Smart Start Research Articles

Rituximab, chidamide, and zanubrutinib (ZCR) ± CHOP as a regimen for treatment naive (TN) double-expressor DLBCL (DE-DLBCL).

e19053 Background: DLBCL patients with co-expression of MYC (≥40%) and BCL2 (≥50%) by immunohistochemistry are considered as DE-DLBCL. The prognosis of DE-DLBCL is usually worse than DLBCL-NOS. The Smart Start trial had established the feasibility of chemotherapy-free targeted therapy before 1L chemotherapy. The BTK inhibitor Zanubrutinib (Z) or epigenetic drug Chidamide (C) with R-CHOP regimen has a potential synergistic effect in the treatment of DE-DLBCL. Under the inspiration of Smart Start, this trial aim to explore the feasibility of ZCR±CHOP regimen in TN DE-DLBCL. Methods: This is a multicenter, open-label, single-arm phase 2 study (NCT05527912) conducted in China. If patients achieve complete response (CR) after cycle-2 (C2), ZCR will be continued for up to 8 cycles. Otherwise, ZCR-CHOP will be given for another 6 cycles. The primary endpoint is CR rate at the end of treatment (CRR-EOT); secondary endpoints included ORR (overall response rate) ,2y-PFS, and 2y-OS. Plasma samples were collected at baseline, C2 and the EOT. In evaluable samples, circulating tumor DNA (ctDNA) assays were performed. Results: From February 2023 till now, 34 TN DE-DLBCL patients were enrolled, with 32 patients evaluable. The median age was 52y (range: 22-68), 55.9% were male, 79.4% were Non-GCB (Table 1). 12 patients who achieved CR by C2 were continued with RCZ chemo-free therapy, and CHOP were added to the 14 PR and 3 SD patients. In the 32 evaluable patients, ORR after C2 of RCZ was 81.25% (26/32, CR 37.5%, PR 43.75%, SD 9.4%, PD 9.4%). Up to now, 12 patients have completed 8 courses (C8) and all of them have achieved CR, both ORR and CR are 100% (12/12). 3 patients withdrew due to PD. For safety information in the trial, 64.3% patients reported grade (G)-3/4 AEs. In the Chemo-Free subgroup, only 4 patients (36.4%, 4/11) reported G-3/4 AEs. the majority of G-3/4 AEs is hematological events, including leukopenia, neutropenia and thrombocytopenia. The CR rate at C2 was 66.7% (6/9) in patients with negative baseline ctDNA results. The patients with BCL6 fusion of ctDNA at baseline were more prone to PD (3/4, 75.0%). Compared to baseline, plasma ctDNA levels decreased significantly after C2. 29 patients were evaluable for ctDNA after C2, 100% (12/12) of C2-CR patients and 58.8% (10/17) of non-C2-CR patients were negative, P=0.023. Compared with Non-C2-CR patients, the number of detected mutations and average VAF level were decreased in C2-CR patients. Conclusions: This trial demonstrates ZCR±CHOP could be a promising regimen with active antitumor effect and acceptable toxicity in TN DE-DLBCL patients. Clinical trial information: NCT05527912 .

Getting a "SMART START" to gestational diabetes mellitus education: a mixed-methods pilot evaluation of a knowledge translation tool in primary care.

South Asian people living in Canada face higher rates of gestational diabetes mellitus (GDM) compared to national trends. The objective of this study was to design and pilot test a knowledge translation (KT) tool to support GDM prevention counselling in primary care. This study is a mixed-methods pilot evaluation of the "SMART START" KT tool involving 2 family physicians in separate practices and 20 pregnant South Asians in Ontario, Canada. We conducted the quantitative and qualitative components in parallel, developing a joint display to illustrate the converging and diverging elements. Between January and July 2020, 20 South Asian pregnant people were enrolled in this study. A high level of acceptability was received from patients and practitioners for timing, content, format, language, and interest in the interventions delivered. Quantitative findings revealed gaps in patient knowledge and behaviour in the following areas: GDM risk factors, the impact of GDM on the unborn baby, weight gain recommendations, diet, physical activity practices, and tracking of weight gain. From the qualitative component, we found that physicians valued and were keen to engage in GDM prevention counselling. Patients also expressed personal perceptions of healthy active living during pregnancy, experiences, and preferences with gathering and searching for information, and key preventative behaviours. Building on this knowledge can contribute to the design and implementation of other research opportunities or test new hypotheses as they relate to GDM prevention among South Asian communities.

Pomalidomide, Rituximab, Orelabrutinib, and Minichop-like (PRO-miniCHOP) in Elderly Patients with Newly Diagnosed Diffuse Large-B Cell Lymphoma: Preliminary Results from a Phase II Study

Introduction: Owing to comorbidities and poor tolerance to standard-dose chemotherapy, elderly patients with newly diagnosed diffuse large-B cell lymphoma (DLBCL) have to reduce their chemotherapy dose, ultimately leading to a poor prognosis (Di M, et al. Oncologist, 2021). Therefore, new therapeutic strategies with superior efficacy and less toxicity are urgently needed. The Smart Start study demonstrated that induction therapy with rituximab (R), lenalidomide, and ibrutinib resulted in a high overall response rate (ORR) in patients with newly diagnosed DLBCL (Westin J, et al. J Clin Oncol, 2023). Orelabrutinib (O), as a novel covalent Bruton's kinase inhibitor (BTKi) with high target selection, was reported to preserve the NK-cell-mediated antibody-dependent cellular cytotoxicity induced by R and thus boosted the antitumor effect of R-based regimen (Yu H, et al. Mol Ther-Oncolytics, 2021). The responders to OR induction therapy have been reported to attain synergistic antitumor effect and high complete remission (CR) rate (CRR) when receiving subsequent treatment (Qu C, et al. Hematol Oncol, 2023). Here, a prospective study was conducted to investigate the efficacy and safety of pomalidomide (P; a third-generation immunomodulatory drug), R, O, and miniCHOP-like (PRO-miniCHOP) in elderly patients with newly diagnosed DLBCL. Methods: Patients aged ≥70 years with newly diagnosed DLBCLwere enrolled in this open-label, single-arm, phase II study (NCT05809180). All eligible patients received one 21-day cycle of induction therapy with PRO (P, 4 mg, d1-7; R, 375 mg/m 2, d1; O, 150 mg, QD). Subsequently, patients who achieved at least mini response (miniR, a reduction in tumor lesions by 25%-50%) were administered additional 6 cycles of PRO-miniCHOP regimen (PRO with reduced-dose CHOP regimen [cyclophosphamide, 400 mg/m 2, d2; doxorubicin/liposomal doxorubicin, 25 mg/m 2/15 mg/m 2, d2; vindesine, 2 mg, d2; and dexamethasone, 7.5 mg/m 2, d2-6]). The subsequent treatment was administrated according to the tumor response after 6 cycles of the PRO-miniCHOP regimen, including the end of treatment for CR, 2 years of pomalidomide maintenance therapy for partial remission (PR), and discharge from the study for stable disease or progression disease. The primary endpoints were ORR and CRR after 6 cycles of the PRO-miniCHOP regimen. Secondary endpoints were ORR and CRR at the end of the induction therapy, as well as 2-year progression-free survival, 2-year overall survival and safety. Results: From January 01, 2023 to July 30, 2023, 10 patients were enrolled in this study. The median age was 76.0 (range, 70.0-84.0) years (Table 1). The majority of patients had an Ann Arbor stage of III or IV (7/10, 70.0%), International Prognostic Index score of ≥3 (6/10, 60.0%), and non-germinal center B-cell-like subtype (6/10, 60.0%). Five (50.0%) patients had hypertension, 4 (40.0%) patients presented with extranodal involvement, and MYC/BCL-2 double expression lymphoma (40.0%). After one cycle of induction therapy with PRO, all (10/10, 100.0%) patients achieved at least miniR, including 3 CR, 6 PR, and 1 miniR (Figure 1). Five patients completed ≥3 cycles of the PRO-miniCHOP regimen, among whom 4 (80.0%) achieved a CR and 1 (20.0%) had a PR, with the best ORR of 100%; of these, one sustained CR at the end of cycle 6. During the induction therapy with PRO, 50.0% (5/10) of patients reported adverse events (AEs) of any grade, the majority of which were grade 1-2, with only 2 patients experiencing grade 3-4 neutropenia. Grade ≥3 AEs during the whole treatment period were neutropenia (6/10, 60.0%), thrombocytopenia (1/10, 10.0%), and lymphopenia (1/10, 10.0%), of which one (1/10, 10.0%) patient developed febrile neutropenia. Notably, the use of prophylactic pegylated recombinant human granulocyte colony stimulating factor significantly reduced the recurrence rate of severe neutropenia in the subsequent treatment, and no treatment-associated death was observed. Moreover, despite half of the patients having the comorbidity of hypertension, no off-target related cardiac events such as atrial fibrillation or atrial flutter were observed. At the time of data cutoff, 9 patients were still under treatment. Conclusions: The present study provided preliminary evidence supporting the use of the PRO-miniCHOP regimen in elderly patients with newly diagnosed DLBCL. More clinical data will be updated from this ongoing study.

Smart Stop: Lenalidomide, Tafasitamab, Rituximab, and Acalabrutinib Alone and with Combination Chemotherapy for the Treatment of Newly Diagnosed Diffuse Large B-Cell Lymphoma

Background: Despite recent advances, first-line (1L) chemoimmunotherapy (CIT) for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades.In the Smart Start trial, we established the feasibility of targeted chemotherapy-free 1L therapy with rituximab (R), lenalidomide (L), and ibrutinib, prior to chemotherapy in patients with newly diagnosed DLBCL with an overall response rate (ORR) and complete response rate (CRR) of 86% and 36%, respectively, prior to chemotherapy, and a 2 year progression free survival rate of 91.3% following 6 cycles of standard CIT (Westin et al, JCO 2023, PMID: 35952327). One patient withdrew from the study after achieving CR and prior to receiving CIT and remains in remission without further therapy at >4 years. BTK inhibitors like acalabrutinib (A) and the immunomodulatory agent L result in synthetic lethality in non-GCB DLBCL models. Both the CD20 antibody R and CD19 antibody tafasitamab (T) demonstrate clinical activity when combined with L in patients with DLBCL. L, T, R, and A are immunomodulatory, driving an anti-tumor immune response. Based upon these data, we are conducting the Smart Stop trial (NCT04978584) to evaluate if the number of CIT cycles can be reduced or omitted after response to targeted therapy, and now report the preplanned interim results from cohort 1. Methods: Eligibility criteria include patients who are 18y+ with previously untreated DLBCL (initially the Hans algorithm was used to select non-GCB DLBCL, but this criteria was removed this criteria) with adequate organ and bone marrow function. Patients with known CNS involvement of lymphoma, recent thrombosis, or inability to tolerate prophylactic anticoagulation are ineligible. Patients receive lenalidomide 25mg on days (d) 1-10, tafasitamab 12mg/kg IV d1, 8, and 15, rituximab 375mg/m2 IV d1, and acalabrutinib 100mg PO twice/d in a 21 day cycle. All patients receive LTRA for 4 cycles, followed by PET/CT scan (CR defined as a 5PS of 1, 2, or 3). In cohort 1, patients receive an additional 6 cycles of LTRA combined with a response adapted number of cycles of CHOP therapy. After 4 cycles of LTRA, patients with CR receive 2 cycles of CHOP, and all other patients receive 6 cycles of CHOP. In the upcoming cohort 2, patients with CR after 4 cycles of LTRA are planned to receive no cycles of CHOP. The primary objectives are to determine the 1A: ORR after 4 cycles of uLTRA and 1B: CRR at of LTRA +/-CHOP at the end of therapy. Results: Cohort 1 enrolled 30 patients from May 2022 - July 2023, with all patients expected to be evaluable for 1A endpoint and 22 patients (73%) evaluable for endpoint 1B by the ASH meeting. The median age was 61 years (range: 32-85), 30% were >= 70 years, and 50% were female. 67% of patients have poor risk R-IPI, 77% had advanced stage, and 83% had an elevated LDH. 83% had the non-GCB subtype and 17% had the GCB subtype of DLBCL. After 4 cycles of LTRA, the ORR is 100% and the CRR is 64% (endpoint 1A, n = 14/22 evaluable at abstract submission, figure 1 schema and swimmer plot). After an additional 2 cycles of LTRA-CHOP, the ORR is 100% and the CRR is 95% (n = 18/19 evaluable at abstract submission). At end of all therapy, the CRR is 100% (endpoint 1B, n = 12 evaluable at abstract submission), including 7 patients who received LTRA for 10 cycles and CHOP for 2 cycles (early CR) and 5 patients who received LTRA for 10 cycles and CHOP for 6 cycles. To date, no patient has progressive lymphoma, including the first 6 patients who have 3 and 6 month follow up scans. 47% of patients experienced rash (13% grade 3), and 40% of patients required a dose reduction of lenalidomide. Conclusions: The Smart Stop trial demonstrates that combination of lenalidomide, tafasitamab, rituximab, and acalabrutinib is highly effective as an initial chemotherapy-free combination in patients with newly diagnosed DLBCL, and may allow for a response adapted reduction in chemotherapy. Response and time to event data will be updated for presentation at the meeting. We will soon open cohort 2 which will enroll an additional 30 patients where those with early CR after 4 cycles of LTRA will receive no cycles of CHOP.

Accuracy of transdermal alcohol monitoring devices in a laboratory setting.

The development of transdermal alcohol sensors (TASs) presents a new method to monitor alcohol consumption with the ability to objectively measure data 24/7. We aimed to evaluate the accuracy of two TASs (BACtrack Skyn and Smart Start BARE) in a laboratory setting. Thirty-two adults received a dose of ethanol 0.56g/kg body weight as a 20% solution while wearing the two TASs and provided Breath Alcohol Concentration (BrAC) measurements for 3.5h postalcohol consumption. Pearson's correlations and repeated measures analysis of variance tests were conducted on the peak, time-to-peak, and area under the curve data. Bland-Altman plots were derived. A time series analysis and cross-correlations were conducted to adjust for time lag. Both TASs were able to detect alcohol and increase within 20min. BrAC peaked significantly quicker than Skyn and BARE. BrAC and Skyn peaks were negatively significantly correlated (r = -0.381, P = .035, n = 31), while Skyn and BARE peaks were positively significantly correlated (r = 0.380, P = .038, n = 30). Repeated measures analysis of variance found a significant difference between BrAC, Skyn, and BARE (F(1.946, 852.301) = 459.873, P < .001)). A time series analysis found when BrAC-Skyn and BrAC-BARE were adjusted for the delay to peak, and there was still a significant difference. Failure rates: 1.7% (Skyn) and 4.8% (BARE). Some evidence was obtained for TAS validity as both consistently detected alcohol. Failure rates and time lag show improvements in older device generations. However, neither TAS presented strong equivalence to the breathalyser even when the lag time was adjusted. With further testing and technology advancements, TAS could be a potential alcohol monitoring tool. Two of the newest TAS devices were worn in laboratory conditions for one afternoon to compare their accuracy of alcohol monitoring to a breathalyser. Findings suggest that the two TASs (BACtrack Skyn and SmartStart BARE) recorded significantly similar data postalcohol consumption, but not with the breathalyser.

Smart Start: Rituximab, Lenalidomide, and Ibrutinib in Patients With Newly Diagnosed Large B-Cell Lymphoma.

Chemoimmunotherapy for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) is largely unchanged for decades. Both preclinical models and clinical data suggest the combination of lenalidomide and ibrutinib may have synergy in DLBCL, particularly in the non-germinal center B-cell-like subset. We enrolled 60 patients with newly diagnosed non-germinal center B-cell-like DLBCL in this investigator-initiated, single-arm phase II trial of rituximab, lenalidomide, and ibrutinib (RLI) with the sequential addition of chemotherapy (ClinicalTrials.gov identifier: NCT02636322). Patients were treated with rituximab 375 mg/m2 intravenous once on day 1, lenalidomide 25 mg once per day on days 1-10, and ibrutinib 560 mg once daily continuously of each 21-day cycle (RLI). After two cycles, standard chemotherapy was added to RLI for six additional cycles. The primary end points were overall response rate (ORR) after two cycles of RLI alone and complete response rate after completion of RLI with chemotherapy. In evaluable samples, circulating tumor DNA and DLBCL90 assays were performed. The median age was 63.5 years (range, 29-83 years) with 28% age 70 years or older. The revised international prognostic index identified 42% as high risk, and 62% were double expressor of MYC and BCL2 protein. The ORR after two cycles of RLI was 86.2%, and the complete response rate at the end of RLI-chemotherapy was 94.5%. With a median follow-up of 31 months, the progression-free survival and overall survival were at 91.3% and 96.6% at 2 years, respectively. Smart Start is the first study, to our knowledge, to treat newly diagnosed DLBCL with a targeted therapy combination before chemotherapy. RLI produced a high ORR, and RLI with chemotherapy resulted in durable responses. This establishes the potential for developing biologically driven and noncytotoxic first-line therapies for DLBCL.

Micro Python Powered Smart Street Light using IOT

The proposal for a smart street lighting system is being considered. In this project, the street light system, in which lights are turned on when needed and turned off when not needed. Street lighting which is turned on when it gets dark and turned off when it gets bright, currently consume large amounts of electric energy around the world. This is the world's largest energy waste and should be changed. The smart street light system consists of an LED light, an ultrasonic sensor, a motion sensor and a short-distance communication network. The lights turn on when pedestrians and vehicles come and turn off or reduce power when there is no one. It will be convenient for pedestrians and drivers of vehicles to travel, since our smart street lamps will turn on when they come. The present status and the future prospects of our smart start light project will be reviewed. This system will aid in conservation of energy through automation.

Implementing adaptive youth-centered adolescent sexual reproductive health programming: learning from the Adolescents 360 project in Tanzania, Ethiopia, and Nigeria (2016-2020).

Adolescents 360 (A360) was a 4.5-year project working directly with young people to increase demand for, and voluntary uptake of, modern contraception among adolescent girls aged 15 to 19 years. A360 utilized human centered design (HCD) to create four adolescent sexual and reproductive health (ASRH) interventions across three countries - Smart Start in Ethiopia, Kuwa Mjanja in Tanzania, Matasa Matan Arewa (MMA) in northern Nigeria, and 9ja Girls in southern Nigeria. A360's interventions tap into girls' aspirations and position contraception as a tool that can support them in pursuing their life goals. As A360 transitioned from its first program phase into its follow-on in 2020, the project examined what it had accomplished, where it had failed, and what it had learned in the process, with the goal of contributing to the global evidence base and building on these lessons in its follow-on program. A360 draws out five key lessons in this publication. These lessons speak to 1) the value of A360's aspirational program components and the need to meaningfully support girls to pursue their life goals holistically; 2) the necessity of taking a consistent and rigorous approach to improving the enabling environment for contraceptive use to promote transformative change; 3) the need to find program and measurement approaches that respond to girls' unique patterns of sexual activity, and support contraceptive continuation; 4) the usefulness of continuous program improvement during implementation to maintain a user-centered focus and create a culture of curiosity and innovation; and 5) the tension between designing for users and beginning with program sustainability in mind from the outset. A360 continues to grow in its understanding of what it takes to support sustained, transformative, holistic change for adolescent girls and commits to openness and transparency regarding successes and failures during its next project phase.

Presidential Address: Forging a developmental science mission to improve population outcomes and eliminate disparities for young children.

Child development science has not fully realized its mission to improve population outcomes for children and eliminate disparities across race and income groups. One domain with great need but also great potential is the challenge parents face in raising a young child. A system of universal primary psychosocial care is proposed, with three components: a comprehensive infrastructure of community resources, such as North Carolina's Smart Start; financial supports for specific interventions, such as pre-kindergarten; and a way to help families identify and address family-specific needs, such as Family Connects. Empirical studies demonstrate the promise of each component for population impact and disparity elimination but also the need for continued improvement. Developmental scientists are called upon to fulfill their mission.

Smart start: It really is SMART!

Smart start: It really is SMART!

Smart Stop: A Phase II Study of Lenalidomide, Tafasitamab, Rituximab, and Acalabrutinib Alone and with Chemotherapy in Patients with Newly Diagnosed DLBCL

Smart Stop: A Phase II Study of Lenalidomide, Tafasitamab, Rituximab, and Acalabrutinib Alone and with Chemotherapy in Patients with Newly Diagnosed DLBCL

Smart Start: a feasible intervention for young children with disabilities and trauma

ABSTRACT The purpose of this study was to contribute information to service delivery gaps within the intervention literature related to the expense and inaccessibility of evidence-informed interventions for children with disabilities who have experienced maltreatment. A non-concurrent multiple baseline method was used to determine a relationship between the intervention and children’s challenging behaviors for five caregiver-child dyads. Results from visual analysis, masked visual analysis, and hierarchical linear modeling supported a statistically and clinically significant relationship between Smart Start and improved caregiver ratings of children’s challenging behaviors. The intervention was implemented with good fidelity, and all caregivers found Smart Start acceptable.

Analysis Of Test Battery For Elite Ice Hockey Players

PURPOSE: The purpose was to conduct a test battery on elite ice-hockey players to better understand the relationships between the different assessments. METHODS: Subject’s (n=41) physical characteristics were measured prior to testing session. Countermovement Jump (CMJ) height was estimated with a Bosco mat. Stationary Broad Jump (BJ) distance was measured from toes (starting line) to the closest heel. The best of 2 completed attempts was retained for both jump tests. On-ice repeated sprints’ time was measured with photo cells timing gates (TCi Smart Start, Brower Timing System, Utah, USA). Protocol consisted of 9 sprints of 40 m with 3 seconds of recovery between sprints that permitted subjects to turn around and return to the finish line which now became the starting line for the next sprint. Heart rate was measured with a heart rate (HR) monitor (RS400, Polar, FI). Local muscle oxygenation (SmO2) was measured on vastus lateralis with a muscle oxygen monitor (MOXY, Minnesota, USA). Blood lactate ([La+]) was measured with a lactate analyzer (Lactate Pro, Akray, Japan). Rated Perceived Exertion (RPE) was measured with a Borg Scale (6-20). Correlations were calculated (SPSS Ver 25) using a 2-tailed Pearson correlation analysis. Significance was set at p<0.05. Subjects characteristics are presented as means and standard deviations. SUMMARY OF RESULTS: Multiple significant (p<0.05) relationships were observed (r=-0.47-0.81). Findings show that age (r=-0.53-0.51), years of experience in resistance training (r=-0.32-0.48), weight (r=-0.33-0.47) and lean body mass (-0.38-0.46) were significantly correlated with jump and on ice sprint performance (Speed, Time, [La+] and RPE). The CMJ seems to be more important than the BJ for on ice sprint performance (r=-0.53-0.40 vs -0.19-0.28). Maximal HR is significantly correlated with fatigue index (r=0.41). The Borg scale seems to be a good tool to see if hockey players gave a maximal effort as it presents multiple significant correlations with sprint performance (r=-0.37-0.34). SmO2 was significantly correlated with [La+] (r=-0.35). CONCLUSION: Results of the present study should be utilised by ice-hockey strength and conditioning coaches to improve their testing battery. Further research should include resistance training exercises in their analysis.

Long-term effects of early childhood programs through eighth grade: Do the effects fade out or grow?

Support for policies to improve early childhood educational development and reduce disparities grew rapidly this century but recently has wavered because of findings that program effects might fade out prematurely. Two programs implemented at scale in North Carolina (Smart Start and More at Four) have been associated with academic success early in elementary school, but it is not known whether these effects fade out or are sustained in middle school. Smart Start provides state funding to support high-quality early childcare in local communities, and More at Four provides state-funded slots for a year of credentialed pre-kindergarten. Funds were allocated for each program at varying rates across counties and years. We used this variation to estimate the long-term impact of each program through eighth grade, by measuring the association between state funding allocations to each program, in each of 100 counties over each of 13 consecutive years, and later student performance. Students were matched to funding levels provided to their home county in their early childhood years and then followed through eighth grade. Analyses using county- and year-fixed-effects regression models with individual- and school-level covariates conducted on nearly 900,000 middle school students indicate significant positive impacts of funding for each program on reading and math test scores and reductions in special education placement and grade retention. These impacts do not fade out and seem instead to grow (for More at Four) as students progress through middle school. Students from economically disadvantaged backgrounds experience particularly large benefits from the More at Four Program.

Smart Start and HER for a Directed and Persistent Reinforcement Learning Exploration in Discrete Environment

Reinforcement learning (RL) solves sequential decision making problems through trial and error, through experiences can be amassed to achieve goals and increase the accumulative rewards. Exploration-exploitation dilemma is a critical challenge in reinforcement learning, particularly environments with misleading or sparse rewards which have shown difficulties to construct a suitable exploration strategy. In this paper a framework for Smart Start (SS) and Hindsight experience replay (HER) is developed to improve the performance of SS and make the exploration more directed especially in the early episodes. The framework Smart Start and Hindsight experience replay (SS+HER) was studied in discrete maze environment with sparse rewards. The results reveal that the framework doubles the rewards at the early episodes and decreases the time of the agent to reach the goal.

Development of a low-cost smart vehicle start up and tracking system using Android and Arduino

Development of a low-cost smart vehicle start up and tracking system using Android and Arduino

Get Smart: Learning and partnership with Ethiopia’s Health Extension Programme to re-envision contraceptive service delivery to young couples

Background: Adolescents 360 (A360) implements the Smart Start (SS) programme through Ethiopia’s Health Extension Programme (HEP). SS is premised on financial planning as an entry point to discuss family planning (FP) with newly married couples and central to its delivery are the health extension workers (HEW). This article evaluates the A360 experience and learning from the process evaluation implemented by Itad to understand contextual barriers and enablers from the perspective of the HEW. Methods: A purposive sampling strategy was employed whereby 27 key stakeholders were identified from Oromia, Addis Ababa and Amhara, based on exposure to the SS programme. Findings from the action research were shared with A360 through a one day sounding workshop. Results: Findings revealed that many local government and communal respondents do not view adolescent pregnancy as a problem, unless out of wedlock, and adolescent pregnancy is closely linked to early marriage. As a result, some providers, including HEWs, acknowledged that married adolescent girls were previously ‘neglected’ by them, while husbands indicated that they had not previously been included in FP counselling. Findings also revealed some challenges with SS implementation as HEWs were ‘deprioritizing’ the intervention and many HEWs had been in situ for several years and were overworked and frustrated. Against this backdrop, A360 was viewed as adding to the HEW workload. While the programme design was focused on adolescent users, there was increasing recognition that HEWs also needed to be at the centre of solution design. Conclusions: Despite challenges associated with the HEP, Ethiopia FP2020 plans to support the ‘next generation’ of HEWs, including a focus on adolescents and youth. To gain deeper insight and put the HEW at the centre of design, A360 will continue to work with the process evaluation to understand contextual barriers and enablers from the perspective of the HEW.

Smart Start: Rituximab, Lenalidomide, and Ibrutinib Alone and in Combination with Standard Chemotherapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Final Phase II Results

Smart Start: Rituximab, Lenalidomide, and Ibrutinib Alone and in Combination with Standard Chemotherapy for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Final Phase II Results

Get Smart: Learning and partnership with Ethiopia's Health Extension Programme to re-envision contraceptive service delivery to young couples.

Background: Adolescents 360 (A360) implements the Smart Start (SS) programme through Ethiopia's Health Extension Programme (HEP). SS is premised on financial planning as an entry point to discuss family planning (FP) with newly married couples and central to its delivery are the health extension workers (HEW). This article evaluates the A360 experience and learning from the process evaluation implemented by Itad to understand contextual barriers and enablers from the perspective of the HEW. Methods: A purposive sampling strategy was employed whereby 27 key stakeholders were identified from Oromia, Addis Ababa and Amhara, based on exposure to the SS programme. Findings from the action research were shared with A360 through a one day sounding workshop. Results: Findings revealed that many local government and communal respondents do not view adolescent pregnancy as a problem, unless out of wedlock, and adolescent pregnancy is closely linked to early marriage. As a result, some providers, including HEWs, acknowledged that married adolescent girls were previously 'neglected' by them, while husbands indicated that they had not previously been included in FP counselling. Findings also revealed some challenges with SS implementation as HEWs were 'deprioritizing' the intervention and many HEWs had been in situ for several years and were overworked and frustrated. Against this backdrop, A360 was viewed as adding to the HEW workload. While the programme design was focused on adolescent users, there was increasing recognition that HEWs also needed to be at the centre of solution design. Conclusions: Despite challenges associated with the HEP, Ethiopia FP2020 plans to support the 'next generation' of HEWs, including a focus on adolescents and youth. To gain deeper insight and put the HEW at the centre of design, A360 will continue to work with the process evaluation to understand contextual barriers and enablers from the perspective of the HEW.

SMART START: RITUXIMAB, LENALIDOMIDE, AND IBRUTINIB ALONE PRIOR TO COMBINATION WITH CHEMOTHERAPY FOR PATIENTS WITH NEWLY DIAGNOSED DIFFUSE LARGE B‐CELL LYMPHOMA

Background: The non-germinal center (non-GCB) subtype of Diffuse Large B-cell Lymphoma (DLBCL) is associated with inferior outcomes with standard therapies. The BTK inhibitor ibrutinib (I) and immunomodulatory agent lenalidomide (L) have promising activity in non-GCB DLBCL as single agents, and result in synthetic lethality in non-GCB DLBCL models when combined. In relapsed non-GCB DLBCL, rituximab (R), L and I result in overall response rate (ORR) of 55% (Ramchandren, ASH 2018). We conducted an investigator initiated, single-arm, open-label, phase 2 study (NCT02636322) of RLI alone and then with chemotherapy in newly diagnosed non-GCB DLBCL patients, and report the final results of the RLI lead in. Methods: Adult patients with newly diagnosed non-GCB DLBCL, determined by the Hans method, with adequate organ function and performance status were eligible. The primary objectives were to determine (1A) the ORR of two cycles of RLI as initial therapy, and (1B) the complete response rate (CRR) after 6 cycles of chemotherapy combined with RLI. All patients were treated with rituximab 375 mg/m2 IV day 1, ibrutinib 560 mg po daily, and lenalidomide 25 mg po days 1-10 of 21 day cycles for 2 cycles, followed by 6 additional cycles of RLI with chemotherapy (CHOP or EPOCH per treating MD choice). Responses were assessed with PET/CT as per the Lugano criteria. Growth factors, venous thromboembolism prophylaxis, and pneumocystis pneumonia prophylaxis were required for all patients. Results: The protocol accrued 60 patients from May 2016 – February 2019, with 52 patients evaluable for disease response (2 withdrew consent prior to restaging, 6 pending restaging prior to abstract deadline). The median age was 64 years (range: 30-83), 28% were >= 70 years, and 50% were female. Half the patients had poor risk IPI, 61% had advanced stage, and 71% had a Ki-67 of >= 80%. One patient had a fatal fungal infection (CNS aspergillosis) attributed to high dose corticosteroids for symptom control during screening and with RLI, leading to prohibition of corticosteroids during the RLI only cycles with no further fungal infections identified. The ORR for 2 cycles of RLI alone was 84.6% (n = 44), and the CRR was 38.5% (n = 20). One patient refused to proceed with the pre-planned chemotherapy after achieving a CR with 2 cycles of RLI, and remains relapse free with no additional therapy 18 months later. Preliminary results demonstrate a CRR of 100% for the full therapy (RLI for 2 cycles, RLI-chemo for 6 cycles), with updates to be presented at the meeting. Conclusions: The Smart Start trial demonstrates the chemotherapy-free combination of rituximab 375 mg/m2, ibrutinib 560 mg, and lenalidomide 25mg is highly effective in patients with newly diagnosed non-GCB DLBCL. Further studies are planned with other novel agents and with fewer cycles of chemotherapy consolidation for patients achieving a CR with RLI alone. Keywords: activated B-cell-like (ABC); BTK inhibitors; IMiDs. Disclosures: Westin, J: Consultant Advisory Role: Celgene, Janssen, Novartis, Kite, Juno, Genentech.