3MPower Evidence Café 1: Report

3MPower will generate evidence on technology use for Teacher Professional Development (TPD) in low- and middle-income countries, with a particular focus on children’s foundation numeracy skills in schools serving marginalised, low-income, rural communities. 3Mpower will study the use of numeracy TPD courses on Muktopaath - a government-led e-Learning platform used by over 400,000 teachers in Bangladesh - to answer the question “How are primary numeracy teachers using mobile learning for teacher development in rural schools and in what ways does this change learning and teaching?” 3MPower will generate evidence about the validity of every step linking teachers’ use of mobile learning to improved student learning outcomes, through at-scale mixed methods research. 3MPower includes four process evaluation studies and two quasi-experimental impact evaluation studies with 240 teachers and 3,600 learners. Qualitative methods include Participatory Ethnographic Evaluation Research (PEER) exploring rural teachers’ experiences of accessing CPD with technology and the practical application CPD to teaching and learning. Throughout the research, 3MPower will engage a broad range of national stakeholders including government policymakers, policy implementers, teacher educators, rural education officers, and rural teachers. Stakeholders will participate in an iterative series of knowledge exchange activities, beginning with co-design and continuing throughout, through a series of Evidence Cafes. to make sense of the emerging evidence, refine the research approach, and identify implications and recommendations for policy and practice. 3MPower findings will address significant gaps in global evidence on the use of technology for teacher development in marginalised schools, the role of communities of practice, and the impacts at-scale on teaching quality and learning outcomes

Diagnosed hematological malignancies in Bangladesh - a retrospective analysis of over 5000 cases from 10 specialized hospitals

Background The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that include hematological malignancies in Bangladesh. Methods This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the “French American British” classification system. Results A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n = 3468) and 30.8% females (n = 1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin’s lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over. Conclusions For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country

ALK Inhibitors-Induced M Phase Delay Contributes to the Suppression of Cell Proliferation

Anaplastic lymphoma kinase (ALK), a receptor-type tyrosine kinase, is involved in the pathogenesis of several cancers. ALK has been targeted with small molecule inhibitors for the treatment of different cancers, but absolute success remains elusive. In the present study, the effects of ALK inhibitors on M phase progression were evaluated. Crizotinib, ceritinib, and TAE684 suppressed proliferation of neuroblastoma SH-SY5Y cells in a concentration-dependent manner. At approximate IC50 concentrations, these inhibitors caused misorientation of spindles, misalignment of chromosomes and reduction in autophosphorylation. Similarly, knockdown of ALK caused M phase delay, which was rescued by re-expression of ALK. Time-lapse imaging revealed that anaphase onset was delayed. The monopolar spindle 1 (MPS1) inhibitor, AZ3146, and MAD2 knockdown led to a release from inhibitor-induced M phase delay, suggesting that spindle assembly checkpoint may be activated in ALK-inhibited cells. H2228 human lung carcinoma cells that express EML4-ALK fusion showed M phase delay in the presence of TAE684 at about IC50 concentrations. These results suggest that ALK plays a role in M phase regulation and ALK inhibition may contribute to the suppression of cell proliferation in ALK-expressing cancer cells

Patient-reported outcomes after posterior surgical stabilization for thoracolumbar junction fractures: A pilot study with combined patient-reported outcome measure methodology

Background: Thoracolumbar junction fractures (TLJFs) attract controversy for several parameters, including surgery versus conservative treatment, fusion versus stabilization, open versus percutaneous surgery, construct length, and downstream metalwork extraction. Aims and Objectives: The aim of this pilot study was to assess the effectiveness of surgical treatment in patients with burst (AO Classification Type A4) TLJFs using patient-reported outcome measures (PROMs) and evaluate and compare different PROMs in this clinical scenario. Materials and Methods: Patient records of consecutive patients who underwent posterior stabilization surgery for TLJFs were retrospectively reviewed. Data were collected on demographics, medical and social history, neurological examination, and postoperative complications. Telephone interviews and a combined PROM methodology (Numerical Rating Scale [NRS], EuroQol [EQ]-5D-5L, and Oswestry Disability Index [ODI]) were utilized to assess the effectiveness of intervention. Descriptive statistics were used to analyze exposure variables and outcome measures. Spearman's rank correlation was used for the outcome measures. Results: Thirteen patients were included. The mean age was 42 ± 16 years; the male: female ratio was 8:5; the mean follow-up was 18.9 ± 6.4 months. The mean NRS score was 3.3 ± 2.5, in line with a median score of 2 (2) on EQ-5D-5L pain/discomfort scale. Statistically significant correlations were found between several PROMs: pain-EQ-5D-5L and NRS (rs = 0.8, P = 0.002), pain-EQ-5D-5L and ODI (rs = 0.8, P = 0.001), usual anxiety/depression-EQ-5D-5L, and ODI (rs = 0.7, P = 0.008). Conclusion: A combined PROM methodology showed supportive evidence for safety and efficacy in the surgical stabilization of burst TLJFs. This alleviated significant pain and prevented neurological deficit and major disability. The preliminary widespread correlation between these PROMs supports further larger studies of their combined use in clinical practice, to measure the outcomes of spine trauma patients

Inhibitors of the VEGF Receptor Suppress HeLa S3 Cell Proliferation via Misalignment of Chromosomes and Rotation of the Mitotic Spindle, Causing a Delay in M-Phase Progression

Cell division is the process by which replicated chromosomes are separated into two daughter cells. Although regulation of M phase has been extensively investigated, not all regulating factors have been identified. Over the course of our research, small molecules were screened to identify those that regulate M phase. In the present study, the vascular endothelial growth factor receptor (VEGFR) inhibitors A83-01, SU4312, and Ki8751 were examined to determine their effects on M phase. Treatment of HeLa S3 cells with these inhibitors suppressed cell proliferation in a concentration-dependent manner, and also suppressed Akt phosphorylation at Ser473, a marker of Akt activation. Interestingly, cleaved caspase-3 was detected in Adriamycin-treated cells but not in inhibitor-treated cells, suggesting that these inhibitors do not suppress cell proliferation by causing apoptosis. A cell cycle synchronization experiment showed that these inhibitors delayed M phase progression, whereas immunofluorescence staining and time-lapse imaging revealed that the M phase delay was accompanied by misalignment of chromosomes and rotation of the mitotic spindle. Treatment with the Mps1 inhibitor AZ3146 prevented the SU4312-induced M phase delay. In conclusion, the VEGFR inhibitors investigated here suppress cell proliferation by spindle assembly checkpoint-induced M phase delay, via misalignment of chromosomes and rotation of the mitotic spindle