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Background: Cardiovascular disease (CVD) is the number 1 killer of women in the United States, yet few younger women are aware of this fact. CVD campaigns focus little attention on physicia...

A Root Cause Analysis (RCA) is "a systematic investigation technique that looks beyond the individuals concerned and seeks to understand the underlying causes and environmental context in which an incident happened". As an investigation technique for patient safety incidents, it looks beyond the individuals concerned and seeks to understand the underlying causes and environmental context in which an incident happened. Increasing learning from clinical incidents and reducing harm to patients is a high priority for National Health Service in the United Kingdom. These priorities directly reflect the priority of its regulatory body, Care Quality Commission (CQC), which stated that there must be an appropriate system in place to monitor quality of care for patients. Finally, if an RCA establishes training needs or key information to be disseminated, simulation can be used in its more traditional role as an educational tool to meet these requirements.

Affiliation 1Muhimbili University of Health and Allied Sciences, Dar es salaam, Tanzania. 2Department of Oncology, University of Oxford, Oxford UK. 3Dar es salaam University College of Education, Dar es salaam, Tanzania. ABSTRACT. Background; SCD constitutes to be a major public health problem in Tanzania. NBS for SCD identify infants with SCD at birth and subsequently enroll them into SCD comprehensive care program and it has been reported to reduce early childhood mortality and morbidity due to SCD and increase life expectancy. There are different methods for Newborn screening for SCD such as HPLC, IEF, DNA analysis, sickle scan and hemotype SC that helps in early detection of SCD and other haemoglobinopathies but we are lacking sufficient information on alternative screening methods that can be used for NBS in Tanzania so this study is aiming at investigating the effectiveness and feasibility of NBS laboratory tests. Aim of the study; To evaluate newborn screening Laboratory assays for sickle cell disease and other haemoglobinopathies in Tanzania. Methodology; This will be a retrospective and prospective study which will be conducted in Dar es Salaam and Mwanza.1000 newborns and 100 children with SCD under five years old will be enrolled. DBS samples will be collected and analyzed by DNA Analysis, sickle scan, Hemotype SC, HPLC, and IEF. SPSS version 16.0 will be used to analyze data. Statistically, significant tests will be declared at a level of p-value < 0.05. Progress: Initially we have conducted a pilot of 12 individuals who were screened for SCD and turned out to be carriers ( Hb AS). However these individuals continuously reported to experience painful events. Initial analysis has include Hb subtyping and quantification by HPLC,Sickle scan and HemotypeSC to ascertain indicator for thalassaemia syndrome. Definitive analysis involved sequencing of thalassaemia and SCD associated regions by using Oxford Nanopore Technology and NGS Expected outcomes; The findings of this study will inform Newborn screening stakeholders on the best point of care screening test and definitive test, in terms of turnaround time and cost. Such findings will assist in planning and scaling up of newborn screening services across the country. Corresponding Author; HChristopher, Email; hchristopher@blood.ac.tz, Tel; +255762175732. Disclosures Schuh: AbbVie: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau; Kite: Speakers Bureau; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau; Bristol-Myers Squibb: Research Funding; Janssen: Speakers Bureau; Verastem: Speakers Bureau.

Following the Spanish-American War of 1898, the USA became a true, European-style imperial power, with overseas colonies populated by diverse peoples with few — if any — connections to American culture and history. The wide-ranging imperial debate that followed 1898 brought two future US presidents firmly to the fore: the New York politician and war hero, Theodore Roosevelt, and the Ohio judge, William H. Taft. This article explores the complex development of these two politicians’ views on the Philippines during this period of imperial rule. Roosevelt began the period as an ardent imperialist and changed his views to reflect a change in US public opinion and strategic concerns. Conversely, Taft began by being a sceptic about US imperialism but ultimately became one of the most ardent retentionists. This article not only charts their paths to convergence and then their subsequent divergence in attitude towards Philippines policy, but also brings to light the much underestimated role that Taft played in ke...

The annexation of the Philippines in the wake of the Spanish–American War of 1898 caused imperialists to contemplate the extent to which US policies ought to be extended to the islands. Central to these discussions was the possibility of applying US Chinese exclusion laws to the new Pacific border, which threatened to become yet another immigrant gateway to the United States. William H. Taft, the first US civil governor of the islands, worked toward a permanent US imperial relationship with the islands, which would involve investment and infrastructural improvements that required additional labor immigration. Called upon by US and European businessmen interested in importing cheap Chinese labor to the Philippines, Taft toyed with the possibility of a separate immigration policy for the archipelago and thus became the center of a complex debate over America's new Pacific border.

Objective To develop and test nutrition messages and supporting content with low-income mothers for use with theory-based interventions addressing fruit and vegetable consumption and child-feeding practices. Design Six formative and 6 evaluative focus groups explored message concepts and tested messages, respectively. Setting Research facilities in Maryland, Texas, California, Florida, North Carolina, New York, Alabama, and Illinois. Participants Ninety-five low-income mothers of 2- to 5-year-old children; over half from households participating in a federal nutrition assistance program. Phenomenon of Interest Preference for and comprehension of nutrition messages. Analysis Qualitative data analysis procedures to generate common themes from transcripts and observers' notes. Results Messages on role modeling, cooking and eating together, having patience when introducing new food items, and allowing children to serve themselves were well received. Mothers preferred messages that emphasized their role as a teacher and noted benefits such as their children becoming more independent and learning new skills. Mothers commonly doubted children's ability to accurately report when they are “full” and disliked messages encouraging mothers to allow children to “decide” whether and how much to eat. Conclusions and Implications This study generated 7 audience-tested messages for incorporation into nutrition education interventions targeting low-income mothers of preschool-age children.

Background Chronic Lymphocytic Leukemia (CLL) is characterised by a highly heterogeneous natural history and treatment response. Indeed, 50% of immunoglobulin heavy chain variable region (IgHV) hypermutated patients have an excellent progression free survival (PFS) after chemoimmunotherapy. Conversely, 25% of FCR treated patients relapse within 24 months (high risk CLL). Recent studies have shown that complex karyotype with or without TP53 disruption predicts for relapse after BCL2 therapy and BTK inhibitors. However, TP53 is the only marker for which routine testing is available. Overall, nearly 80% of patients relapsing after frontline FCR do not present a known poor risk genomic marker. Additional candidate genomic predictors of poor outcome including mutations in coding regions of NOTCH1, SF3B1 and RPS15, non-coding regions of NOTCH1 and enhancer regions of PAX5, telomere length, IgHV status, and DNA Damage Repair (DDR) germline mutations including TP53 and ATM have been reported in CLL. Further, the role of mutational signatures and regions of kataegis also merit additional investigation in progressive CLL. Evaluating all candidate predictors requires complex time consuming, multi-modality testing outside the scope of routine clinical diagnostic practice, however, in isolation, each has low predictive value. Here, we show preliminary data on a novel patient stratification method based on whole genome sequencing (WGS) data incorporating multiple genomic features in a single test. Patients and Methods Tumor (peripheral blood) and germline (saliva) samples were collected from 321 patients from 6 UK trials via the Genomics England CLL pilot: ARCTIC (n=61), AdMIRe (n=64), CLL 210 (n=30), CLEAR (n=12), RIAltO (n=88) and FLAIR (n=66). We performed WGS on the HiSeqX (Illumina). After read alignment, we detected somatic variants using Strelka 2.4.7 for small variants detection (SNV and InDels), Manta 0.28.0 for structural variant (SV) detection, and Canvas 1.3.1 for copy number variant (CNV) detection (Illumina). Non-coding regions were annotated with information from primary CLL, CLL cell lines and B-cell ENCODE databases. Mutational signatures and putative regions of kataegis were calculated based on Alexandrov et al. (Nature, 2013) and Lawrence et al. (Nature, 2013). Telomere lengths were assessed using Telomerecat. Data aggregation was performed using contingency tables combined with non-negative matrix factorization. Results Mean coverage was 94.2X for tumor and 28.5X for germline samples. We found a median of 9172 SNPs/sample after filtering and 2348 indels/sample across 321 patients. High risk CLL was enriched for genomic complexity and poor prognostic mutations. The most frequently mutated genes were SF3B1 (17%), TP53 (13%), NOTCH1 (12%), IGLL5 (12%), and ATM (11%). Analysis of non-coding regions using DNA methylation markers, ATAC-seq and Hi-C revealed potential candidate regions associated with early relapse. Using CNA and SV data, we identified interesting patterns of genomic complexity and structural variants, including a trend towards enrichment of del8p in Relapse/Refractory and FCR non-responders. Additionally, we investigated mutation signatures and kataegis across coding and non-coding regions of the genome. We correlated exonic regions of DDR genes in germline data with clinical outcomes and extended this to genes mutated in both tumor and germline data, termed germline-tumor double-hits. We examined the relationship between the Alexandrov hypermutation signature, IgHV status (determined by % homology to the reference genome) and PFS, and combined mutational density at the Ig locus with mutation signature aiming to predict IgHV status. Finally, we produced a binary contingency matrix, using non-negative matrix factorization to cluster the samples. This method highlighted patient groups with shared genomic profiles. Conclusion We present preliminary data on a patient stratification method derived from WGS of 321 paired germline and CLL trial samples. Our predictive signature includes driver gene mutations, CNAs, IgHV status, genomic complexity, telomere length, overall mutation burden and genes with germline-tumor double-hits. Our comprehensive, NGS-based patient stratification attempts to predict patient outcome in a single sequencing run. Disclosures Becq: Illumina: Employment. He:Illumina: Employment. Ross:Illumina: Employment. Bentley:Illumina: Employment. Pettitt:Celgene: Research Funding; Gilead: Research Funding; Roche: Research Funding; GSK/Novartis: Research Funding; Napp: Research Funding; AstraZeneca: Research Funding; Chugai: Research Funding. Hillmen:Novartis: Research Funding; Gilead Sciences, Inc.: Honoraria, Research Funding; Alexion Pharmaceuticals, Inc: Consultancy, Honoraria; F. Hoffmann-La Roche Ltd: Research Funding; Celgene: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schuh:Giles, Roche, Janssen, AbbVie: Honoraria.

Background Dental Practitioners are required to be competent in Basic Life Support and have the requisite knowledge and skills to manage common medical emergencies (GDC 2002) (Balmer and Longman 2012). Studies have shown that utilising simulation in training can have a positive effect on the learner’s self-confidence and effectiveness allowing them to practice skills and enact scenarios in a safe, structured and supervised environment (Aggarwal et al , 2010). In September 2013, 16 dental students attended a District General Hospital to undertake a Human Disease elective. It was not always possible to observe medical emergencies in the week allocated to them. In order to meet the objectives specified by the Dental School, the students partcipated in a series of simulated exercises utilising an ALS and 3G (TM) manikins represent to represent the emergencies they may encounter in practice. Methodology The scenarios were based in a mock ward/dental surgery to simulate the environment in which the dentists would work. The following scenarios were undertaken: Retained throat swab/Laryngospasm Communication with a simualted patient unhappy with treatment Cardiac arrest (BLS) Each student "led" a scenario supported by peers. A debrief at the end of each scenario allowed for reflection and analysis - placing the scenario in context to dental practice. A questionnaire allowed for qualitative aspects of feedback and quantitative perception on the effectiveness of the day as expressed by a 5-point Likert scale. Outcomes 16 students participated in the evaluation. 100% felt that the study day had relevance to their work/training and gave them a better understanding of how to deal with medical emergencies. Conclusion The simulated medical emergency training was highly rated as an overall learning experience allowing students to gain an understanding of how to deal with common medical emergencies in a supportive environment conducive to building on prior knowledge. (Davies at al 2009). References Aggarwal R, Mytton OM, MacAulay C, Ziv A, Reznick R. Training for Patient Safety Quality and Safety in Healthcare 2010;19:34–43 Balmer MC, Longman LP. The Management of Medical Emergencies. The Role of the Dental Care Professional. Clinical Handbook of Dental and Hygiene Therapy; 2012. Oxford; Wiley-Blackwell Davies BR, Leung AN. Perceptions of a simulated general dental practice facility-reported experiences from past students at the Maurice Wohl General Dental Practice Centre 2001-2008. British Dental Journal 2009;207:371–376 General Dental Council (2002) The First Five Years: A Framework for Undergraduate Dental Education"

A survey of training conducted by the Royal College of Physicians of UK 1 had identified that junior medical trainees were intimidated by the prospect of becoming medical registrars. Previously there were no simulation based educational programmes addressing the needs of acute medicine trainees. We have designed a comprehensive four year programme of simulation activities for acute medicine trainees and we wish to present the results of the first year’s programme. Methods The design of the programme was based on three aspects: Curriculum - Our course is mapped to the JRCPTB curriculum. Stakeholders - The three training programme directors (TPD) were approached for information on trainees’ training gaps. Trainees - An e-mail survey of training needs was conducted where all the Acute Medicine trainees were sent questions related to procedural skills, technical skills and non-technical skills. A simultaneous inventory of simulation equipment and facilities was conducted and where deficiency was identified, equipment was procured. Based on training needs assessments we have created a comprehensive programme which runs as four separate days for trainees at different levels of training. Trainees in their first year have already attended a practical skills course. (Chest drain insertion, Abdominal paracentesis, Knee arthrocentesis, Electrical Cardioversion and Central Venous catheter placement), and second year trainees have attended a simulation day in challenging clinical cases. Results The courses run so far have demonstrated increase in participants’ confidence levels. Conclusion We believe our courses meet training needs as identified by our trainee survey and fill gaps in the training where there is lack of experience due to limited exposure to these technical and non-technical skills. Faculty recruitment and sustainability are two limiting factors identified. Human factors course will run for year three trainees and year four trainees will learn Temporary cardiac pacing and Sengstaken tube insertion. Reference The Royal College of Physicians. The medical registrar: empowering the unsung heroes of patient care. London: RCP, 2013

Whole-exome sequencing in del(5q) myelodysplastic syndromes in transformation to acute myeloid leukemia

This study analyses lecturers’ perceptions of feedback provided to university undergraduates and why in many cases it appears to prove so unsatisfactory to students. Recent research into the issue of feedback in higher education (HE) suggests that most existing studies on the subject have focused on students, whereas there is far less work on teachers in relation to formative learning (Bailey, 2008; Bailey and Garner, 2010). Indeed, Evans (2013) notes that only 7.1% of research articles she explored in her wide-ranging review of existing assessment and feedback literature focused exclusively on lecturer perspectives. Therefore, in addition to considering the findings of existing literature, this study explores the results of five interviews with HE History lecturers to explore their understanding of the issue of student dissatisfaction with feedback.

Background Historically diagnosis and prognosis of myeloid disorders including acute myeloid leukemia (AML) have been determined using a combination of morphology, immunophenotype, cytogenetic and more recently single gene, if not single mutation, analysis. The introduction of NGS technology has resulted in an explosion in the quantity of mutation data available. However, the feasibility and utility of NGS technology with regards to decision-making in routine clinical practice of myeloid disorders is currently unknown. We therefore developed an advanced NGS tool for simultaneous assessment of multiple myeloid candidate genes from low amounts of input DNA and present clinical utility analysis below. Methods We designed a targeted resequencing assay using a TruSeq Custom Amplicon panel with the MiSeq platform (both Illumina) consisting of 341 amplicons (~56 kb) designed around exons of genes frequently mutated in myeloid malignancies (ASXL1, ATRX, CBL, CBLB, CBLC, CEBPA, CSF3R, DNMT3a, ETV6, EZH2, FLT3, HRAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PDGFRA, PHF6, PTEN, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1, WT1 & ZRSR2). Filtering, variant calling and annotation were performed using Basespace and Variant Studio (Illumina) with additional indel detection achieved using Pindel. A cohort of samples previously characterised with conventional techniques was used for validation and the lower limit of detection established using qPCR. Post-validation, DNA from 152 diagnostic blood or bone marrow samples from patients with confirmed or suspected myeloid disorders; both AML (n=46) and disorders with the potential to transform to AML i.e. myelodysplasia (confirmed n=54, suspected n=10) and myeloproliferative neoplasms (n=42), were analysed using this assay. To gather clinical utility data we developed a reporting algorithm to feed back information to clinicians; only those variants with a variant allele frequency (VAF) of >10% and described as acquired in publically available databases were reported with the exception of novel mutations predicted to result in a truncated protein. Further utility data was obtained using published mutation algorithms to determine the proportion of patients in whom mutation data altered prognosis. Results In the validation cohort, initial concordance for detection of clinically significant mutations was 88% rising to 100% once Pindel was used to identify FLT3 ITDs. The lower limit of detection was 3% VAF, and mean amplicon coverage was 390 reads. Using our reporting algorithm 66% of patients in the post-validation cohort had a suspected pathogenic mutation relevant to a myeloid disorder, rising to 74% in patients with confirmed diagnoses. The median number of reported variants per sample for all diagnoses was one (range 0-6). When mutation data for patients with AML with intermediate risk cytogenetics was analysed using the algorithm of Patel et al (N Engl J Med. 2012;366:1079-1089), 4/22 (18%) moved into another risk category. A further two patients had double CEBPA mutations, improving their prognosis. Identification of complex mutations in KIT exon 8 in 2/6 patients with core binding factor AML resulted in more intensive MRD monitoring due to the increased risk of relapse. Interpretation of mutation data for patients with confirmed myelodysplasia using the work of Bejar et al (N Engl J Med. 2011;364:2496-2506) revealed 13/54 (24%) had a high risk mutation independently associated with poor overall survival. 2/8 (25%) patients with chronic myelomonocytic leukemia and 1/12 (8.3%) patients with primary myelofibrosis had high risk ASXL1 exon 12 mutations, independently associated with a poor prognosis. Among suspected diagnoses confirmatory mutations were found in 2/19 (11%), while the absence of mutations reduced the probability of myeloid disease in 11/19 (58%), in some cases sparing elderly patients invasive bone marrow sampling. A further 20 patients had clinically relevant mutations. Conclusions The NGS Myeloid Gene Panel provided extra information to clinicians in 57/152 patients (38%) helping inform diagnosis, individualize disease monitoring schedules and support treatment decisions. The targeted panel approach requires rigorous validation and standardisation in particular of bio-informatics pipelines, but can be adapted to incorporate new genes as their relevance is described and will become central to treatment decisions. Disclosures No relevant conflicts of interest to declare.

The plan for the USDA MyPyramid Food Guidance System included a new graphic and slogan, clear and concise nutrition messages, and a variety of materials and tools to help motivate and educate consumers to follow a healthful diet. Given the widespread availability of the Internet in homes and through schools and public libraries, and the Internet’s ability to deliver quantities of information efficiently, it was decided to use the Internet as a primary dissemination tool for the new food guidance system. The MyPyramid.gov Web site was developed to provide a range of tools and information to meet the needs of varied audiences.