To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.
An international Task Force formed the questions for the systematic ...literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.
The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.
The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
Predicting the ocean's role in the global carbon cycle requires an understanding of the stoichiometric coupling between carbon and growth-limiting elements in biogeochemical processes. A recent ...addition to such knowledge is that the carbon/nitrogen ratio of inorganic consumption and release of dissolved organic matter may increase in a high-CO(2) world. This will, however, yield a negative feedback on atmospheric CO(2) only if the extra organic material escapes mineralization within the photic zone. Here we show, in the context of an Arctic pelagic ecosystem, how the fate and effects of added degradable organic carbon depend critically on the state of the microbial food web. When bacterial growth rate was limited by mineral nutrients, extra organic carbon accumulated in the system. When bacteria were limited by organic carbon, however, addition of labile dissolved organic carbon reduced phytoplankton biomass and activity and also the rate at which total organic carbon accumulated, explained as the result of stimulated bacterial competition for mineral nutrients. This counterintuitive 'more organic carbon gives less organic carbon' effect was particularly pronounced in diatom-dominated systems where the carbon/mineral nutrient ratio in phytoplankton production was high. Our results highlight how descriptions of present and future states of the oceanic carbon cycle require detailed understanding of the stoichiometric coupling between carbon and growth-limiting mineral nutrients in both autotrophic and heterotrophic processes.
Abstract
A fast and reliable range monitoring method is required to take full advantage of the high linear energy transfer provided by therapeutic ion beams like carbon and oxygen while minimizing ...damage to healthy tissue due to range uncertainties. Quasi-real-time range monitoring using in-beam positron emission tomography (PET) with therapeutic beams of positron-emitters of carbon and oxygen is a promising approach. The number of implanted ions and the time required for an unambiguous range verification are decisive factors for choosing a candidate isotope. An experimental study was performed at the FRS fragment-separator of GSI Helmholtzzentrum für Schwerionenforschung GmbH, Germany, to investigate the evolution of positron annihilation activity profiles during the implantation of
$$^{14}$$
14
O and
$$^{15}$$
15
O ion beams in a PMMA phantom. The positron activity profile was imaged by a dual-panel version of a Siemens Biograph mCT PET scanner. Results from a similar experiment using ion beams of carbon positron-emitters
$$^{11}$$
11
C and
$$^{10}$$
10
C performed at the same experimental setup were used for comparison. Owing to their shorter half-lives, the number of implanted ions required for a precise positron annihilation activity peak determination is lower for
$$^{10}$$
10
C compared to
$$^{11}$$
11
C and likewise for
$$^{14}$$
14
O compared to
$$^{15}$$
15
O, but their lower production cross-sections make it difficult to produce them at therapeutically relevant intensities. With a similar production cross-section and a 10 times shorter half-life than
$$^{11}$$
11
C,
$$^{15}$$
15
O provides a faster conclusive positron annihilation activity peak position determination for a lower number of implanted ions compared to
$$^{11}$$
11
C. A figure of merit formulation was developed for the quantitative comparison of therapy-relevant positron-emitting beams in the context of quasi-real-time beam monitoring. In conclusion, this study demonstrates that among the positron emitters of carbon and oxygen,
$$^{15}$$
15
O is the most feasible candidate for quasi-real-time range monitoring by in-beam PET that can be produced at therapeutically relevant intensities. Additionally, this study demonstrated that the in-flight production and separation method can produce beams of therapeutic quality, in terms of purity, energy, and energy spread.
Context.
Methanol masers of Class I (collisionally pumped) and Class II (radiatively pumped) have been studied in great detail in our Galaxy in a variety of astrophysical environments such as shocks ...and star-forming regions and are they are helpful to analyze the properties of the dense interstellar medium. However, the study of methanol masers in external galaxies is still in its infancy.
Aims.
Our main goal is to search for methanol masers in the central molecular zone (CMZ; inner 500 pc) of the nearby starburst galaxy NGC 253.
Methods.
Covering a frequency range between 84 and 373 GHz (
λ
= 3.6–0.8 mm) at high angular (1.
″
6 ∼ 27 pc) and spectral (∼8–9 km s
−1
) resolution with ALCHEMI (ALMA Comprehensive High-resolution Extragalactic Molecular Inventory), we have probed different regions across the CMZ of NGC 253. In order to look for methanol maser candidates, we employed the rotation diagram method and a set of radiative transfer models.
Results.
We detect for the first time masers above 84 GHz in NGC 253, covering an ample portion of the
J
−1
→ (
J
− 1)
0
−
E
line series (at 84, 132, 229, and 278 GHz) and the
J
0
→ (
J
− 1)
1
−
A
series (at 95, 146, and 198 GHz). This confirms the presence of the Class I maser line at 84 GHz, which was already reported, but now being detected in more than one location. For the
J
−1
→ (
J
− 1)
0
−
E
line series, we observe a lack of Class I maser candidates in the central star-forming disk.
Conclusions.
The physical conditions for maser excitation in the
J
−1
→ (
J
− 1)
0
−
E
line series can be weak shocks and cloud-cloud collisions as suggested by shock tracers (SiO and HNCO) in bi-symmetric shock regions located in the outskirts of the CMZ. On the other hand, the presence of photodissociation regions due to a high star-formation rate would be needed to explain the lack of Class I masers in the very central regions.
Two-Neutron Halo is Unveiled in F 29 Bagchi, S.; Kanungo, R.; Tanaka, Y. K. ...
Physical review letters,
06/2020, Volume:
124, Issue:
22
Journal Article
Peer reviewed
Open access
We report the measurement of reaction cross sections (σexR) of 27,29F with a carbon target at RIKEN. The unexpectedly large σexR and derived matter radius identify 29F as the heaviest two-neutron ...Borromean halo to date. The halo is attributed to neutrons occupying the 2p3/2 orbital, thereby vanishing the shell closure associated with the neutron number N=20. The results are explained by state-of-the-art shell model calculations. Coupled-cluster computations based on effective field theories of the strong nuclear force describe the matter radius of 27F but are challenged for 29F.
Despite the continuing development of immunomodulatory agents and supportive care, the prognosis associated with lupus nephritis (LN) has not improved substantially in the past decade, with end-stage ...kidney disease still developing in 5-30% of patients within 10 years of LN diagnosis. Moreover, inter-ethnic variation in the tolerance of, clinical response to and level of evidence regarding various therapeutic regimens for LN has led to variation in treatment prioritization in different international recommendations. Modalities that better preserve kidney function and reduce the toxicities of concomitant glucocorticoids are unmet needs in the development of therapeutics for LN. In addition to the conventional recommended therapies for LN, there are newly approved treatments as well as investigational drugs in the pipeline, including the newer generation calcineurin inhibitors and biologic agents. In view of the heterogeneity of LN in terms of clinical presentation and prognosis, the choice of therapies depends on a number of clinical considerations. Molecular profiling, gene-signature fingerprints and urine proteomic panels might enhance the accuracy of patient stratification for treatment personalization in the future.
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