To evaluate the clinical immunogenicity of eight antibody–drug conjugates (ADCs), multi-domain biotherapeutics that could theoretically pose a greater immunogenicity risk than monoclonal antibodies ...(mAbs) because they contain non-natural structural motifs.
Immunogenicity strategies and assays for these ADCs included those commonly used for conventional biotherapeutics with additional characterization. A tiered approach was adopted for testing Phase I and II clinical study samples with screening, confirmatory assays and additional domain characterization. Antidrug antibody incidences with these ADCs were within those reported for mAb biotherapeutics with no apparent impact on clinical outcomes.
These data suggest that the ADC hapten-like structure across these eight ADCs does not appear to increase patient immune responses beyond those generally observed for mAb biotherapeutics.
SYNOPSIS This study explores the use of audit data analytics (ADA) in current audit practice. First, we interviewed the heads of professional practice of five international public accounting firms in ...Norway. We find that they differ in strategies on how to implement ADA and the heads report significant uncertainty about the supervisory inspection authorities' response to the use of ADA. Second, we administered a questionnaire to 216 engagement partners and managers about their perceptions of ADA and their actual ADA use on 109 audit engagements. Overall, the attitudes toward ADA usefulness are positive. Analysis of the audit engagements suggests use of ADA is relatively limited and use of more “advanced” ADA is rare. More ADA are used for clients with integrated ERP/IT systems and for newly tendered audit engagements. We also provide details of ADA use on each phase of the audit. We discuss our findings from an institutional theory perspective. Data Availability: The data used in this study are confidential by agreement with the participants.
Severe combined immunodeficiency (SCID) is a rare genetic syndrome caused by aberrant immune cell development or function and is fatal without early identification and treatment. The Centers for ...Disease Control estimates the annual incidence of SCID to be one case per 40,000 to 100,000 live births. Newborn screening using T-cell receptor excision circles (TREC) allows for early detection and timely treatment of SCID. Adenosine deaminase (ADA) is a vital enzyme in the purine salvage pathway, and its deficiency results in disruption of T, B and NK cell development, accounting for 10–20% of SCID cases. The timing of ADA-SCID presentation ranges from birth to delayed onset disease. Importantly, without early recognition and treatment, delayed onset ADA-SCID results in accumulation of toxic metabolites causing immune dysfunction, recurrent infections, and subsequent organ damage. Recently, some groups have questioned whether traditional TREC newborn screening adequately identifies ADA-SCID, especially those cases with delayed onset. We present the case of a 2-year-old male with normal newborn screening but a history of recurrent otitis media and respiratory infections who developed multisystem organ failure and septicemia with Escherichia coli, candida, adenovirus and enterovirus despite broad-spectrum antimicrobials. The patient also had features of a hyperinflammatory syndrome with fever, pancytopenia, hypertriglyceridemia, and hyperferritinemia and was treated for hemophagocytic lymphohistiocytosis (HLH) with dexamethasone and plasma exchange followed by anakinra, etoposide, and emapalumab. The patient was maximally supported with mechanical ventilation, extracorporeal membrane oxygenation, and renal replacement therapy but had progressive clinical deterioration and ultimately expired. Autopsy was notable for thymic aplasia and erythrophagocytosis in the bone marrow and lymph nodes. Genetic testing revealed a heterozygous missense pathogenic variant in exon 7 in the ADA gene as well as novel heterozygous intronic variant of unknown significance in the ADA gene. Postmortem data suggests this patient had ADA-SCID with multi-pathogen infections and secondary HLH. This case potentially identifies a novel pathogenic variant in ADA missed by traditional TREC newborn screening and highlights the need to retain a high clinical suspicion of SCID in patients with a history of recurrent infections despite normal TREC screening.
Assuring the Safety of Dental Materials Megremis, Spiro J.
The Dental clinics of North America,
October 2022, 2022-10-00, Volume:
66, Issue:
4
Journal Article
Peer reviewed
The formal history of standards and dentistry in the United States goes back to World War I and was prompted by the government’s need to buy large quantities of dental materials to treat “an army of ...teeth in disrepair.” This article covers the use of scientific research to establish specifications and standards used to evaluate dental materials and products, and how a practitioner can use these standards to assure the safety and performance of the materials that they use in their everyday practice.
The concept of adding inorganic fillers into hydrogels to form hydrogel nanocomposites often provides advantageous properties which can be exploited for successful 3D biofabrication. In this study, a ...new composite hydrogel combining oxidized alginate–gelatin (ADA‐GEL) hydrogel and Laponite® nanoclay as inorganic nanofiller was successfully developed and characterized. The results showed that the addition of 0.5% (wt/vol) Laponite® nanoplatelets improved the printability of ADA‐GEL hydrogels enabling the fabrication of detailed structures since a low effect of material spreading and reduced tendency to pore closure appeared. Furthermore, a comparison of different needle types (cylindrical and conical; same inner diameter of 250 μm) in filament fusion test showed that the pattern dispensed by cylindrical tip has enhanced printing accuracy and pattern fidelity when compared with the pattern from conical tip. A glass flip test determined a processing window of 1–2 h after composite ink preparation. Overall, Laponite® /ADA‐GEL hydrogel composites are confirmed as promising inks for 3D bioprinting.
PDF
