Internal Review Boards Research Articles

Ending Tobacco Use Through Interactive Tailored Messaging for Cambodian People With HIV (Project EndIT): Protocol for a Randomized Controlled Trial.

The prevalence of smoking remains high in many low- and middle-income countries (LMICs), including the Southeast Asian nation of Cambodia. Smoking is especially hazardous for people with HIV. In Cambodia, approximately 43%-65% of men with HIV and 3%-5% of women with HIV smoke cigarettes. Thus, there is a critical need for cost-effective smoking cessation interventions for Cambodian people with HIV. This paper describes the design, methods, and data analysis plans for a randomized controlled trial assessing the efficacy of a theory-based mobile health smoking cessation intervention in Cambodian people with HIV. This 2-group randomized controlled trial compares the efficacy of a mobile health-based automated messaging (AM) intervention versus standard care (SC) in facilitating smoking cessation among Cambodian people with HIV. Cambodian people with HIV who currently smoke and are receiving antiretroviral treatment (target, N=800) will be randomized to (1) SC or (2) the AM intervention. SC participants will receive brief advice to quit smoking, written self-help materials, nicotine patches, and will complete weekly app-delivered dietary assessments for 26 weeks. AM participants will receive all SC components (but will complete smoking-related weekly assessments instead of dietary assessments), in addition to a fully automated tailored messaging program driven by the weekly assessments to facilitate smoking cessation. In the Phase-Based Model of smoking cessation, the cessation process is partitioned into 4 phases: motivation, preparation (precessation), cessation (quit date to 2 weeks post quit), and maintenance (up to 6 months post quit). Our AM program targets processes within these phases, including increasing motivation to quit, enhancing self-efficacy, obtaining social support, skills to cope with nicotine withdrawal symptoms and stress, and skills to maintain abstinence. All participants will complete baseline and 3-, 6-, and 12-month in-person follow-up assessments. The primary outcome is biochemically confirmed abstinence at 12 months, with 3- and 6-month abstinence as secondary outcomes. Potential mediators and moderators underlying treatment effects will be explored, and cost-effectiveness will be assessed. This study was approved by all relevant domestic and international institutional and ethical review boards. Participant recruitment commenced in January 2023. Data collection is expected to conclude by the end of 2025. By demonstrating the greater efficacy and cost-effectiveness of AM relative to SC, this study has the potential to transform HIV care in Cambodia and prevent tobacco-related diseases. Furthermore, it may be adapted for use in other Cambodian populations and in other low- and middle-income countries. Ultimately, the AM approach to smoking cessation could greatly improve public health in the developing world and beyond. ClinicalTrials.gov NCT05746442; https://clinicaltrials.gov/ct2/show/NCT05746442. PRR1-10.2196/48923.

Understanding Internal Review Boards and Their Role in Biophysics Education

Understanding Internal Review Boards and Their Role in Biophysics Education

Narrative Medicine and Service Learning for Medical Students Working with Persons Living with Cancer in Qatar

Objective: The study reports on medical student learning outcomes from a cancer survivorship narrative medicine service-learning project in Doha, State of Qatar. Methodology: From 2014-2017 students at Weill Cornell Medical College in Qatar in collaboration with persons living with cancer wrote stories of the patients’ cancer journeys published in a dual language Arabic / English book entitled قصة الامل (Story of Hope). The stories examined the socioeconomic, psychosocial, and familial impact of acute and chronic disease from the patients’ perspective. The Story of Hope is used throughout Qatar in peer-peer patient education groups. The research was approved for human subjects research by the Internal Review Boards of Weill Cornell Medicine-Qatar and Hamad Medical Corporation in 2014 and 2016. A convenience sample of 9 medical and premedical students participated in semi-structured taped audio interviews and filled out a questionnaire with free response and 5-point Likert Scale items (mixed methods research). Grounded Theory methods (Glaser & Strauss) were used to establish nine themes in the transcribed interview data, and themes were correlated with the questionnaire data. Results: On average, the student participants in the study only had previous encounters with cancer patients of less than 1 hour. The project represented the first one-on-one meeting with a cancer patient for 80.0% of the students. Most students agreed (20.0%=strongly agreed, with 60.0%=agreed) that their encounters with patients changed their perspective on all aspects of cancer. The students unanimously agreed (80.0%=strongly agreed, and 20.0% =agreed) that service learning should be formally integrated into medical education. Some of the key themes from the interviews included: 1. Cancer Stigma: “M9: “as long as there is a strong stereotype against cancer, there is a big fear from the society about cancer. So, I don’t see how people would be willing to actually volunteer to go out of their daily routine and do a checkup for cancer.” 2. Delivering Diagnosis: “M3: I will spend a lot of time, I mean maybe an equivalent amount of time thinking about how to find a way to break this news down to people, as opposed to spending a lot of time discovering what treatment plans, I mean obviously that is very important…. on how to actually introduce this new change.” 3. Family Dynamics in Cancer: “M8: ...and family support is important and even when we deal with a patient as a physician, we should not deal with the patient himself, we should deal with the whole group, like the patient, the sister, the mother, brother….I have to orchestrate how everyone can help.” Conclusions: The study provides proof of concept for the teaching of narrative medicine in a service-learning format in medical education in a high-income but developing Middle Eastern country. Positive effects in student learning were observed, as well as improvements in the psychosocial functioning of persons living with cancer. The research additionally provides evidence for the value of incorporating the patient perspective on disease into health training to teach human factors in disease and social determinants of health.

216 An Example for Establishing a Clinically Translational Innovation Lab at a University Setting

OBJECTIVES/GOALS: This poster shares a case study on how a group at The Johns Hopkins University formed a translational lab missioned to reinvent currently existing treatments for acute spinal cord injuries, implanting in humans within a five-year window. The poster showcases how a project funded by the Defense Advanced Research Projects Agency has been implemented. METHODS/STUDY POPULATION: The translational team; Holistic Electrical; ultrasonic and Physiological Interventions Unburdening those with Spinal cord injury• (HEPIUS) Lab is composed of many parts as listed below: neurosurgeons; engineers; radiologists; public health specialists; statisticians; patient advocates; ethicists; sonographers; researchers; academic collaborators; and specialized industry partners. Sometimes physically separated; the team has videoconferencing carts across locations to stay connected at every step in the process. The lab facilities were organized with several key facets in mind: research and development (R&D); prototyping; fabrication; verification; and validation (V&V); animal model testing; cadaveric testing accessibility; mock operating room for simulations; and collaboration hubs. RESULTS/ANTICIPATED RESULTS: Due to communications with the US Food and Drug Administration (FDA), DARPA, patient advocates, ethicists, internal review boards, and other bodies, the team has a clear path towards clinical translation. The team has the following stages in progress or scheduled: manufacturing devices, benchtop testing, rat and pig models, biocompatibility testing, cadaveric testing, and clinical use. The lab space was designed to achieve these core functions. For rapid, in-house manufacturing, the lab has unique capabilities including 3D metal printing. For experiments, industry collaborations and equipment acquisitions enable the highest quality research. These technologies are assembled into diagnostic, therapeutic, testing, and manufacturing hubs to drive real change in the lives of many; the patient comes first. DISCUSSION/SIGNIFICANCE: This laboratory, team, and system of operation is aimed to enable novel practices for the clinical translation of spinal cord medical solutions. For researchers interested in launching their own translational work, this poster may serve as a reference, example, and inspiration for similar hopeful university-centered hubs.

Mental health in time of pandemics: Study protocol to incorporate risk and protective factors contributing to psychological stress among portuguese and swiss higher education students

IntroductionThe ongoing COVID-19 pandemic is inducing fear, and a timely understanding of mental health status is urgently needed for society. Previous research has revealed a profound and wide range of psychosocial impacts on people at the individual, community, and international levels. On an individual level, people are likely to experience fear of falling sick or dying themselves, feelings of helplessness, and stigma. Currently, there is little understanding of mental well-being assessment under scenarios of pandemics that oblige to social isolation and quarantine.ObjectivesThis study aims to: a) establish the prevalence of psychiatric symptoms; b) identify risk and protective factors contributing to psychological stress; and c) identify coping strategies to promote better adjustment during and after the pandemic crisis.MethodsWe will adopt a mixed-method approach, firstly with a cross-sectional survey design (in both Portugal and Swiss context) to assess the higher education student’s psychosocial response during and after the pandemic, by using an anonymous online questionnaire. In a 2nd phase, and in order to gain more insight into the psychological stress faced by the students as a result of pandemic, a qualitative approach was chosen, focusing on the experiences of the participants.ResultsThis study has received ethical approval from both international and local institutional review boards. Data collection will start in November 2020 and will be completed at February 2021.ConclusionsThe findings of this study will provide important data to assist government agencies and healthcare professionals in safeguarding the psychosocial wellbeing of the community in the face of COVID-19 outbreak expansion.

Dihydropyrimidinase Like 2 Promotes Bladder Cancer Progression via Pyruvate Kinase M2-Induced Aerobic Glycolysis and Epithelial–Mesenchymal Transition

Background: Aerobic glycolysis and epidermal–mesenchymal transition (EMT) play key roles in the development of bladder cancer. This study aimed to investigate the function and the underlying mechanism of dihydropyrimidinase like 2 (DPYSL2) in bladder cancer progression. Methods: The expression pattern of DPYSL2 in bladder cancer and the correlation of DPYSL2 expression with clinicopathological characteristics of bladder cancer patients were analyzed using the data from different databases and tissue microarray. Gain- and loss-of-function assays were performed to explore the role of DPYSL2 in bladder cancer progression in vitro and in mice. Proteomic analysis was performed to identify the interacting partner of DPYSL2 in bladder cancer cells. Findings: The results showed that DPYSL2 expression was upregulated in bladder cancer tissue compared with adjacent normal bladder tissue and in more aggressive cancer stages compared with lower stages. DPYSL2 promoted malignant behavior of bladder cancer cells in vitro, as well as tumor growth and distant metastasis in mice. Mechanistically, DPYSL2 interacted with pyruvate kinase M2 (PKM2) and promoted the conversion of PKM2 tetramers to PKM2 dimers. Knockdown of PKM2 completely blocked DPYSL2-induced enhancement of the malignant behavior, glucose uptake, lactic acid production, and epithelial-mesenchymal transition in bladder cancer cells. Funding Statement: The present study was financially supported by the Natural Science Foundation of Guangdong Province (grant no. 2018A0303130327) and The Third Affiliated Hospital of Guangzhou Medical University (grant no. 2018Q10). Declaration of Interests: The authors declare no competing interests in this study. Ethics Approval Statement: Each patient provided written informed consent before sample collection. This study was approved by the Internal Review and Ethics Boards at the Cancer Center of Guangzhou Medical University. All animal experiments were conducted according to the Principles of Laboratory Animal Care (National Society for Medical Research). These experiments were approved by the Internal Research Ethics Board at the Third Affiliated Hospital of Guangzhou Medical University.

Bridging the Gap Between Ethics and Practice

This article attempts to bridge the gap between widely discussed ethical principles of Human-centered AI (HCAI) and practical steps for effective governance. Since HCAI systems are developed and implemented in multiple organizational structures, I propose 15 recommendations at three levels of governance: team, organization, and industry. The recommendations are intended to increase the reliability, safety, and trustworthiness of HCAI systems: (1) reliable systems based on sound software engineering practices, (2) safety culture through business management strategies, and (3) trustworthy certification by independent oversight. Software engineering practices within teams include audit trails to enable analysis of failures, software engineering workflows, verification and validation testing, bias testing to enhance fairness, and explainable user interfaces. The safety culture within organizations comes from management strategies that include leadership commitment to safety, hiring and training oriented to safety, extensive reporting of failures and near misses, internal review boards for problems and future plans, and alignment with industry standard practices. The trustworthiness certification comes from industry-wide efforts that include government interventions and regulation, accounting firms conducting external audits, insurance companies compensating for failures, non-governmental and civil society organizations advancing design principles, and professional organizations and research institutes developing standards, policies, and novel ideas. The larger goal of effective governance is to limit the dangers and increase the benefits of HCAI to individuals, organizations, and society.

A Novel Predictive Model of Diabetic Macular Edema Based on Plasma Cytokines via Machine Learning Algorithms

Objective: The study aimed to investigate the change of plasma cytokines and to build a prediction model for diabetic macular edema (DME) in type 2 diabetes mellitus (T2DM). Methods: In pilot cohort, plasma samples were selected from 15 DM patients and 9 DME patients for screening changes of angiogenesis and inflammation related cytokines by the human cytokine antibody array. These screening cytokines were further validated by ELISA in validation cohort, which containing 100 T2DM with DME (DME group) and 100 T2DM without DME (T2DM group) patients. Pearson correlation were calculated to investigate relationship between cytokines and clinical characteristics. Finally, a prediction model based on plasma cytokines was built by machine learning algorithms. Results: In pilot cohort, 12 plasma cytokines were significant higher, among which there was obvious increase of platelet-derived growth factor-BB (PDGF-BB), tissue inhibitors of metalloproteinase 1 (TIMP-1), angiopoietin 1 (ANG-1), CXC-chemokine ligand 16 (CXCL16) and vascular endothelial cell growth factor receptor 2 (VEGF R2) in DME group (Foldchange > 6 and adjusted p < 0.05), comparing with T2DM group. PDGF-BB, TIMP-1, ANG-1, CXCL16 and VEGFR2 were further confirmed significant elevated in validation cohort. Machine learning algorithms employing random forests (RF) yielded the best performance. In the test set, accuracy, sensitivity, specificity, AUROC and f1 score of RF model were 83.3%, 86.2%, 80.6%, 0.83 and 0.83, respectively. Conclusion: Plasma cytokines were closely association with DME. The prediction model consisting of 4 plasma cytokines in the study was a novel tool for predicting DME in T2DM patients. Funding Statement: This study was funded by Science and Technology Committee of Tongzhou District (Number: KJ2019CX014-25). Declaration of Interests: The authors declare they have no conflict of interest. Ethics Approval Statement: In our research, all procedures complied with the Helsinki Declaration for investigation of human subjects. The study received ethical approval from the competent Institutional Review Boards of Beijing Luhe Hospital. All patient-related procedures were performed strictly following the approval of the internal review and ethics boards of the indicated hospitals.

&lt;i&gt;PCSK9&lt;/i&gt; rs11591147 R46L Loss-of-Function Variant Protects Against Liver Damage in Individuals with NAFLD

Background and Aims: The proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower LDL-C levels. In this study, we examined the impact of PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models. Methods: We considered 1,874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9, was genotyped by TaqMan assays. We also evaluated 1) PCSK9 mRNA hepatic expression in human liver, and 2) the impact of a NASH-inducing diet in mice with hepatic overexpression of human PCSK9. Results: Carriers of PCSK9 rs11591147 had lower circulating LDL-C levels and were protected against NAFLD (OR 0.42;95%C.I0.22-0.81;P=0.01), NASH (OR 0.39;95%C.I.0.20-0.75;P=0.005) and more severe fibrosis (OR 0.44;95%C.I.0.26-0.74;P=0.002) independently of clinical, metabolic and genetic confounding factors. PCSK9 hepatic expression was directly correlated with steatosis (P=0.03). Finally, liver-specific overexpression of human PCSK9 in mice drives NAFLD and fibrosis upon a dietary challenge. Conclusions: In individuals at risk, PCSK9 was induced with hepatic fat accumulation and PCSK9 rs11591147 LOF variant was protective against liver steatosis, NASH and fibrosis, suggesting PCSK9 inhibition may be a new therapeutic strategy to treat NASH. Funding Statement: This work was supported by project grant by the Swedish Research Council [Vetenskapsradet (VR), 2016-01527], the Swedish state under the Agreement between the Swedish government and the county councils (the ALF-agreement) [SU 2018-04276], the Novonordisk Foundation Grant for Excellence in Endocrinology [Excellence Project, 9321- 430], the Swedish Diabetes Foundation [DIA 2017-205], the Swedish Heart Lung Foundation [20120533], the Wallenberg Academy Fellows from the Knut and Alice Wallenberg Foundation [KAW 2017.0203]. LV was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute [RF-2016-02364358], Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Fondazione Sviluppo Ca Granda [PR-0316], the European Union Programme Horizon 2020 [No. 777377]. Declaration of Interests: SR has been consulting for AMGEN, SANOFI, Astra Zeneca, Pfizer, AKCEA, Celgene, Medacorp, Foresite Labs, CAMP4 and received research grants from Astra Zeneca, AMGEN, SANOFI. SB, DK-P, A-CA, GP, MB-Y and DL are AstraZeneca employees. LV reports having received during the last 5 years speaking fees from MSD, Gilead, AlfaSigma, AbbVie, having served as a consultant of: Gilead, Pfizer, Astra Zeneca, Novo Nordisk, Diatech Pharmacogenetics and Intercept, and having received research grants from: Gilead. Ethics Approval Statement: The study was carried out in accordance with the principles of the Helsinki Declaration, and with local and national laws. Approval was obtained from Internal Review Boards and their Ethics Committees, and written informed consent for the study was obtained from all patients All animal experiments were performed with humane care and were approved by the Gothenburg Ethics Committee for Experimental Animals in Sweden. The holding facility has received full accreditation from the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).

&lt;i&gt;NR1H4&lt;/i&gt; rs35724 G&amp;gt;C Variant Modulates Liver Damage in Nonalcoholic Fatty Liver Disease

Background and Aims: Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 variant, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis. Methods: We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms was genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n=124). Results: The NR1H4 rs35724 variant was protective against severity of steatosis (OR 0.89, 95% C.I. 0.80-0.98; p=0.02), steatohepatitis (OR 0.83, 95% C.I. 0.73-0.94; p=0.004) and severity of fibrosis (OR 0.89, 95% C.I. 0.80-0.99; p=0.03), these results were confirmed after adjusting for clinico-metabolic and genetic confounders. The variant was associated with higher total circulating cholesterol (p=0.01). Patients carrying the NR1H4 rs35724 variant had significantly higher hepatic mRNA levels of FXR and associated with higher hepatic FGFR4 and Cyp39A1 that are in turn involved in bile acid synthesis. Conclusions: Increased hepatic FXR expression due to rs35724 variant is linked to higher serum cholesterol but protects against steatosis, steatohepatitis and liver fibrosis. The translational relevance of these results for patient risk stratification and FXR- targeted therapy warrants further investigation. Funding Statement: None. Declaration of Interests: None to declare. Ethics Approval Statement: Approval was obtained from the Internal Review Boards and their Ethics Committees, and written informed consent for the study was obtained from all controls and patients.

High-Throughput RNA Sequencing Analysis Reveals Distinct Molecular Signature in NRAS and PTPN11 JMML Patients

Introduction Juvenile myelomonocytic leukemia (JMML) is a rare pediatric hematological disease, characterized by aberrant proliferation of myeloid precursors and hypersensitivity to GM-CSF stimulation. Mutations in PTPN11, N/K-RAS, CBL, or NF1 genes are found in ~90% of the cases. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for those patients harboring somatic PTPN11 mutations, while in patients with somatic NRAS mutations, transplantation need a careful evaluation, as these patients may have spontaneous resolution of the disease. Here, we show data from a deep-sequencing analysis enlightening typical molecular features of CD33+/34+ and CD14+ primary cells from NRAS and PTPN11 mutated patients compared with healthy donors (HDs). Patients and Methods Four Cord Blood samples from healthy donors (HDs) and 16 Bone Marrow (BM) samples from PTPN11 (N=8) and NRAS (n=8) mutated JMML patients were collected after approvals from International Review Boards of each Institution. CD33+/34+ and CD14+ cells were magnetically sorted following MACS protocols (Miltenyi). TruSeq and NextSeq kits (Illumina) were used for libraries preparation in order to perform the global transcriptomic and smallRNAs sequencing analyses on Illumina platform, according to the company protocols. StringTie and DESeq2 were used for differential expression analysis and REDItools python scripts for RNA editing analysis. Results In our first analysis, we screened ~60000 gene transcripts, finding different expression signatures between HDs, PTPN11 and NRAS samples. We built Expression Heat-Maps reporting the top 100 most statistically significant (Fig. 1, 2; adjusted p &lt; 0.001) deregulated sequences in all the possible pairwise comparisons. Among the top 100 transcripts, we identified differential expression of 5 different genes: ZNF185, MRLPL30 resulted upregulated in PTPN11 vs NRAS CD14+ cells while CD36, RAG2 and CAMK2A resulted downregulated. Interestingly, comparison of PTPN11 and NRAS cohorts in CD33+/34+ subset, these 5 transcripts showed the opposite expression trend. Moreover, among the upregulated genes, we identified a subset of PRAME paralog transcripts in both NRAS and PTPN11 patients when compared to HDs. Seven transcripts (PRAMEF4, 5, 6, 9, 11, 15, 26) were shared between CD33+/34+ and CD14+ populations, while PRAMEF7, 8, 20, 21 resulted upregulated in CD33+/34+ cells and PRAME, PRAMEF22, 23, 25 were upregulated in CD14+ cells, as compared to HDs. In addition, we found aberrant upregulation of Hemoglobin γ chains 1 and 2 (HBG1, 2, i.e. those needed for fetal hemoglobin) in all JMML vs HDs in CD14+ cells, while in CD33+/34+ a downregulation of Hemoglobin α and β chains (HBA1,2 and HBB) in PTPN11 samples vs NRAS was detected. We also report an enhanced LIN28B expression in JMML samples vs HDs but only in CD33+/34+ cells. A global ADAR-dependent RNA editing analysis revealed differences in CD33+/34+ cells showing an enhanced Adenine to Inosine conversion in NRAS patients vs PTPN11 and HDs. Finally, microRNAs sequencing reveals a significant upregulation of miR-144-3p in all JMML samples and cell lineages compared to HDs, while the miR-146a-5p was upregulated only in CD14+ cells. Also the miR-22 showed decreased expression in PTPN11 vs HDs in CD33+/34+ subset, while the miR-29a-3p was downregulated in NRAS vs HDs in CD14+ cells. Discussion We report different expression and editing signatures among samples cohorts and cellular lineages, showing novel insights in JMML molecular biology. Upregulation of several PRAME paralog genes depicts an interesting array of possible targets for immunotherapies (e.g., using genetically modified T cells with a PRAME-specific T-cell receptor), although their expression have to be further validated. Differences in the expression of microRNAs subsets, LIN28B and subunits of the HbA and HbF already described in JMML, but here related to specific mutations and cell lineages, could help to better understand the pathogenic processes and peculiar clinical behaviors. Finally, the novel evidence of differential RNA editing in JMML opens new perspectives for further studies regarding differential protein isoforms expression and regulation as well as microRNA targeting. Disclosures Niemeyer: Celgene: Consultancy. Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy. Merli:Novartis: Honoraria; Sobi: Consultancy; Amgen: Honoraria; Bellicum: Consultancy.

Barriers to conducting a multi-center randomized controlled trial of surgical stabilization of rib fractures (and how to overcome them).

Surgical stabilization of rib fractures (SSRF) has become a standardized procedure, routinely performed at trauma centers over the last 40 years, however, it remains a controversial practice. Multicenter, randomized controlled trials (RCT) would provide compelling evidence in the efficacy of SSRF but there are theoretical obstacles involved with execution and design of this type of investigation. Through the systematic review of current literature on the topics of SSRF for flail and non-fail patterns, medical device industry conflicts of interests, working with international review boards (IRB), the surveyed opinions of surgeons, and through the experience gained from conducting a multicenter RCT on SSRF, it was possible to identify the major barriers that come with successful implementation of this type of study. In identifying these obstacles, it was then possible to propose their solutions, specifically to the issues that make the effort underpowered, underfunded, understaffed, with not enough time for completion. These barriers can be overcome with understanding, up front, that a mutlicenter RCT of SSRF will involve a multi-year and multi-hundred thousand dollar commitment, with support from parent organizations, and a dedicated, full-time research staff (and the solutions of how to overcome them). These barriers stem from poor planning which result specifically in an effort that is underpowered, under funded, under staffed, with not enough time for completion.

Youth as Navigators: A Study Protocol to Incorporate Narrative and Visual Methods Into Research on Adolescent Sexual and Gender Development Among Syrian and Jordanian Youth

Background: The determinants of adolescent sexual and reproductive health originate in childhood and may stem from prepubescent experiences. There has been limited research on adolescent sexual and reproductive health from a life-course perspective globally, especially in the Middle East. Youth in Jordan are exposed to rigid social expectations and gender roles, which may influence sexual and reproductive health outcomes. The ongoing conflict in Syria and refugee crisis is thought to have altered community norms thereby influencing experiences that lead toward sexual development. Aim: This study seeks to understand how social, cultural, environmental, and biological factors influence adolescent sexual development and reproductive health among Jordanian and Syrian youth. This study will explore how social and gender norms have influenced adolescent sexual development across the life cycle related to key transitions between childhood and adulthood. Study Design and Methods: Sixty-four Jordanian and Syrian males and females aged between 15 and 19 years will be recruited by convenience from community centers in four cities across Jordan. This study will integrate both visual and narrative qualitative methods. By constructing a visual time line during semistructured in-depth interviews, we seek to give youth control in the retelling of their own life stories. Ethics and Discussion: This study has received ethical approval from both international and local institutional review boards. The findings of this study will provide important data on emergent priorities in the field of adolescent sexual and reproductive health, such as those related to gender, sexual maturation, and social norms, that will be of national, regional, and global significance.

Health Outcomes, Pathogenesis and Epidemiology of Severe Acute Malnutrition (HOPE-SAM): rationale and methods of a longitudinal observational study

IntroductionMortality among children hospitalised for complicated severe acute malnutrition (SAM) remains high despite the implementation of WHO guidelines, particularly in settings of high HIV prevalence. Children continue to be at...

A Multi-Component Breastfeeding Promotion and Support Intervention Improves Six-Month Exclusivity in a Middle-Income Country: A Randomised Clinical Trial

Background Breastfeeding is a cost-effective intervention that improves maternal and child health outcomes. Countries with low breastfeeding rates need to implement effective evidence-based breastfeeding promotion and support interventions to bolster breastfeeding practices. This trial investigated the effects on six-month exclusivity of a multi-component breastfeeding support package in the hospital and home settings, relative to standard care in a cohort of Lebanese women. Methods This participant-blind, parallel group trial randomly allocated 446 healthy pregnant women to receive a multi-component intervention that included antenatal breastfeeding education, professional, and peer breastfeeding support for six months postpartum (n=222), or to standard prenatal and postnatal care (n=224). The primary outcome was six-month breastfeeding exclusivity. Secondary outcomes were exclusive and any breastfeeding rates at one and three months, maternal breastfeeding knowledge, attitude, and behaviour at six months, and satisfaction with the intervention. We conducted descriptive and regression analyses following the intention to treat principle. This trial is registered with Current Controlled Trials, ISRCTN17875591. Findings The crude six-month breastfeeding exclusivity rates were similar in both groups (experimental=35·2%, control=28·1%; p=0·16). In regression analysis, exclusive breastfeeding was twice as likely to be continued for six months in the experimental group relative to standard care (OR=2·02; 95%CI: 1·20 to 3·39); whereas the rates of any breastfeeding were similar in both groups. Participants compliant with all three components were six times more likely to be exclusively breastfeeding at six months relative to the control group (OR=6·63; 95% CI: 3·03 to 14·51). Breastfeeding knowledge was significantly improved in the experimental group but there were no changes in their breastfeeding attitude or behaviour at six months when compared to standard care. Most of the participants were satisfied with the multicomponent intervention. Interpretation Combining education with peer and professional breastfeeding support improved six-month exclusivity in a middle income country. Trial registration Number: Current Controlled Trials ISRCTN17875591 Funding: This study was supported by a grant from the Medical Dean’s Program Projects in Biomedical Research, American University of Beirut. Declaration of Interest: None declared. Ethical Approval: The study is approved by the Internal Review Boards of the American University of Beirut and Al-Sahel General Hospital. All participant pregnant women and support mothers will be requested to give their written informed consent prior to any study procedure.

Legislative Issues in Disclosing Financial Conflicts of Interest to Participants in Biomedical Research: Effectiveness and Methodology.

This research focuses on the analysis regarding disclosure of financial conflicts of interest (FCOI) after Gelsinger v. University of Pennsylvania (Penn). The main legal issue was that the participants did not have enough opportunity to make an autonomous decision about participating in the research because he was not informed about the researchers' and the institution's substantial FCOI. The disclosure system was adopted by the Code of Federal Regulations. Under the regulation, researchers and institutions need to report FCOI over $5,000 to the institution, and the internal review boards have to report to the federal authority if needed. In case of human research, the disclosure to Food and Drug Administration is mandatory. FCOI disclosure system would help participants to make an autonomous decision, and increase trust to the research process and researchers. Moreover, the system would let researchers keep fiduciary duty while (possibly) lowering legal liability in case of a lawsuit. There were discussions about the disclosure methodology in the United States. However, there have not been a lot of discussions in Korea even after the “Humidifier Disinfectant” case. Therefore, new legislations need to be considered. First, the system requires disclosure funded by not only government but also private institutions. Second, like California Supreme Court, the subject would be reviewed under the reasonable person standard by participants, including patents, equity, and stock. Third, the disclosure needs to include simple or brief explanation to the FCOI to be better understood by the participants. Fourth, the disclosure should be in the informed consent process.

Remixing the Remix: Fannish Appropriation and the Limits of Unauthorised Use

Remixing the Remix: Fannish Appropriation and the Limits of Unauthorised Use

Micropolitical and Identity Challenges Influencing New Faculty Participation in Teacher Education Reform: When Will We Learn?

Background/Context Teacher education faculty face increasing pressure to simultaneously strengthen and reform teacher education programs while maintaining research productivity. The demands placed on teacher education programs to increase relevancy by strengthening clinical components of teacher preparation has once again reached the fore. The energy for this reform often rests on the shoulders of tenure-earning faculty who have developed as Engaged Scholars during their doctoral preparation and wish to continue this work as they enter the professoriate. Purpose/Objective/Research Question/Focus of Study This article investigates and describes the experiences of new, tenure-earning faculty who sought working conditions that would support their involvement in reform oriented, clinically rich teacher education, and Engaged Scholarship. Population/Participants/Subjects This is a qualitative study with seven participants who worked as assistant professors across four different research-intensive state universities. Each university has a history of involvement in either the Holmes Partnership or the National Network for Educational Renewal, organizations that target integrating faculty members into partnership schools making this a part of their teacher education work. Research Design This qualitative self-study, guided by a constructivist epistemology (Crotty, 1998, 2005), seeks to understand tenure-earning faculties’ experiences as they enter the professoriate. This study makes use of interpretivism (Crotty, 1998) as a theoretical perspective. Data Collection and Analysis This research uses focus group transcripts as the primary data source. Additional data sources include program artifacts such as meeting agendas and minutes, blog entries, and field notes that were used during the four taped focus groups to generate discussion related to research questions. Findings/Results The study describes six challenges faced by new faculty who assume leadership in clinically rich teacher education reform, and identifies faculty identity and micro-political concerns as central to navigating challenges. These challenges include: (a) complications associated with negotiating workload, (b) entrée to schools, (c) negotiating roles, (d) negotiating Internal Review Boards and school district research policies, (e) influencing promotion and tenure policies, and (f) facilitating pockets of program renewal and innovation. Conclusions/Recommendations This study suggests that while doctoral programs are now preparing new faculty who embrace clinically rich teacher preparation, they do not receive adequate support as they enter academia. Discussed are three assertions that must be resolved by university, college, and department leadership, as well as tenured colleagues, to support new faculty involvement in developing clinically rich teacher education reform.

Were the Interests of the Vulnerable Truly Served? The Predictable Failure of HIVIG

Were the Interests of the Vulnerable Truly Served? The Predictable Failure of HIVIG

Use of discard pleural fluid in molecular research

We thank Grannis for his comments and interest in our article—The ethical use of mandatory research biopsies. Nat. Rev. Clin. Oncol. 8, 620–6251 (Use of discard pleural fluid in molecular research. Nat. Rev. Clin. Oncol. doi:10.138/nrclinonc.2011.114-c1).2 We agree that when research biopsies are included in clinical trials involving patients with metastatic cancer, the most accessible location of the disease is the preferred site of tissue collection. In patients with lung and breast cancers, malignant pleural effusions are common, and cytologically positive cancer cells can be readily collected from these effusions and analyzed in translational studies. Genomic, transcriptomic, methylation and proteomic studies can be performed on both fresh specimens and formalin-fixed paraffin-embedded (FFPE) blocks prepared with the cells collected from these effusions.3–4 Importantly, molecular analyses of lung adenocarcinoma cells from pleural fluid have been used to predict response to targeted agents.6,7 Investigations about the biological aspects of metastatic cells in the pleural fluid can be incorporated into the clinical trial protocols, and via serial pleural throacenteses, the molecular characteristics of these cells and potential mechanisms of acquired resistance to investigational agents can be analyzed. The internal review boards will likely approve the protocols in which pleural fluid—that would have otherwise been discarded—is collected for scientific analysis. This approach adds minimal additional risk for the patients undergoing a clinically indicated thoracentesis. However, safety issues will arise if a protocol proposes serial or a single thoracentesis for only research purposes. Iatrogenic pneumothorax is more likely to occur after therapeutic thoracentesis and frequently requires insertion of a chest tube.8 Nevertheless, as outlined by Grannis, in patients with indwelling pleural catheters there is a unique opportunity to regularly collect tumor cells without the need for repeated biopsies.