 ORF1p expressed in granulocytes correlate with granulocyte consumption and disease activity in pediatric systemic lupus erythematosus

BACKGROUND: Most patients with systemic lupus erythematosus (SLE) have IgG autoantibodies against the RNA-binding p40 (ORF1p) protein encoded by the L1 retroelement. This study tested if these autoantibodies are also present in children with pediatric SLE (pSLE) and if the p40 protein itself could be detected in immune cells. METHODS: Autoantibodies in the plasma of pSLE patients (n = 30), healthy children (n = 37), and disease controls juvenile idiopathic arthritis (JIA) (n = 32) and juvenile dermatomyositis (JDM) (n = 60), were measured by ELISA. Expression of p40 in immune cells was assessed by flow cytometry. Markers of neutrophil activation and death were quantitated by ELISA. RESULTS: IgG and IgA autoantibodies reactive with p40 were detected in the pSLE patients, but were low in healthy controls and in JIA or JDM. pSLE patients with active disease (13 of them newly diagnosed) had higher titers than the same patients after effective therapy (p = 0.0003). IgG titers correlated with SLEDAI (r = 0.65, p = 0.0001), ESR (r = 0.43, p = 0.02), and anti-dsDNA antibodies (r = 0.49, p < 0.03), and inversely with complement C3 (r = -0.55, p = 0.002) and C4 (r = -0.51, p = 0.006). p40 protein was detected in a subpopulation of CD66b(+) granulocytes in pSLE, as well as in adult SLE patients. Myeloperoxidase and neutrophil elastase complexed with DNA and the neutrophil-derived S100A8/A9 were elevated in plasma from pSLE patients with active disease and correlated with anti-p40 autoantibodies and disease activity. CONCLUSIONS: Children with active SLE have elevated IgG and IgA autoantibodies against L1 p40, and this protein can be detected in circulating granulocytes in both pediatric and adult SLE patients. P40 expression and autoantibody levels correlate with disease activity. Markers of neutrophil activation and death also correlate with these autoantibodies and with disease activity, suggesting that neutrophils express L1 and are a source of p40. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-021-02538-3

TOWARD TARGET 2 OF THE GLOBAL STRATEGY FOR PLANT CONSERVATION: AN EXPERT ANALYSIS OF THE PUERTO RICAN FLORA TO VALIDATE NEW STREAMLINED METHODS FOR ASSESSING CONSERVATION STATUS

Target 2 of the 2020 Global Strategy for Plant Conservation (GSPC) calls for a comprehensive list of the world\u27s threatened plant species. The lack of such a list is one of the greatest impediments to protecting the full complement of the world\u27s plant species, and work to achieve this has been slow. An efficient system for identifying those species that are at risk of extinction could help to achieve this goal in a time frame sensitive to today\u27s conservation needs. Two systems that efficiently use available data to assess conservation status were tested against a provisional International Union for Conservation of Nature and Natural Resources (IUCN) Red List analysis to evaluate the native seed plant species of Puerto Rico. It was demonstrated that both systems efficiently identify species at risk, which is a step toward both the GSPC Target 2 and a more comprehensive IUCN Red List for plants. Both systems were effective at identifying plant species at risk, with the New York analysis identifying 98% and the Smithsonian analysis 85% of the plant species considered Threatened in the IUCN Red List. Both analyses to some extent overestimated those plants at risk, but the species identified are all range restricted and, thus, of some conservation interest

Observations of the 2019 April 4 Solar Energetic Particle Event at the Parker Solar Probe

A solar energetic particle event was detected by the Integrated Science Investigation of the Sun (IS⊙IS) instrument suite on Parker Solar Probe (PSP) on 2019 April 4 when the spacecraft was inside of 0.17 au and less than 1 day before its second perihelion, providing an opportunity to study solar particle acceleration and transport unprecedentedly close to the source. The event was very small, with peak 1 MeV proton intensities of ~0.3 particles (cm² sr s MeV)⁻¹, and was undetectable above background levels at energies above 10 MeV or in particle detectors at 1 au. It was strongly anisotropic, with intensities flowing outward from the Sun up to 30 times greater than those flowing inward persisting throughout the event. Temporal association between particle increases and small brightness surges in the extreme-ultraviolet observed by the Solar TErrestrial RElations Observatory, which were also accompanied by type III radio emission seen by the Electromagnetic Fields Investigation on PSP, indicates that the source of this event was an active region nearly 80° east of the nominal PSP magnetic footpoint. This suggests that the field lines expanded over a wide longitudinal range between the active region in the photosphere and the corona

Solar Energetic Particles Produced by a Slow Coronal Mass Ejection at ∼0.25 au

We present an analysis of Parker Solar Probe (PSP) IS⊙IS observations of ~30–300 keV n⁻¹ ions on 2018 November 11 when PSP was about 0.25 au from the Sun. Five hours before the onset of a solar energetic particle (SEP) event, a coronal mass ejection (CME) was observed by STEREO-A/COR2, which crossed PSP about a day later. No shock was observed locally at PSP, but the CME may have driven a weak shock earlier. The SEP event was dispersive, with higher energy ions arriving before the lower energy ones. Timing suggests the particles originated at the CME when it was at ~7.4R_⊙. SEP intensities increased gradually from their onset over a few hours, reaching a peak, and then decreased gradually before the CME arrived at PSP. The event was weak, having a very soft energy spectrum (−4 to −5 spectral index). The earliest arriving particles were anisotropic, moving outward from the Sun, but later, the distribution was observed to be more isotropic. We present numerical solutions of the Parker transport equation for the transport of 30–300 keV n⁻¹ ions assuming a source comoving with the CME. Our model agrees well with the observations. The SEP event is consistent with ion acceleration at a weak shock driven briefly by the CME close to the Sun, which later dissipated before arriving at PSP, followed by the transport of ions in the interplanetary magnetic field

Energetic Particle Increases Associated with Stream Interaction Regions

The Parker Solar Probe was launched on 2018 August 12 and completed its second orbit on 2019 June 19 with perihelion of 35.7 solar radii. During this time, the Energetic Particle Instrument-Hi (EPI-Hi, one of the two energetic particle instruments comprising the Integrated Science Investigation of the Sun, IS⊙IS) measured seven proton intensity increases associated with stream interaction regions (SIRs), two of which appear to be occurring in the same region corotating with the Sun. The events are relatively weak, with observed proton spectra extending to only a few MeV and lasting for a few days. The proton spectra are best characterized by power laws with indices ranging from −4.3 to −6.5, generally softer than events associated with SIRs observed at 1 au and beyond. Helium spectra were also obtained with similar indices, allowing He/H abundance ratios to be calculated for each event. We find values of 0.016–0.031, which are consistent with ratios obtained previously for corotating interaction region events with fast solar wind ≤ 600 km s⁻¹. Using the observed solar wind data combined with solar wind simulations, we study the solar wind structures associated with these events and identify additional spacecraft near 1 au appropriately positioned to observe the same structures after some corotation. Examination of the energetic particle observations from these spacecraft yields two events that may correspond to the energetic particle increases seen by EPI-Hi earlier

Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

Analysing and Recommending Options for Maintaining Universal Coverage with Long-Lasting Insecticidal Nets: The Case of Tanzania in 2011.

Tanzania achieved universal coverage with long-lasting insecticidal nets (LLINs) in October 2011, after three years of free mass net distribution campaigns and is now faced with the challenge of maintaining high coverage as nets wear out and the population grows. A process of exploring options for a continuous or "Keep-Up" distribution system was initiated in early 2011. This paper presents for the first time a comprehensive national process to review the major considerations, findings and recommendations for the implementation of a new strategy. Stakeholder meetings and site visits were conducted in five locations in Tanzania to garner stakeholder input on the proposed distribution systems. Coverage levels for LLINs and their decline over time were modelled using NetCALC software, taking realistic net decay rates, current demographic profiles and other relevant parameters into consideration. Costs of the different distribution systems were estimated using local data. LLIN delivery was considered via mass campaigns, Antenatal Care-Expanded Programme on Immunization (ANC/EPI), community-based distribution, schools, the commercial sector and different combinations of the above. Most approaches appeared unlikely to maintain universal coverage when used alone. Mass campaigns, even when combined with a continuation of the Tanzania National Voucher Scheme (TNVS), would produce large temporal fluctuations in coverage levels; over 10 years this strategy would require 63.3 million LLINs and a total cost of $444 million USD. Community mechanisms, while able to deliver the required numbers of LLINs, would require a massive scale-up in monitoring, evaluation and supervision systems to ensure accurate application of identification criteria at the community level. School-based approaches combined with the existing TNVS would reach most Tanzanian households and deliver 65.4 million LLINs over 10 years at a total cost of$449 million USD and ensure continuous coverage. The cost of each strategy was largely driven by the number of LLINs delivered. The most cost-efficient strategy to maintain universal coverage is one that best optimizes the numbers of LLINs needed over time. A school-based approach using vouchers targeting all students in Standards 1, 3, 5, 7 and Forms 1 and 2 in combination with the TNVS appears to meet best the criteria of effectiveness, equity and efficiency

GrassPlot v. 2.00 – first update on the database of multi-scale plant diversity in Palaearctic grasslands

Abstract: GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). Following a previous Long Database Report (Dengler et al. 2018, Phyto- coenologia 48, 331–347), we provide here the first update on content and functionality of GrassPlot. The current version (GrassPlot v. 2.00) contains a total of 190,673 plots of different grain sizes across 28,171 independent plots, with 4,654 nested-plot series including at least four grain sizes. The database has improved its content as well as its functionality, including addition and harmonization of header data (land use, information on nestedness, structure and ecology) and preparation of species composition data. Currently, GrassPlot data are intensively used for broad-scale analyses of different aspects of alpha and beta diversity in grassland ecosystems

The cost of changing physical activity behaviour: Evidence from a "physical activity pathway" in the primary care setting

Copyright @ 2011 Boehler et al.BACKGROUND: The ‘Physical Activity Care Pathway’ (a Pilot for the ‘Let’s Get Moving’ policy) is a systematic approach to integrating physical activity promotion into the primary care setting. It combines several methods reported to support behavioural change, including brief interventions, motivational interviewing, goal setting, providing written resources, and follow-up support. This paper compares costs falling on the UK National Health Service (NHS) of implementing the care pathway using two different recruitment strategies and provides initial insights into the cost of changing physical activity behaviour. METHODS: A combination of a time driven variant of activity based costing, audit data through EMIS and a survey of practice managers provided patient-level cost data for 411 screened individuals. Self reported physical activity data of 70 people completing the care pathway at three month was compared with baseline using a regression based ‘difference in differences’ approach. Deterministic and probabilistic sensitivity analyses in combination with hypothesis testing were used to judge how robust findings are to key assumptions and to assess the uncertainty around estimates of the cost of changing physical activity behaviour. RESULTS: It cost £53 (SD 7.8) per patient completing the PACP in opportunistic centres and £191 (SD 39) at disease register sites. The completer rate was higher in disease register centres (27.3% vs. 16.2%) and the difference in differences in time spent on physical activity was 81.32 (SE 17.16) minutes/week in patients completing the PACP; so that the incremental cost of converting one sedentary adult to an ‘active state’ of 150 minutes of moderate intensity physical activity per week amounts to £ 886.50 in disease register practices, compared to opportunistic screening. CONCLUSIONS: Disease register screening is more costly than opportunistic patient recruitment. However, additional costs come with a higher completion rate and better outcomes in terms of behavioural change in patients completing the care pathway. Further research is needed to rigorously evaluate intervention efficiency and to assess the link between behavioural change and changes in quality adjusted life years (QALYs).This article is available through the Brunel Open Access Publishing Fund