Recruiting general practitioners and patients with dementia into a cluster randomised controlled trial: strategies, barriers and facilitators

Background: Recruitment of general practitioners (GPs) and their patients is reported as one of the most challenging steps when undertaking primary care research. The present paper describes the recruitment process of a cluster randomised controlled trial (cRCT) aiming to improve dementia care in the primary care setting. Methods: Recruitment data was analysed descriptively using frequency tables to investigate comparisons of recruitment rates and results of different recruitment strategies as well as reasons for participation and non-participation of GPs, patients with dementia (PwD) and their caregivers. Results: Over a period of 23 months, N = 28 GPs were successfully included in the cRCT. This represents an overall recruitment rate of 4.6%. The most efficient strategy in terms of high response and low labour-intensity involved the dissemination of calls for participation in a GP research network. Most frequently reported reasons for GP's participation were Improvement of patient's well-being (n = 22, 79%) followed by Interest in dementia research (n = 18, 64%). The most common reasons for non-participation were Lack of time (n = 71, 34%) followed by Not interested in participation (n = 63, 30%). On a patient level, N = 102 PwD were successfully recruited. On average, each GP referred about n = 7 PwD (range: 1-17; mdn = 6; IQR = 3.5) and successfully recruited about n = 4 PwD (range: 1-11; mdn = 3; IQR = 3.5). Conclusion: First, our findings propose GP research networks as a promising strategy to promote recruitment and participation of GPs and their patients in research. Second, present findings highlight the importance of including GPs and their interests in specific research topics in early stages of research in order to ensure a successful recruitment. Finally, results do not support cold calls as a successful strategy in the recruitment of GPs

Progress in Reducing Aerodynamic Drag for Higher Efficiency of Heavy Duty Trucks (Class 7-8)

This paper describes research and development for reducing the aerodynamic drag of heavy vehicles by demonstrating new approaches for the numerical simulation and analysis of aerodynamic flow. In addition, greater use of newly developed computational tools holds promise for reducing the number of prototype tests, for cutting manufacturing costs, and for reducing overall time to market. Experimental verification and validation of new computational fluid dynamics methods are also an important part of this approach. Experiments on a model of an integrated tractor-trailer are underway at NASA Ames Research Center and the University of Southern California. Companion computer simulations are being performed by Sandia National Laboratories, Lawrence Livermore National Laboratory, and California Institute of Technology using state-of-the-art techniques, with the intention of implementing more complex methods in the future

MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199

Targeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the BCL-2 gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias. Therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of research. Mutations in the MLL gene cause aggressive incurable leukemias. Benito et al. show that MLL leukemias are highly sensitive to BCL-2 inhibitors, especially when combined with drugs that target mutant MLL complex activity

sodC-Based Real-Time PCR for Detection of Neisseria meningitidis

Real-time PCR (rt-PCR) is a widely used molecular method for detection of Neisseria meningitidis (Nm). Several rt-PCR assays for Nm target the capsule transport gene, ctrA. However, over 16% of meningococcal carriage isolates lack ctrA, rendering this target gene ineffective at identification of this sub-population of meningococcal isolates. The Cu-Zn superoxide dismutase gene, sodC, is found in Nm but not in other Neisseria species. To better identify Nm, regardless of capsule genotype or expression status, a sodC-based TaqMan rt-PCR assay was developed and validated. Standard curves revealed an average lower limit of detection of 73 genomes per reaction at cycle threshold (Ct) value of 35, with 100% average reaction efficiency and an average R2 of 0.9925. 99.7% (624/626) of Nm isolates tested were sodC-positive, with a range of average Ct values from 13.0 to 29.5. The mean sodC Ct value of these Nm isolates was 17.6±2.2 (±SD). Of the 626 Nm tested, 178 were nongroupable (NG) ctrA-negative Nm isolates, and 98.9% (176/178) of these were detected by sodC rt-PCR. The assay was 100% specific, with all 244 non-Nm isolates testing negative. Of 157 clinical specimens tested, sodC detected 25/157 Nm or 4 additional specimens compared to ctrA and 24 more than culture. Among 582 carriage specimens, sodC detected Nm in 1 more than ctrA and in 4 more than culture. This sodC rt-PCR assay is a highly sensitive and specific method for detection of Nm, especially in carriage studies where many meningococcal isolates lack capsule genes

COBRA Master Class: Providing deep-sea expedition leadership training to accelerate early career advancement

Leading deep-sea research expeditions requires a breadth of training and experience, and the opportunities for Early Career Researchers (ECRs) to obtain focused mentorship on expedition leadership are scarce. To address the need for leadership training in deep-sea expeditionary science, the Crustal Ocean Biosphere Research Accelerator (COBRA) launched a 14-week virtual Master Class with both synchronous and asynchronous components to empower students with the skills and tools to successfully design, propose, and execute deep-sea oceanographic field research. The Master Class offered customized and distributed training approaches and created an open-access syllabus with resources, including reading material, lectures, and on-line resources freely-available on the Master Class website (cobra.pubpub.org). All students were Early Career Researchers (ECRs, defined here as advanced graduate students, postdoctoral scientists, early career faculty, or individuals with substantial industry, government, or NGO experience) and designated throughout as COBRA Fellows. Fellows engaged in topics related to choosing the appropriate deep-sea research asset for their Capstone “dream cruise” project, learning about funding sources and how to tailor proposals to meet those source requirements, and working through an essential checklist of pre-expedition planning and operations. The Master Class covered leading an expedition at sea, at-sea operations, and ship-board etiquette, and the strengths and challenges of telepresence. It also included post-expedition training on data management strategies and report preparation and outputs. Throughout the Master Class, Fellows also discussed education and outreach, international ocean law and policy, and the importance and challenges of team science. Fellows further learned about how to develop concepts respectfully with regard to geographic and cultural considerations of their intended study sites. An assessment of initial outcomes from the first iteration of the COBRA Master Class reinforces the need for such training and shows great promise with one-quarter of the Fellows having submitted a research proposal to national funding agencies within six months of the end of the class. As deep-sea research continues to accelerate in scope and speed, providing equitable access to expedition training is a top priority to enable the next generation of deep-sea science leadership