Maximum Percentage Change Research Articles

Chronic, closed‐loop, cervical epidural stimulation elicits diaphragm motor plasticity after spinal cord injury

Cervical spinal cord injury (cSCI) accounts for over half of all traumatic SCI (NSCISC, 2020). Unfortunately, respiratory insufficiency due to cSCI is the leading cause of mortality and morbidity after SCI. Electrical epidural stimulation (EES) can partially restore volitional locomotor function after SCI in humans while high-frequency EES activates respiratory muscles (DiMarco and Kowalski, 2009) and may lead to at least short-term plasticity (Gonzalez-Rothi et al., 2017). We've shown that our model of cervical closed-loop epidural stimulation (CL-ES) in awake, freely-behaving rats with C2 hemisection (C2HS) elicits short term plasticity in diaphragm motor output (Malone et al., FASEB J 2020). Here we show that this expression of plasticity may be bimodal in that there are “responders” and “non-responders” just as that seen in people with SCI (Tan et al., 2020; Lamy and Boakye, 2013). Rats were implanted with CL-ES electrodes at C4 and bilateral diaphragm EMG electrodes to record respiratory muscle activity in awake rats. Four groups were studied: C2HS + CL-ES (n=8); C2HS + no stim (n=6); Sham + CL-ES (n=6); Sham + no stim (n=6). As expected, increasing current (range: 50–750 μA; inspiratory-triggered) increased the magnitude of evoked potentials. Further, four days of chronic (12-20 hours/day) CL-ES elicited facilitation of ipsilesional evoked responses in 6 of 8 animals with C2HS. Data were calculated as maximum percent change from baseline (-/+) of the stimulus triggered averages at the current with the largest dispersion during sweeps. CL-ES in C2HS rats elicited facilitation in max percent change in stimulus triggered average: 1) peak amplitude (pA; 879% ± 455%) vs. Sham + CL-ES and Sham + no stim (109% ± 76%; p=0.04 and 92% ± 68% p=0.05, respectively) and 2) area under the curve (AUC; 555% ± 142%) vs. groups without stimulation (C2HS + no stim: 99% ± 52%, p=0.05; Sham + no stim: 73% ± 60%, p=0.038). The lack of robust facilitation in Sham + CL-ES rats suggests the possibility of an intact inhibitory modulatory network in healthy rats. These results are preliminary and highly variable, thus we can only speculate about mechanisms giving rise to this form of respiratory neuroplasticity. Ongoing RTqPCR experiments utilizing correlative measures of spinal neurotrophic factor expression (e.g. brain derived neurotrophic factor) and siRNA knock-down of relevant receptors on phrenic motor neurons (Dale et al., 2017) may give more insight. We hypothesize that facilitation of these evoked potentials may depend on activation of neurotrophic factor receptors within the phrenic motor network. This work demonstrates for the first time that CL-ES can elicit respiratory motor plasticity after cSCI, demonstrating potential for a neuroceutical therapy to address breathing impairment in individuals with spinal cord injury. Data presented as mean ± SEM.

Prevalence and Clinical Predictors of Aspirin Resistance in Heart Transplant Recipients

<h3>Purpose</h3> Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Aspirin is thought to be associated with improved graft survival and reduced cardiac allograft vasculopathy in heart transplant (HT) recipients. The assessment of aspirin resistance by laboratory methods is potentially of great therapeutic importance, as it would enable identification of patients at risk for clinical events and allow intervention to prevent subsequent morbidity or mortality. We aimed to determine the prevalence and clinical predictors of aspirin resistance following HT. <h3>Methods</h3> We evaluated 67 stable HT recipients receiving antiplatelet monotherapy with aspirin (100 mg/day≥1 month). Platelets were stimulated with adenosine diphosphate (ADP) and arachidonic acid (AA), and aggregation was assessed using light-transmitted aggregometry. Aggregation was expressed as the maximal percent change in light transmittance from baseline. Aspirin resistance was defined as AA-induced platelet aggregation of ≥20%. <h3>Results</h3> Mean AA-induced aggregation was 29.6 ±24.8%. Of the total cohort, 40 patients (60%) were aspirin resistant and 27 (40%) were not. Aspirin-resistant patients had higher HbA1c values (7.7%±1.5 vs 5.3%±0.9, p<0.001) and higher prevalence of de-novo donor specific antibodies (DSA) (43 vs 11%, p=0.013). There were no differences in aspirin resistance by baseline donor and recipient characteristics (i.e., age, gender, etiology, BMI, hypertension, hemodynamics, immunosuppression). In a multivariable analysis (Figure) HbA1c and DSA were independently associated with a significantly higher risk of aspirin resistance. <h3>Conclusion</h3> Our study suggests a high rate of aspirin resistance in HT patients, which was associated with higher DSA and HbA1c levels, both known risk factors for transplant vasculopathy and survival. Further studies are needed to correlate aspirin resistance with clinical outcomes and hence to tailor therapeutic interventions.

Experimental investigation into nano-finishing of β-TNTZ alloy using magnetorheological fluid magnetic abrasive finishing process for orthopedic applications

This study describes the effect of magnetorheological fluid assisted magnetic abrasive finishing (MRAF) process on the surface topography of fine finished high strength biomedical grade β-phase Ti–Nb–Ta–Zr (β-TNTZ) alloy for orthopedic applications. β-type Ti–35Nb–7Ta–5Zr alloy exhibit high strength, better corrosion resistance and excellent bioactivity in comparison with Ti–6Al–4V alloy. The topographic features of finished surfaces (including surface roughness, skewness, and kurtosis), percentage change in surface roughness, and material removal have been studied to understand the influence of MRAF processing parameters, such as carbonyl iron particles proportion, diamond abrasive particles proportion, rotational speed of the abrasive tool, and work gap between workpiece and abrasive tool. Furthermore, MRAF finishing has been conducted using raster and spiral strategies. The topographic characteristics of the finished surfaces have been measured using a noncontact three-dimensional Surface Profilometer and atomic force microscopy. The results of the study showed that all the input process parameters have strongly influenced the surface characteristics in both quantitative (material removal) and qualitative measures (Surface roughness). The β-TNTZ have possed excellent bio-mechanical properties such as high compressive strength (1195 MPa), micro-hardness (515 HV), corrosion resistance, and excellent bioactivity. The best optimal condition to obtain lowest SR (9 nm) and highest MR (65 mg) was obtained in the case of rater path finishing strategy at CIP – 40%vol., Dv – 3.5%vol., Nt – 900 rpm, and Gp – 1 mm. The maximum percentage change in surface roughness (%ΔRa) was measured around 97.68% and 93.27% in raster and spiral path strategy, respectively. The minimum surface finish ranging about 9 nm has been achieved through the MRAF process. Further, the raster path strategy has been found more effective in producing negative skewness (Ssk), kurtosis (Sku) value less than 3, and minimum number of peaks density (Spd). The overall results of the study suggested that MRAF of β-TNTZ alloy is a good solution for obtaining fine-finished orthopedic devices while sustaining their tribological and wear properties.

High storage capacity and small volume change of potassium-intercalation into novel vanadium oxychalcogenide monolayers V2S2O, V2Se2O and V2Te2O: An ab initio DFT investigation

A new category of two-dimensional electrode materials, i.e., V2Ch2O (Ch = S, Se and Te) monolayers was explored for K-ion batteries (PIBs) based on principle of chemical exfoliation, density functional theory and ab initio molecular dynamics simulations. The V2Ch2O monolayers show low cleavage energies and excellent thermal, dynamical and mechanical stabilities. Adsorption energies of a potassium atom on the V2Ch2O monolayers are exothermic, which are of benefit to prevent forming dendrites. The existence of electrode potentials substantially decreases the diffusion barriers of potassium atoms on the three V2Ch2O monolayers. The V2Ch2O monolayers are able to maintain their metallic characteristics and single surface phase during the whole K-intercalation process, avoiding the decrease in electronic conductivity and the appearance of potential hysteresis. The theoretical specific capacities of the V2S2O, V2Se2O and V2Te2O monolayers are predicted to be 883.6, 583.1 and 431.0 mAh g−1, respectively, and the corresponding average open-circuit voltages are 0.449, 0.390 and 0.293 V, respectively. The maximum percentage changes in lattice parameters are 4.21%, 6.07% and 7.26% for the V2S2O, V2Se2O and V2Te2O monolayers, respectively. All the calculated properties indicate that the V2Ch2O monolayers are promising electrode materials for PIBs with high capacities and long cycle lives.

Can maximal handgrip strength and endurance be improved by an 8-week specialized strength training program in older women? A randomized controlled study

Maximal handgrip strength and endurance are important indicators of upper limb function in older adults. Up to now, there is insufficient information regarding the efficacy of specialized strength training programs for improving handgrip strength. The purpose of this study was to investigate the effectiveness of an 8-week specialized handgrip strength training program on maximal handgrip strength and endurance in healthy older women. A randomized controlled trial was performed. Thirty-six healthy older women (>65 years) were randomly divided into a training group (TG) (n = 18) and a control group (CG) (n = 18). The TG participated in an 8-week specialized handgrip strength training program using rubber balls and hand grippers (2 training sessions/week, 10−15 min, 8–15 repetitions/set, 4–6 total sets/session). Prior to and after the completion of the program, maximal handgrip strength and dynamic endurance (indices: repeated maximal repetitions and percentage change in handgrip strength between first and last 6 repetitions) were assessed in both hands. Repeated measures MANOVA results indicated that maximal handgrip strength (+9.3%–10.4%) and strength values during repeated maximal repetitions (+14% to 27%) significantly increased in TG (p < 0.001), while the percentage change in handgrip strength between the first and last 6 repetitions decreased significantly (−6%) (p < 0.05), irrespective of the tested hand. The results of this study showed that an 8-week specialized handgrip strength training program can be used effectively by athletic trainers, physical and hand therapists to counteract the detrimental effects of the aging process on maximal handgrip strength and endurance in older adults.

Toxicity and Efficacy of Stereotactic Body Radiotherapy plus Nivolumab with Urelumab or Cabiralizumab in Patients with Advanced Solid Tumors

The objective was to evaluate the safety and efficacy of SBRT combined with dual-agent immunotherapy in patients with advanced solid tumors. Urelumab (ure), a CD137 agonist, or cabiralizumab (cab), a CSF1R antagonist, were combined with nivolumab (nivo), a PD-1 inhibitor, and SBRT given their potential to overcome treatment resistance and deepen responses. A phase I, single-institution study was conducted to investigate nivo (480 mg IV every 4 weeks) and investigator’s choice of ure (8 mg IV every 4 weeks) or cab (4 mg/kg IV every 2 weeks) delivered concurrently and following SBRT to 1-4 metastatic sites. Eligible patients had advanced solid tumors of any histology with progression on prior therapies and ECOG performance status 0-1. The primary endpoint was dose-limiting toxicity (DLT) defined as any grade 3+ CTCAEv4 toxicity occurring within 3 months of day 1 of protocol-directed therapy. Recommended anatomic location-specific SBRT doses were deemed safe if associated with a DLT rate ≤33%. Secondary endpoints included RECIST response, progression-free survival, and overall survival. Sixty patients were enrolled with median follow-up of 13.8 months for living patients. Twenty-three patients (38.3%) received SBRT+nivo+ure and 37 (61.7%) received SBRT+nivo+cab. Eleven (18.3%) received prior immune checkpoint blockade, and 17 of 41 patients (41.5%) with evaluable PD-L1 expression had PD-L1-negative tumors. Seven patients (11.7%) experienced a DLT (n = 3 grade 3, n = 4 grade 4, n = 0 grade 5) with these occurring in 3/17 (17.6%), 1/13 (7.7%), 2/14 (14.3%), and 1/12 (8.3%) patients assigned to abdominal/pelvic, liver, central lung, and peripheral lung SBRT anatomic cohorts, respectively. No patients in the osseous cohort experienced a DLT (0/4, 0%), and all 7 DLTs occurred in the SBRT+nivo+cab arm. Specific DLTs included grade 4 creatine phosphokinase elevation (n = 3), grade 3 colitis (n = 1), grade 4 hyperglycemia (n = 1), grade 3 periorbital edema (n = 1), and grade 3 maculopapular rash (n = 1). Of 41 patients with 55 radiated and 23 unirradiated target lesions evaluable for overall RECIST response, 2 had complete responses (4.9%, 1 ure/1 cab), 7 had partial responses (17.1%, 3 ure/4 cab), 12 had stable disease (29.3%, 6 ure/6 cab), 20 had progression (48.9%, 11 ure/9 cab), and 13 (31.7%, 9 ure/4 cab) had at least stable disease for ≥6 months. PD-L1 positivity was associated with maximum percent change in aggregate diameter of radiated RECIST target lesions (p = 0.02). Median estimated progression-free survival and overall survival are 3.0 months (3.0 ure/3.0 cab) and 17.0 months (not reached ure/10.4 cab), respectively. SBRT with nivo+ure or nivo+cab is associated with acceptable toxicity and early anti-tumor activity for patients with advanced solid tumors that have progressed on standard therapy.

Clotting functional stability of withdrawing blood in storage for acute normovolemic hemodilution: a pilot study

PurposeThis study was conducted to time-course changes of clotting function of withdrawing blood for acute normovolemic hemodilution (ANH).MethodsTwelve enrolled patients who underwent ANH from August, 2018 to January, 2019. Blood was withdrawn into blood collection pack and shaken at 60–80 rpm for 24 h in room temperature. Clot formation was evaluated using rotational thromboelastometry (ROTEM™) just after blood withdrawal (control) and 4, 8, 12 and 24 h after blood withdrawal. We compared with the control value and each value of extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor (FIBTEM).ResultsMaximum clot firmness (MCF) of FIBTEM did not change significantly. MCF of EXTEM was significantly decreased time-dependent manner but all MCF of EXTEM were within a normal range. Maximum percent change in MCF of EXTEM was 12.4% [95% confidence interval (CI): 9.0–15.8%]. The difference in the maximum clot elasticity (MCE) between EXTEM and FIBTEM (MCEEXTEM−MCEFIBTEM) was significantly decrease from 8 h after blood withdrawal. Maximum percent change in MCEEXTEM−MCEFIBTEM was 30.2% (95% CI:17.6–42.9%) at 24 h after blood withdrawal.ConclusionEven though the MCE significantly decreased in a time-dependent manner, MCF of FIBTEM and EXTEM was normal up to 24 h storage. The blood of ANH can use for the purpose of hemostasis at least 8 h stored at room temperature after blood withdrawal. Future studies are needed to elucidate the clinical impact on the patient after delayed transfusion of ANH blood with regard to patient’s hemostasis.

Equatorial ionospheric TEC and scintillations under the space weather events of 4–9 September 2017: M-class solar flares and a G4 geomagnetic storm

The observations of vertical total electron content (VTEC) and L1 and L2 band ionospheric scintillations at an equatorial station, Tarawa (Geomag. Coordinates, 2.68°S, 114.26°W), Kiribati, under a complex severe space weather event of 4–9 September 2017, are presented. The VTEC increased significantly by 1.03 and 1.31 TEC units under M5.5 class flare at 20:28 UT on 04 September and M4.2 flare at 01:03 UT on 05 September, respectively, under the quiet geomagnetic conditions. A positive ionospheric storm with a maximum percentage change in VTEC (ΔVTEC%) of 16.7% followed by a negative ionospheric storm with ΔVTEC% of 32.8% occurred during the first main phase (Dst=- 142 nT) and recovery of 7–8 September storm. This positive ionospheric effect occurred due to the combined effects of prompt penetrating electric fields (PPEFs) and suddenly enhanced EUV and X-radiations associated with M class (3.9, 1.3 &1.2) flares whereas negative ionospheric effect could be accounted for the disturbance dynamo electric fields (DDEFs) and change in the storm-time O/N2 gas composition. A long duration (~10 h) positive ionospheric storm with a maximum ΔVTEC% of 26.3% was observed during the second main phase (Dst=-124 nT) which lasted well into its recovery. This is mainly due to the combined effect of PPEFs associated with the long duration of southward turning of Z - component of the interplanetary magnetic field of the second main phase and DDEFs of the first main phase. L1 and L2 band scintillations did not occur during both the phases of storm implying that ionospheric irregularities do not necessarily occur under severe geomagnetic storms. However, two events of nighttime scintillations one before and other after the storm were observed.

Abstract 1044: Frequency of circulating CX3CR1+ CD8+ T cells to predict response to immune checkpoint inhibitor therapy

Abstract While immune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers including non-small cell lung cancer (NSCLC), only a subset of patients receives durable clinical benefit. Discovery of blood-based biomarkers that reflect dynamic change of tumor microenvironment, and predict response to ICI will markedly improve current treatment regimens. Emerging evidence has shown that the frequency of peripheral blood (PB) CD8+ T cells expressing CX3CR1, a marker of effector T-cell differentiation increases in patients receiving ICI. However, no studies have rigorously evaluated the utility of CX3CR1 as a PB biomarker to predict response to ICI, and identify responders and non-responders. Here, we evaluated the utility of circulating T-cell biomarkers to predict response to ICI therapy in preclinical models and NSCLC patients (n=35). We found successful treatment with ICI significantly increases the frequency of PB CX3CR1+ CD8+ T-cell subsets that enrich neoantigen- as well as shared tumor-associated antigen-specific T cells in mice bearing MC38 and CT26 colon adenocarcinoma. Significantly increased expression of IFN-γ and Ki67 suggests that these subsets are highly proliferative effector CD8+ T cells. Interestingly, upregulation of Ki67 was transient; however, expression of CX3CR1 remained high on tumor-specific tetramer+ CD8+ T cells. Moreover, high-throughput sequencing of the T-cell receptor (TCR) identified significantly higher clonality and overlapping TCR repertoires in between peripheral CX3CR1+ CD8+ T cells and CD8+ tumor-infiltrating lymphocytes (TILs), suggesting the potential utility as a dynamic biomarker early on-treatment. Most importantly, changes in the frequency of PB CX3CR1+ CD8+ T cells associate with response to ICI therapy in individual mice. Phenotypic analysis of PB CD8+ T cells from 35 NSCLC patients undergoing PD-1/PD-L1 blockade revealed that the maximum percent change of these T-cell subsets from baseline identified responders and non-responders as early as 3 weeks from the initiation of ICI therapy with higher sensitivity, specificity, positive and negative predictive value compared to PD-L1 expression in the tumor, tumor mutational burden, and pre-existing TILs. Importantly, TCR sequencing confirmed clonally-expanding TCR repertoires within the T-cell subsets that were also found in TILs. Collectively, the frequency of circulating CX3CR1+ CD8+ T cells correlates with response to ICI therapy, and identifies responders vs non-responders early on-treatment. These findings provide a solid foundation for future development of clinical trials with large cohorts of patients undergoing ICI therapy not only for NSCLC, but also for a wide variety of malignancies. Citation Format: Takayoshi Yamauchi, Toshifumi Hoki, Takaaki Oba, Kristopher Attwood, Sebastiano Battaglia, Igor Puzanov, Hongbin Chen, Grace Dy, Brahm Segal, Marc Ernstoff, Fumito Ito. Frequency of circulating CX3CR1+ CD8+ T cells to predict response to immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1044.

Abstract 5347: Preliminary evaluation of BB2r TAT using 212Pb-RM2 in a PC3 human prostate cancer xenograft model

Abstract Introduction: Targeted alpha therapy (TAT) employing radiolabeled receptor targeted peptides holds the potential to be clinically effective for the treatment of advanced prostate cancer. We are evaluating the use of the TAT agent, Pb-212-RM2, for targeting the BB2r receptor shown to be expressed in prostate cancer. The current study is the initial therapeutic efficacy evaluation of Pb-212-RM2 TAT administered as a single bolus injection using the androgen independent/insensitive PC3 human prostate cancer xenograft model. Methods: SCID mice (4-5 weeks of age) were injected subcutaneously with 5 million cultured PC3 cells in both rear flanks as a suspension in RPMI 1640 media. The RM2 peptide was obtained commercially. Pb-212 was eluted from a Ra-224/Pb-212 generator and synthesis of Pb-212-RM2 performed using an Eckert &amp; Ziegler PharmTracer. QC was conducted using HPLC. PC3 xenografted SCID mice were administered a single intravenous bolus of saline (NTC), 0.3ug Pb-RM2 (Cold RM2), 50uCi or 100uCi of 212Pb-RM2 in approximately 100uL via the tail vein. Weekly caliper tumor measurements, complete blood counts (CBC), body weight (BW), and body condition score (BCS) were taken predose and up to 17 weeks post injection (pi). Results: At 18 days pi, tumor regression was observed in the 100uCi group with a maximum percent change of -49.3%, while the 50uCi dose group revealed slight tumor growth (+17.2%). As expected, the NTC and Cold RM2 groups demonstrated rapid tumor growth (+325.3% and +304.5% change, respectively). By day 40 pi, tumor regrowth was observed in the 100uCi group (+91.6% change from predose with a +221.1% change by day 47). Body weights of the NTC, Cold RM2, 50uCi and 100uCi groups at 7 days pi were 101.5%, 101.5%, 98.5%, and 95.4%, respectively. Platelet count comparisons between the NTC group and the 50uCi (P=0.0544) and 100uCi (P=0.0624) groups were comparable. Conclusions: Both Pb-212-RM2 TAT treatment groups (50uCi and 100uCi) demonstrated initial tumor control for 4-5 weeks post treatment. While tumor growth suppression was evident in only the 100uCi dose group, this suppression was transient with tumor volume increasing steadily beginning at 32 days pi. As expected, the non-radioactive Pb-RM2 had no effect on tumor growth. Body weights for all dose groups remained &amp;gt;95% of predose weights until disease progression required subject removal from the study. These results warrant further evaluation of multi-dose administration of Pb-212-RM2 with and without standard of care chemotherapy to evaluate optimal tumor control properties of BB2r TAT. This work was supported by USVA IK6BX004856, USVA IO1BX001699, and NCI RO1CA222293. Citation Format: Tammy L. Rold, Elisabeth A. Devanny, Nkemakonam C. Okoye, Thomas P. Quinn, Timothy J. Hoffman. Preliminary evaluation of BB2r TAT using 212Pb-RM2 in a PC3 human prostate cancer xenograft model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5347.

Design of a Biosensor Based on Interdigitated Microelectrodes with Detection Zone Controlled by an Integrated Microfluidic Channel

The design and simulation of a biosensor based on interdigitated microelectrodes for bacteria detection is presented. The biosensor includes a microchannel to ensure the flow of the sample through the space between microelectrodes, where the surface is biofunctionalized with antibodies to capture the bacteria. The design was built on COMSOL Multiphysics® software. The effects of the microelectrode thickness and the channel depth on the biosensor sensitivity were studied by simulation. There is a specific microelectrode thickness at which the sensitivity is maximum for Escherichia coli. The microchannel depth affects the sensitivity of the device when it is below 10 μm, approximately. The sensitivity increases when the biosensor is made with low-permittivity materials. A maximum percentage change in capacitance of around 46% was obtained by covering the total sensing area with bacteria.

Prostate-specific antigen (PSA) kinetics in patients (pts) with advanced prostate cancer treated with apalutamide: Results from the TITAN and SPARTAN studies.

5541 Background: The phase III TITAN and SPARTAN studies demonstrated improved outcomes with the addition of apalutamide (APA) to androgen deprivation therapy (ADT); outcomes included prolonging overall survival and radiographic progression-free survival (rPFS) in metastatic castration-sensitive prostate cancer (mCSPC) in TITAN, and metastasis-free survival (MFS) in nonmetastatic castration-resistant PC (nmCRPC) in SPARTAN. A post hoc analysis of PSA kinetics in pts from both studies is reported. Methods: Baseline PSA at randomization, time to PSA nadir, and proportion of pts achieving a PSA decline of ≥ 90% (PSA90) and of pts achieving a PSA ≤ 0.2 ng/mL at 3 and 12 months and at any time after treatment in the APA arms of the TITAN and SPARTAN studies were evaluated. Within each study, rPFS/MFS were compared between pts achieving a PSA90 or PSA ≤ 0.2 ng/mL response vs not. Results: 525 TITAN pts and 806 SPARTAN pts treated with APA were included in the analysis. Median baseline PSA, time to PSA nadir, median PSA nadir, and maximum percentage changes from baseline PSA are shown in the table. PSA90 and confirmed PSA ≤ 0.2 ng/mL were evident as early as 3 months in both TITAN and SPARTAN, and percentage of confirmed response continued to increase at 12 months. Pts treated with APA who achieved PSA90 were at lower risk of rPFS events in TITAN and of MFS events in SPARTAN, with a hazard ratio (95% confidence interval) of 0.46 (0.321-0.653) and 0.36 (0.271-0.489) in each respective study (both p &lt; 0.0001), compared with APA pts who did not achieve PSA90. Pts with confirmed PSA ≤ 0.2 ng/mL had similar rPFS and MFS benefits. Conclusions: Pts with advanced PC, whether mCSPC or nmCRPC, treated with APA + ADT demonstrated rapid PSA declines that continued over time. There was a high rate of pts with PSA90 and with PSA ≤ 0.2 ng/mL responses, with a majority of pts reaching PSA90 by 12 months. Pts achieving PSA90 and/or PSA nadir of ≤ 0.2 ng/mL had a prolonged rPFS and MFS in TITAN and SPARTAN, respectively. Clinical trial information: NCT02489318; NCT01946204 . [Table: see text]

Prevalence and Clinical Predictors of Aspirin Resistance in Heart Transplant Recipients

Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Aspirin is thought to be associated with improved graft survival and reduced cardiac allograft vasculopathy in heart transplant (HT) recipients. The assessment of aspirin resistance by laboratory methods is potentially of great therapeutic importance, as it would enable identification of patients at risk for clinical events and allow intervention to prevent subsequent morbidity or mortality. We aimed to determine the prevalence and clinical predictors of aspirin resistance following HT. We evaluated 67 stable HT recipients receiving antiplatelet monotherapy with aspirin (100 mg/day≥1 month). Platelets were stimulated with adenosine diphosphate (ADP) and arachidonic acid (AA), and aggregation was assessed using light-transmitted aggregometry. Aggregation was expressed as the maximal percent change in light transmittance from baseline. Aspirin resistance was defined as AA-induced platelet aggregation of ≥20%. Mean AA-induced aggregation was 29.6 ±24.8%. Of the total cohort, 40 patients (60%) were aspirin resistant and 27 (40%) were not. Aspirin-resistant patients had higher HbA1c values (7.7%±1.5 vs 5.3%±0.9, p<0.001) and higher prevalence of de novo donor-specific antibodies (DSA) (43 vs 11%, p=0.013). There were no differences in aspirin resistance by baseline donor and recipient characteristics (i.e., age, gender, etiology, BMI, hypertension, hemodynamics, immunosuppression). In a multivariable analysis (Figure) HbA1c and DSA were independently associated with a significantly higher risk of aspirin resistance. Our study suggests a high rate of aspirin resistance in HT patients, which was associated with higher DSA and HbA1c levels, both known risk factors for transplant vasculopathy and survival. Further studies are needed to correlate aspirin resistance with clinical outcomes and hence to tailor therapeutic interventions.

Free Convection Heat Transfer Around a Cylinder Embedded in an Enclosure Filled with Porous Media

An experimental and theoretical study of free convection heat transfer for a cylinder placed in an iron test section of dimensions (0.2x0.2x0.2 m3), the test section filled with saturated porous material glass balls (5 mm), and the air is the working fluid with Raleigh number (7692.6 ≤ Ra ≤ 17654). The circular cylinder heater (D = 0.015 m, L = 0.2 m) is heated electrically, made of Copper and located in different positions (in X &amp; Y direction). The theoretical part includes solving the free convection heat transfer using the ANSYS program (fluent). The experimental and theoretical results showed that the surface temperature values around the cylinder perimeter when changing its position within the test section are changing as moving up and down where the effect of buoyancy force appears. The maximum difference between the upper and lower position at the experimental result is 7.22%, and the average Nusselt number increases with Raleigh number and heat flux. Also, the experimental results showed that the use of porous material significantly improves the heat transfer by 48.6%. The maximum percentage change between the experimental and theoretical results is 5.46%. Moreover, experimental correlations were achieved, and a comparison was performed between the present results with the previous studies and it gives a good agreement.

Photoluminescence and photo-induced conductivity in 2D siloxene nanosheet for optoelectronic applications

Semiconducting 2D siloxene nanosheets of thickness 1.7 nm and band gap of 2.54 eV are synthesized using simple chemical route. Strong photoluminescence is observed in the as-synthesized nanosheets due to presence of oxygen atoms. The photoluminescence behaviour of siloxene nanosheets is investigated by controlling temperature, excitation and pH of the solution to understand the optical response and stability of the material. The as-synthesized sample heated with temperature 200 °C shows a blue shift of 90 nm compared to the sample synthesized at room temperature. The low temperature luminescence measurements of as-synthesized samples dried at different temperatures viz. 27, 100 and 200 °C. It is seen that the luminescence intensity is increasing with decreasing temperature for the sample dried at room temperature. However, after heating the sample at 100 °C, the luminescence intensity is not only increased but also red-shifted up to 52 nm. The photocurrent has been measured for the device structure of ITO/PEDOT: PSS/Siloxene/Al with different film thicknesses to optimize the photocurrent and the maximum percentage change in photo power gain. The maximum photopower gain of 2693% is observed for the film thickness of 600 nm.

Validation of Region of Interest Measurements for the Objective Assessment of Post-Contrast Enhancement of Renal Lesions on MRI.

The aim of this study was to validate the use of region of interest (ROI) measurements in MRI to objectively assess for enhancement in suspected solid renal masses and to determine a minimum threshold value for true enhancement. Contrast-enhanced renal MRI studies performed between January 2015 and December 2017 for patients with a known renal mass who had subsequent biopsy, or partial/radical nephrectomy were included. Two body imaging fellows independently measured the mean ROI values of renal masses, normal renal parenchyma, the ipsilateral psoas muscle and external air on the pre- and post-contrast sequences. The absolute and percentage changes in the mean ROI values were calculated. The readers were blinded to the pathology results. 104 patients were included in this study (mean age of 65 years; 58 males and 46 females). 74 patients (71%) had a diagnosis of renal cell carcinoma (RCC). Pathology showed clear-cell RCC in 55%, papillary RCC in 22%, and other RCC subtypes in 23%. There were 30 non-RCC renal lesions (29%), including oncocytoma, renal papillary adenoma, and renal metastasis.The minimum percentage change in ROI values in the pre- versus post-contrast images for all pathology-proven RCCs was 23% (range: 23-437%, mean: 143%); this represents relative enhancement and was referred to as the Signal Intensity Index (SII). The percentage change for normal renal parenchyma ranged from 32-317%. The maximum percentage change in ROI values for pathology proven renal cysts was 13% (range: -5-13%, mean: 3.5%). There was excellent inter observer agreement between the two readers [Intra-class correlation coefficient (r) 0.81]. The percentage change in ROI values (SII) can be a helpful tool in the objective assessment of true enhancement of renal masses and can supplement subtraction images. The minimum threshold for enhancement in our study was 23%. Enhancement of a renal lesion can be determined using the objective tool of ROI measurements in the pre- and post-contrast MR images with a percentage change of 20% or above indicating enhancement. This is an additional objective tool, which in conjunction with the subtraction images may improve detection and appropriate diagnosis of renal lesions. It could also be helpful in cases where the subtraction images are degraded by motion artefact.

Relationship Between Tumor Response and Tumor-Related Symptoms in RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses From 3 Panitumumab Trials

BackgroundThere is no standardized assessment of symptomatic events in metastatic colorectal cancer (mCRC) despite disease symptoms that affect treatment decisions. Data from 3 first-line panitumumab in mCRC trials were retrospectively analyzed to assess whether early tumor shrinkage (ETS) and depth of response (DpR) were associated with time to occurrence of tumor-related symptoms. Patients and MethodsPatients with RAS wild-type mCRC from PRIME, PEAK, and Study 314 were included. ETS was defined as a reduction of ≥ 30% in the sum of the longest diameters of lesions at 8 weeks. DpR was calculated as maximum percentage change in tumor size from baseline to nadir. The proportion of patients who developed symptoms (including a composite symptomatic endpoint) during study treatment was calculated. This study was registered at ClinicalTrials.gov as PRIME (NCT00364013), PEAK (NCT00819780), and Study 314 (NCT00508404). ResultsOverall, data of 659 patients were analyzed. Onset of symptoms was delayed in patients with ETS ≥ 30% versus ETS < 30% and in patients with greater DpR. In patients with symptoms at baseline who experienced ETS ≥ 30%, overall survival was similar to that seen for patients without symptoms at baseline. ConclusionBoth ETS and DpR were associated with delayed onset of symptoms in RAS wild-type mCRC patients. Treatments with high cytoreductive potential may delay symptom development.

Preparation of natural rubber elastomeric bridge bearing pad compound formula on various curing systems

Commercial elastomeric bridge bearing (EBB) pad is dominated by the laminated type. Laminated EBB pad comprises of rubber composite layers which are arranged intermittently among the thin steel plates. The rubber composite uses natural rubber or chloroprene synthetic rubber as the base elastomer. Local EBB pad industries mostly produce natural rubber bridge bearing pad type due to the enormous availability of natural rubber in Indonesia. However, the quality of natural rubber bridge bearing pad product often cannot fulfil the standard requirement in compression set and accelerated aging parameters. The research studied the design of EBB pad compound formula based on natural rubber type. The EBB compound formulas were prepared by varring the curing system such as sulphur (efficient and semi-efficient) and peroxide curing system. Designing the compound formula was in accordance to the methods required in improving the compression set and accelerating aging quality of natural rubber bridge bearing pad. The result of curing characteristic of the natural rubber bridge bearing pad compound showed that peroxide curing system gave the longest optimum curing time. Further, sulphur curing system produced high crosslink density followed with good mechanical properties of natural rubber bridge bearing pad vulcanizate. The compression set value of natural rubber bridge bearing pad vulcanizates which were obtained by efficient and semi-efficient curing systems as 14.09% and 24.81%, respectively were regarded to be below the maximum requirement (25%). The peroxide curing system was not recommended due to the high compression set value of 40.68%. Meanwhile, maximum percent changes of tensile properties and retention values which indicated accelerated aging parameter of natural rubber bridge bearing pads were formed either by sulphur and peroxide curing system could fulfilled the standard requirement of EBB Duro 70 refered to SNI 3967:2013.

The depth of response was associated with the progression-free survival in advanced non-small cell lung cancer patients treated with EGFR-TKI.

e20509 Background: Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate the new therapeutic strategies in cancer, however, RECIST fails to differentiate the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as maximum percent change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods: Advanced NSCLC patients harboring EGFR driver mutation (L858R or 19del) treated with EGFR-TKI from August 2014 to July 2017 in two sites were retrospetively collected for analysis. Patients were divided into four groups by maximal tumor shrinkage (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS by DepOR and the hazard ratio (HR) was determined through univariable and multivariable Cox regression models. Results: In total, 265 patients were included for analysis. The number for Group Q1-Q4 was 91, 73, 65 and 36, respectively. The greater DepOR was significantly associated with a longer PFS (Log-rank P for trend &lt; 0.0001). The DepOR vs PFS analyses HR were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3 and 0.33 (0.22-0.50) for Q4 compared with Q1. In the multivariable cox regression model, abnormal LDH, brain metastasis and male were also found to be associated with poorer PFS (P &lt; 0.05). Conclusions: Greater DepOR was significantly associated with a longer PFS in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to more efficiently evaluate the response of targeted therapy.

Impact of free-breathing CT on quantitative measurements of static and quiescent period-gated PET Images

Measurements of standardized uptake values (SUV) can vary due to many causes, including respiratory motion. Various methodologies have been introduced to correct for motion in PET, with quiescent-period-gated (QPG) PET being the most popular approach. QPG has been shown to improve PET image quantification compared to static-whole-body (SWB) PET. However, to achieve this improvement, QPG PET requires CT attenuation correction data that matches the QPG PET data. In this paper we investigated the effect of using free-breathing CT for attenuation correction of QPG PET on SUVmax and SUVpeak and compared the results to those of SWB PET. 34 lesions in 27 patients were included. All patients were injected with F-18 FDG. 4D-CT datasets representing all possible phases of respiration that could result from a free-breathing CT were acquired. The 4D-CT datasets were used for attenuation correction of the QPG and SWB PET data. Percentage change in the SUVmax and SUVpeak range was calculated for the reconstructions and compared between QPG and SWB PET. The mean percentage change in the lesion SUVmax and SUVpeak ranges were 19.1% (p = 0.0178) and 25.2% (p = 0.0002) higher for QPG compared to SWB, respectively. The maximum percent change in SUVmax and SUVpeak ranges were 58.5% and 59.0% for QPG, respectively compared to 46.1% and 45.3% for SWB, respectively. The highest SUVmax and SUVpeak measurements corresponded to the CT phase that matched the QPG phase. Utilizing free-breathing CT for attenuation correction can lead to large changes in quantification due to misalignment with PET data. This misalignment has a large quantitative impact on QPG PET as compared to SWB PET. When interpreting quantitative changes in lesions, it is critical to consider the influences of free-breathing CT-based attenuation correction.