Plasma Focused Ion Beam Serial Sectioning as a Technique to Characterize Nonmetallic Inclusions in Superelastic Nitinol Fine Wires.

Nonmetallic inclusion (NMI) populations in superelastic (SE) Nitinol fine wires (<140 µm in diameter) were investigated by combining plasma focused ion beam (PFIB) serial sectioning with scanning electron microscopy (SEM). High purity (HP)­lower oxygen content and standard purity (SP)­higher oxygen content Nitinol wires were sectioned and imaged. The three-dimensional (3D) reconstructions provided more complete connectivity of NMIs and pores as well as information about the distribution of the features within the wire volume that is not possible with traditional two-dimensional (2D) imaging techniques. NMIs were present alone and with pores in the leading and/or trailing edges of the inclusions, in addition to stringers (i.e., fractured, elongated NMI, and intermixed with pores adjacent to each other), all of which were parallel to the wire drawing axis. The area percentages for the NMIs were 0.01% (HP Nitinol) and 0.04% (SP Nitinol), while the volume percentages measured 0.09% (HP Nitinol) and 0.47% (SP Nitinol). The combined PFIB-SEM serial sectioning approach provided the requisite resolution necessary to distinguish between NMIs and pores at micron and submicron sizes. Information gathered from this technique can be used to better inform models and predictions for fatigue lifetimes based on statistical analyses of these feature populations.

The Use of Miniature Specimens to Determine Local Properties and Fracture Behavior of LPBF-Processed Inconel 718 in as-Deposited and Post-Treated States.

This paper summarizes the assessment of directional anisotropy in local mechanical properties for Laser Powder Bed Fusion (LPBF) IN-718 bulk samples via the use of miniature samples excised from the bulk for both as-deposited and post-treated states. The quasi-static tensile properties at room temperature are investigated at several different locations along the build direction and at different orientations for both considered states. A comparison between the excised miniature tensile specimens and standard-sized sample results have also been conducted and exhibit very good agreement. Significant anisotropy is present in mechanical properties at different build heights for the as-deposited state, while the post-treated material exhibited more homogenous properties, both along the height and for different sampling orientations. However, significant reductions (e.g., >30%) in the strength (Yield, UTS) along with a significant increase in the reduction in area at fracture is found for post-processed materials. Metallography and fractography analyses were conducted in order to begin to determine the source(s) of this anisotropy for the as-deposited state.

Current trends in surgical society membership: What does the future hold?

BACKGROUND: Motivations for joining and maintaining surgical society memberships include networking, educational, and social opportunities. We hypothesized surgeons have membership lapses despite these benefits. We aimed to assess society members motivations for joining, satisfaction with membership, any lapses and if so, reasons for these lapses. METHODS: A survey was sent via email to members of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), American Society for Metabolic and Bariatric Surgery (ASMBS), and the Society for Surgery of the Alimentary Tract (SSAT), using society directories. RESULTS: The majority (60%) of respondents felt satisfied with membership. However, 68% reported a lapse in membership. The most common reason for lapse was cost, followed closely by time constraints. CONCLUSION: Despite a high rate of member satisfaction, a majority of respondents had allowed a membership to lapse, with cost and time constraints being the most common reasons. Surgical societies should take these trends into account as they expand and recruit new membership.

Critical Salt Loading in Flexible Poly(vinyl alcohol) Sensors Fabricated by an Inkjet Printing and Plasma Reduction Method.

We report a low-temperature inkjet printing and plasma treatment method using silver nitrate ink that allows the fabrication of conductive silver traces on poly(vinyl alcohol) (PVA) film with good fidelity and without degrading the polymer substrate. In doing so, we also identify a critical salt loading in the film that is necessary to prevent the polymer from reacting with the silver nitrate-based ink, which improves the resolution of the silver trace while simultaneously lowering its sheet resistance. Silver lines printed on PVA film using this method have sheet resistances of around 0.2 Ω/□ under wet/dry and stretched/unstretched conditions, while PVA films without prior treatment double in sheet resistance upon wetting or stretching the substrate. This low resistance of printed lines on salt-treated films can be preserved under multiple bending cycles of 0-90° and stretching cycles of 0-6% strain if the polymer is prestretched prior to inkjet printing.

Phase 2 Study of Pomalidomide (CC-4047) Monotherapy for Children and Young Adults With Recurrent or Progressive Primary Brain Tumors.

INTRODUCTION: Treatment of recurrent primary pediatric brain tumors remains a major challenge, with most children succumbing to their disease. We conducted a prospective phase 2 study investigating the safety and efficacy of pomalidomide (POM) in children and young adults with recurrent and progressive primary brain tumors. METHODS: Patients with recurrent and progressive high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), ependymoma, or medulloblastoma received POM 2.6 mg/m2/day (the recommended phase 2 dose [RP2D]) on days 1-21 of a 28-day cycle. A Simon's Optimal 2-stage design was used to determine efficacy. Primary endpoints included objective response (OR) and long-term stable disease (LTSD) rates. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 46 patients were evaluable for response (HGG, n = 19; DIPG, ependymoma, and medulloblastoma, n = 9 each). Two patients with HGG achieved OR or LTSD (10.5% [95% CI, 1.3%-33.1%]; 1 partial response and 1 LTSD) and 1 patient with ependymoma had LTSD (11.1% [95% CI, 0.3%-48.2%]). There were no ORs or LTSD in the DIPG or medulloblastoma cohorts. The median PFS for patients with HGG, DIPG, ependymoma, and medulloblastoma was 7.86, 11.29, 8.43, and 8.43 weeks, respectively. Median OS was 5.06, 3.78, 12.02, and 11.60 months, respectively. Neutropenia was the most common grade 3/4 adverse event. CONCLUSIONS: Treatment with POM monotherapy did not meet the primary measure of success in any cohort. Future studies are needed to evaluate if POM would show efficacy in tumors with specific molecular signatures or in combination with other anticancer agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03257631; EudraCT, identifier 2016-002903-25.

Nano-sized ultrasound contrast agent: salting-out method.

Tumor imaging by ultrasound is greatly enhanced by the use of ultrasound contrast agents (UCAs), stabilized, gas-filled bodies. They are generally less than 7 microm to pass freely through the capillary bed. Development of a nano-sized agent would enable them to extravasate through the leaky pores of angiogenic vessels. We describe the development of an echogenic, nano-sized polylactic acid UCA by adaptation of a salting-out method. The viscosity of the initial colloidal suspension (concentration and molecular weight of protective colloid [polyvinyl alcohol (PVA)] and concentration of polymer) was key in determining particle size and polydispersity (increasing viscosity increased both). Addition of the porogens ammonium carbonate and camphor, required to produce hollow echogenic capsules, also increased the size (eg, 5 wt% PVA, mean solid nanocapsule size 386 +/- 25 nm, polydispersity index 0.367 +/- 0.14, and mean UCA size 640 +/- 18 nm, polydispersity index 0.308 +/- 0.027). Viscosity had the opposite effect on echogenicity of the resultant nano-UCA, which ranged from 21.69 +/- 0.78 dB for 2% PVA to 12.1 +/- 0.8 dB for 10% PVA. The UCA prepared with 10% PVA, however, had a longer half-life in the ultrasound beam (t(1/2) > 15 minutes vs t(1/2) < 10 minutes), suggesting a thicker shell. Optimization will require compromise among size, echogenicity, and stability.

Tension and fatigue behavior of 316LVM 1x7 multi-strand cables used as implantable electrodes.

The mechanical behavior of 316LVM 1x7 cables were evaluated in uniaxial tension, and in cyclic strain-controlled fatigue with the use of a Flex tester operated to provide fully reversed bending fatigue. The magnitude of cyclic strains imparted to each cable tested was controlled via the use of different diameter mandrels. Smaller diameter mandrels produced higher values of cyclic strain and lower fatigue life. Multiple samples were tested and analyzed via scanning electron microscopy. The fatigue results were analyzed via a Coffin-Manson-Basquin approach and compared to fatigue data obtained from the literature where testing was conducted on similar materials, but under rotating bending fatigue conditions.

A Critical Review on Metallic Glasses as Structural Materials for Cardiovascular Stent Applications.

Functional and mechanical properties of novel biomaterials must be carefully evaluated to guarantee long-term biocompatibility and structural integrity of implantable medical devices. Owing to the combination of metallic bonding and amorphous structure, metallic glasses (MGs) exhibit extraordinary properties superior to conventional crystalline metallic alloys, placing them at the frontier of biomaterials research. MGs have potential to improve corrosion resistance, biocompatibility, strength, and longevity of biomedical implants, and hence are promising materials for cardiovascular stent applications. Nevertheless, while functional properties and biocompatibility of MGs have been widely investigated and validated, a solid understanding of their mechanical performance during different stages in stent applications is still scarce. In this review, we provide a brief, yet comprehensive account on the general aspects of MGs regarding their formation, processing, structure, mechanical, and chemical properties. More specifically, we focus on the additive manufacturing (AM) of MGs, their outstanding high strength and resilience, and their fatigue properties. The interconnection between processing, structure and mechanical behaviour of MGs is highlighted. We further review the main categories of cardiovascular stents, the required mechanical properties of each category, and the conventional materials have been using to address these requirements. Then, we bridge between the mechanical requirements of stents, structural properties of MGs, and the corresponding stent design caveats. In particular, we discuss our recent findings on the feasibility of using MGs in self-expandable stents where our results show that a metallic glass based aortic stent can be crimped without mechanical failure. We further justify the safe deployment of this stent in human descending aorta. It is our intent with this review to inspire biodevice developers toward the realization of MG-based stents.

RKIP Inhibits Local Breast Cancer Invasion by Antagonizing the Transcriptional Activation of MMP13.

Raf Kinase Inhibitory Protein or RKIP was initially identified as a Raf-1 binding protein using the yeast 2-hybrid screen. RKIP inhibits the activation phosphorylation of MEK by Raf-1 by competitively inhibiting the binding of MEK to Raf-1 and thus exerting an inhibitory effect on the Raf-MEK-Erk pathway. RKIP has been identified as a metastasis suppressor gene. Expression of RKIP is low in cancer metastases. Although primary tumor growth remains unaffected, re- expression of RKIP inhibits cancer metastasis. Mechanistically, RKIP constrains metastasis by inhibiting angiogenesis, local invasion, intravasation, and colonization. The molecular mechanism of how RKIP inhibits these individual steps remains undefined. In our present study, using an unbiased PCR based screening and by analyzing DNA microarray expression datasets we observe that the expression of multiple metalloproteases (MMPs) including MMP1, MMP3, MMP10 and MMP13 are negatively correlated with RKIP expression in breast cancer cell lines and clinical samples. Since expression of MMPs by cancer cells is important for cancer metastasis, we hypothesize that RKIP may mediate suppression of breast cancer metastasis by inhibiting multiple MMPs. We show that the expression signature of RKIP and MMPs is better at predicting high metastatic risk than the individual gene. Using a combination of loss- and gain-of-function approaches, we find that MMP13 is the cause of RKIP-mediated inhibition of local cancer invasion. Interestingly expression of MMP13 alone is not sufficient to reverse the inhibition of breast cancer cell metastasis to the lung due to the expression of RKIP. We find that RKIP negatively regulates MMP13 through the Erk2 signaling pathway and the repression of MMP13 by RKIP is transcription factor AP-1 independent. Together, our findings indicate that RKIP inhibits cancer cell invasion, in part, via MMP13 inhibition. These data also implicate RKIP in the regulation of MMP transcription, suggesting a potential mechanism by which RKIP inhibits tumor progression and metastasis.

Mathematical modeling and mechanical and histopathological testing of porous prosthetic pylon for direct skeletal attachment.

This article presents recent results in the development of the skin and bone integrated pylon (SBIP) intended for direct skeletal attachment of limb prostheses. In our previous studies of the porous SBIP-1 and SBIP-2 prototypes, the bond site between the porous pylons and residuum bone and skin did not show the inflammation characteristically observed when solid pylons are used. At the same time, porosity diminished the strength of the pylon. To find a reasonable balance between the biological conductivity and the strength of the porous pylon, we developed a mathematical model of the composite permeable structure. A novel manufacturing process was implemented, and the new SBIP-3 prototype was tested mechanically. The minimal strength requirements established earlier for the SBIP were exceeded threefold. The first histopathological analysis of skin, bone, and the implanted SBIP-2 pylons was conducted on two rats and one cat. The histopathological analysis provided new evidence of inflammation-free, deep ingrowth of skin and bone cells throughout the SBIP structure.