Next Generation Asthma Care Position Paper

The Next Generation Asthma Care position paper sets out a collaborative research project led by the Digital Health and Care Institute (DHI) with input from Asthma UK

The use of operationally-defined sequential Fe extraction methods for mineralogical applications: a cautionary tale from Mössbauer spectroscopy

Reactive iron minerals are crucial components of global nutrient cycles, directly controlling carbon transport and storage in marine sediments. Sequential selective extraction is frequently used for quantitatively characterising, and chemically isolating, individual Fe mineral phases. Reagent-specific mineral solubility is fundamental to the success of any sequential extraction, but is strongly affected by the varying physical and chemical morphology intrinsic to natural mineral samples. Natural sediment, rock, and soil samples often contain a mineral mixture, which further modifies solvent efficacy. 57Fe Mössbauer spectroscopy only probes the hyperfine interactions between next-nearest neighbouring atomic nuclei in the crystal lattice and is less affected by variation in mineral grain size and crystallinity than conventional, X-ray-based methods. In this study, we used Mössbauer spectroscopy in a novel context to cross-calibrate and optimise a popular, but frequently misused, sequential Fe extraction protocol. Our results showed that incomplete and premature removal of the target Fe minerals could occur at nearly every stage of the extraction and, in many cases, the leachate Fe content did not represent the target phase at all. Crystalline, natural siderite and amorphous, synthetic goethite were detected in the Mössbauer spectrum of the ammonium oxalate extraction for magnetite, after which all reactive Fe minerals should have been removed. Consistent with previous studies, and unlike many other clay minerals, nontronite was extracted as part of the highly reactive Fe pool, and in fact our data indicate that this mineral was extracted by the initial Na-acetate extraction that targets 'carbonate-bound Fe'. Matrix effects appeared to cause variable yield efficiencies: synthetic goethite was successfully removed when present as an individual mineral yet persisted beyond its target extraction when present in an Fe mineral mixture. Although suitable for the quantification of operationally-defined Fe pools, we caution the unverified use of sequential Fe extraction protocols for mineral specific applications. The application of sequential Fe extractions to define the reactive Fe pools as a paleoredox proxy of depositional conditions appears relatively robust. The premature removal of 2-line ferrihydrite observed in this study (due to the use of the more aggressive Na-acetate extraction for crystalline siderite), does not limit the quantitative use of the sequential Fe extraction in ancient sediments, where such 'easily reducible' oxides are unlikely to persist. In contrast, attributing the outcomes of operationally-defined Fe pools to specific Fe minerals is precarious and potentially entirely erroneous. Where Fe mineral specificity or separation is required, we recommend post-extraction validation by another secondary technique. Mössbauer spectroscopy offers such a method that can independently verify extraction stages and assess mineral specificity

Gross Motor Development, Movement Abnormalities, and Early Identification of Autism

Gross motor development (supine, prone, rolling, sitting, crawling, walking) and movement abnormalities were examined in the home videos of infants later diagnosed with autism (regression and no regression subgroups), developmental delays (DD), or typical development. Group differences in maturity were found for walking, prone, and supine, with the DD and Autism-No Regression groups both showing later developing motor maturity than typical children. The only statistically significant differences in movement abnormalities were in the DD group; the two autism groups did not differ from the typical group in rates of movement abnormalities or lack of protective responses. These findings do not replicate previous investigations suggesting that early motor abnormalities seen on home video can assist in early identification of autism

Impact by design: evaluating knowledge exchange as a lens for evaluating the wider impacts of a design-led business support programme.

This paper reports on the evaluation of knowledge exchange and impact generated through Design in Action (DIA), a design-led business support approach to answering the Arts and Humanities Research Council's call for knowledge exchange hubs. Can evaluation approaches to knowledge exchange reveal the complexity of impacts from design-led business support? Does design have a particular set of methods and processes relevant to knowledge exchange? To address these questions the paper draws on both interview and Survey material, and uses Nutley/Meagher Prism to analyse the emergent data. Nutley/Meagher Prism enables us to see different aspects of something in process which is otherwise indistinguishable, just as a prism enables us to see different wave lengths of light manifest as the colour spectrum. The paper addresses the interests of multiple stakeholders including economic development agencies, research councils, arts and cultural development bodies as well as design researchers and knowledge exchange intermediaries through demonstrating the multi-faceted value of design-led business support approaches to knowledge exchange programmes

Investing in Emerging and Frontier Economies: How Blended Finance can make the most of public funding

Combating climate change and achieving the SDGs require vast investment in sustainable projects in developing countries, but the world is falling short.A crucial reason is that a rich source of funds is not being fully tapped into: the private sector, which is eager to significantly increase its sustainable investments, but is constrained by avoidable obstacles.Private investors face an unattractive risk-return nexus; they lack easy access to crucial information: e.g. which projects the public sector is planning that they could take part in, and what they entail.Exposure to the risks of investing in less mature markets, with insufficient insurance available, deters them as well.In this report, the Investor Leadership Network (ILN), whose members manage over USD 9 trillion of investments, offers solutions.It calls for better collaboration between public and private sectors to make blended finance (public/private investment partnerships) a driving force in this area.Compiled with the support of The Rockefeller Foundation, the report calls for a sea change in how multilateral development banks (MDBs), governments, foundations, and other public institutions see private-sector involvement

Homogeneous Subgroups of Young Children with Autism Improve Phenotypic Characterization in the Study to Explore Early Development

The objective of this study was to identify homogenous classes of young children with autism spectrum disorder (ASD) to improve phenotypic characterization. Children were enrolled in the Study to Explore Early Development between 2 and 5 years of age. 707 children were classified with ASD after a comprehensive evaluation with strict diagnostic algorithms. Four classes of children with ASD were identified from latent class analysis: mild language delay with cognitive rigidity, mild language and motor delay with dysregulation, general developmental delay, and significant developmental delay with repetitive motor behaviors. We conclude that a four-class phenotypic model of children with ASD best describes our data and improves phenotypic characterization of young children with ASD. Implications for screening, diagnosis, and research are discussed

The Future of Our Seas: Marine scientists and creative professionals collaborate for science communication

To increase awareness of the current challenges facing the marine environment, the Future of Our Seas (FOOS) project brought together the expertise of scientists, public engagement experts and creatives to train and support a group of marine scientists in effective science communication and innovative public engagement. This case study aims to inspire scientists and artists to use the FOOS approach in training, activity design and development support (hereafter called the ‘FOOS programme’) to collaboratively deliver novel and creative engagement activities. The authors reflect on the experiences of the marine scientists: (1) attending the FOOS communication and engagement training; (2) creating and delivering public engagement activities; (3) understanding our audience; and (4) collaborating with artists. The authors also share what the artists and audiences learned from participating in the FOOS public engagement activities. These different perspectives provide new insights for the field with respect to designing collaborative training which maximizes the impact of the training on participants, creative collaborators and the public. Long-term benefits of taking part in the FOOS programme, such as initiating future collaborative engagement activities and positively impacting the scientists’ research processes, are also highlighted

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

Dexamethasone reduces emesis after major gastrointestinal surgery (DREAMS)

BACKGROUND: Postoperative nausea and vomiting is one of the most common complications affecting patients after surgery and causes significant morbidity and increased length of hospital stay. It is accepted that patients undergoing surgery on the bowel are at a higher risk. In the current era of minimally invasive colorectal surgery combined with enhanced recovery, reducing the incidence and severity of postoperative nausea and vomiting is particularly important. Dexamethasone is widely, but not universally used. It is known to improve appetite and gastric emptying, thus reduce vomiting. However, this benefit is not established in patients undergoing bowel surgery, and dexamethasone has possible side effects such as increased risk of wound infection and anastomotic leak that could adversely affect recovery. DESIGN: DREAMS is a phase III, double-blind, multicenter, randomized controlled trial with the primary objective of determining if preoperative dexamethasone reduces postoperative nausea and vomiting in patients undergoing elective gastrointestinal resections. DREAMS aims to randomize 1,350 patients over 2.5 years. Patients undergoing laparoscopic or open colorectal resections for malignant or benign pathology are randomized between 8 mg intravenous dexamethasone and control (no dexamethasone). All patients are given one additional antiemetic at the time of induction, prior to randomization. Both the patient and their surgeon are blinded as to the treatment arm. Secondary objectives of the DREAMS trial are to determine whether there are other measurable benefits during recovery from surgery with the use of dexamethasone, including quicker return to oral diet and reduced length of stay. Health-related quality of life, fatigue and risks of infections will be investigated. TRIAL REGISTRATION: ISRCTN2197362