IgM Augments Complement Bactericidal Activity with Serum from a Patient with a Novel CD79a Mutation

Antibody replacement therapy for patients with antibody deficiencies contains only IgG. As a result, concurrent IgM and IgA deficiency present in a large proportion of antibody deficient patients persists. Especially patients with IgM deficiency remain at risk for recurrent infections of the gastrointestinal and respiratory tract. The lack of IgM in the current IgG replacement therapy is likely to contribute to the persistence of these mucosal infections because this antibody class is especially important for complement activation on the mucosal surface. We evaluated whether supplementation with IgM increased serum bactericidal capacity in vitro. Serum was collected from a patient with agammaglobulinemia and supplemented with purified serum IgM to normal levels. Antibody and complement deposition on the bacterial surface was determined by multi-color flow cytometry. Bacterial survival in serum was determined by colony-forming unit counts. We present a patient previously diagnosed with agammaglobulinemia due to CD79A (Igα) deficiency revealing a novel pathogenic insertion variant in the CD79a gene (NM_001783.3:c.353_354insT). Despite IgG replacement therapy and antibiotic prophylaxis, this patient developed a Campylobacter jejuni spondylodiscitis of lumbar vertebrae L4–L5. We found that serum IgM significantly contributes to complement activation on the bacterial surface of C. jejuni. Furthermore, supplementation of serum IgM augmented serum bactericidal activity significantly. In conclusion, supplementation of intravenous IgG replacement therapy with IgM may potentially offer greater protection against bacterial infections, also in the context of increasing antibiotic resistance

Full vector archaeomagnetic records from Anatolia between 2400 and 1350 BCE: Implications for geomagnetic field models and the dating of fires in antiquity

Anatolia, as one of the busiest crossroads of ancient civilizations, provides an ideal platform for archaeomagnetic studies. Previous results from the Middle East have suggested the occurrence of a strong peak in geomagnetic intensity at ∼1000 BCE associated with dramatic field strength variations that could require a radical rethinking of geodynamo theory. The behavior of the field in the centuries preceding this peak remains poorly constrained, however. Here we present the results of full-vector archaeomagnetic experiments performed on 18 sets of samples from three archaeological sites belonging to Assyrian Trade Colony and Hittite periods. Associated rock magnetic analyses showed that the major magnetic carrier is magnetite chemically stable up to 700 °C and the magnetic mineral assemblage is composed mostly of non-interacting PSD grains. The directional results are compared with existing data and with the most recent global geomagnetic field models pfm9k.1b and SHA.DIF.14k. The directions are in remarkably good agreement with SHA.DIF.14k which is based on archaeomagnetic and lava flow data. Together with our earlier results from Anatolia, we triple the existing database of directions for the 700 year long period 2200–1500 BCE, over a large region from Greece to Azerbaijan, and from Moldavia/Ukraine to Egypt. Three archaeointensity methods: thermal IZZI-Thellier, microwave Thellier and the multi-specimen protocol (MSP) produced virtual axial dipole moment estimates () that are somewhat higher than contemporaneous (regional and global) data and model predictions suggesting that the field was already substantially stronger than today more than 800 years prior to the reported peak. In addition to constraining geomagnetic variability, our data also allow us to assign relative dates to inferred fire events in the Assyrian Trade Colony Period sites. This allows us to conclude that the fire events at the largest site, Kültepe, were not all contemporaneous with one another and with the abandonment of the site as has been previously hypothesized

Dielectric material options for integrated capacitors

Future MIM capacitor generations will require significantly increased specific capacitances by utilization of high-k dielectric materials. In order to achieve high capacitance per chip area, these dielectrics have to be deposited in three-dimensional capacitor structures by ALD or AVD (atomic vapor deposition) process techniques. In this study eight dielectric materials, which can be deposited by these techniques and exhibit the potential to reach k-values of over 50 were identified, prepared and characterized as single films and stacked film systems. To primarily focus on a material comparison, preliminary processes were used for film deposition on planar test devices. Measuring leakage current density versus the dielectric constant k shows that at low voltages (=1 V) dielectrics with k-values up to 100 satisfy the typical leakage current density specification o

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

Pediatric long-COVID: an overlooked phenomenon?

Background: Long-COVID is a well-documented multisystem disease in adults. Far less is known about long-term sequelae of COVID in children. Here, we report on the occurrence of long-COVID in Dutch children.Patients and Methods: We conducted a national survey asking Dutch pediatricians to share their experiences on long-COVID in children. We furthermore describe a case series of six children with long-COVID to explore the clinical features in greater detail.Results: With a response rate of 78% of Dutch pediatric departments, we identified 89 children, aged 2-18 years, suspected of long-COVID with various complaints. Of these children, 36% experienced severe limitations in daily function. The most common complaints were fatigue, dyspnea, and concentration difficulties with 87%, 55%, and 45% respectively. Our case series emphasizes the nonspecific and broad clinical manifestations seen in post-COVID complaints.Conclusion: Our study shows that long-COVID is also present in the pediatric population. The main symptoms resemble those previously described in adults. This novel condition demands a multidisciplinary approach with international awareness and consensus to aid early detection and effective management.Transplantation and immunomodulatio

Probing Tectonic Topography in the Aftermath of Continental Convergence in Central Europe

Continental topography is at the interface of processes taking place at depth in the Earth,at its surface,and above it.Topography influences society, not only in terms of slow processes of landscape change and earthquakes,but also in terms of how it affects climate.The Pannonian Basin–Carpathian Orogen System in Central and Eastern Europe represents a key natural laboratory for the development of a new generation of models for ongoing orogeny and its effect on continental topography development (Figure 1).This system comprises some of the best documented sedimentary basins in the world,located within the Alpine orogenic belt, at the transition between the western European lithosphere and the East European Craton. It includes one of the most active seismic zones in Europe,with intermediate depth (50–220 km) mantle earthquakes of significant magnitude occurring in a geographically restricted area in the Vrancea zone of southeastern Romania