A Positive Deviance Inquiry on Effective Communicative Practices of Rural Indian Women Entrepreneurs

Why do some rural women entrepreneurs in India succeed despite low levels of literacy, staggering household responsibility, unsupportive social structures, and oppressive cultural practices? The present article employed the Positive Deviance (PD) approach to identify the effective communication practices of rural women entrepreneurs in Uttar Pradesh, India, who succeed against overwhelming odds. Starting with an initial pool of 21,024 rural Indian women who received microloans for income-generation, and through several sieving rounds of focus group conversations with over 1,100 women, 24 PD women entrepreneurs were identified. A variety of participatory processes and liberating structures—Discovery and Action Dialogues (DADs), improvisational theater and prototyping, personal storytelling, and card-sorting games—were employed to identify the highly uncommon practices of PD entrepreneurs. These uncommon practices included micro interpersonal behaviours to connect deeply with customers, personalised branding of their businesses, daily diary jottings to monitor sales and profits, reframing value propositions to persuade customers, and others.publishedVersio

Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer.

PURPOSE: Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. METHODS: Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORR RESULTS: At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORR CONCLUSION: Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile

Quality of life assessment in children and their caregivers suffering from allergic rhinitis and/or asthma

INTRODUCTION: Asthma and allergic rhinitis (AR) are among the most prevalent diseases worldwide and they frequently persist throughout the life. These have significant effect on physical, financial, and mental wellbeing of patients and caregivers. There have been few attempts previously, assessing the quality of life (QOL) in affected families suffering from these diseases. However, the data from developing countries are scarce. QOL assessment in children and caregivers of patients suffering can help in symptomatic management and provide inputs for the better utilization of resources to achieve optimal treatment. MATERIALS AND METHODS: Patient and caregiver QOLs were ascertained using Mini Pediatric Asthma QOL Questionnaire and Pediatric Asthma Caregiver's QOL Questionnaire, respectively, in the study and correlated with disease severity and chronicity using the parametric and nonparametric statistical tools. RESULTS: There were 246 pairs of children diagnosed with asthma and/or AR and their caregivers attending the pediatric allergy and asthma clinic. Symptom score, emotional domain, and activity limitation in children did not validate a statistically significant difference in QOL in the various grades of AR/asthma/AR with asthma (P = 0.632) (P = 0.772) (P = 0.496) (P = 0.918) (P = 0.384) and (P = 0.561), respectively. In addition, there was no significant correlation between the severity of asthma and caregiver emotional disturbance (P = 0.594) or caregiver activity limitation (P = 0.446). CONCLUSIONS: QOL in children and caregivers where children are suffering from either AR or asthma, or both has not shown any significant difference as per the disease severity or chronicity in various domains. There was no significant difference in QOL noted as per the change in age group, gender of patients, or education status of caregivers

Systematic Analysis of Genetic and Pathway Determinants of Eribulin Sensitivity across 100 Human Cancer Cell Lines from the Cancer Cell Line Encyclopedia (CCLE)

Eribulin, a natural product-based microtubule targeting agent with cytotoxic and noncytotoxic mechanisms, is FDA approved for certain patients with advanced breast cancer and liposarcoma. To investigate the feasibility of developing drug-specific predictive biomarkers, we quantified antiproliferative activities of eribulin versus paclitaxel and vinorelbine against 100 human cancer cell lines from the Cancer Cell Line Encyclopedia, and correlated results with publicly available databases to identify genes and pathways associated with eribulin response, either uniquely or shared with paclitaxel or vinorelbine. Mean expression ratios of 11,985 genes between the most and least sensitive cell line quartiles were sorted by p-values and drug overlaps, yielding 52, 29 and 80 genes uniquely associated with eribulin, paclitaxel and vinorelbine, respectively. Further restriction to minimum 2-fold ratios followed by reintroducing data from the middle two quartiles identified 9 and 13 drug-specific unique fingerprint genes for eribulin and vinorelbine, respectively; surprisingly, no gene met all criteria for paclitaxel. Interactome and Reactome pathway analyses showed that unique fingerprint genes of both drugs were primarily associated with cellular signaling, not microtubule-related pathways, although considerable differences existed in individual pathways identified. Finally, four-gene (C5ORF38, DAAM1, IRX2, CD70) and five-gene (EPHA2, NGEF, SEPTIN10, TRIP10, VSIG10) multivariate regression models for eribulin and vinorelbine showed high statistical correlation with drug-specific responses across the 100 cell lines and accurately calculated predicted mean IC50s for the most and least sensitive cell line quartiles as surrogates for responders and nonresponders, respectively. Collectively, these results provide a foundation for developing drug-specific predictive biomarkers for eribulin and vinorelbine

A Positive Deviance Inquiry on Effective Communicative Practices of Rural Indian Women Entrepreneurs

Why do some rural women entrepreneurs in India succeed despite low levels of literacy, staggering household responsibility, unsupportive social structures, and oppressive cultural practices? The present article employed the Positive Deviance (PD) approach to identify the effective communication practices of rural women entrepreneurs in Uttar Pradesh, India, who succeed against overwhelming odds. Starting with an initial pool of 21,024 rural Indian women who received microloans for income-generation, and through several sieving rounds of focus group conversations with over 1,100 women, 24 PD women entrepreneurs were identified. A variety of participatory processes and liberating structures—Discovery and Action Dialogues (DADs), improvisational theater and prototyping, personal storytelling, and card-sorting games—were employed to identify the highly uncommon practices of PD entrepreneurs. These uncommon practices included micro interpersonal behaviours to connect deeply with customers, personalised branding of their businesses, daily diary jottings to monitor sales and profits, reframing value propositions to persuade customers, and others

First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE2-receptor E-type 4 (EP4), in patients with advanced cancers

Background E7046 is a highly selective, small-molecule antagonist of the E-type prostanoid receptor 4 (EP4) for prostaglandin E2, an immunosuppressive mediator of the tumor immune microenvironment. This first-in-human phase 1 study assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD) and recommended phase 2 dose of E7046.Methods This first-in-human study enrolled 30 patients with advanced tumors of cancer types associated with high levels of myeloid infiltrates. E7046 was administered orally once-daily in sequential escalating dose cohorts (125, 250, 500, and 750 mg) with ≥6 patients per cohort. Tumor assessments were performed every 6 weeks. Paired tumor biopsies and blood samples, before and on treatment, were collected for pharmacokinetic and pharmacodynamic characterization of the treatment.Results No dose-limiting toxicities were observed, and the MTD was not reached. E7046 had an elimination half-life (t1/2) of 12 hours, and drug exposure increased dose-dependently from 125 to 500 mg. Target modulation by E7046 was supported by changes in genes downstream of EP4 with concurrent enhanced antitumoral immune responses. A best response of stable disease (per irRECIST) was reported in 23% of patients treated with E7046 (n=30) (125 mg: n=2; 250 mg: n=2; 750 mg: n=3). Over half (4/7) of the patients with stable disease had treatment duration of 18 weeks or more, and three patients (3/15; 20%) achieved metabolic responses.Conclusions In this first-in-human study, E7046 administered orally once daily demonstrated manageable tolerability, immunomodulatory effects, and a best response of stable disease (≥18 weeks) in several heavily pretreated patients with advanced malignancies. The 250 and 500 mg doses are proposed for further development in the combination setting.Trial registration number NCT02540291