Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.

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.

In addition to being associated with a higher risk of complications during pregnancy, twinning may also be a proxy for altered hormonal exposure for mothers and twin offspring, with implications for their health later in life. We compared maternal and fetal steroid hormone and insulin-like growth factor concentrations between singleton (n=62) and twin (n=41) pregnancies. Maternal concentrations of androgens, estrogens, insulin-like growth factor (IGF)-1, IGF-binding protein (BP)-3 and prolactin were quantified during the third trimester and at delivery, as well as in the fetal circulation at birth. Geometric means accounting for gestational age were calculated for hormone concentrations and compared between matched twin and singleton pregnancies. Most maternal hormone concentrations were modestly higher in twin than in singleton pregnancies in the third trimester (ranging from 8.3% for IGF-1 to 17.1% for estradiol) and at delivery (ranging from 11.1% for IGFBP-3 to 15.2% for estriol). Cord serum hormones were generally similar in twin and singleton pregnancies, except for IGFBP-3, which was 200% lower in twins. The modest differences in maternal hormones in late gestation seem unlikely to explain alterations in hormonally related disease risk in mothers of twins compared with singletons. The large deficit of IGFBP-3 in the fetal circulation of twins at birth may allow for sufficient concentrations of IGF-2 for growth and development in an environment of shared nutritional resources.

Certain morphological changes at the subcellular level caused by the current techniques for in vitro embryo production seem to affect mitochondria. Many of these, including dysfunctional changes, have been associated with the presence of serum in the culture medium. Thus, the aim of the present work was to assess the mitochondrial dynamics occurring in embryos during the first 4 days of development, in order to analyze the most appropriate time for adding the serum. We used transmission electron microscopy (TEM) micrographs to calculate the embryo area occupied by the different morphological types of mitochondria, and analyzed them with Image Pro Plus analyzer. The results showed hooded mitochondria as the most representative type in 1- to 4-day-old embryos. Swollen, on-fusion, orthodox and vacuolated types were also present. When analyzed in embryos cultured without serum, the dynamics of the different mitochondrial types appeared to be similar, a fact that may provide evidence that the developmental changes control the mitochondrial dynamics, and that swollen mitochondria may not be completely inactive. In contrast, in culture medium supplemented with serum from estrous cows, we observed an increased area of hooded mitochondria by developmental day 4, a fact that may indicate an increased production of energy compared with previous days. According to these results, the bovine serum added to the culture medium seems not to be responsible for the functional changes in mitochondria.

In January 2009, the IAEA EMRAS II (Environmental Modelling for Radiation Safety II) program was launched. The goal of the program is to develop, compare and test models for the assessment of radiological impacts to the public and the environment due to radionuclides being released or already existing in the environment; to help countries build and harmonize their capabilities; and to model the movement of radionuclides in the environment. Within EMRAS II, nine working groups are active; this paper will focus on the activities of Working Group 1: Reference Methodologies for Controlling Discharges of Routine Releases. Within this working group environmental transfer and dose assessment models are tested under different scenarios by participating countries and the results compared. This process allows each participating country to identify characteristics of their models that need to be refined. The goal of this working group is to identify reference methodologies for the assessment of exposures to the public due to routine discharges of radionuclides to the terrestrial and aquatic environments. Several different models are being applied to estimate the transfer of radionuclides in the environment for various scenarios. The first phase of the project involves a scenario of nuclear power reactor with a coastal location which routinely (continuously) discharges 60Co, 85Kr, 131I, and 137Cs to the atmosphere and 60Co, 137Cs, and 90Sr to the marine environment. In this scenario many of the parameters and characteristics of the representative group were given to the modellers and cannot be altered. Various models have been used by the different participants in this inter-comparison (PC-CREAM, CROM, IMPACT, CLRP POSEIDON, SYMBIOSE and others). This first scenario is to enable a comparison of the radionuclide transport and dose modelling. These scenarios will facilitate the development of reference methodologies for controlled discharges.

The eastern English Channel, the narrow channel of water separating northern France and southeast England is an area of intense human use of the array of resources concentrated into its relative small area. The vulnerability of living resources and their habitats brought together French and British maritime experts within a common project (called CHARM): to create an atlas of marine resource habitats in the eastern English Channel so as to provide planners and decision-makers with the necessary information to help managing the use of its living and non-living resources. This multidisciplinary and richly illustrated atlas provides abundant information on the legal framework and physical environment; benthic invertebrates, fish and their habitats; fishing activities; and a first attempt at developing a trophic network model (using ECOPATH software) and a marine conservation planning exercise (using MARXAN software, at a spatial resolution of 25 km $^{2})$ . Although most of the data used were collected elsewhere, some were collected especially for the project. Similarly, most of the analyses performed on the data where entirely original for this geographical area. The CHARM atlas has significantly improved the knowledge about the eastern Channel while contributing to the recognition that such holistic or multidisciplinary approaches to exploited marine systems are necessary to efficiently and durably manage their resources use.