Prognostic value of low-level MRD in adult acute lymphoblastic leukemia detected by low- and high-throughput methods

Persistence of minimal residual disease (MRD) after induction/consolidation therapy in acute lymphoblastic leukemia is the leading cause of relapse. The GMALL 07/2003 study used MRD detection by RQ-PCR of clonal immune gene rearrangements with 1x10-4 as discriminating cut-off: levels ≥1x10-4 define molecular failure and MRD-negativity with an assay sensitivity of at least 1x10-4 defines complete molecular response. The clinical relevance of MRD results not fitting in these categories is unclear and termed "molecular not evaluable" (MolNE) towards MRD-based treatment decisions. Within the GMALL 07/03 study, 1019 consecutive bone marrow samples after first consolidation were evaluated for MRD. Patients with complete molecular response had significantly better outcome (five-year overall survival, 5y-OS=85±2%, n=603; five-year disease-free survival, 5y-DFS=73±2%, n=599) compared to patients with molecular failure 5y-OS=40±3%, n=238; 5y-DFS=29±3%, n=208), with MolNE patients in-between (5y-OS=66±4%, 5y-DFS=52±4%, n=178). Of MolNE samples re-analyzed using next-generation sequencing (NGS), patients with undetectable NGS-MRD (n=44; 5y-OS=88±5%, 5y-DFS=70±7%) had significantly better outcome than those with positive NGS-MRD (n=42; 5y-OS=37±8%, 5y-DFS=33±8%). MolNE MRD results are not just borderline values with questionable relevance, but form an intermediate risk group, assignment of which can be further improved by NGS.

The effectiveness of cooperative learning in an online learning environment through a comparison of group and individual marks

Cooperative learning is a learning approach where students are placed into groups to work towards a common goal. Prominent learning theories state that students learn best when they construct their own knowledge in an active learning environment where they can socially interact and collaborate to reach a desired outcome. Cooperative learning provides such a learning environment and has the benefit of creating an active learning community where students can develop transferable skills. Online learning has grown steadily over the past few years, but even more so during the COVID-19 pandemic where tertiary institutions’ only option was to continue with their academic programmes remotely through online learning platforms. With online learning becoming a prominent feature, calls are made to educators to examine teamwork and cooperation and how this can be facilitated in an online setting. In the online learning environment it is important to promote collaborative engagement to counteract feelings of isolation and encourage deep learning to occur. In the second accounting module of a fully online degree, students are exposed to a case study, with a group assignment as well as an individual assignment component. The aim of this study is to determine whether group work can be effective by comparing group marks to individual marks. The study further elicits the perceptions of the online students to determine their views regarding group work, the process that they followed to collaborate, as well as their perceptions regarding skills developed using the case study approach. A mixed-methods approach was followed, using the group and individual marks and combining those with the survey analysis and qualitative data analysis from a questionnaire. It was found that the average mark for the group assignment is higher than for the individual assignment and that the individual assignment shows a greater spread of marks. For male students who prefer to work within a group, their group mark is higher than their individual mark, showing that they did receive the benefit from working within a group. Students agreed that group work is a valuable skill that will be needed in their future careers and that the group work enabled them to learn from their group members. Working in a group requires a lot of time and effort, but students will elicit the strategies required to gain the necessary knowledge and solve the problem posed to them. Students mentioned several other skills that they perceived were developed through their exposure to the group work; skills such as communicating well, listening with intent, negotiating a point of view, researching alternatives and solving a problem were all enhanced through their participation in their groups. The results suggest that group work can be effectively achieved and managed in an online setting, albeit with special care around the logistical and technological challenges that can be experienced. Cooperative learning in the form of group work is not always welcomed by all students, but it will enable them to navigate their future careers where teamwork will be a prominent feature.

Prevention of Intra-Abdominal Adhesions Using the Combination of Mediclore® and a Statin

<b><i>Purpose:</i></b> This study investigated the antiadhesive effects of Mediclore®, rosuvastatin, and a combination of Mediclore and rosuvastatin in a rat adhesion model. <b><i>Methods:</i></b> The adhesion models (a total of 58 adult male rats) were divided into 4 groups. The control group (group C) received no special materials except for a saline. The experimental groups were treated with 5 mL of Mediclore (group M), rosuvastatin (group R), or rosuvastatin and Mediclore (group RM), and these materials were intraperitoneally placed under the incision. At postoperative day 14, the rats underwent re-laparotomy and adhesiolysis. Three investigators blinded to group assignment scored the extent of adhesion formation, the numbers of remote adhesions, and the extent of acute/chronic inflammation, fibrosis, edema, and congestion on resected specimens via histologic examination. <b><i>Results:</i></b> The macroscopic adhesion score in group RM (7.27 ± 3.51) was significantly lower than those in groups C (13.36 ± 2.24) and R (11.71 ± 1.98); group M (9.13 ± 4.09) had a significantly lower adhesion score than group C. The number of remote adhesions was significantly lower in groups R and RM than in group C. The acute inflammation score, chronic inflammation score, and fibrosis score in group RM; the acute inflammation score in group R; and the fibrosis score in group M were significantly lower than those in group C. <b><i>Conclusion:</i></b> The intraperitoneal application of Mediclore and a combination of Mediclore and rosuvastatin effectively reduced postoperative adhesions.

Abstract 14213: Injury Characteristics of Chest Compressions in a Swine Model of Infant Asphyxial Cardiac Arrest Using Either 1.5 inch or 1/3 Anterior-Posterior Diameter Depth Targets

Background: Current AHA guidelines for the delivery of chest compressions (CC) for infants and children are largely consensus based, and recommended depths of 1.5 inches or 1/3 anterior-posterior chest diameter (APD). It is unclear whether these have equal potential for injury. Objectives: We sought to examine and compare injury characteristics of CC delivered at 1.5 inches or 1/3 APD in an infant-sized model of asphyxial OHCA. Methods: Thirty-six juvenile swine weighing 10.6kg +/- 0.84 (approximating the 50 th percentile for a 12-month-old) were anesthetized, paralyzed, intubated, and mechanically ventilated (FiO2 21%). APD was measured and by two investigators via a sliding T-square. After instrumentation, the endotracheal tube was manually occluded to induce asphyxia, and occlusion was maintained for 9 minutes. Animals with an organized rhythm after 8 minutes 45 seconds of asphyxia received a single, 3-second transthoracic shock to induce ventricular fibrillation. At 9 minutes, each was then randomized to receive CC with a depth of 1.5 inches (Group 1) or 1/3 APD (Group 2), both with a rate of 100 per minute. ALS drugs were administered after 13 minutes, followed by initial defibrillation attempt at 14 minutes. Resuscitation continued until return of spontaneous circulation (ROSC) or 20 minutes of failed resuscitation. Survivors were sacrificed with KCl after 20 minutes of observation. Veterinary staff blinded to group assignment conducted necropsies to assess lung injury, rib fracture, hemothorax, airway bleeding, great vessel dissection, and heart/liver/spleen contusion. Characteristics were compared via Chi-Squared test or Mann-Whitney U-test using an alpha = 0.05. Results: Group 1 had n=18 and Group 2 had n=18 animals. Mean (SD) APD overall was 5.58 (0.22) inches, yielding a mean 1/3 APD depth of 1.86 inches. APD did not differ between groups. ROSC rates did not differ between groups (Group 1: 66.7% vs Group 2: 83.33%; p = 0.248. No injury characteristics differed significantly between groups. Airway bleeding rates were noteworthy though not different between groups (Group 1: 18.8% vs Group 2: 42.1%; p = 0.219). Conclusions: In a swine model of infant OHCA and resuscitation, both CC depth strategies had similar injury characteristics.

Effects of personalized invitation letters on research participation among general practitioners: a randomized trial

Background Participation of general practitioners is crucial for health care studies. However, recruiting them is an ongoing challenge and participation rates of general practitioners around the globe are often low. One feasible and cost-efficient approach to potentially enhance participation rates among general practitioners are personalized invitation letters, since they may increase one’s attention to and appreciation of a study. Still, evidence whether this method actually affects participation is scarce and ambiguous in relation to physicians. Methods We undertook a randomized trial in a sample of general practitioners from three German states in the context of a large, observational study on physicians’ coordination and uptake of recommended cardiovascular ambulatory care. An intervention group (n = 757 general practitioners) received a personalized invitation to participate in the observational study, the control group (n = 754 general practitioners) received a generic invitation. Both groups were blinded to group assignment. Eventual participation rates as well as the number and types of responses overall were compared between arms. Besides the main intervention, sociodemographic and geographical context factors were considered as well. Results The overall participation rate among physicians was 2.6% (2.8% in the intervention group and 2.4% in the control group). No statistically significant effect of personalization on participation of physicians was found (relative risk to participate when receiving a personalized invitation of 1.17 [95%-CI: 0.62, 2.21]). However, the number of responses to the invitation varied significantly between the geographical regions. Conclusions Personalization of first written contact alone did not improve research participation among general practitioners, which was overall very low. Trial registration The study in which the trial was embedded has been registered prospectively at the German Clinical Trials Register (DRKS) under registration number DRKS00019219.

Innovative Approach in Teaching Graph Theory

Learners tend to get bored in learning Graph Theory and this results them getting low performance. Thus, this study was conducted to find empirical evidence on the attempt of having an innovative approach in teaching graph theory through the utilization of games to college students. This study was a pre - experimental research in which pretest-post test was used. Moreover, it also utilized a qualitative research method to find out learners’ feedback on the approach. The learners have their permanent group assignment and games were utilized for every topic. Pretest and post test were administered. The test scores were recorded, tabulated, analyzed and interpreted. Data were analyzed using paired-sample t-test. Results revealed a highly significant difference from pretest to post test of the students. Additionally, students give positive feedback on the attempt of this innovative approach in teaching graph theory. Such that, the following are some of their response: “I am excited to study graph theory because of games”, “I look forward to games every meeting”, etc. Therefore, college students exposed to games while learning shows very high knowledge in Graph Theory.

Impact of Spirulina corn soy blend on Iron deficient children aged 6–23 months in Ndhiwa Sub-County Kenya: a randomized controlled trial

Background Iron deficiency anemia (IDA) remains high in Kenya despite interventions. Twenty-seven percent of children aged 6 months-14 years are anemic, with low iron intake (7%) among children aged 6–23 months. Standard food interventions involve a corn soy blend (CSB), which is limited in micronutrients, and fortifiers are not accessible locally. Moreover, the use of spirulina as a strategy for mitigating IDA has not been adequately documented. This study compared the impact of a spirulina corn soy blend (SCSB) on IDA among children aged 6–23 months. Methods A total of 240 children with IDA were randomly assigned to study groups at a ratio of 1:1:1 through lotteries, and caregivers and research assistants were blinded to group assignment. Dry-take-home SCSB, CSB and placebo flour (1.7 kg) was given to caregivers to prepare porridges using a flour water ratio of 1:4, producing 600 ml–700 ml of porridge to feed children 200 ml of porridge three times a day for 6 months. Impact was assessed as plasma hematocrit at baseline and after the study. Blood drawing, preparation and analysis were performed in accordance with approved procedures by the EthicsResearchCommittee. Monthly follow-up and data collection on dietary intake, anthropometry, morbidity and infant feeding practices were performed using questionnaires. Relative risk, magnitude of change and log-rank tests were used to compare the impact of the intervention, and significant differences were determined at P < 0.05. Results The survival probabilities for children consuming SCSB were significantly higher than those consuming CSB (log-rank-X2 = 0.978; CI: 0.954–1.033, P = 0.001) and the placebo (log-rankX2 = 0.971; CI: 0.943–0.984, P = 0.0001). Children consuming SCSB had a mean recovery time of 8 days (CI: 7–12 days) compared to those consuming CSB (19 days; CI: 20–23 days) and placebo (33 days; CI: 3 1–35 days). The recovery rate was 15.4 per 100 persons per day for children who consumed SCSB as opposed to 4.6 and 1.8 per 100 persons per day for those who consumed CSB and the placebo, respectively. Conclusion Management of IDA with SCSB compared to CSB and the placebo led to faster reversal and large numbers of recoveries from IDA. The recovery rates were above the World Health Organizations (WHO) minimums standards for food interventions. Efforts to realize high and faster recoveries from IDA should be heightened by fortifying CSB with spirulina powder.

Differentiating Between Us & Them: Reduced In-Group Bias as a Novel Mechanism Linking Childhood Violence Exposure with Internalizing Psychopathology

Strong in-group bonds may promote mental health across development. Violence exposure influences social information processing biases and may also relate to social categorization processes. We examined associations of violence exposure with psychopathology and behavioral and neural indices of implicit and explicit in-group bias after minimal group assignment in children followed longitudinally across three time points from ages 5 to 10 years old (n = 101). In a pre-registered analysis, violence exposure was associated with lower implicit in-group bias, which in turn was associated prospectively with higher internalizing symptoms and mediated the longitudinal association between violence exposure and internalizing symptoms. Violence-exposed children did not exhibit the negative functional coupling between the left vmPFC and left amygdala when classifying in-group vs. out-group members that was observed in children without violence exposure. Reduced implicit bias for one’s in-group may represent a novel mechanism linking violence exposure with the development of internalizing symptoms.

Developmental Trajectories of Justice System-Involved Friendship Proportion: Relevance for Predicting Continued Offending Risk in Emerging Adulthood

There is limited research which has examined the developmental nature of friendships and their relevance for offending. This study examined heterogeneity in the development of justice system-involved friendship proportionality and its relevance for predicting offending continuity in emerging adulthood. Having a greater proportion of such peers within a friendship collective as individuals exit adolescence may lead to continued risk of offending in adulthood. The Pathways to Desistance data were used in analyses. Group-based trajectory modeling was used to identify developmental patterns of justice system-involved friendship proportionality during adolescence and emerging adulthood. Logistic regression was used to assess the relevance of trajectory group assignment for predicting offending risk in emerging adulthood. Findings indicated that a six-group trajectory model best fit the data. All other trajectory groups in the model indicated a lower risk of offending in emerging adulthood than the High Chronic justice system-involved friendship proportionality group. Sensitivity analyses indicated that separation from criminal peers following adolescence may be a more conservative predictor of offending risk in emerging adulthood.

Locating Organizations and Their Methods in Registrations of Clinical Migraine Trials: Analysis of ClinicalTrials.gov

Background and Objective:ClinicalTrials.gov is a centralized venue for monitoring clinical research and allows access to information on publicly and privately funded studies. To better recognize influential institutions in the field of headache, we identified major organizations conducting clinical trials in migraine research. Furthermore, we examined the frequency of different study designs.Methods: Utilizing the ClinicalTrials.gov application programming interface, we extracted studies including individuals with migraine from February 29, 2000, to July 28, 2020, for the following: (1) host organization, (2) study type, (3) primary purpose, (4) intervention model, and (5) allocation.Results: We included 921 entries encompassing 423 organizations. Thirty-two organizations produced ≥5 entries each and 40.0% of all entries. Most, 86%, were interventional studies while 13.6% were observational studies. The most common study design had a randomized allocation of participants. The most frequent primary purpose was treatment (62.4%) followed by prevention (13.0%). There were 56.9% parallel assignment models, 15.2% single group assignment models, and 12.4% crossover assignment models.Conclusion: A minority of organizations contribute to a significant number of registrations of clinical migraine trials, suggesting that clinical research in migraine is oligarchic. The most common study is interventional and randomized, with parallel assignment of participants with treatment as the primary purpose. This likely reflects the need to evaluate novel putative pharmacological medications.