Emerg Infect Dis

Nucleophilic aromatic substitution (S_NAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain ¹⁸F for use in positron-emission tomography (PET) imaging¹. A wide range of nucleophiles exhibit S_NAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales². During S_NAr, attack of a nucleophile at a carbon atom bearing a ‘leaving group’ leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of S_NAr reactions: the most common S_NAr substrates contain strong π-acceptors in the ortho and/or para position(s)³. Here we present an unusual concerted nucleophilic aromatic substitution reaction (CS_NAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CS_NAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group-tolerant ¹⁸F−deoxyfluorination reaction of phenols, which can be used to synthesize ¹⁸F-PET probes. Selective ¹⁸F introduction, without the need for the common, but cumbersome, azeotropic drying of ¹⁸F, can now be accomplished from phenols as starting materials, and provides access to ¹⁸F-labelled compounds not accessible through conventional chemistry

The Invaluable Nature of Speech Evaluation Training for New Basic Course Instructors

Recent reforms in higher education recognize the centrality of communication in general education programs (e.g., Association of American Colleges and Universities, American Association of State Colleges and Universities, LEAP, Common Core State Standards). As oral communication knowledge and skills are becoming recognized as integral to general education programs across the country, many basic course directors are finding themselves in the position of offering multiple sections of the course taught by multiple instructors. Additionally, basic course directors find themselves with the responsibility of providing clear measures of what they do and how well they do it. Because oral communication assessment is key to remaining integral to general education (Allen, 2002), basic course directors must provide instructor training on how to fairly and consistently evaluate student performances. But before this training can take place, basic course directors need to have an evaluation system in place that is fair, consistent, and reflective of actual student performance. There are several challenges to speech evaluation that warrant such a process. This essay will address those challenges and propose a systematic evaluation process that can serve as an impetus to instructor training in this area

Commercial Cargo Derivative Study of the Advanced Hybrid Wing Body Configuration with Over-Wing Engine Nacelles

LM has leveraged our partnership with the Air Force Research Laboratory (AFRL) and NASA on the advanced hybrid wing body (HWB) concept to develop a commercial freighter which addresses the NASA Advanced Air Transport Technology (AATT) Project goals for improved efficiency beyond 2025. The current Air Force Research Laboratory (AFRL) Revolutionary Configurations for Energy Efficiency (RCEE) program established the HWB configuration and technologies needed for military transports to achieve aerodynamic and fuel efficiencies well beyond the commercial industry's most modern designs. This study builds upon that effort to develop a baseline commercial cargo aircraft and two HWB derivative commercial cargo aircraft to quanitify the benefit of the HWB and establish a technology roadmap for further development

Experimental philosophy leading to a small scale digital data base of the conterminous United States for designing experiments with remotely sensed data

Research using satellite remotely sensed data, even within any single scientific discipline, often lacked a unifying principle or strategy with which to plan or integrate studies conducted over an area so large that exhaustive examination is infeasible, e.g., the U.S.A. However, such a series of studies would seem to be at the heart of what makes satellite remote sensing unique, that is the ability to select for study from among remotely sensed data sets distributed widely over the U.S., over time, where the resources do not exist to examine all of them. Using this philosophical underpinning and the concept of a unifying principle, an operational procedure for developing a sampling strategy and formal testable hypotheses was constructed. The procedure is applicable across disciplines, when the investigator restates the research question in symbolic form, i.e., quantifies it. The procedure is set within the statistical framework of general linear models. The dependent variable is any arbitrary function of remotely sensed data and the independent variables are values or levels of factors which represent regional climatic conditions and/or properties of the Earth's surface. These factors are operationally defined as maps from the U.S. National Atlas (U.S.G.S., 1970). Eighty-five maps from the National Atlas, representing climatic and surface attributes, were automated by point counting at an effective resolution of one observation every 17.6 km (11 miles) yielding 22,505 observations per map. The maps were registered to one another in a two step procedure producing a coarse, then fine scale registration. After registration, the maps were iteratively checked for errors using manual and automated procedures. The error free maps were annotated with identification and legend information and then stored as card images, one map to a file. A sampling design will be accomplished through a regionalization analysis of the National Atlas data base (presently being conducted). From this analysis a map of homogeneous regions of the U.S.A. will be created and samples (LANDSAT scenes) assigned by region

Structure of 10N in 9C+p resonance scattering

The structure of exotic nucleus 10N was studied using 9C+p resonance scattering. Two L=0 resonances were found to be the lowest states in 10N. The ground state of 10N is unbound with respect to proton decay by 2.2(2) or 1.9(2) MeV depending on the 2- or 1- spin-parity assignment, and the first excited state is unbound by 2.8(2) MeV.Comment: 6 pages, 4 figures, 1 table, submitted to Phys. Lett.

Effect of abdominal binding on respiratory mechanics during exercise in athletes with cervical spinal cord injury

West CR, Goosey-Tolfrey VL, Campbell IG, Romer LM. Effect of abdominal binding on respiratory mechanics during exercise in athletes with cervical spinal cord injury. J Appl Physiol 117: 36–45, 2014. First published May 22, 2014; doi:10.1152/japplphysiol.00218.2014.—We asked whether elastic binding of the abdomen influences respiratory mechanics during wheelchair propulsion in athletes with cervical spinal cord injury (SCI). Eight Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) performed submaximal and maximal incremental exercise tests on a treadmill, both with and without abdominal binding. Measurements included pulmonary function, pressure-derived indices of respiratory mechanics, operating lung volumes, tidal flow-volume data, gas exchange, blood lactate, and symptoms. Residual volume and functional residual capacity were reduced with binding (77 18 and 81 11% of unbound, P 0.05), vital capacity was increased (114 9%, P 0.05), whereas total lung capacity was relatively well preserved (99 5%). During exercise, binding introduced a passive increase in transdiaphragmatic pressure, due primarily to an increase in gastric pressure. Active pressures during inspiration were similar across conditions. A sudden, sustained rise in operating lung volumes was evident in the unbound condition, and these volumes were shifted downward with binding. Expiratory flow limitation did not occur in any subject and there was substantial reserve to increase flow and volume in both conditions. V ˙ O2 was elevated with binding during the final stages of exercise (8 –12%, P 0.05), whereas blood lactate concentration was reduced (16 –19%, P 0.05). V ˙ O2/heart rate slopes were less steep with binding (62 35 vs. 47 24 ml/beat, P 0.05). Ventilation, symptoms, and work rates were similar across conditions. The results suggest that abdominal binding shifts tidal breathing to lower lung volumes without influencing flow limitation, symptoms, or exercise tolerance. Changes in respiratory mechanics with binding may benefit O2 transport capacity by an improvement in central circulatory function.This article has been made available through the Brunel Open Access Publishing Fund

Nuclear structure beyond the neutron drip line: the lowest energy states in 9^9He via their T=5/2 isobaric analogs in 9^9Li

The level structure of the very neutron rich and unbound $^9$He nucleus has been the subject of significant experimental and theoretical study. Many recent works have claimed that the two lowest energy $^9$He states exist with spins $J^\pi=1/2^+$ and $J^\pi=1/2^-$ and widths on the order of hundreds of keV. These findings cannot be reconciled with our contemporary understanding of nuclear structure. The present work is the first high-resolution study with low statistical uncertainty of the relevant excitation energy range in the $^8$He$+n$ system, performed via a search for the T=5/2 isobaric analog states in $^9$Li populated through $^8$He+p elastic scattering. The present data show no indication of any narrow structures. Instead, we find evidence for a broad $J^{\pi}=1/2^+$ state in $^9$He located approximately 3 MeV above the neutron decay threshold

Quantitative high throughput analytics to support polysaccharide production process development.

The rapid development of purification processes for polysaccharide vaccines is constrained by a lack of analytical tools current technologies for the measurement of polysaccharide recovery and process-related impurity clearance are complex, time-consuming, and generally not amenable to high throughput process development (HTPD). HTPD is envisioned to be central to the improvement of existing polysaccharide manufacturing processes through the identification of critical process parameters that potentially impact the quality attributes of the vaccine and to the development of de novo processes for clinical candidates, across the spectrum of downstream processing. The availability of a fast and automated analytics platform will expand the scope, robustness, and evolution of Design of Experiment (DOE) studies. This paper details recent advances in improving the speed, throughput, and success of in-process analytics at the micro-scale. Two methods, based on modifications of existing procedures, are described for the rapid measurement of polysaccharide titre in microplates without the need for heating steps. A simplification of a commercial endotoxin assay is also described that features a single measurement at room temperature. These assays, along with existing assays for protein and nucleic acids are qualified for deployment in the high throughput screening of polysaccharide feedstreams. Assay accuracy, precision, robustness, interference, and ease of use are assessed and described. In combination, these assays are capable of measuring the product concentration and impurity profile of a microplate of 96 samples in less than one day. This body of work relies on the evaluation of a combination of commercially available and clinically relevant polysaccharides to ensure maximum versatility and reactivity of the final assay suite. Together, these advancements reduce overall process time by up to 30-fold and significantly reduce sample volume over current practices. The assays help build an analytical foundation to support the advent of HTPD technology for polysaccharide vaccines. It is envisaged that this will lead to an expanded use of Quality by Design (QbD) studies in vaccine process development

Development and validation of the BRIGHTLIGHT Survey, a patient-reported experience measure for young people with cancer

BACKGROUND: Patient experience is increasingly used as an indicator of high quality care in addition to more traditional clinical end-points. Surveys are generally accepted as appropriate methodology to capture patient experience. No validated patient experience surveys exist specifically for adolescents and young adults (AYA) aged 13-24 years at diagnosis with cancer. This paper describes early work undertaken to develop and validate a descriptive patient experience survey for AYA with cancer that encompasses both their cancer experience and age-related issues. We aimed to develop, with young people, an experience survey meaningful and relevant to AYA to be used in a longitudinal cohort study (BRIGHTLIGHT), ensuring high levels of acceptability to maximise study retention. METHODS: A three-stage approach was employed: Stage 1 involved developing a conceptual framework, conducting literature/Internet searches and establishing content validity of the survey; Stage 2 confirmed the acceptability of methods of administration and consisted of four focus groups involving 11 young people (14-25 years), three parents and two siblings; and Stage 3 established survey comprehension through telephone-administered cognitive interviews with a convenience sample of 23 young people aged 14-24 years. RESULT: Stage 1: Two-hundred and thirty eight questions were developed from qualitative reports of young people's cancer and treatment-related experience. Stage 2: The focus groups identified three core themes: (i) issues directly affecting young people, e.g. impact of treatment-related fatigue on ability to complete survey; (ii) issues relevant to the actual survey, e.g. ability to answer questions anonymously; (iii) administration issues, e.g. confusing format in some supporting documents. Stage 3: Cognitive interviews indicated high levels of comprehension requiring minor survey amendments. CONCLUSION: Collaborating with young people with cancer has enabled a survey of to be developed that is both meaningful to young people but also examines patient experience and outcomes associated with specialist cancer care. Engagement of young people throughout the survey development has ensured the content appropriately reflects their experience and is easily understood. The BRIGHTLIGHT survey was developed for a specific research project but has the potential to be used as a TYA cancer survey to assess patient experience and the care they receive