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There is a paucity of utility and cost data regarding the launch of 3D printing in a hospital. The objective of this project is to benchmark utility and costs for radiology-based in-hospital 3D printing of anatomic models in a single, adult academic hospital.All consecutive patients for whom 3D printed anatomic models were requested during the first year of operation were included. All 3D printing activities were documented by the 3D printing faculty and referring specialists. For patients who underwent a procedure informed by 3D printing, clinical utility was determined by the specialist who requested the model. A new metric for utility termed Anatomic Model Utility Points with range 0 (lowest utility) to 500 (highest utility) was derived from the specialist answers to Likert statements. Costs expressed in United States dollars were tallied from all 3D printing human resources and overhead. Total costs, focused costs, and outsourced costs were estimated. The specialist estimated the procedure room time saved from the 3D printed model. The time saved was converted to dollars using hospital procedure room costs.The 78 patients referred for 3D printed anatomic models included 11 clinical indications. For the 68 patients who had a procedure, the anatomic model utility points had an overall mean (SD) of 312 (57) per patient (range, 200-450 points). The total operation cost was $213,450. The total cost, focused costs, and outsourced costs were $2,737, $2,180, and $2,467 per model, respectively. Estimated procedure time saved had a mean (SD) of 29.9 (12.1) min (range, 0-60 min). The hospital procedure room cost per minute was $97 (theoretical $2,900 per patient saved with model).Utility and cost benchmarks for anatomic models 3D printed in a hospital can inform health care budgets. Realizing pecuniary benefit from the procedure time saved requires future research.

Plasmonic catalysis in the colloidal phase requires robust surface ligands that prevent particles from aggregation in adverse chemical environments and allow carrier flow from reagents to nanoparticles. This work describes the use of a water-soluble conjugated polymer comprising a thiophene moiety as a surface ligand for gold nanoparticles to create a hybrid system that, under the action of visible light, drives the conversion of the biorelevant NAD+ to its highly energetic reduced form NADH. A combination of advanced microscopy techniques and numerical simulations revealed that the robust metal–polymer heterojunction, rich in sulfonate functional groups, directs the interaction of electron-donor molecules with the plasmonic photocatalyst. The tight binding of polymer to the gold surface precludes the need for conventional transition-metal surface cocatalysts, which were previously shown to be essential for photocatalytic NAD+ reduction but are known to hinder the optical properties of plasmonic nanocrystals. Moreover, computational studies indicated that the coating polymer fosters a closer interaction between the sacrificial electron-donor triethanolamine and the nanoparticles, thus enhancing the reactivity., This work was supported by grant PID2019-111772RB-I00 funded by MCIN/AEI/10.13039/501100011033 and grant IT 1254-19 funded by Basque Government. The authors acknowledge the financial support of the European Commission (EUSMI, Grant 731019). S.B. is grateful to the European Research Council (ERC-CoG-2019 815128).

Background. Robotic exoskeleton devices have become a promising modality for restoration of extremity function in individuals with limb loss or functional weakness. However, there exists no consistent or reliable way to record efferent motor action potentials from intact peripheral nerves to control device movement. Peripheral nerve motor action potentials are similar in amplitude to that of background noise, producing an unfavorable signal-to-noise ratio (SNR) that makes these signals difficult to detect and interpret. To address this issue, we have developed the muscle cuff regenerative peripheral nerve interface (MC-RPNI), a construct consisting of a free skeletal muscle graft wrapped circumferentially around an intact peripheral nerve. Over time, the muscle graft regenerates, and the intact nerve undergoes collateral axonal sprouting to reinnervate the muscle. The MC-RPNI amplifies efferent motor action potentials by several magnitudes, thereby increasing the SNR, allowing for higher fidelity signaling and detection of motor intention. The goal of this study was to characterize the signaling capabilities and viability of the MC-RPNI over time.Methods. Thirty-seven rats were randomly assigned to one of five experimental groups (Groups A-E). For MC-RPNI animals, their contralateral extensor digitorum longus (EDL) muscle was harvested and trimmed to either 8 mm (Group A) or 13 mm (Group B) in length, wrapped circumferentially around the intact ipsilateral common peroneal (CP) nerve, secured, and allowed to heal for 3 months. Additionally, one 8 mm (Group C) and one 13 mm (Group D) length group had an epineurial window created in the CP nerve immediately preceding MC-RPNI creation. Group E consisted of sham surgery animals. At 3 months, electrophysiologic analyses were conducted to determine the signaling capabilities of the MC-RPNI. Additionally, electromyography and isometric force analyses were performed on the CP-innervated EDL to determine the effects of the MC-RPNI on end organ function. Following evaluation, the CP nerve, MC-RPNI, and ipsilateral EDL muscle were harvested for histomorphometric analysis.Results. Study endpoint analysis was performed at 3 months post-surgery. All rats displayed visible muscle contractions in both the MC-RPNI and EDL following proximal CP nerve stimulation. Compound muscle action potentials were recorded from the MC-RPNI following proximal CP nerve stimulation and ranged from 3.67 ± 0.58 mV to 6.04 ± 1.01 mV, providing efferent motor action potential amplification of 10-20 times that of a normal physiologic nerve action potential. Maximum tetanic isometric force (Fo) testing of the distally-innervated EDL muscle in MC-RPNI groups producedFo(2341 ± 114 mN-2832 ± 102 mN) similar to controls (2497 ± 122 mN), thus demonstrating that creation of MC-RPNIs did not adversely impact the function of the distally-innervated EDL muscle. Overall, comparison between all MC-RPNI sub-groups did not reveal any statistically significant differences in signaling capabilities or negative effects on distal-innervated muscle function as compared to the control group.Conclusions. MC-RPNIs have the capability to provide efferent motor action potential amplification from intact nerves without adversely impacting distal muscle function. Neither the size of the muscle graft nor the presence of an epineurial window in the nerve had any significant impact on the ability of the MC-RPNI to amplify efferent motor action potentials from intact nerves. These results support the potential for the MC-RPNI to serve as a biologic nerve interface to control advanced exoskeleton devices.

PURPOSE The dimensional accuracy of three-dimensional (3D) printed anatomical models is essential to correctly understand spatial relationships and enable safe presurgical planning. Most recent accuracy studies focused on 3D printing of a single pathology for surgical planning. This study evaluated the accuracy of medical models across multiple pathologies, using desktop inverted vat photopolymerization (VP) to 3D print anatomic models using both rigid and elastic materials. METHODS In the primary study, we 3D printed seven models (six anatomic models and one reference cube) with volumes ranging from ~2 to ~209 cc. The anatomic models spanned multiple pathologies (neurological, cardiovascular, abdominal, musculoskeletal). Two solid measurement landing blocks were strategically created around the pathology to allow high-resolution measurement using a digital micrometer and/or caliper. The physical measurements were compared to the designed dimensions, and further analysis was conducted regarding the observed patterns in accuracy. All of the models were printed in three resins: Elastic, Clear, and Grey Pro in the primary experiments. A full factorial block experimental design was employed and a total of 42 models were 3D printed in 21 print runs. In the secondary study, we 3D printed two of the anatomic models in triplicates selected from the previous six to evaluate the effect of 0.1 mm vs 0.05 mm layer height on the accuracy. RESULTS In the primary experiment, all dimensional errors were less than 1 mm. The average dimensional error across the 42 models was 0.238 ± 0.219 mm and the relative error was 1.10 ± 1.13%. Results from the secondary experiments were similar with an average dimensional error of 0.252 ± 0.213 mm and relative error of 1.52% ± 1.28% across 18 models. There was a statistically significant difference in the relative errors between the Elastic resin and Clear resin groups. We explained this difference by evaluating inverted VP 3D printing peel forces. There was a significant difference between the Solid and Hollow group of models. There was a significant difference between measurement landing blocks oriented Horizontally and Vertically. In the secondary experiments, there was no difference in accuracy between the 0.10 and 0.05 mm layer heights. CONCLUSIONS The maximum measured error was less than 1 mm across all models, and the mean error was less than 0.26mm. Therefore, inverted VP 3D printing technology is suitable for medical 3D printing if 1 mm is considered the cutoff for clinical use cases. The 0.1 mm layer height is suitable for 3D printing accurate anatomical models for presurgical planning in a majority of cases. Elastic models, models oriented horizontally, and models that are hollow tend to have relatively higher deviation as seen from experimental results and mathematical model predictions. While clinically insignificant using a 1 mm cutoff, further research is needed to better understand the complex physical interactions in VP 3D printing which influence model accuracy.

The literature has peer reviewed many projects focused on 3D printing of personal protective equipment (PPE). In addition, several presentations in the news media and other forms of communication including social media are included in this chapter. The purpose of this chapter is to provide a cohesive review of this dynamic body of knowledge as of July 2020. The chapter is organized into face shields; masks to include N95 respirators, surgical masks, and community masks; and additional medical devices such as nasopharyngeal swabs and ventilator parts. This format will enable important periodic updates as the literature continues to rapidly expand.

Summary: Tubulin glutamylation is a reversible posttranslational modification that accumulates on stable microtubules (MTs). While abnormally high levels of this modification lead to a number of disorders such as male sterility, retinal degeneration, and neurodegeneration, very little is known about the molecular mechanisms underlying the regulation of glutamylase activity. Here, we found that CSAP forms a complex with TTLL5, and we demonstrate that the two proteins regulate their reciprocal abundance. Moreover, we show that CSAP increases TTLL5-mediated glutamylation and identify the TTLL5-interacting domain. Deletion of this domain leads to complete loss of CSAP activating function without impacting its MT binding. Binding of CSAP to TTLL5 promotes relocalization of TTLL5 toward MTs. Finally, we show that CSAP binds and activates all of the remaining autonomously active TTLL glutamylases. As such, we present CSAP as a major regulator of tubulin glutamylation and associated functions. : Bompard et al. describe an activator of tubulin glutamylases that modify the microtubule-based cytoskeleton. They find that CSAP forms a complex with TTLL5, which controls its localization and activity on microtubules. Keywords: posttranslational modification, MAPs, microtubule dynamics, severing, brain, tubulin code

Most heritable cases of pulmonary arterial hypertension (PAH) are explained by mutations in BMPR2, which encodes the bone morphogenetic protein type 2 receptor (BMPR-II). Additionally, mutations in the endothelial type 1 receptor, ALK1, can cause PAH. Growth and differentiation factor 2 (GDF2; also known as BMP9) is a circulating vascular quiescence factor that possesses high affinity for the BMPR-II/ALK1 complex. Furthermore, exogenous GDF2 administration reverses PAH in animal models. Recently, an unbiased case-control analysis revealed rare missense mutations in GDF2 in PAH cases.1 Here we determined the functional impact and pathogenicity of disease-associated mutations in GDF2. Sixteen GDF2 missense variants were generated in an overexpression system and characterised by ELISAs, western blotting, signalling and apoptosis assays. BMP9 and BMP10 levels were assayed in plasma samples from PAH patients harbouring GDF2 missense variants and deletions at the GDF2 locus, and age/sex matched healthy controls. Missense variants predicted to be pathogenic by in silico analysis exhibited severely reduced secretion and activity of GDF2 in vitro. For most variants, reduced secretion was associated with disruption of the interaction between the prodomain and growth factor domain of GDF2, leading to destabilisation of the molecule. In contrast, missense variants predicted to be benign exhibited normal signalling and functional responses. Similarly, plasma from pathogenic GDF2 mutation carriers exhibited greatly reduced levels of the GDF2 growth factor domain compared to healthy controls and benign missense carriers. Intriguingly, plasma levels of BMP10, the other circulating ligand for ALK1/BMPR-II, were also markedly reduced in patients with pathogenic GDF2 variants, suggesting co-regulation of these circulating BMPs. These studies provide evidence for the pathogenicity of rare missense mutations in GDF2 and demonstrate that the major mechanism involves destabilisation of the GDF2 molecule leading to reduced secretion of the growth factor domain. These data provide support for the central role of the GDF2/BMPR-II/ALK1 axis in PAH and suggest that GDF2 replacement may be an effective therapeutic strategy in these individuals. This study was produced by the Morrell group on behalf of the UK PAH Cohort Study. Reference Nat Commun 12 April 2018;9(1):1416. doi:10.1038/s41467-018-03672-4

The author's research has been directed towards inference involving observables rather than parameters. In this book, he brings together his views on predictive or observable inference and its advantages over parametric inference. While the book discusses a variety of approaches to prediction including those based on parametric, nonparametric, and nonstochastic statistical models, it is devoted mainly to predictive applications of the Bayesian approach. It not only substitutes predictive analyses for parametric analyses, but it also presents predictive analyses that have no real parametric analogues. It demonstrates that predictive inference can be a critical component of even strict parametric inference when dealing with interim analyses. This approach to predictive inference will be of interest to statisticians, psychologists, econometricians, and sociologists.

BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality because of impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular, it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

SummaryMicrotubules are filamentous polymers essential for cell viability. Microtubule plus-end tracking proteins (+TIPs) associate with growing microtubule plus ends and control microtubule dynamics and interactions with different cellular structures during cell division, migration, and morphogenesis. EB1 and its homologs are highly conserved proteins that play an important role in the targeting of +TIPs to microtubule ends, but the underlying molecular mechanism remains elusive. By using live cell experiments and in vitro reconstitution assays, we demonstrate that a short polypeptide motif, Ser-x-Ile-Pro (SxIP), is used by numerous +TIPs, including the tumor suppressor APC, the transmembrane protein STIM1, and the kinesin MCAK, for localization to microtubule tips in an EB1-dependent manner. Structural and biochemical data reveal the molecular basis of the EB1-SxIP interaction and explain its negative regulation by phosphorylation. Our findings establish a general “microtubule tip localization signal” (MtLS) and delineate a unifying mechanism for this subcellular protein targeting process.