Embedding a surface acoustic wave sensor and venting into a metal additively manufactured injection mould tool for targeted temperature monitoring.

Injection moulding (IM) tools with embedded sensors can significantly improve the process efficiency and quality of the fabricated parts through real-time monitoring and control of key process parameters such as temperature, pressure and injection speed. However, traditional mould tool fabrication technologies do not enable the fabrication of complex internal geometries. Complex internal geometries are necessary for technical applications such as sensor embedding and conformal cooling which yield benefits for process control and improved cycle times. With traditional fabrication techniques, only simple bore-based sensor embedding or external sensor attachment is possible. Externally attached sensors may compromise the functionality of the injection mould tool, with limitations such as the acquired data not reflecting the processes inside the part. The design freedom of additive manufacturing (AM) enables the fabrication of complex internal geometries, making it an excellent candidate for fabricating injection mould tools with such internal geometries. Therefore, embedding sensors in a desired location for targeted monitoring of critical mould tool regions is easier to achieve with AM. This research paper focuses on embedding a wireless surface acoustic wave (SAW) temperature sensor into an injection mould tool that was additively manufactured from stainless steel 316L. The laser powder bed fusion (L-PBF) "stop-and-go" approach was applied to embed the wireless SAW sensor. After embedding, the sensor demonstrated full functionality by recording real-time temperature data, which can further enhance process control. In addition, the concept of novel print-in-place venting design, applying the same L-PBF stop-and-go approach, for vent embedding was successfully implemented, enabling the IM of defectless parts at faster injection rates, whereas cavities designed and tested without venting resulted in parts with burn marks.

Impact of Acute Exacerbation of Idiopathic Pulmonary Fibrosis on Lung Transplant Outcomes.

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are acute, significant respiratory deteriorations in patients with IPF and can lead to increased morbidity and mortality. It remains unclear how AE-IPF impacts lung transplant (LTX) outcomes. METHODS: All adult patients who were listed for LTX between July 2005 and October 2020 at the Loyola University Medical Center with a diagnosis of IPF were included. Pretransplant characteristics and posttransplant outcomes were gathered via retrospective chart review. The primary outcome was short- and long-term survival for patients transplanted during stable IPF versus those with AE-IPF. RESULTS: One hundred fifty-nine patients were included in this study, 17.6% of whom were transplanted during AE-IPF. AE-IPF patients were more likely to have higher oxygen needs pretransplant, have higher lung allocation score, and were more likely to be intubated or be on extracorporeal membrane oxygenation as compared with stable IPF patients. Survival by AE status at transplant did not differ at 90 d or 1 y posttransplantation. There were also no significant differences in rates of severe primary graft dysfunction or acute rejection within 1 y. CONCLUSIONS: Patients with AE-IPF were more likely to have higher oxygenation requirements and higher lung allocation score at the time of LTX than those with stable IPF. Despite this, there were no differences in survival at 90 d, 1 y, or 3 y, or differences in incidence of severe primary graft dysfunction or acute cellular rejection. Transplantation of patients with AE-IPF has clinical outcomes comparable with transplantation of patients with stable IPF. This contrasts with previous studies examining LTX in patients with AE-IPF.

Condition Monitoring of Additively Manufactured Injection Mould Tooling: A Review of Demands, Opportunities and Potential Strategies.

Injection moulding (IM) is an important industrial process, known to be the most used plastic formation technique. Demand for faster cycle times and higher product customisation is driving interest in additive manufacturing (AM) as a new method for mould tool manufacturing. The use of AM offers advantages such as greater design flexibility and conformal cooling of components to reduce cycle times and increase product precision. However, shortcomings of metal additive manufacturing, such as porosity and residual stresses, introduce uncertainties about the reliability and longevity of AM tooling. The injection moulding process relies on high volumes of produced parts and a minimal amount of tool failures. This paper reviews the demands for tool condition monitoring systems for AM-manufactured mould tools; although tool failures in conventionally manufactured tooling are rare, they do occur, usually due to cracking, deflection, and channel blockages. However, due to the limitations of the AM process, metal 3D-printed mould tools are susceptible to failures due to cracking, delamination and deformation. Due to their success in other fields, acoustic emission, accelerometers and ultrasound sensors offer the greatest potential in mould tool condition monitoring. Due to the noisy machine environment, sophisticated signal processing and decision-making algorithms are required to prevent false alarms or the missing of warning signals. This review outlines the state of the art in signal decomposition and both data- and model-based approaches to determination of the current state of the tool, and how these can be employed for IM tool condition monitoring. The development of such a system would help to ensure greater industrial uptake of additive manufacturing of injection mould tooling, by increasing confidence in the technology, further improving the efficiency and productivity of the sector.

Assessment of CBCT-based synthetic CT generation accuracy for adaptive radiotherapy planning.

PURPOSE: Cone-beam CT (CBCT)-based synthetic CT (sCT) dose calculation has the potential to make the adaptive radiotherapy (ART) pathway more efficient while removing subjectivity. This study assessed four sCT generation methods using 15 head-and-neck rescanned ART patients. Each patient's planning CT (pCT), rescan CT (rCT), and CBCT post-rCT was acquired with the CBCT deformably registered to the rCT (dCBCT). METHODS: The four methods investigated were as follows: method 1-deformably registering the pCT to the dCBCT. Method 2-assigning six mass density values to the dCBCT. Method 3-iteratively removing artifacts and correcting the dCBCT Hounsfield units (HU). Method 4-using a cycle general adversarial network machine learning model (trained with 45 paired pCT and CBCT). Treatment plans were created on the rCT and recalculated on each sCT. Planning target volume (PTV) and organ-at-risk (OAR) structures were contoured by clinicians on the rCT (high-dose PTV, low-dose PTV, spinal canal, larynx, brainstem, and parotids) to allow the assessment of dose-volume histogram statistics at clinically relevant points. RESULTS: The HU mean absolute error (MAE) and minimum dose gamma index pass rate (2%/2 mm) were calculated, and the generation time was measured for 15 patients using the rCT as the comparator. For methods 1-4 the MAE, gamma index analysis, and generation time were as follows: 59.7 HU, 100.0%, and 143 s; 164.2 HU, 95.2%, and 232 s; 75.7 HU, 99.9%, and 153 s; and 79.4 HU, 99.8%, and 112 s, respectively. Dose differences for PTVs and OARs were all <0.3 Gy except for method 2 (<0.5 Gy). CONCLUSION: All methods were considered clinically viable. The machine learning method was found to be most suitable for clinical implementation due to its high dosimetric accuracy and short generation time. Further investigation is required for larger anatomical changes between the CBCT and pCT and for other anatomical sites.

Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.

Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective tissue growth factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. Our aim was to test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cε (PKCε) mouse model of DCM. Transgenic mice expressing constitutively active PKCε in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to cardiac fibrosis, heart failure, and increased mortality. Beginning at 3 months of age, PKCε mice were treated with a neutralizing monoclonal antibody to CTGF (FG-3149) for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic functions in PKCε mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling was elevated in PKCε mice, but significantly decreased by CTGF inhibition. However total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCε mice suggests that CTGF inhibition may benefit patients with DCM. Additional studies to explore this potential are warranted.

Oxidative Stress in Caenorhabditis elegans: Protective Effects of Spartin.

Troyer syndrome is caused by a mutation in the SPG20 gene, which results in complete loss of expression of the protein spartin. We generated a genetic model of Troyer syndrome in worms to explore the locomotor consequences of a null mutation of the Caenorhabditis elegans SPG20 orthologue, F57B10.9, also known as spg-20. Spg-20 mutants showed decreased length, crawling speed, and thrashing frequency, and had a shorter lifespan than wild-type animals. These results suggest an age-dependent decline in motor function in mutant animals. The drug paraquat was used to induce oxidative stress for 4 days in the animals. We measured survival rate and examined locomotion by measuring crawling speed and thrashing frequency. After 4 days of paraquat exposure, 77% of wild-type animals survived, but only 38% of spg-20 mutant animals survived. Conversely, animals overexpressing spg-20 had a survival rate of 95%. We also tested lifespan after a 1 hour exposure to sodium azide. After a 24 hour recovery period, 87% of wild type animals survived, 57% of spg-20 mutant animals survived, and 82% of animals overexpressing spg-20 survived. In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals. Importantly, the locomotor phenotype for both crawling and thrashing was rescued in animals overexpressing spg-20. The animals overexpressing spg-20 had crawling speeds and thrashing frequencies similar to those of wild-type animals. These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress.

Preclinical evaluation of an anti-alpha5beta1 integrin antibody as a novel anti-angiogenic agent.

Integrin alpha5beta1, the principal fibronectin receptor, is an important survival factor, playing a key role in angiogenesis. Angiogenesis is critical for tumor growth, and anti-angiogenic therapies have met clinical success. To validate the therapeutic potential of an anti-alpha5beta1 strategy, we generated volociximab (M200) a chimeric human IgG4 version of the alpha5beta1 function-blocking murine antibody IIA1; and F200, the Fab derivative. Volociximab, F200 and IIA1 showed similar activity by ELISA (EC50= 0.2nM), Biacore (Kd= 0.1-0.4nM) and inhibition of fibronectin binding (IC50= 2-3nM). The inhibitory potential of alpha5beta1 antibodies was compared to HuMV833, an anti-VEGF antibody. Both volociximab and HuMV833 inhibited HUVEC proliferation (IC50 of volociximab = 0.2-0.5nM; IC50 of HuMV833 = 45nM). However, IIA1, volociximab and F200 were also potent inhibitors of an in vitro model of angiogenesis (HUVEC tube formation assay), unlike HuMV833. Additionally, volociximab inhibited in vitro tube formation induced by VEGF and/or bFGF, suggesting a mechanism of action independent of growth factor stimulus. In fact, inhibition of alpha5beta1 function by volociximab induced apoptosis of actively proliferating, but not resting, endothelial cells. Volociximab does not cross-react with rodent alpha5beta1, therefore in vivo validation of an anti-alpha5beta1 approach was conducted in a cynomolgus model of choroidal revascularization. Volociximab and F200 were potent inhibitors of neovessel formation in this model. These data demonstrate that volociximab has therapeutic potential in diseases in which new vessel formation is a component of the pathology.