Academic literature on the topic 'Flexible Link (FL)'

Flexible Learning (FL) is a pedagogical approach allowing for flexibility of time, place, and audience, including but not solely focused on the use of technologies. We describe Flexible Learning as a pedagogical approach in four courses framed by three key themes: 1) objectives and aspects of course design, 2) evaluation and assessment, and 3) challenges and improvements. Examples of strategies include: digital media-based assignments; iClicker and on-line quizzes; a librarian-created tutorial and links to copyright-cleared readings; use of Calibrated Peer Review as formative feedback; TurnItIn for self-review; wiki sites, group blogs and community work through Community-based Action Research (CBAR) conducted through the pedagogy of Community-Based Experiential-Learning (CBEL). We believe that the transferability of our experiences and findings is most relevant to educators seeking to create learning experiences that increase student engagement with complexity and uncertainty. FL approaches can help educators create learning environments that more closely resemble the contexts that students find upon graduation.

Abstract Abstract 4441 Background: In ENESTnd, newly-diagnosed adult patients with Ph+ CML-CP were stratified by Sokal score (low [LS], intermediate [IS], and high [HS]) and randomized to frontline (FL) tyrosine kinase inhibitor (TKI) therapy with nilotinib (NI) 300 mg BID, NI 400 mg BID, or imatinib (IM) 400 mg QD. NI 300 mg BID demonstrated superior rates of molecular response and significantly fewer progressions to accelerated phase (AP)/blast crisis (BC) vs. IM. NI 300mg BID is the approved FL dose. Objective: To use microsimulation to estimate the life expectancy of individual Ph+ CML-CP patients treated with FL IM or NI 300 mg BID based on ENESTnd. Methods: Life expectancy of individual patients was predicted over a 60-year period beginning from FL therapy initiation. Simulated patients were tracked through the following (groups of) health states: i) FL in CP, ii) 2nd-line TKI therapy in CP or AP, iii) off TKI in CP, AP, or BC, iv) stem-cell transplant and post-transplant in CP, BC, or AP. Time spent in each state was dictated by transition probabilities that depended on each patient's FL treatment (IM or NI), Sokal score, and baseline age. Sokal score and baseline age are related (LS: 41.21 yrs; IS: 50.73 yrs, HS: 49.81 yrs), and inform non-CML mortality. FL treatment discontinuation probabilities by Sokal score and therapy were estimated by fitting parametric survival functions (e.g., Weibull) to ENESTnd (36 month minimum follow-up). Transition probabilities among the health states occurring after FL therapy discontinuation were estimated from published sources and population-based life tables. Modeled outcomes are reported by FL treatment, Sokal score, and in aggregate. In the base case, outcomes reflect a population matching the ENESTnd mean age at trial entry (47 years) and Sokal score distribution (37%, 36% and 28%, for LS, IS, and HS). Sensitivity analyses were conducted using the IRIS trial mean age at study entry (46 years) and Sokal score distribution (52%, 29%, and 19%) to compare results with previously reported survival estimates based on IRIS and to determine the impact of the higher proportion of high Sokal score patients in ENESTnd. Two additional scenarios were examined for comparison to other models: a) the absence of a 2nd-line TKI treatment, and b) adjusting baseline age to 57. Results: Modeled life expectancy estimates are presented in the Table. Life expectancy in the base case scenario, with patient Sokal score distribution and baseline age from ENESTnd and use of 2nd line TKI treatment, is presented in aggregate and by Sokal score. Alternate scenario life expectancy is presented in aggregate. Discussion: Patients treated with FL NI are predicted to live 3–8 years longer than patients treated with FL IM. Sokal score, baseline age, and availability of 2nd-line TKI therapy are factors influencing long-term CML survival estimates. Presented life expectancy estimates are comparable to previous estimates derived with similar methodologies. Results observed in IRIS long-term follow up (86% overall survival at 8 years) and findings from an alternative model that relied on cytogenetic and molecular response to predict FL discontinuation both independently suggest actual life expectancy may be somewhat higher than reported herein. This microsimulation approach is unique in that it combines individual patient characteristics with clinical trial findings to estimate life expectancy within a flexible framework. This framework can be easily adapted to accommodate additional patient characteristics and treatment strategies and provide insight into the impact of treatment decisions on patient survival. Disclosures: Snedecor: Novartis: Consultancy. Ji:Novartis: Consultancy. Magestro:Novartis: Employment, Equity Ownership. Stein:Novartis Pharmaceuticals: Employment. Botteman:Novartis: Consultancy.

Purpose: Follicular lymphoma (FL) is generally regarded as an indolent malignancy, yet the clinical outcome is highly variable. In recent years, POD24 (progression of disease within 24 months) has emerged as a potential prognostic marker for overall survival (OS) in FL and other non-Hodgkin lymphomas. The association with survival, however, has mostly been studied in selected clinical trial cohorts and among patients treated with R-CHOP. We aimed to investigate OS by timing of progression and type of primary treatment in a population-based setting in Sweden. Methods: We identified all patients diagnosed with FL in stages II-IV and grade 1-3a between 2007 and 2014, using the population-based Swedish lymphoma register. Data were complemented with information on progression, transformation and second-line treatment through medical charts review up to December 31st, 2017. The analysis covered 4 out of 6 health care regions (75% of all patients diagnosed nationally). The patients were categorized according to type of first-line treatment: R-chemo of any type, R-Benda, R-CHOP (including R-CHOEP), or other (including immunotherapy only). Among patients where it was decided to start first-line treatment within 6 months of diagnosis (and where treatment was started within nine months), POD was defined as either lack of response to first-line therapy (stable [SD] or progressive disease [PD]), or initial response and subsequent relapse/progression/transformation as indication for second-line therapy. To quantify the impact of timing of POD on survival, the five-year OS conditional on either being progression-free (PF) or having experienced POD at different time points during follow-up, was estimated using a flexible parametric illness-death model. Results: Among a total of 970 FL patients, median age at diagnosis was 66 years and patients were followed for a median of 6.4 years (range 0-12 years). The 5-year OS was 75% and progression-free survival was 59%. Six hundred (62%) patients had a first-line treatment within nine months of diagnosis and were hence analyzed further, whereas the remaining 370 (38%) patients were classified as wait-and-watch and were not analyzed further. Among the 600 treated patients, 337 (56%) had R-chemo (R-CHOP or alike (n=210), R-Benda (n=97), other (n=30)), and 263 (44%) received non-R-chemo treatment (mainly R-monotherapy, radiotherapy only, or R-lenalidomide). Patients who received R-Benda were on average older than the other groups. Among patients treated with R-chemo, those who stayed progression-free had a 5-year conditional OS above 75% regardless of PF time point. For patients who progressed, the 5-year conditional OS improved as time point of POD was prolonged (Fig 1a, left panel). Early POD (within 12-24 months) was associated with a particularly poor prognosis (5-year conditional OS below 55%). The OS improvement over time of POD was especially pronounced among R-Benda treated patients (Fig 1b, right panel). Among patients receiving non-R-chemo treatments, early POD was associated with a slightly worse 5-year OS but differences between POD and PF patients were less marked (Fig 1a, right panel). Conclusion: This population-based study of Swedish stage II-IV FL patients shows that among immunochemotherapy-treated patients, progression of disease was always associated with worse survival in comparison to progression-free patients regardless of timing of progression. This reduction in survival was more pronounced the earlier the progression (as described by others). Interestingly, among patients selected for milder non-immunochemotherapy-based treatments, progression of disease did not have a strong effect on survival. Disclosures Weibull: Janssen Cilag: Research Funding. Wahlin:Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding. Smedby:Takeda: Research Funding; Janssen: Research Funding; Celgene: Consultancy.

Abstract Introduction Rituximab was approved in December 1997 and has since become the standard of care in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). Clinical trials have shown statistically significant improvements in progression-free and overall survival. The objective of this study was to estimate the real-world effectiveness of first-line rituximab plus chemotherapy (R+Chemo) relative to chemotherapy alone (Chemo Alone) in the United States (US) from 1998 to 2013. Methods For each cancer, we constructed a population effectiveness model from 1998-2013 comprised of 3 modules: epidemiology, utilization and survival. The epidemiology module included age group, gender, and year-specific incidence rates for each cancer from the Surveillance, Epidemiology, and End Results (SEER) program from 2000-2010. Published SEER-based join-point estimates were used to extrapolate to other years. Census population data using the same age group, gender, and year strata were combined with incidence rates to project total diagnosed patient counts. The utilization module was based on SEER-Medicare linked data from 1999-2009. Drug utilization (defined as first infusion within 180 days of diagnosis for each cancer) for R+Chemo and for Chemo Alone was estimated as a proportion of all diagnosed patients, and stratified by age group, gender, and calendar year of diagnosis in the SEER-Medicare data. Utilization proportions were then multiplied by the diagnosed population counts to estimate treated patient counts for each cancer, by age group, gender, and calendar year. The survival module was calculated using SEER-Medicare data, starting from 30-days after first infusion, with follow up through 12/31/2010. For each cancer, flexible parametric (Royston-Parmar) survival models were applied to estimate restricted (10-year) mean survival times for each person, adjusted for individual patient covariates. These estimates were averaged across patients within strata defined by age group, gender and treatment. Life years lived were estimated for patients receiving R+Chemo, first by using mean survival for treatment with R+Chemo, and then by using mean survival estimates for Chemo Alone. The incremental life years saved were calculated as the difference between the projected survival from using R+Chemo and from using Chemo Alone. These differences were summed over age group, gender, and calendar year for each cancer. Monte Carlo sampling was used to estimate the 95% uncertainty intervals (UI). Results Across all three cancers, there were 289,793 cumulative life years saved (95% UI, 248,300-330,618; see Figure) from 1998 to 2013. For DLBCL, an estimated 177,952 patients were treated with R+Chemo. In these patients, an estimated 199,323 (95% UI 169,534-231,214) additional life years were lived compared to what might have occurred if Chemo Alone had been used instead. For FL, an estimated 84,303 patients were treated with R+Chemo, and an additional 80,338 (95% UI 53,876-106,709) life years were lived compared to Chemo Alone. For CLL, an estimated 14,398 patients were treated with R+Chemo, and an additional 10,132 (95% UI 4,469-15,998) life years were lived compared to Chemo Alone. Conclusions For DLBCL, FL and CLL patients treated with first-line therapy within 180 days of diagnosis in the US, approximately 290,000 cumulative life years were saved by adding rituximab to chemotherapy between 1998 and 2013. Next generation therapies may be able to extend these survival gains for patients with CLL, FL and DLBCL. Disclosures: Danese: Amgen: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Medimmune: Consultancy, Research Funding. Gleeson:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Halperin:Genentech: Consultancy, Research Funding; Medimmune: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Skettino:Genentech: Employment, stock Other. Reyes:Genentech, inc: Employment, Equity Ownership.

Abstract Background. Immunochemotherapy is effective in follicular lymphoma (FL), but most patients (pts) eventually relapse. MRD analysis, based on the detection of Bcl-2/IGH rearrangement by highly sensitive PCR-based tools, is effective in identifying pts at risk of relapse [Ladetto Blood 2012; Pott EHA23]. However, several issues are still unresolved, including: i) which is the best tissue source and the most reliable technique; ii) which are the most predictive time points; iii) which is the role of disease kinetics during the long natural history of FL. The FIL FOLL12 prospective, phase III randomized clinical trial (EudraCT: 2012-003170-60) included a systematic MRD analysis on both peripheral blood (PB) and bone marrow (BM) taken at eight different pre-planned time points, by both nested and real time quantitative (RQ)-PCR. Therefore, it allows addressing these unresolved issues. Methods. The FOLL12 compared conventional rituximab maintenance [Salles et al, Lancet 2010] vs a combined PET/MRD response-based post-induction approach in pts with advanced FL after first line chemo-immunotherapy. Clinical results have been already reported [Luminari et al, ICML16]. PB and BM samples were centralized at four Italian Euro-MRD certified laboratories. MRD was assessed with consensus primers on Bcl-2/IGH rearrangements (MBR, mcr and minor rearrangements) by both nested and RQ-PCR at eight time points: baseline, end of induction (EoI) and every six months thereafter till month 36. MRD data were treated as a time-varying covariate and analyzed by means of flexible parametric survival model (Parmar-Royston) with the log cumulative baseline hazard function. MRD data were modeled with restricted cubic spline as function of time. Effect of fixed covariates and landmark analysis were performed with the Cox PH regression. Any estimation was reported with its 95%CI. Results. Overall, 10,702 analytical results were generated, (3,000 for marker screening and 7,702 for MRD). 780 of 786 eligible pts (99%) were screened at baseline for the presence of a molecular marker. 443/780 (57%) had a detectable Bcl-2/IGH rearrangement, as expected. High rates of MRD negativity were observed at EoI, with similar results by both techniques (87% in BM and 95% in PB by nested-PCR, 90% in BM and 95% in PB with RQ-PCR). Overall, the presence of one MRD positive result was associated during the entire follow-up period with an increased risk of relapse in the subsequent six months interval (HR for PFS 2.82, 95% CI 1.84-4.34, p<0.001), independently from randomization arm (heterogenous test for HR in PFS 0.330), treatment received (HR 0.859) and FLIPI-2 (HR 0.302). Most notably, a sharp increase of HR was observed during follow-up, with time points after 6 and particularly after 12 months or later outperforming the earliest evaluation. Interestingly, very similar results were recorded in BM or PB and using nested or RQ-PCR (Figure 1A). Despite inferior performance compared to later timepoints, MRD positivity in BM at EoI was nevertheless predictive of a shorter 4y-PFS (61% vs 75% by nested-PCR and 54% vs 74% by RQ-PCR, p=0.03 and p=0.003, respectively). Moreover, a kinetic analysis showed that pts scoring MRD+ at EoI but converting to MRD- in the following time points showed superimposable outcome to pts persistently MRD- (HR for PFS 0.66, 95% CI 0.24-1.82, p=0.420), while pts scoring MRD- at EoI but then converting to MRD+ showed a worse outcome (HR for PFS 1.75, 95% CI 1.21-2.53, p=0.003) (Figure 1B). Actually, Kaplan Meier landmark analyses stratified by updated MRD results at each punctual timepoint after EoI were overall highly discriminant in terms of PFS, with PB results (Figure 1C) substantially overlapping BM performances from months 12 after EoI (not shown) and thereafter. Conclusions. This comprehensive MRD study in FL clearly indicates that: i) punctual MRD analysis is predictive of poor outcome at multiple pre-planned time points taken over a 36 months period; ii) both nested and RQ-PCR performed adequately, the latter being preferable as broadly used and internationally standardized; iii) BM allows better prediction at the early time points but, starting from month 12 after EoI PB is superimposable to BM, allowing effective and reliable long-term non-invasive MRD monitoring; iv) the high predictive value of punctual time point analysis is further improved by a kinetic approach to the interpretation of MRD results. Figure 1 Figure 1. Disclosures Ladetto: AbbVie, Jazz, Gentili, Incyte, ADC Therapeutics, Acerta, Pfizer: Honoraria; Roche, J&J, Celgene, Novartis, Amgen, Gilead, Beigene, GSK: Honoraria. Ferrero: Servier: Speakers Bureau; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Morphosys: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding, Speakers Bureau; Clinigen: Membership on an entity's Board of Directors or advisory committees. Del Giudice: Tolero: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees. Galimberti: Incyte: Speakers Bureau; AbbVie, Janssen: Honoraria, Other: Travel grants. Gattei: abbVie: Research Funding; Janssen: Research Funding; Menarini: Research Funding. Mannina: Janssen,Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Falini: Rasna Therapeutics: Honoraria. Luminari: Roche, Celgene, Teva Pharmaceuticals, Gilead Sciences, and Takeda Pharmaceuticals: Honoraria.

The hybrid arms robot (HAR) is a new modified robot which consists of a rigid link (RL) and a flexible link (FL), and it carries a laser head at the end-effector for laser contour machining (CM). The HAR is inspired from a rigid-flexible links manipulator (RFLM) and the aim is to bring the advantages of flexible link manipulators (FLMs) to industrial robots. The HAR gains the advantages of lightweight robots and FLMs such as fast response, less power consumption due to using small actuators, low cost, and safe to surrounding operators. However, the HAR has the drawback of a tip vibration caused by the flexibility of the second FL and leads to a position error at the end-effector position. Furthermore, the HAR has more parameters to be incorporated in a dynamic model such as the tip vibration, the laser head weight, and a force generated by the assist gas pressure. This research aims to obtain the dynamic model of the HAR using the finite element method (FEM) in conjunction with the Lagrangian equation and to propose an integrated optimal controller (IOC) which is an integration of a linear quadratic regulator (LQR) and a fuzzy logic controller (FLC). The derived dynamic model of the HAR is efficient due to the close match response with the SimMechanics model response of the HAR. The proposed IOC is tested for point-to-point (PTP) position control of the HAR and demonstrates improved response and better capability for the tip vibration suppression. The proposed IOC also reveals enhanced triangular CM trajectory, rhombic CM trajectory, and circular CM trajectory of the HAR laser head compared to the LQR performance in a proper cutting speed to ensure the machining quality.

Трунін, К. С. Математична модель динаміки гнучкого зв’язку морської прив’язної системи з урахуванням впливу кручення гнучкого зв’язку на його силу розтягування = The mathematical model of flexible link marine tethered system dynamic’s with account of torsion to it tensile force / К. С. Трунін // Матеріали XII міжнар. наук.-техн. конф. "Інновації в суднобудуванні та океанотехніці". – Миколаїв : НУК, 2021. – С. 115–119.
Важливою характеристикою гнучкого зв’язку (ГЗ) є опір крученню, яке виникає від процесу набігання на блок і вигину на блоці, і яке необхідно враховувати в умовах експлуатації. Запропоновано метод визначення векторів узагальнених сил кручення ГЗ. Досліджено вплив від кручення ГЗ на його силу розтягування на конкретних прикладах, у ряді випадків кручення ГЗ помітним чином впливає на характер руху ППС в цілому. Тема розробки ММ динаміки МПС з урахуванням впливу кручення є важливою і актульною.
The important of characteristic of flexible link (FL) is rigidity in bending (RB) which is probability be taken into account at regular service conditions. The elements of rope (wire) by endues testing also tension and bend with torsion. The method of calculation of vectors of generalized of forces of bend of FL was proposed. One of the causes of torsional stresses in the power plant of the Underwater Tethered Systems (UTS) is the interaction with ship equipment, in which the spiral winding on the winch drum, friction on the flanges of the pulleys or winch drums, bends on various blocks and rolls cause torsion. The source of torsional stresses in FL there may by technological reasons related to both the manufacture and storage, transportation and placement on the drooms ship’s winch.