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Volumetric additive manufacturing techniques are a promising pathway to ultra-rapid light-based 3D fabrication. Their widespread adoption, however, demands significant improvement in print fidelity. Currently, volumetric additive manufacturing prints suffer from systematic undercuring of fine features, making it impossible to print objects containing a wide range of feature sizes, precluding effective adoption in many applications. Here, we uncover the reason for this limitation: light dose spread in the resin due to chemical diffusion and optical blurring, which becomes significant for features ⪅0.5 mm. We develop a model that quantitatively predicts the variation of print time with feature size and demonstrate a deconvolution method to correct for this error. This enables prints previously beyond the capabilities of volumetric additive manufacturing, such as a complex gyroid structure with variable thickness and a fine-toothed gear. These results position volumetric additive manufacturing as a mature 3D printing method, all but eliminating the gap to industry-standard print fidelity.

3D printing has enabled materials, geometries and functional properties to be combined in unique ways otherwise unattainable via traditional manufacturing techniques, yet its adoption as a mainstream manufacturing platform for functional objects is hindered by the physical challenges in printing multiple materials. Vat polymerization offers a polymer chemistry-based approach to generating smart objects, in which phase separation is used to control the spatial positioning of materials and thus at once, achieve desirable morphological and functional properties of final 3D printed objects. This study demonstrates how the spatial distribution of different material phases can be modulated by controlling the kinetics of gelation, cross-linking density and material diffusivity through the judicious selection of photoresin components. A continuum of morphologies, ranging from functional coatings, gradients and composites are generated, enabling the fabrication of 3D piezoresistive sensors, 5G antennas and antimicrobial objects and thus illustrating a promising way forward in the integration of dissimilar materials in 3D printing of smart or functional parts. 3D printing has enabled materials, geometries and functional properties to be combined in unique ways but printing multiple materials remains challenging. Here, the authors demonstrate how spatial distribution of different material phases can be modulated by controlling the kinetics of gelation, cross-linking density and material diffusivity in vat polymerization.

Light-based additive manufacturing techniques enable a rapid transition from object design to production. In these approaches, a 3D object is typically built by successive polymerization of 2D layers in a photocurable resin. A recently demonstrated technique, however, uses tomographic dose patterning to establish a 3D light dose distribution within a cylindrical glass vial of photoresin. Lensing distortion from the cylindrical vial is currently mitigated by either an index matching bath around the print volume or a cylindrical lens. In this work, we show that these hardware approaches to distortion correction are unnecessary. Instead, we demonstrate how the lensing effect can be computationally corrected by resampling the parallel-beam radon transform into an aberrated geometry. We also demonstrate a more general application of our computational approach by correcting for non-telecentricity inherent in most optical projection systems. We expect that our results will underpin a more simple and flexible class of tomographic 3D printers where deviations from the assumed parallel-beam projection geometry are rectified computationally.

Additive manufacturing techniques are revolutionizing product development by enabling fast turnaround from design to fabrication. However, the throughput of the rapid prototyping pipeline remains constrained by print optimization, requiring multiple iterations of fabrication and ex-situ metrology. Despite the need for a suitable technology, robust in-situ shape measurement of an entire print is not currently available with any additive manufacturing modality. Here, we address this shortcoming by demonstrating fully simultaneous 3D metrology and printing. We exploit the dramatic increase in light scattering by a photoresin during gelation for real-time 3D imaging of prints during tomographic volumetric additive manufacturing. Tomographic imaging of the light scattering density in the build volume yields quantitative, artifact-free 3D + time models of cured objects that are accurate to below 1% of the size of the print. By integrating shape measurement into the printing process, our work paves the way for next-generation rapid prototyping with real-time defect detection and correction.

Unconsciousness is a fundamental component of general anesthesia (GA), but anesthesiologists have no reliable ways to be certain that a patient is unconscious. To develop EEG signatures that track loss and recovery of consciousness under GA, we recorded high-density EEGs in humans during gradual induction of and emergence from unconsciousness with propofol. The subjects executed an auditory task at 4-s intervals consisting of interleaved verbal and click stimuli to identify loss and recovery of consciousness. During induction, subjects lost responsiveness to the less salient clicks before losing responsiveness to the more salient verbal stimuli; during emergence they recovered responsiveness to the verbal stimuli before recovering responsiveness to the clicks. The median frequency and bandwidth of the frontal EEG power tracked the probability of response to the verbal stimuli during the transitions in consciousness. Loss of consciousness was marked simultaneously by an increase in low-frequency EEG power (<1 Hz), the loss of spatially coherent occipital alpha oscillations (8–12 Hz), and the appearance of spatially coherent frontal alpha oscillations. These dynamics reversed with recovery of consciousness. The low-frequency phase modulated alpha amplitude in two distinct patterns. During profound unconsciousness, alpha amplitudes were maximal at low-frequency peaks, whereas during the transition into and out of unconsciousness, alpha amplitudes were maximal at low-frequency nadirs. This latter phase–amplitude relationship predicted recovery of consciousness. Our results provide insights into the mechanisms of propofol-induced unconsciousness, establish EEG signatures of this brain state that track transitions in consciousness precisely, and suggest strategies for monitoring the brain activity of patients receiving GA.

Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central’s Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols—PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.

In this phase 3 trial, among children with later-onset spinal muscular atrophy, those who received nusinersen had improvement in motor-function scores and those who underwent a sham procedure did not.

Background: In the US in 2021, 76,080 kidney cancers are expected and >80% are renal cell carcinomas (RCCs). Along with excess fat, metabolic dysfunction is implicated in RCC etiology. To identify RCC-associated metabolites, we conducted a 1:1 matched case–control study nested within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We measured 522 serum metabolites in 267 cases/control pairs. Cases were followed for a median 7.1 years from blood draw to diagnosis. Using conditional logistic regression, we computed adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing risk between 90th and 10th percentiles of log metabolite intensity, with the significance threshold at a false discovery rate <0.20. Results: Four metabolites were inversely associated with risk of RCC during follow-up—C38:4 PI, C34:0 PC, C14:0 SM, and C16:1 SM (ORs ranging from 0.33–0.44). Two were positively associated with RCC risk—C3-DC-CH3 carnitine and C5 carnitine (ORs = 2.84 and 2.83, respectively). These results were robust when further adjusted for metabolic risk factors (body mass index (BMI), physical activity, diabetes/hypertension history). Metabolites associated with RCC had weak correlations (|r| < 0.2) with risk factors of BMI, physical activity, smoking, alcohol, and diabetes/hypertension history. In mutually adjusted models, three metabolites (C38:4 PI, C14:0 SM, and C3-DC-CH3 carnitine) were independently associated with RCC risk. Conclusions: Serum concentrations of six metabolites were associated with RCC risk, and three of these had independent associations from the mutually adjusted model. These metabolites may point toward new biological pathways of relevance to this malignancy.

This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed. The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex. We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed “SNAREopathies.”

A Correction to this paper has been published: https://doi.org/10.1038/s41436-020-01090-w