Stability Analysis of Mathematical Modeling of Interaction between Target Cells and COVID-19 Infected Cells

The stability analysis in this mathematical model was related to the infection of the Coronavirus Disease 2019 (Covid-19). In this mathematical model there were two balance points, namely the point of balance free from Covid-19 and the one infected with Covid-19. The stability of the equilibrium point was influenced by all parameters, i.e. target cells die during each cycle, number of target cells at  = 0, target cells infected during each cycle based on virion unit density, effective surface area of the network, the ratio of the number of virus particles to the number of virions, infected cells die during each cycle, the number of virus particles produced by each infected cell during each cycle, and virus particles die during each cycle. In the simulation model, immunity is divided into high, medium and low immunity. For high, moderate and low immunity, respectively, the highest number of target cells is in high, medium and low immunity, whereas for the number of infected cells and the number of Covid-19, it is in the opposite sequence of the number of target cells.

Measurement of weight change after change in frequency of a locally recognised habit. How much weight is lost while one higher-protein breakfast more is eaten per week?

It is not known how much reduction in weight is caused by an increased frequency of breakfasts including more protein, or whether such a practice suppresses intake by subconscious post-ingestional effects or intentional reduction in frequency of consumption of other foods. Participants with low frequency of what they believed to be higher protein breakfasts (HPBs) were asked to increase HPB frequency for 4 weeks and then to decrease HPB frequency for the subsequent 4 weeks, while participants with high HPB frequency were asked to follow the opposite sequence. Participants recorded daily if they ate an HPB that morning and had eaten perceived energy-dense foods (EDFs) and/or taken exercise at any time. Greater amounts of fat and weight were lost with perceived HPBs increase than decrease. One more perceived HPB per week for 4 weeks lowered body fat by a mean of 0.05 % (95% CLs: 0.15, -0.04), and weight by 97 g (171, 24). One less perceived EDF occasion a week reduced fat 0.04 % (0.11, -0.03) and weight 81 g (134, 27). These findings show that a sustained change in the frequency of a culturally specified habit can influence weight by a measured amount. This effect could come from the delayed gluconeogenesis from dietary protein amino acids but beliefs about protein at breakfast and energy-dense foods may also play a part.

Use of nivolumab (N) and cabozantinib (C) for treatment of the metastatic renal cell carcinoma (mRCC) in the Veneto region: Results of AMOUR study.

290 Background: Second (2L) or third-line (3L) treatment options for mRCC have dramatically changed in the last years. The standard of care as per Italian Regulatory Agencies approvals is N or C. To date, there are no criteria for the choice between N and C, which both demonstrated OS gain in the pivotal trials. Methods: We planned a retrospective, real world analysis of the use of N and C as 2L and 3L treatment in 17 Oncology Units of Veneto Region. All consecutive patients (pts) with mRCC treated in advanced setting in 2017-2018 were included. Results: We identified 170 pts, 73% males, median age 68.4 years. All pts started a 2L treatment while only 59% received a 3L treatment. In our cohort, patients with NLR > 3 at treatment start had a shorter OS (43 vs 90 months (mos), p < 0.0001); IMDC classification maintained its prognostic role. In 2L, N was administrated in 108 pts (63%), C in 29 pts (17%); in 3L N was administrated in 42 pts (25%), C in 49 pts (29%). Reported oncologists’ reasons for 2L choice were: change of mechanism of action compared to first line (28%), response to previous TKI (21.2%), intolerance to TKI (17.6%), previous toxicity (12.9%), tumor burden (11.2%), age of the patient (4.1%). Median OS and PFS in 2L were 28.4 and 6.6 mos for N, 16.8 and 6.6 mos for 2L C. Median OS and PFS in 3L were 27 and 5.2 mos for N, 16.6 and 7.5 mos for C. 46 pts received the sequence of drugs N > C, 12 the opposite sequence C > N. Median OS for N > C vs C > N were 96.6 vs 36 mos (p > 0.0001); median PFS for both the sequences were similar at 5.7 mos (p = ns). The cost per patient of the sequence N > C is 51.606 € while for the sequence C > N is 31.480,00 €. Between the two sequences a cost effectiveness per month of survival analysis was performed: the cost per month of OS for the sequence N > C was 534,18 € while for the sequence C > N was 874,46 €, heavily higher. Conclusions: In our real-world setting cohort, most of the pts received N as 2L treatment and a minority received C. Outcome of single drug are superimposable to published literature. With the limits of the retrospective nature of the study, with a cost per month of OS lower a much longer OS, the sequence N > C appear to be a better treatment strategy.

Establishment of the New Zealand white rabbit animal model of fatty keratopathy associated with corneal neovascularization

The term fatty keratopathy is used to describe the phenomenon of fat deposition caused by corneal neovascularization, which will severely affect the eye’s beauty and vision. The purpose of this study was to establish a New Zealand white rabbit animal model of fatty keratopathy, that is, the establishment of an animal model of fatty keratopathy. The goal was achieved by the combination of a corneal neovascularization animal model and a hyperlipidemia animal model. Two groups were created according to the experimental sequence. The first group initially induced a corneal neovascularization pattern and later induced a hyperlipidemia pattern, and the second group followed the opposite sequence. The results of the two groups showed that all the significant crystalline deposits of the cornea were visible. So the animal models of fatty keratopathy were successfully established in both groups.

Influence of nitrogen ion implantation on the electrophysical properties of the gate dielectric of power MOSFETs

Power MOS-transistors with vertical structure are investigated. Additionally, in some devices, ion implantation of nitrogen with energies of 20 and 40 keV was carried out in a dose range of 1 ⋅1013–5 ⋅ 1014 cm –2 through a sacrificial oxide 20 nm thick. For one group of wafers, rapid thermal annealing was first carried out, then oxide removal (forward order), for the other group – in the opposite sequence (reverse order). It was found that with the additional doping of nitrogen ions in doses of 1⋅1013–5 ⋅ 1013 cm –2 with energy of 20 keV, an increasing of gate dielectric charge to breakdown for both types of annealing is observed. The maximum effect occurred for the samples at a dose of nitrogen ions of 1⋅1013 cm –2 with the forward heat treatment order. This is due to the interaction of nitrogen atoms with dangling bonds of the Si – SiO2 interface during annealing, as a result of which strong chemical bonds are formed that prevent charge accumulation on the surface of the Si – SiO2 interface. It is assumed that the main contribution to the gate leakage current is made by the tunneling of charge carriers through traps.

Quality of life (QOL) for the treatment sequence of abiraterone acetate plus prednisone (AAP) followed by enzalutamide (ENZ) versus the opposite sequence for metastatic castration-resistant prostate cancer (mCRPC): Results from a phase II randomized clinical trial.

5578 Background: A randomized cross-over phase II trial (Lancet Oncol 20(12):1730, 2019) showed the sequence of AAP followed by ENZ is associated with a better time to PSA progression compared with the opposite sequence and superior 2nd line activity of ENZ. It is unknown whether one treatment sequence is associated with better QOL than the other. Methods: 202 Patients were randomized (1:1) to receive either AAP followed by ENZ at PSA progression (arm A) or the opposite sequence of ENZ followed by AAP (arm B). FACT-P questionnaires were completed at baseline, cross-over and every 4 weeks on treatment. Time to QOL deterioration (TTQOLD) for the treatment sequence was determined from start of 1st line treatment to first questionnaire with a clinically meaningful decrease from baseline and compared between arms using the log-rank test. TTQOLD was also determined for 1st line and 2nd line separately. The proportion of patients with QOL deterioration for total FACT-P score and FACT-P subscores from baseline to week 12 of 1st and 2nd line treatment was compared between arms using X2 test. Results: Median follow-up for 1st and 2nd line and whole sequence were 9.3, 6.6 and 22.0 months (mos) respectively and questionnaire completion rate was 81%. TTQOLD for total FACT-P score for the whole sequence for arm A vs B was 10.5 mo (95% CI 5.0-15.5) vs 10.8 mo (5.5-13.1), p = 0.74. For 1st-line AAP vs ENZ, median TTQOLD was 15.5 mo (5.5-21.2) vs 11.0 (5.5-13.3) respectively (p = 0.23). For 2nd line ENZ vs ABI, median TTQOLD was 3.7 mo (2.0-5.4) vs 5.8 (2.8-12.1), p = 0.13. There was a higher rate of deterioration in physical well-being (PWB) for 1st line ENZ (arm B) and 2nd line ENZ (arm A) (Table). Conclusions: There was no difference in TTQOLD between the two treatment sequences of AAP and ENZ. Although treatment with second line ENZ has been associated with greater anti-cancer effects, ENZ was associated worse PWB QOL scores. Clinical trial information: NCT02125357 . [Table: see text]

Crop coefficient and water requirement of prickly pear in the Agreste region of Alagoas state, Brazil

ABSTRACT Prickly pear cultivation has played an important role in the Brazilian livestock farming, being used as forage for animals in the Northeast region, especially during the drying season, because it is an excellent source of water. Thus, the objective of this study was to estimate the crop coefficient and water requirement of prickly pear in the Agreste region of Alagoas state, Brazil. Prickly pear crop evapotranspiration (ETc) was determined using five drainage lysimeters, made of polyethylene with dimensions of 0.35 x 0.40 m (side and depth). Four soil layers were separated and put into the lysimeters in the opposite sequence, in order to maintain it as close as possible to the initial soil structure. The reference evapotranspiration (ETo) was estimated by the Penman-Monteith, Hargreaves-Samani and FAO-Radiation methods, using climatic data from the meteorological station of the Instituto Nacional de Meteorologia (INMET) in the city of Arapiraca, AL, Brazil. Crop coefficient (kc) was calculated by the ratio between ETc and ETo. The average kc obtained was 0.72, 0.84 and 0.48 for the Penman-Monteith, Hargreaves-Samani and FAO-Radiation methods, respectively. Keeping the soil under field capacity during the experimental period, the total crop evapotranspiration was 637.84 mm, with daily value equal to 4.22 mm d-1.

Optimal sequencing of enzalutamide and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC).

308 Background: Both enzalutamide and abiraterone are approved for the treatment of mCRPC, each demonstrating improved overall survival (OS) versus placebo. However, it is unclear what the optimal sequencing of these two therapies should be to maximize clinical outcomes and survival. Here, we compare clinical outcomes among patients with mCRPC who received enzalutamide first followed immediately by abiraterone (enza-to-abi) or the opposite sequence (abi-to-enza). Methods: A retrospective review of consecutive mCRPC patients treated at Johns Hopkins with enza-to-abi or abi-to-enza was conducted. The combined PFS (PFS = PFS1 + PFS2) was the primary endpoint, measured from the start of the first therapy (i.e. enza or abi) until disease progression on the subsequent therapy (i.e.abi or enza). The OS from the start of the first therapy until death was the secondary endpoint. Cox proportional hazards multivariable regression analysis was performed to determine whether one sequence was better than the other after adjusting for baseline characteristics. Results: 71 patients were identified: 58 received abi-to-enza and 13 received enza-to-abi. Comparisons of baseline characteristics between groups identified differences in PSA levels (P = 0.007), hemoglobin (P < 0.001), and presence of visceral disease (P = 0.035). The abi-to-enza group had a longer combined PFS than the enza-to-abi group: median 16.3 vs 12.5 mo (HR 0.53, P = 0.04). There was also a numeric improvement in OS in the abi-to-enza group compared to the enza-to-abi group: median 29.0 vs 21.0 mo (HR 0.51, P < 0.10). In multivariable analyses incorporating PSA level, hemoglobin, visceral disease and prior docetaxel use, both combined PFS (HR 2.59, P = 0.03) and OS (HR 4.59, P < 0.01) demonstrated improved outcomes with the abi-to-enza sequence. Conclusions: This hypothesis-generating study potentially suggests superior PFS and OS in men with mCRPC receiving abiraterone then enzalutamide (compared to enzalutamide then abiraterone), although this could be due to baseline imbalances or the small sample size of this study. Prospective validation of this concept is ongoing (NCT02125357).

Optimal sequencing of docetaxel and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC).

252 Background: Currently there are multiple agents approved for the treatment of mCRPC based on prolongation of life. However, it is unclear what the optimal sequencing of these therapies is to maximize clinical benefit and survival. Here, we aimed to compare clinical outcomes among men with mCRPC who received docetaxel first followed immediately by abiraterone (doce-to-abi) or the opposite sequence (abi-to-doce). Only men that were treated with sequential therapy using these two agents (i.e. without intervening treatments) were included. Methods: A retrospective review of consecutive mCRPC patients treated at Johns Hopkins was conducted. A combined PFS (PFS = PFS1 + PFS2) was the primary endpoint, measured from the start of the first therapy (i.e. doce or abi) until the time of clinical/radiographic progression on the subsequent therapy (i.e. abi or doce). Overall survival (OS) from the start of the first therapy until death was the main secondary endpoint. Multivariable regressions were performed to determine whether one sequence was better than the other (doce-to-abi versus abi-to-doce) after adjusting for a number of baseline patient and treatment characteristics. Results: In total, 86 patients were identified that met our study criteria: 53 men received doce-to-abi and 33 men received abi-to-doce. PFS was longer in the doce-to-abi cohort: median 19.1 (95% CI 13.0–27.4) mo versus 10.4 (95% CI 9.1–11.5) mo (HR 2.6, 95% CI 1.5 – 4.5). OS was also superior in the doce-to-abi cohort: median 30.3 (95% CI 25.4–44.3) mo compared to 18.2 (95% CI 14.1–21.1) mo (HR 2.3, 95% CI 1.2 – 4.1). In multivariable analyses, superior outcomes were still observed in the doce-to-abi group with respect to PFS (HR 2.77, 95% CI 1.5–5.0, P=0.0008) and OS (HR 2.8, 95% CI 1.5–5.3, P=0.0016) after adjusting for Gleason score, baseline PSA and ECOG status at study initiation. Conclusions: This hypothesis-generating study seems to suggest superior PFS and OS in men with mCRPC receiving doce followed by abi (rather than the opposite sequence). These findings are in alignment with the results of the CHAARTED trial supporting earlier docetaxel use, but require prospective validation.

Community oncology treatment patterns and clinical effectiveness in metastatic castration-resistant prostate cancer (mCRPC) patients who progressed after docetaxel.

118 Background: Cabazitaxel (C) and abiraterone (A) improve survival in mCRPC after progression on docetaxel (D). We examined whether mCRPC patients progressing on D received C and/or A, in which sequence, and how they compared with patients not receiving C or A. Methods: This retrospective study used medical records from the ACORN Data Warehouse. Eligible patients were: diagnosed with mCRPC, progressed after 1st-line D, treated 2nd-line with C (DC) or A (DA). Some went to 3rd-line C or A (DCA, DAC). A random sample of comparable patients without A or C (DO) was included. Demographic and clinical characteristics were extracted. Cox regression analyses assessed PFS and OS by 2nd-line group after D. Results: Screened out patients were: 60 with no progression on D; 41 absent records; 18 with another cancer. Table below shows patients by treatment sequence group. Age, PS, and PSA did not differ significantly. More patients appear to have received A after C (56.7%) than C after A (25.7%). In the 3-drug sequence groups, more patients received DCA in the 6-month period from April-October 2011 (n = 17/19) than in the 6-month period from June-December 2012 (n = 2/10), suggesting a drop-off in use of C immediately after D. Cox PFS treatment effect was not significant. Cox OS treatment effect was significant (DA vs DC, HR = 1.693 [95% CI: 1.066, 2.691], p = 0.0258). Conclusions: Patterns suggest comparable outcomes in PFS. Controlling for patient characteristics, OS may be longer in DC vs DA. Patients appear undertreated in third line with fewer receiving C after A than the opposite sequence. We hypothesize that DAC may not be as feasible as DCA. Reasons for underutilization of C are being examined. [Table: see text]