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Late phonological development in Spanish children with bilateral hearing loss / Desarrollo fonologico tardio en ninos espanoles con perdidas auditivas bilaterales
This study has a twofold objective: to analyse and compare the phonological processes in a sample of Spanish children with hearing loss, both with a cochlear implant and with a hearing aid, with a group with normal hearing; and to determine whether there are differences between the participants with a cochlear implant and with a hearing aid in the frequency and nature of the phonological processes. The sample is made up of 168 participants, eight with hearing loss (four with an implant and four with a hearing aid) and 160 with normal hearing. Samples of spontaneous speech were collected and transcribed using the tools from the CHILDES project. For the analysis, the phonological processes paradigm was adopted, evaluating phonological development based on normative error rates. The participants with a hearing loss show slower phonological development in terms of phonological processes, along with atypical processes. Furthermore, the participants with cochlear implants committed more phonological errors than those that wear a hearing aid. The implications of the results are discussed, and it is recommended that auditory stimulation should be done early in children with hearing loss regardless of their technical aid
Site-Specifically Labeled Immunoconjugates for Molecular Imaging—Part 1: Cysteine Residues and Glycans
Due to their remarkable selectivity and specificity for cancer biomarkers, immunoconjugates have emerged as extremely promising vectors for the delivery of diagnostic radioisotopes and fluorophores to malignant tissues. Paradoxically, however, these tools for precision medicine are synthesized in a remarkably imprecise way. Indeed, the vast majority of immunoconjugates are created via the random conjugation of bifunctional probes (e.g., DOTA-NCS) to amino acids within the antibody (e.g., lysines). Yet antibodies have multiple copies of these residues throughout their macromolecular structure, making control over the location of the conjugation reaction impossible. This lack of site specificity can lead to the formation of poorly defined, heterogeneous immunoconjugates with suboptimal in vivo behavior. Over the past decade, interest in the synthesis and development of site-specifically labeled immunoconjugates—both antibody-drug conjugates as well as constructs for in vivo imaging—has increased dramatically, and a number of reports have suggested that these better defined, more homogeneous constructs exhibit improved performance in vivo compared to their randomly modified cousins. In this two-part review, we seek to provide an overview of the various methods that have been developed to create site-specifically modified immunoconjugates for positron emission tomography, single photon emission computed tomography, and fluorescence imaging. We will begin with an introduction to the structure of antibodies and antibody fragments. This is followed by the core of the work: sections detailing the four different approaches to site-specific modification strategies based on cysteine residues, glycans, peptide tags, and unnatural amino acids. These discussions will be divided into two installments: cysteine residues and glycans will be detailed in Part 1 of the review, while peptide tags and unnatural amino acids will be addressed in Part 2. Ultimately, we sincerely hope that this review fosters interest and enthusiasm for site-specific immunoconjugates within the nuclear medicine and molecular imaging communities