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The utility of antibody therapeutics is hampered by potential cross-reactivity with healthy tissue. Over the past decade, significant advances have been made in the design of activatable antibodies, which increase, or create altogether, the therapeutic window of a parent antibody. Of these, antibody prodrugs (pro-antibodies) are masked antibodies that have advanced the most for therapeutic use. They are designed to reveal the active, parent antibody only when encountering proteases upregulated in the microenvironment of the targeted disease tissue, thereby minimizing off-target activity. However, current pro-antibody designs are relegated to fusion proteins that append masking groups restricted to the use of only canonical amino acids, offering excellent control of the site of introduction, but with no authority over where the masking group is installed other than the N-terminus of the antibody. Here, we present a palladium-based bioconjugation approach for the site-specific introduction of a masked tyrosine mimic in the complementary determining region of the FDA approved antibody therapeutic ipilimumab used as a model system. The approach enables the introduction of a protease cleavable group tethered to noncanonical polymers (polyethylene glycol (PEG)) resulting in 47-fold weaker binding to cells expressing CTLA-4, the target antigen of ipilimumab. Upon exposure to tumor-associated proteases, the masking group is cleaved, unveiling a tyrosine-mimic (dubbed hydroxyphenyl cysteine (HPC)) that restores (>90% restoration) binding affinity to its target antigen.

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Fahr's disease is a rare condition characterised by the presence of idiopathic familial bilateral basal ganglia calcifications, transmitted in an autosomal-dominant fashion. Diagnosis is based on clinical features of neuropsychiatric and somatic symptoms in conjunction with radiological findings. Our patient, a man in his early 50s, presented with pneumonia. History was significant for five admissions in the last 2 years for pneumonia and falls, with gradual cognitive and motor decline since his late 30s. Hypophonia, bradykinesia and dementia were noted on examination. CT of the brain revealed bilateral thalamic calcinosis, consistent with Fahr's syndrome. Further investigations and retrospective history taking, and similar radiological findings within first-degree and second-degree relatives with early deaths, transitioned the diagnosis from Fahr's syndrome to Fahr's disease. We present this case of Fahr's disease to emphasise the value of collaboration among multidisciplinary professionals to improve quality of care for such patients.

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To evaluate the impact of implementing the Supporting Oral Feeding in Fragile Infants (SOFFI) program in a tertiary-level neonatal intensive care unit (NICU) on the oral feeding, growth, and length of stay outcomes of a heterogeneous population of medically fragile infants at discharge and feeding and growth outcomes postdischarge at 3 to 5 months postterm. Data related to feeding, growth, and length of stay from a convenience sample of 81 infants recruited pre-SOFFI training were compared with data for 75 infants recruited post-SOFFI training of the NICU staff. Subjects were not excluded on the basis of level of illness or medical diagnoses. To establish comparability of subject groups, infants were assigned scores using the Neonatal Medical Index. At 3 to 5 months postterm, semistructured parent phone interviews related to feeding and growth at home were conducted (n = 128). Post-SOFFI infants born at less than 37 weeks' gestation achieved full oral feedings in significantly fewer days than pre-SOFFI infants (P = .01). Time to achieve full oral feedings was not significantly different in post-SOFFI infants born at 37 or more weeks' gestation. Growth and length of stay were not significantly different at discharge. At follow-up, parents of post-SOFFI infants reported significantly fewer feeding problems overall (P = .01), less arching (P = .003), less vomiting (P = .006), and fewer infants seeing feeding specialists (P = .03). Results of the study support that NICU implementation of the SOFFI feeding program positively influences feeding outcomes before and following discharge.

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Digital information displays are becoming more common in public spaces such as museums, galleries, and libraries. However, the public nature of these locations requires special considerations concerning the design of information visualization in terms of visual representations and interaction techniques. We discuss the potential for, and challenges of, information visualization in the museum context based on our practical experience with EMDialog, an interactive information presentation that was part of the Emily Carr exhibition at the Glenbow Museum in Calgary. EMDialog visualizes the diverse and multi-faceted discourse about this Canadian artist with the goal to both inform and provoke discussion. It provides a visual environment that allows for exploration of the interplay between two integrated visualizations, one for information access along temporal, and the other along contextual dimensions. We describe the results of an observational study we conducted at the museum that revealed the different ways visitors approached and interacted with EMDialog, as well as how they perceived this form of information presentation in the museum context. Our results include the need to present information in a manner sufficiently attractive to draw attention and the importance of rewarding passive observation as well as both short- and longer term information exploration.