ANTIRESORPTIVE BONE THERAPY USE IN ADVANCED LUNG CANCER AND ASSOCIATED OUTCOMES

Background/Rationale: Studies have shown antiresorptive agents decrease skeletal related events in metastatic non-small cell lung cancer. However, two prevalence studies have found low utilization rates of antiresorptive therapy in advanced lung cancer. The first study reported a rate of 14.8% during the 1995-2009 time period, while the second study reported a 33% usage rate during the time frame of 2002-2011. We believe these low utilization rates are associated with the poor prognosis of these patients. The prognosis of advanced lung cancer has improved significantly since these trials were conducted, and the utilization of denosumab has not been evaluated. We hypothesize that intravenous antiresportive bone therapies are underutilized in patients with metastatic lung cancer. Objectives: To characterize the utilization of antiresportive therapies in patients with metastatic lung cancer and to evaluate predictive factors in their initiation. Methods: This study was a retrospective analysis of EHR data from the University of Kentucky Enterprise Data Warehouse (UKEDW) linked to Kentucky Cancer Registry (KCR) containing patients from 1/1/2013 to 1/31/2020. Patients diagnosed with metastatic lung cancer are included with “index date” being date of first systemic treatment. Key exclusion criteria included lack of systemic therapy provided at UK. Incidence of antiresorptive bone therapy initiation was measured. Descriptive statistics and multivariate logistic regressions were performed to assess factors predicting use and selection of agent. Results: Over the study time period, only 16.3 % of patients who received their first systemic therapy at UK were initiated on an antiresorptive bone medication, with denosumab being the primary agent used (~65%). Logistic regression analysis shows that patients with bone metastasis present at diagnosis of stage IV NSCLC had 4.26 times the odds of receiving an antiresorptive bone medication (95% [CI: 2.146,8.442]) than those who did not have bone metastasis at diagnosis. Conclusions: For metastatic non-small cell lung cancer patients receiving their first systemic therapy at the University of Kentucky, antiresorptive bone therapies are being underutilized with the primary predictor of use as bone metastasis at diagnosis

Activity-Based User Authentication Using Smartwatches

Smartwatches, which contain an accelerometer and gyroscope, have recently been used to implement gait and gesture- based biometrics; however, the prior studies have long-established drawbacks. For example, data for both training and evaluation was captured from single sessions (which is not realistic and can lead to overly optimistic performance results), and in cases when the multi-day scenario was considered, the evaluation was often either done improperly or the results are very poor (i.e., greater than 20% of EER). Moreover, limited activities were considered (i.e., gait or gestures), and data captured within a controlled environment which tends to be far less realistic for real world applications. Therefore, this study remedies these past problems by training and evaluating the smartwatch-based biometric system on data from different days, using large dataset that involved the participation of 60 users, and considering different activities (i.e., normal walking (NW), fast walking (FW), typing on a PC keyboard (TypePC), playing mobile game (GameM), and texting on mobile (TypeM)). Unlike the prior art that focussed on simply laboratory controlled data, a more realistic dataset, which was captured within un-constrained environment, is used to evaluate the performance of the proposed system. Two principal experiments were carried out focusing upon constrained and un-constrained environments. The first experiment included a comprehensive analysis of the aforementioned activities and tested under two different scenarios (i.e., same and cross day). By using all the extracted features (i.e., 88 features) and the same day evaluation, EERs of the acceleration readings were 0.15%, 0.31%, 1.43%, 1.52%, and 1.33% for the NW, FW, TypeM, TypePC, and GameM respectively. The EERs were increased to 0.93%, 3.90%, 5.69%, 6.02%, and 5.61% when the cross-day data was utilized. For comparison, a more selective set of features was used and significantly maximize the system performance under the cross day scenario, at best EERs of 0.29%, 1.31%, 2.66%, 3.83%, and 2.3% for the aforementioned activities respectively. A realistic methodology was used in the second experiment by using data collected within unconstrained environment. A light activity detection approach was developed to divide the raw signals into gait (i.e., NW and FW) and stationary activities. Competitive results were reported with EERs of 0.60%, 0% and 3.37% for the NW, FW, and stationary activities respectively. The findings suggest that the nature of the signals captured are sufficiently discriminative to be useful in performing transparent and continuous user authentication.University of Kuf

Additive manufacturing of thin-walled SS316L-IN718 functionally graded materials by direct laser metal deposition

Functionally graded materials (FGMs) are a good response to those advanced applications that service requirements are diverse and require high performance. Additive manufacturing (AM) technology, with its many advantages, including high flexibility for complex geometries and near-net-shape integration, has attracted special attention in the development of FGMs. In this research, the solidification behavior and microstructure evolution in the laser additive manufacturing of thin-walled stainless steel 316L-Inconel 718 graded materials have been studied with the help of solidification concepts in the welding metallurgy, according to the common principles of welding and additive manufacturing processes. For this purpose, optical and electron microscopy techniques, X-ray energy dispersive spectroscopy, and microhardness measurement were used along the build direction of FGMs with different transition designs. Microstructure evaluation showed that due to re-melting of layers, despite the increased undercooling in the build direction, morphological evolution occasionally occurred periodically between solidification modes, and due to thermal accumulation, a coarser microstructure is formed in the final layers. In addition, in the chemical analysis, it was observed that the mixing of adjacent layers caused by dilution led to a deviation of the composition distribution from the desired design. Also, the microsegregation of some elements during the non-equilibrium solidification of the process caused secondary phases such as carbides and intermetallic compound of Laves, which can have an adverse effect on the mechanical properties of the structure. However, microhardness variations along the cross-section of the samples showed that the gradation of the dissimilar thin-walled structure can effectively bring the properties and behavior of adjacent layers closer together and therefore be very useful in improving the service life

Tuning the properties of carbon fiber-reinforced poly (phenylene sulphide) laminates via incorporation of inorganic fullerene-like WS2 nanoparticles

Novel carbon fiber (CF)-reinforced poly(phenylene sulphide) (PPS) laminates incorporating inorganic fullerene-like tungsten disulfide (IF-WS2) nanoparticles were prepared via melt-blending and hot-press processing. The influence of the IF-WS2 on the morphology, thermal, mechanical and tribological properties of PPS/CF composites was investigated. Efficient nanoparticle dispersion within the matrix was attained without using surfactants. A progressive rise in thermal stability was found with increasing IF-WS2 loading, as revealed by thermogravimetric analysis. The addition of low nanoparticle contents retarded the crystallization of the matrix, whereas concentrations equal or higher than 1.0 wt% increased both the crystallization temperature and degree of crystallinity compared to those of PPS/CF. Mechanical tests indicated that with only 1.0 wt% IF-WS2 the flexural modulus and strength of PPS/CF improved by 17 and 14%, respectively, without loss in toughness, ascribed to a synergistic effect between the two fillers. A significant enhancement in the storage modulus and glass transition temperature was also observed. Moreover, the wear rate and coefficient of friction strongly decreased, attributed to the lubricant role of the IF-WS2 combined with their reinforcing effect. These inorganic nanoparticles show great potential to improve the mechanical and tribological properties of conventional thermoplastic/CF composites for structural applications

Non-Isothermal cold-crystallization behavior and kinetics of poly(L-lactic acid)/WS2 inorganic nanotube nanocomposites

In order to accelerate the crystallization of poly(L-lactic acid) (PLLA) biopolymer and enhance its crystallizability, biocompatible and environmentally friendly tungsten disulphide inorganic nanotubes (INT-WS) were introduced into the polymer matrix. The non-isothermal cold-crystallization and subsequent melting behaviour of pure PLLA and PLLA/INT-WS nanocomposites were investigated in detail by varying both the heating rate and INT-WS loading. The kinetic parameters of the cold-crystallization process of PLLA chains under confined conditions, successfully described using Liu model, shows that the addition of INT-WS significantly increased the crystallization rate and reduced the total cold-crystallinity of PLLA, while the crystallization mechanism and crystal structure of PLLA remained unchanged in spite of the INT-WS loading. Similarly, the final crystallinity and melting behaviour of PLLA were controlled by both the incorporation INT-WS and variation of the heating rate. The differential isoconversional method of Friedman was applied to estimate the dependence of the effective activation energy on the relative crystallinity and temperature for PLLA and PLLA/INT-WS. On the other hand, the double-melting peaks, mainly derived from melting-recrystallization-melting processes upon heating, and their dynamic behaviour is coherent with a remarkable nucleation-promoting effect of INT-WS involved in accelerating the cold-crystallization of PLLA. These observations have considerable practical significance for the future sustainable, economic and effective technological utilisation of PLLA, as it will enable the development of novel melt-processable biopolymer nanocomposite materials.This work was supported by the Spanish Ministry Economy and Competitivity (MINECO), Projects MAT-2010-21070-C02-01 and MAT2013-41021-P. Mohammed Naffakh would also like to acknowledge the MINECO for a “Ramón y Cajal” Senior Research Fellowship.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

Thermoplastic Polymer Nanocomposites Based on Inorganic Fullerene-like Nanoparticles and Inorganic Nanotubes

Using inorganic fullerene-like (IF) nanoparticles and inorganic nanotubes (INT) in organic-inorganic hybrid composite, materials provide the potential for improving thermal, mechanical, and tribological properties of conventional composites. The processing of such high-performance hybrid thermoplastic polymer nanocomposites is achieved via melt-blending without the aid of any modifier or compatibilizing agent. The incorporation of small quantities (0.1-4 wt.%) of IF/INTs (tungsten disulfide, IF-WS2 or molybdenum disulfide, MoS2) generates notable performance enhancements through reinforcement effects and excellent lubricating ability in comparison with promising carbon nanotubes or other inorganic nanoscale fillers. It was shown that these IF/INT nanocomposites can provide an effective balance between performance, cost effectiveness, and processability, which is of significant importance for extending the practical applications of diverse hierarchical thermoplastic-based composites

Mechanical and thermal behaviour of isotactic polypropylene reinforced with inorganic fullerene-like WS2 nanoparticles: Effect of filler loading and temperature

The thermal and mechanical behaviour of isotactic polypropylene (iPP) nanocomposites reinforced with different loadings of inorganic fullerene-like tungsten disulfide (IF-WS2) nanoparticles was investigated. The IF-WS2 noticeably enhanced the polymer stiffness and strength, ascribed to their uniform dispersion, the formation of a large nanoparticle?matrix interface combined with a nucleating effect on iPP crystallization. Their reinforcement effect was more pronounced at high temperatures. However, a drop in ductility and toughness was found at higher IF-WS2 concentrations. The tensile behaviour of the nanocomposites was extremely sensitive to the strain rate and temperature, and their yield strength was properly described by the Eyring s equation. The activation energy increased while the activation volume decreased with increasing nanoparticle loading, indicating a reduction in polymer chain motion. The nanoparticles improved the thermomechanical properties of iPP: raised the glass transition and heat deflection temperatures while decreased the coefficient of thermal expansion. The nanocomposites also displayed superior flame retardancy with longer ignition time and reduced peak heat release rate. Further, a gradual rise in thermal conductivity was found with increasing IF-WS2 loading both in the glassy and rubbery states. The results presented herein highlight the benefits and high potential of using IF-nanoparticles for enhancing the thermomechanical properties of thermoplastic polymers compared to other nanoscale fillers

Development of novel melt-processable biopolymer nanocomposites based on poly(L-lactic acid) and WS2 inorganic nanotubes.

The use of tungsten disulphide inorganic nanotubes (INT-WS2) offers the opportunity to produce novel and advanced biopolymer-based nanocomposite materials with excellent nanoparticle dispersion without the need for modifiers or surfactants via conventional melt blending. The study of the non-isothermal melt-crystallization kinetics provides a clear picture of the transformation of poly(L-lactic acid) (PLLA) molecules from the non-ordered to the ordered state. The overall crystallization rate, final crystallinity and subsequent melting behaviour of PLLA were controlled by both the incorporation of INT-WS2 and the variation of the cooling rate. In particular, it was shown that INT-WS2 exhibits much more prominent nucleation activity on the crystallization of PLLA than other specific nucleating agents or nano-sized fillers. These features may be advantageous for the enhancement of mechanical properties and process-ability of PLLA-based materials. PLLA/INT-WS2 nanocomposites can be employed as low cost biodegradable materials for many eco-friendly and medical applications, and the exceptional crystallization behaviour observed opens new perspectives for scale-up and broader applications

Polymer blend nanocomposites based on poly(L-lactic acid), polypropylene and WS2 inorganic nanotubes

Tungsten disulphide inorganic nanotubes (INT-WS2) have been incorporated into poly(L-lactic acid) (PLLA)/ polypropylene (PP) blends compatibilized with polypropylene-grafted-maleic anhydride (PP-g-MAH), and their effects on the morphology, thermal and mechanical properties of the resulting nanocomposites have been investigated. The nanofillers were uniformly dispersed at the nanoscale via a melt-blending process. The addition of 1.0 wt% INT-WS2 to the PLLA/PP blends hardly affected their thermal stability or their degradation mechanism. Differential scanning calorimetry (DSC) thermograms revealed the nucleating role of INT-WS2 on both polymeric components, reflected not only in an increase in the crystallization temperature from the melt but also in a rise in the crystallization enthalpy and the suppression of the cold-crystallization process; this effect was found to be more pronounced on PLLA and the blends rich in this component. Dynamic mechanical analysis (DMA) measurements demonstrated that the storage modulus of the nanocomposites was higher than those of the binary blends in the whole temperature range studied, ascribed to a synergistic effect of their increased crystallinity and the high INT-WS2 rigidity. This study opens up new perspectives to develop novel INTWS2/polymer blend hybrid nanocomposites that show great potential for biomedical applications

Differential Effect of Nucleotide Substitutions in the 3′ Arm of the Influenza A Virus vRNA Promoter on Transcription/Replication by Avian and Human Polymerase Complexes Is Related to the Nature of PB2 Amino Acid 627

AbstractUsing a genetic system that allows the in vivo reconstitution of active ribonucleoproteins, the ability to ensure transcription/replication of a viral-like reporter RNA harboring the G3 → A3, U5 → C5, and C8 → U8 mutations (triple 3-5-8 mutations) in the 3′ arm of the promoter was examined with core proteins from human or avian strains of influenza A viruses. The efficiency of transcription/replication of the viral-like RNA with the triple 3-5-8 mutations in COS-1 cells was found to be slightly decreased as compared to the wild-type RNA when the polymerase was derived from a human virus. In contrast, it was found to be considerably increased when the polymerase was derived from an avian virus, in agreement with published observations using the avian A/FPV/Bratislava virus (G. Neumann and G. Hobom, 1995, J. Gen. Virol. 76, 1709–1717). This increase could be attributed to the compensation of the defect in transcription/replication activity in the COS-1 mammalian cell line due to the presence of a glutamic acid at PB2 residue 627, characteristic of avian strains of influenza viruses. Our results thus suggest that PB2 and/or cellular proteins interacting with PB2 could be involved in RNA conformational changes during the process of transcription/replication