Surface Roughness and Grain Size Variation When 3D Printing Polyamide 11 Parts Using Selective Laser Sintering.

Selective laser sintering (SLS) is a well-established technology that is used for additive manufacturing. Significant efforts have been made to improve SLS by optimizing the powder deposition, laser beam parameters, and temperature settings. The purpose is to ensure homogeneous sintering and prevent geometric and appearance inaccuracies in the manufactured objects. We evaluated the differences in the surface roughness and grain size of curved objects manufactured by using upcoming SLS technology that features two CO laser sources. Our analysis was carried out on polyamide 11 (PA11), which is a sustainable biobased polymer that has been gaining popularity due to its high-performance properties: its low melting point, high viscosity, and excellent mechanical properties. By using a Taguchi experimental design and analysis of variance (ANOVA), we examined the influence on the surface roughness and grain size of the build setup, the presence of thin walls, and the position of the sample on the powder bed. We found significant differences in some surface roughness and grain size measurements when these parameters were changed.

3-D-Printed Models for Temporal Bone Training: A Validity Study.

OBJECTIVE: 3-D printing offers convenient and low-cost mastoidectomy training; nonetheless, training benefits using 3-D-printed temporal bones remain largely unexplored. In this study, we have collected validity evidence for a low-cost, 3-D-printed temporal bone for mastoidectomy training and established a credible pass/fail score for performance on the model. STUDY DESIGN: A prospective educational study gathering validity evidence using Messick's validity framework. SETTING: Seven Danish otorhinolaryngology training institutions. PARTICIPANTS: Eighteen otorhinolaryngology residents (novices) and 11 experienced otosurgeons (experts). INTERVENTION: Residents and experienced otosurgeons each performed two to three anatomical mastoidectomies on a low-cost, 3-D-printed temporal bone model produced in-house. After drilling, mastoidectomy performances were rated by three blinded experts using a 25-item modified Welling scale (WS). MAIN OUTCOME MEASURE: Validity evidence using Messick's framework including reliability assessment applying both classical test theory and Generalizability theory. RESULTS: Novices achieved a mean score of 13.9 points; experienced otosurgeons achieved 23.2 points. Using the contrasting groups method, we established a 21/25-point pass/fail level. The Generalizability coefficient was 0.91, and 75% of the score variance was attributable to participant performance, indicating a high level of assessment reliability. Subsequent D studies revealed that two raters rating one performance or one rater rating two performances were sufficiently reliable for high-stakes assessment. CONCLUSION: Validity evidence supports using a low-cost, 3-D-printed model for mastoidectomy training. The model can be printed in-house using consumer-grade 3-D printers and serves as an additional training tool in the temporal bone curriculum. For competency-based training, we established a cut-off score of 21 of 25 WS points using the contrasting groups method.

Acetyl-CoA carboxylase 1 is a suppressor of the adipocyte thermogenic program.

Disruption of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) in mice induces browning in inguinal white adipose tissue (iWAT). However, adipocyte FASN knockout (KO) increases acetyl-coenzyme A (CoA) and malonyl-CoA in addition to depletion of palmitate. We explore which of these metabolite changes triggers adipose browning by generating eight adipose-selective KO mouse models with loss of ATP-citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), ACC2, malonyl-CoA decarboxylase (MCD) or FASN, or dual KOs ACLY/FASN, ACC1/FASN, and ACC2/FASN. Preventing elevation of acetyl-CoA and malonyl-CoA by depletion of adipocyte ACLY or ACC1 in combination with FASN KO does not block the browning of iWAT. Conversely, elevating malonyl-CoA levels in MCD KO mice does not induce browning. Strikingly, adipose ACC1 KO induces a strong iWAT thermogenic response similar to FASN KO while also blocking malonyl-CoA and palmitate synthesis. Thus, ACC1 and FASN are strong suppressors of adipocyte thermogenesis through promoting lipid synthesis rather than modulating the DNL intermediates acetyl-CoA or malonyl-CoA.

3D-printing a cost-effective model for mastoidectomy training.

BACKGROUND: 3D-printed temporal bone models can potentially provide a cost-effective alternative to cadaver surgery that can be manufactured locally at the training department. The objective of this study was to create a cost-effective 3D-printed model suitable for mastoidectomy training using entry level and commercially available print technologies, enabling individuals, without prior experience on 3D-printing, to manufacture their own models for basic temporal bone training. METHODS: Expert technical professionals and an experienced otosurgeon identified the best material for replicating the temporal bone and created a cost-effective printing routine for the model using entry-level print technologies. Eleven participants at a temporal bone dissection course evaluated the model using a questionnaire. RESULTS: The 3D-printed temporal bone model was printed using a material extrusion 3D-printer with a heat resistant filament, reducing melting during drilling. After printing, a few simple post-processing steps were designed to replicate the dura, sigmoid sinus and facial nerve. Modifying the 3D-printer by installing a direct-drive and ruby nozzle resulted in more successful prints and less need for maintenance. Upon evaluation by otorhinolaryngology trainees, unanimous feedback was that the model provided a good introduction to the mastoidectomy procedure, and supplementing practice to cadaveric temporal bones. CONCLUSION: In-house production of a cost-effective 3D-printed model for temporal bone training is feasible and enables training institutions to manufacture their own models. Further, this work demonstrates the feasibility of creating new temporal bone models with anatomical variation to provide ample training opportunity.

Alteration history of Séítah formation rocks inferred by PIXL x-ray fluorescence, x-ray diffraction, and multispectral imaging on Mars.

Collocated crystal sizes and mineral identities are critical for interpreting textural relationships in rocks and testing geological hypotheses, but it has been previously impossible to unambiguously constrain these properties using in situ instruments on Mars rovers. Here, we demonstrate that diffracted and fluoresced x-rays detected by the PIXL instrument (an x-ray fluorescence microscope on the Perseverance rover) provide information about the presence or absence of coherent crystalline domains in various minerals. X-ray analysis and multispectral imaging of rocks from the Séítah formation on the floor of Jezero crater shows that they were emplaced as coarsely crystalline igneous phases. Olivine grains were then partially dissolved and filled by finely crystalline or amorphous secondary silicate, carbonate, sulfate, and chloride/oxychlorine minerals. These results support the hypothesis that Séítah formation rocks represent olivine cumulates altered by fluids far from chemical equilibrium at low water-rock ratios.

Contaminant concentrations and risks associated with the Pacific oyster in the highly urbanized San Diego Bay.

Contaminant concentrations in filter-feeding shellfish may indicate the health of coastal waters and consumption risks. Widespread expansion of the Pacific oyster (Crassostrea gigas) and its popularity as food make it a useful sentinel. We surveyed intertidal Pacific oysters in San Diego Bay, California for contaminants during summer 2018 and winter 2019. We compared contaminants in Pacific oyster to California mussel from California's State Mussel Watch Program (1993-2003) and human consumption thresholds. Contaminants such as neonicotinoid and chlorinated pesticides, selenium, and several metals were higher in Pacific oysters in summer, while PBDEs, benzylbutyl phthalate, and plastics were higher in winter. Contaminant levels were generally lower in Pacific oyster than mussel except for copper and zinc. Bay-wide PCB concentrations in oysters exceeded thresholds but individual samples (locations) also met or surpassed chlordane, PCB and PAH thresholds. Monitoring and risk assessments that consider species' biology, season, location, effects of multiple contaminants, and human consumption patterns will contribute to more effective consumption guidelines.

Effect of 3D-Printed Models on Cadaveric Dissection in Temporal Bone Training.

OBJECTIVE: Mastoidectomy is a cornerstone in the surgical management of middle and inner ear diseases. Unfortunately, training is challenged by insufficient access to human cadavers. Three-dimensional (3D) printing of temporal bones could alleviate this problem, but evidence on their educational effectiveness is lacking. It is largely unknown whether training on 3D-printed temporal bones improves mastoidectomy performance, including on cadavers, and how this training compares with virtual reality (VR) simulation. To address this knowledge gap, this study investigated whether training on 3D-printed temporal bones improves cadaveric dissection performance, and it compared this training with the already-established VR simulation. STUDY DESIGN: Prospective cohort study of an educational intervention. SETTING: Tertiary university hospital, cadaver dissection laboratory, and simulation center in Copenhagen, Denmark. METHODS: Eighteen otorhinolaryngology residents (intervention) attending the national temporal bone dissection course received 3 hours of mastoidectomy training on 3D-printed temporal bones. Posttraining cadaver mastoidectomy performances were rated by 3 experts using a validated assessment tool and compared with those of 66 previous course participants (control) who had received time-equivalent VR training prior to dissection. RESULTS: The intervention cohort outperformed the controls during cadaver dissection by 29% (P < .001); their performances were largely similar across training modalities but remained at a modest level (~50% of the maximum score). CONCLUSION: Mastoidectomy skills improved from training on 3D-printed temporal bone and seemingly more so than on time-equivalent VR simulation. Importantly, these skills transferred to cadaveric dissection. Training on 3D-printed temporal bones can effectively supplement cadaver training when learning mastoidectomy.

Enabling Micro Injection Moulding Using a Soft Tooling Process Chain with Inserts Made of Mortar Material.

The manufacturing of inserts for micro injection moulding made of mortar material is presented in this work. The fabrication of the mortar insert described in this publication relied on a versatile and relatively fast rapid prototyping process based on soft tooling. The mortar insert has a QR code with micro features on its surface, which was replicated in acrylonitrile butadiene styrene (ABS) polymer by the micro injection moulding process. With this approach, it is possible to fabricate hard inserts for micro injection moulding purposes that are able to compete with conventional-made inserts made of tool steel.

Degradation Mechanisms of Metal-Supported Solid Oxide Cells and Countermeasures: A Review.

Metal-supported oxide cells (MSCs) are considered as the third-generation solid oxide cells (SOCs) succeeding electrolyte-supported (first generation) and anode-supported (second generation) cells, which have gained much attention and progress in the past decade. The use of metal supports and advanced technical methods (such as infiltrated electrodes) has vastly improved cell performance, especially with its rapid startup ability and power density, showing a significant decrease in raw materials cost. However, new degradation mechanisms appeared, limiting the further improvement of the performance and lifetime. This review encapsulates the degradation mechanisms and countermeasures in the field of MSCs, reviewing the challenges and recommendations for future development.

3D-Printed Models for Temporal Bone Surgical Training: A Systematic Review.

OBJECTIVE: 3D-printed models hold great potential for temporal bone surgical training as a supplement to cadaveric dissection. Nevertheless, critical knowledge on manufacturing remains scattered, and little is known about whether use of these models improves surgical performance. This systematic review aims to explore (1) methods used for manufacturing and (2) how educational evidence supports using 3D-printed temporal bone models. DATA SOURCES: PubMed, Embase, the Cochrane Library, and Web of Science. REVIEW METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, relevant studies were identified and data on manufacturing and validation and/or training extracted by 2 reviewers. Quality assessment was performed using the Medical Education Research Study Quality Instrument tool; educational outcomes were determined according to Kirkpatrick's model. RESULTS: The search yielded 595 studies; 36 studies were found eligible and included for analysis. The described 3D-printed models were based on computed tomography scans from patients or cadavers. Processing included manual segmentation of key structures such as the facial nerve; postprocessing, for example, consisted of removal of print material inside the model. Overall, educational quality was low, and most studies evaluated their models using only expert and/or trainee opinion (ie, Kirkpatrick level 1). Most studies reported positive attitudes toward the models and their potential for training. CONCLUSION: Manufacturing and use of 3D-printed temporal bones for surgical training are widely reported in the literature. However, evidence to support their use and knowledge about both manufacturing and the effects on subsequent surgical performance are currently lacking. Therefore, stronger educational evidence and manufacturing knowhow are needed for widespread implementation of 3D-printed temporal bones in surgical curricula.

Performance of the Sysmex White Precursor Channel to discover circulating leukemic blast cells.

INTRODUCTION: Circulating immature precursor cells indicate malignant diseases like acute myeloid or lymphoid leukemia, and blast cells are key finds for disease management. Automatized cell counters are an essential contemporary appliance for blast detection, but false-positive samples remain challenging in terms of time and resources. To reduce this issue, the White Precursor Channel (WPC) was introduced to Sysmex XN series; however, sensitivity may reduce when accommodating low specificity. Therefore, our aim was to evaluate WPC blast alarm flag performance with regard to detecting blast cells. METHODS: At two major Danish hospitals, random blood samples were collected from the routine setting   in a four-week period and analyzed on WPC XN20 (Sysmex, Japan). Results were compared with manual differential white blood cell count (Manual WBCC) assisted by CellaVisionDM96. RESULTS: In 117 samples, we found 0.2 to 34.4% blasts, WPC blast flag specificity = 82% and a low sensitivity = 40%. However, other XN alarm flags forwarded samples to Manual WBCC, so blast cells were detected despite missing a specific blast flag: With all alarm flags, combined sensitivity increased to 88%. Overall, the WPC application stopped 18% of the 117 samples going to Manual WBCC (three false negatives). Q values are arbitrary probability measurements for the blast flag, and in five samples (0.5 to 47.3% blasts) imprecision ranged from 5.3 to 122 CV%. CONCLUSIONS: WPC blast alarm flags are imprecise and inaccurate, especially when blast counts are low. However, the XN20 will alarm samples with other flags so that most samples containing blast cells will be manually reviewed after all. Hence, the presented flag types should not bias the decisions of manual reviewers.

Clinical Utility of Advanced Microbiology Testing Tools.

Advanced microbiology technologies are rapidly changing our ability to diagnose infections, improve patient care, and enhance clinical workflow. These tools are increasing the breadth, depth, and speed of diagnostic data generated per patient, and testing is being moved closer to the patient through rapid diagnostic technologies, including point-of-care (POC) technologies. While select stakeholders have an appreciation of the value/importance of improvements in the microbial diagnostic field, there remains a disconnect between clinicians and some payers and hospital administrators in terms of understanding the potential clinical utility of these novel technologies. Therefore, a key challenge for the clinical microbiology community is to clearly articulate the value proposition of these technologies to encourage payers to cover and hospitals to adopt advanced microbiology tests. Specific guidance on how to define and demonstrate clinical utility would be valuable. Addressing this challenge will require alignment on this topic, not just by microbiologists but also by primary care and emergency room (ER) physicians, infectious disease specialists, pharmacists, hospital administrators, and government entities with an interest in public health. In this article, we discuss how to best conduct clinical studies to demonstrate and communicate clinical utility to payers and to set reasonable expectations for what diagnostic manufacturers should be required to demonstrate to support reimbursement from commercial payers and utilization by hospital systems.

A Soft Tooling Process Chain for Injection Molding of a 3D Component with Micro Pillars.

The purpose of this paper is to present the method of a soft tooling process chain employing Additive Manufacturing (AM) for fabrication of injection molding inserts with micro surface features. The Soft Tooling inserts are manufactured by Digital Light Processing (vat photo polymerization) using a photopolymer that can withstand relatively high temperaturea. The part manufactured here has four tines with an angle of 60°. Micro pillars (Ø200 µm, aspect ratio of 1) are arranged on the surfaces by two rows. Polyethylene (PE) injection molding with the soft tooling inserts is used to fabricate the final parts. This method demonstrates that it is feasible to obtain injection-molded parts with microstructures on complex geometry by additive manufactured inserts. The machining time and cost is reduced significantly compared to conventional tooling processes based on computer numerical control (CNC) machining. The dimensions of the micro features are influenced by the applied additive manufacturing process. The lifetime of the inserts determines that this process is more suitable for pilot production. The precision of the inserts production is limited by the additive manufacturing process as well.

Neuronal modulation of brown adipose activity through perturbation of white adipocyte lipogenesis.

OBJECTIVE: Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of "beige" adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT). METHODS AND RESULTS: Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. This increased sympathetic innervation could be observed at both 22 °C and 30 °C, indicating it is not a response to heat loss but rather adipocyte signaling. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. CONCLUSION: These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.

Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming.

BACKGROUND: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood. METHODS & RESULTS: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT. CONCLUSIONS: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT.

A major role of insulin in promoting obesity-associated adipose tissue inflammation.

OBJECTIVE: Adipose tissue (AT) inflammation is associated with systemic insulin resistance and hyperinsulinemia in obese rodents and humans. A longstanding concept is that hyperinsulinemia may promote systemic insulin resistance through downregulation of its receptor on target tissues. Here we tested the novel hypothesis that insulin also impairs systemic insulin sensitivity by specifically enhancing adipose inflammation. METHODS: Circulating insulin levels were reduced by about 50% in diet-induced and genetically obese mice by treatments with diazoxide or streptozotocin, respectively. We then examined AT crown-like structures, macrophage markers and pro-inflammatory cytokine expression in AT. AT lipogenesis and systemic insulin sensitivity was also monitored. Conversely, insulin was infused into lean mice to determine its affects on the above parameters. RESULTS: Lowering circulating insulin levels in obese mice by streptozotocin treatment decreased macrophage content in AT, enhancing insulin stimulated Akt phosphorylation and de novo lipogenesis (DNL). Moreover, responsiveness of blood glucose levels to injected insulin was improved by streptozotocin and diazoxide treatments of obese mice without changes in body weight. Remarkably, even in lean mice, infusion of insulin under constant euglycemic conditions stimulated expression of cytokines in AT. Consistent with these findings, insulin treatment of 3T3-L1 adipocytes caused a 10-fold increase in CCL2 mRNA levels within 6 h, which was blocked by the ERK inhibitor PD98059. CONCLUSION: Taken together, these results indicate that obesity-associated hyperinsulinemia unexpectedly drives AT inflammation in obese mice, which in turn contributes to factors that suppress insulin-stimulated adipocyte DNL and systemic insulin sensitivity.

The Lipid Droplet Protein Hypoxia-inducible Gene 2 Promotes Hepatic Triglyceride Deposition by Inhibiting Lipolysis.

The liver is a major site of glucose, fatty acid, and triglyceride (TG) synthesis and serves as a major regulator of whole body nutrient homeostasis. Chronic exposure of humans or rodents to high-calorie diets promotes non-alcoholic fatty liver disease, characterized by neutral lipid accumulation in lipid droplets (LD) of hepatocytes. Here we show that the LD protein hypoxia-inducible gene 2 (Hig2/Hilpda) functions to enhance lipid accumulation in hepatocytes by attenuating TG hydrolysis. Hig2 expression increased in livers of mice on a high-fat diet and during fasting, two states associated with enhanced hepatic TG content. Hig2 expressed in primary mouse hepatocytes localized to LDs and promoted LD TG deposition in the presence of oleate. Conversely, tamoxifen-inducible Hig2 deletion reduced both TG content and LD size in primary hepatocytes from mice harboring floxed alleles of Hig2 and a cre/ERT2 transgene controlled by the ubiquitin C promoter. Hepatic TG was also decreased by liver-specific deletion of Hig2 in mice with floxed Hig2 expressing cre controlled by the albumin promoter. Importantly, we demonstrate that Hig2-deficient hepatocytes exhibit increased TG lipolysis, TG turnover, and fatty acid oxidation as compared with controls. Interestingly, mice with liver-specific Hig2 deletion also display improved glucose tolerance. Taken together, these data indicate that Hig2 plays a major role in promoting lipid sequestration within LDs in mouse hepatocytes through a mechanism that impairs TG degradation.

Activated Kupffer cells inhibit insulin sensitivity in obese mice.

Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF-κB, in KCs in obese mice. We used glucan-encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Following intravenous injections, GeRPs containing siRNA against p65 of the NF-κB complex caused loss of NF-κB p65 expression in KCs without disrupting NF-κB in hepatocytes or macrophages in other tissues. Silencing of NF-κB expression in KCs in obese mice decreased cytokine secretion and improved insulin sensitivity and glucose tolerance without affecting hepatic lipid accumulation. Importantly, GeRPs had no detectable toxic effect. Thus, KCs are key contributors to hepatic insulin resistance in obesity and a potential therapeutic target for metabolic disease.

Protein kinase Cε modulates insulin receptor localization and trafficking in mouse embryonic fibroblasts.

We have previously shown that deletion of protein kinase C epsilon (PKCε) in mice results in protection against glucose intolerance caused by a high fat diet. This was in part due to reduced insulin uptake by hepatocytes and insulin clearance, which enhanced insulin availability. Here we employed mouse embryonic fibroblasts (MEFs) derived from wildtype (WT) and PKCε-deficient (PKCε(-/-)) mice to examine this mechanistically. PKCε(-/-) MEFs exhibited reduced insulin uptake which was associated with decreased insulin receptor phosphorylation, while downstream signalling through IRS-1 and Akt was unaffected. Cellular fractionation demonstrated that PKCε deletion changed the localization of the insulin receptor, a greater proportion of which co-fractionated with flotillin-1, a marker of membrane microdomains. Insulin stimulation resulted in redistribution of the receptor in WT cells, while this was markedly reduced in PKCε(-/-) cells. These alterations in insulin receptor trafficking were associated with reduced expression of CEACAM1, a receptor substrate previously shown to modulate insulin clearance. Virally-mediated reconstitution of PKCε in MEFs increased CEACAM1 expression and partly restored the sensitivity of the receptor to insulin-stimulated redistribution. These data indicate that PKCε can affect insulin uptake in MEFs through promotion of receptor-mediated endocytosis, and that this may be mediated by regulation of CEACAM1 expression.