Showing papers by "University of Hertfordshire published in 2017"

Beyond Adoption: A New Framework for Theorizing and Evaluating Nonadoption, Abandonment, and Challenges to the Scale-Up, Spread, and Sustainability of Health and Care Technologies

Abstract: Background: Many promising technological innovations in health and social care are characterized by nonadoption or abandonment by individuals or by failed attempts to scale up locally, spread distantly, or sustain the innovation long term at the organization or system level. Objective: Our objective was to produce an evidence-based, theory-informed, and pragmatic framework to help predict and evaluate the success of a technology-supported health or social care program. Methods: The study had 2 parallel components: (1) secondary research (hermeneutic systematic review) to identify key domains, and (2) empirical case studies of technology implementation to explore, test, and refine these domains. We studied 6 technology-supported programs-video outpatient consultations, global positioning system tracking for cognitive impairment, pendant alarm services, remote biomarker monitoring for heart failure, care organizing software, and integrated case management via data sharing-using longitudinal ethnography and action research for up to 3 years across more than 20 organizations. Data were collected at micro level (individual technology users), meso level (organizational processes and systems), and macro level (national policy and wider context). Analysis and synthesis was aided by sociotechnically informed theories of individual, organizational, and system change. The draft framework was shared with colleagues who were introducing or evaluating other technology-supported health or care programs and refined in response to feedback. Results: The literature review identified 28 previous technology implementation frameworks, of which 14 had taken a dynamic systems approach (including 2 integrative reviews of previous work). Our empirical dataset consisted of over 400 hours of ethnographic observation, 165 semistructured interviews, and 200 documents. The final nonadoption, abandonment, scale-up, spread, and sustainability (NASSS) framework included questions in 7 domains: the condition or illness, the technology, the value proposition, the adopter system (comprising professional staff, patient, and lay caregivers), the organization(s), the wider (institutional and societal) context, and the interaction and mutual adaptation between all these domains over time. Our empirical case studies raised a variety of challenges across all 7 domains, each classified as simple (straightforward, predictable, few components), complicated (multiple interacting components or issues), or complex (dynamic, unpredictable, not easily disaggregated into constituent components). Programs characterized by complicatedness proved difficult but not impossible to implement. Those characterized by complexity in multiple NASSS domains rarely, if ever, became mainstreamed. The framework showed promise when applied (both prospectively and retrospectively) to other programs. Conclusions: Subject to further empirical testing, NASSS could be applied across a range of technological innovations in health and social care. It has several potential uses: (1) to inform the design of a new technology; (2) to identify technological solutions that (perhaps despite policy or industry enthusiasm) have a limited chance of achieving large-scale, sustained adoption; (3) to plan the implementation, scale-up, or rollout of a technology program; and (4) to explain and learn from program failures.

The Met Office Unified Model Global Atmosphere 7.0/7.1 and JULES Global Land 7.0 configurations

Abstract: . We describe Global Atmosphere 3.0 (GA3.0): a configuration of the Met Office Unified Model (MetUM) developed for use across climate research and weather prediction activities. GA3.0 has been formulated by converging the development paths of the Met Office's weather and climate global atmospheric model components such that wherever possible, atmospheric processes are modelled or parametrized seamlessly across spatial resolutions and timescales. This unified development process will provide the Met Office and its collaborators with regular releases of a configuration that has been evaluated, and can hence be applied, over a variety of modelling regimes. We also describe Global Land 3.0 (GL3.0): a configuration of the JULES community land surface model developed for use with GA3.0. This paper provides a comprehensive technical and scientific description of the GA3.0 and GL3.0 (and related GA3.1 and GL3.1) configurations and presents the results of some initial evaluations of their performance in various applications. It is to be the first in a series of papers describing each subsequent Global Atmosphere release; this will provide a single source of reference for established users and developers as well as researchers requiring access to a current, but trusted, global MetUM setup.

The LOFAR Two-metre Sky Survey. I. Survey description and preliminary data release

Abstract: The LOFAR Two-metre Sky Survey (LoTSS) is a deep 120-168 MHz imaging survey that will eventually cover the entire northern sky. Each of the 3170 pointings will be observed for 8 h, which, at most declinations, is sufficient to produce ~5? resolution images with a sensitivity of ~100 ?Jy/beam and accomplish the main scientific aims of the survey, which are to explore the formation and evolution of massive black holes, galaxies, clusters of galaxies and large-scale structure. Owing to the compact core and long baselines of LOFAR, the images provide excellent sensitivity to both highly extended and compact emission. For legacy value, the data are archived at high spectral and time resolution to facilitate subarcsecond imaging and spectral line studies. In this paper we provide an overview of the LoTSS. We outline the survey strategy, the observational status, the current calibration techniques, a preliminary data release, and the anticipated scientific impact. The preliminary images that we have released were created using a fully automated but direction-independent calibration strategy and are significantly more sensitive than those produced by any existing large-Area low-frequency survey. In excess of 44 000 sources are detected in the images that have a resolution of 25?, typical noise levels of less than 0.5 mJy/beam, and cover an area of over 350 square degrees in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00?00? to 57°00?00?).

Core outcome measures for interventions to prevent or slow the progress of dementia for people living with mild to moderate dementia: Systematic review and consensus recommendations

Abstract: Background There are no disease-modifying treatments for dementia. There is also no consensus on disease modifying outcomes. We aimed to produce the first evidence-based consensus on core outcome measures for trials of disease modification in mild-to-moderate dementia. Methods and findings We defined disease-modification interventions as those aiming to change the underlying pathology. We systematically searched electronic databases and previous systematic reviews for published and ongoing trials of disease-modifying treatments in mild-to-moderate dementia. We included 149/22,918 of the references found; with 81 outcome measures from 125 trials. Trials involved participants with Alzheimer’s disease (AD) alone (n = 111), or AD and mild cognitive impairment (n = 8) and three vascular dementia. We divided outcomes by the domain measured (cognition, activities of daily living, biological markers, neuropsychiatric symptoms, quality of life, global). We calculated the number of trials and of participants using each outcome. We detailed psychometric properties of each outcome. We sought the views of people living with dementia and family carers in three cities through Alzheimer’s society focus groups. Attendees at a consensus conference (experts in dementia research, disease-modification and harmonisation measures) decided on the core set of outcomes using these results. Recommended core outcomes were cognition as the fundamental deficit in dementia and to indicate disease modification, serial structural MRIs. Cognition should be measured by Mini Mental State Examination or Alzheimer's Disease Assessment Scale-Cognitive Subscale. MRIs would be optional for patients. We also made recommendations for measuring important, but non-core domains which may not change despite disease modification. Limitations Most trials were about AD. Specific instruments may be superseded. We searched one database for psychometric properties. Interpretation This is the first review to identify the 81 outcome measures the research community uses for disease-modifying trials in mild-to-moderate dementia. Our recommendations will facilitate designing, comparing and meta-analysing disease modification trials in mild-to-moderate dementia, increasing their value.

A deep ALMA image of the Hubble Ultra Deep Field

Abstract: European Research Council via the award of an Advanced Grant; EC [312725]; European Research Council via the award of a Consolidator Grant; UK Science and Technology Facilities Council; FWO Pegasus Marie Curie Fellowship; European Research Council through the Advanced Grant [321302, 669253, 670193]; JSPS KAKENHI [JP15K17604]; Chulalongkorn University's CUniverse (CUAASC); Royal Society

The SCUBA-2 Cosmology Legacy Survey: 850 μm maps, catalogues and number counts

Abstract: We present a catalogue of similar to 3000 submillimetre sources detected (>= 3.5 sigma) at 850 mu m over similar to 5 deg(2) surveyed as part of the James Clerk Maxwell Telescope (JCMT) SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850 mu m, increasing the sample size of 850 mu m selected submillimetre galaxies by an order of magnitude. The wide 850 mu m survey component of S2CLS covers the extragalactic fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1s depth of S2CLS is 1.2 mJy beam(-1), approaching the SCUBA-2 850 mu m confusion limit, which we determine to be sigma(c) approximate to 0.8 mJy beam(-1). We measure the 850 mu m number counts, reducing the Poisson errors on the differential counts to approximately 4 per cent at S-850 approximate to 3 mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5 degrees-1 degrees scales are generally within 50 per cent of the S2CLS mean for S-850 > 3 mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2 sigma) density enhancement in GOODS-North. The observed counts are in reasonable agreement with recent phenomenological and semi-analytic models, although determining the shape of the faint-end slope (S-850 10 mJy there are approximately 10 sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850 mu m emission

The LCES HIRES/Keck Precision Radial Velocity Exoplanet Survey

Abstract: This document is the Accepted Manuscript version of the following article: R. Paul Butler, et al, The LCES HIRES/Keck Precision Radial Velocity Exoplanet Survey, The Astronomical Journal, Vol 153 (5), 19 pp., published 13 April 2017. The Version of Record is available online at doi: https://doi.org/10.3847/1538-3881/aa66ca. Paper data available at: http://home.dtm.ciw.edu/ebps/data/. © 2017. The American Astronomical Society. All rights reserved.

Fetal Bovine Serum (FBS): Past - Present - Future.

Abstract: The supplementation of culture medium with fetal bovine serum (FBS, also referred to as "fetal calf serum") is still common practice in cell culture applications. Due to a number of disadvantages in terms of quality and reproducibility of in vitro data, animal welfare concerns, and in light of recent cases of fraudulent marketing, the search for alternatives and the development of serum-free medium formulations has gained global attention. Here, we report on the 3rd Workshop on FBS, Serum Alternatives and Serum-free Media, where regulatory aspects, the serum dilemma, alternatives to FBS, case-studies of serum-free in vitro applications, and the establishment of serum-free databases were discussed. The whole process of obtaining blood from a living calf fetus to using the FBS produced from it for scientific purposes is de facto not yet legally regulated despite the existing EU-Directive 2010/63/EU on the use of animals for scientific purposes. Together with the above-mentioned challenges, several strategies have been developed to reduce or replace FBS in cell culture media in terms of the 3Rs (Refinement, Reduction, Replacement). Most recently, releasates of activated human donor thrombocytes (human platelet lysates) have been shown to be one of the most promising serum alternatives when chemically-defined media are not yet an option. Additionally, new developments in cell-based assay techniques, advanced organ-on-chip and microphysiological systems are covered in this report. Chemically-defined serum-free media are shown to be the ultimate goal for the majority of culture systems, and examples are discussed.

The kepler follow-up observation program. i. a catalog of companions to kepler stars from high-resolution imaging

Abstract: We present results from high-resolution, optical to near-IR imaging of host stars of Kepler Objects of Interest (KOIs), identified in the original Kepler field. Part of the data were obtained under the Kepler imaging follow-up observation program over six years (2009–2015). Almost 90% of stars that are hosts to planet candidates or confirmed planets were observed. We combine measurements of companions to KOI host stars from different bands to create a comprehensive catalog of projected separations, position angles, and magnitude differences for all detected companion stars (some of which may not be bound). Our compilation includes 2297 companions around 1903 primary stars. From high-resolution imaging, we find that ~10% (~30%) of the observed stars have at least one companion detected within 1" (4"). The true fraction of systems with close (≾4") companions is larger than the observed one due to the limited sensitivities of the imaging data. We derive correction factors for planet radii caused by the dilution of the transit depth: assuming that planets orbit the primary stars or the brightest companion stars, the average correction factors are 1.06 and 3.09, respectively. The true effect of transit dilution lies in between these two cases and varies with each system. Applying these factors to planet radii decreases the number of KOI planets with radii smaller than 2 R_⊕ by ~2%–23% and thus affects planet occurrence rates. This effect will also be important for the yield of small planets from future transit missions such as TESS.

Activation and discovery of earth-abundant metal catalysts using sodium tert -butoxide

Abstract: First-row, earth-abundant metals offer an inexpensive and sustainable alternative to precious-metal catalysts. As such, iron and cobalt catalysts have garnered interest as replacements for alkene and alkyne hydrofunctionalization reactions. However, these have required the use of air- and moisture-sensitive catalysts and reagents, limiting both adoption by the non-expert as well as applicability, particularly in industrial settings. Here, we report a simple method for the use of earth-abundant metal catalysts by general activation with sodium tert-butoxide. Using only robust air- and moisture-stable reagents and pre-catalysts, both known and, significantly, novel catalytic activities have been successfully achieved, covering hydrosilylation, hydroboration, hydrovinylation, hydrogenation and [2π+2π] alkene cycloaddition. This activation method allows for the easy use of earth-abundant metals, including iron, cobalt, nickel and manganese, and represents a generic platform for the discovery and application of non-precious metal catalysis.

Policies for biosimilar uptake in Europe: An overview.

Abstract: markdown__Background__ Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. __Objectives__ The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. __Methods__ An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. __Results__ In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. __Conclusions__ Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market.

The Horizon-AGN simulation: evolution of galaxy properties over cosmic time

Abstract: We compare the predictions of Horizon-AGN, a hydro-dynamical cosmological simulation that uses an adaptive mesh refinement code, to observational data in the redshift range 0 6. We study the reproduction, by the simulation, of quantities that trace the aggregate stellar-mass growth of galaxies over cosmic time: luminosity and stellar-mass functions, the star formation main sequence, rest-frame UV-optical-near infrared colours and the cosmic star-formation history. We show that Horizon-AGN, which is not tuned to reproduce the local Universe, produces good overall agreement with these quantities, from the present day to the epoch when the Universe was 5% of its current age. By comparison to Horizon-noAGN, a twin simulation without AGN feedback, we quantify how feedback from black holes is likely to help shape galaxy stellar-mass growth in the redshift range 0 6, particularly in the most massive galaxies. Our results demonstrate that Horizon-AGN successfully captures the evolutionary trends of observed galaxies over the lifetime of the Universe, making it an excellent tool for studying the processes that drive galaxy evolution and making predictions for the next generation of galaxy surveys.

Structural insight into allosteric modulation of protease-activated receptor 2

Abstract: Crystal structures of protease-activated receptor 2 (PAR2) in complex with two different antagonist ligands and with a blocking antibody reveal binding sites that are distinct from those found on PAR1, offering new leads for structure-based drug design. Protease-activated receptors (PARs) are a family of G-protein-coupled receptors (GPCRs) with roles in diverse diseases, such as neuroinflammation and cancer, and are considered important target for drug discovery. Here, Fiona Marshall and colleagues have determined three crystal structures of PAR2 in complex with two different antagonists and a blocking antibody, respectively. The antagonists bind to distinct allosteric sites on the receptor and these binding sites are different to the one previously found on PAR1. Therefore this family of GPCRs can be inhibited by a number of different allosteric mechanisms, offering new leads for structure-based drug design. Protease-activated receptors (PARs) are a family of G-protein-coupled receptors (GPCRs) that are irreversibly activated by proteolytic cleavage of the N terminus, which unmasks a tethered peptide ligand that binds and activates the transmembrane receptor domain, eliciting a cellular cascade in response to inflammatory signals and other stimuli. PARs are implicated in a wide range of diseases, such as cancer and inflammation1,2,3. PARs have been the subject of major pharmaceutical research efforts3 but the discovery of small-molecule antagonists that effectively bind them has proved challenging. The only marketed drug targeting a PAR is vorapaxar4, a selective antagonist of PAR1 used to prevent thrombosis. The structure of PAR1 in complex with vorapaxar has been reported previously5. Despite sequence homology across the PAR isoforms, discovery of PAR2 antagonists has been less successful, although GB88 has been described as a weak antagonist6. Here we report crystal structures of PAR2 in complex with two distinct antagonists and a blocking antibody. The antagonist AZ8838 binds in a fully occluded pocket near the extracellular surface. Functional and binding studies reveal that AZ8838 exhibits slow binding kinetics, which is an attractive feature for a PAR2 antagonist competing against a tethered ligand. Antagonist AZ3451 binds to a remote allosteric site outside the helical bundle. We propose that antagonist binding prevents structural rearrangements required for receptor activation and signalling. We also show that a blocking antibody antigen-binding fragment binds to the extracellular surface of PAR2, preventing access of the tethered ligand to the peptide-binding site. These structures provide a basis for the development of selective PAR2 antagonists for a range of therapeutic uses.

Self-piercing riveting-a review

Abstract: Self-piercing riveting (SPR) is a cold mechanical joining process used to join two or more sheets of materials by driving a rivet piercing through the top sheet or the top and middle sheets and subsequently lock into the bottom sheet under the guidance of a suitable die. SPR is currently the main joining method for aluminium and mixed-material lightweight automotive structures. SPR was originated half century ago, but it only had significant progress in the last 25 years due to the requirement of joining lightweight materials, such as aluminium alloy structures, aluminium-steel structures and other mixed-material structures, from the automotive industry. Compared with other conventional joining methods, SPR has many advantages including no pre-drilled holes required, no fume, no spark and low noise, no surface treatment required, ability to join multi-layer materials and mixed materials and ability to produce joints with high static and fatigue strengths. In this paper, research investigations that have been conducted on self-piercing riveting will be extensively reviewed. The current state and development of SPR process is reviewed and the influence of the key process parameters on joint quality is discussed. The mechanical properties of SPR joints, the corrosion behaviour of SPR joints, the distortion of SPR joints and the simulation of SPR process and joint performance are reviewed. Developing reliable simulation methods for SPR process and joint performance to reduce the need of physical testing has been identified as one of the main challenges.

A review on prognostics and health monitoring of proton exchange membrane fuel cell

Abstract: Fuel cell technology can be traced back to 1839 when British scientist Sir William Grove discovered that it was possible to generate electricity by the reaction between hydrogen and oxygen gases. However, fuel cell still cannot compete with internal combustion engines although they have many advantages including zero carbon emissions. Fossil fuels are cheaper and present very high volumetric energy densities compared with the hydrogen gas. Furthermore, hydrogen storage as a liquid is still a huge challenge. Another important disadvantage is the lifespan of the fuel cell because of their durability, reliability and maintainability. Prognostics is an emerging technology in sustainability of engineering systems through failure prevention, reliability assessment and remaining useful lifetime estimation. Prognostics and health monitoring can play a critical role in enhancing the durability, reliability and maintainability of the fuel cell system. This paper presents a review on the current state-of-the-art in prognostics and health monitoring of Proton Exchange Membrane Fuel Cell (PEMFC), aiming at identifying research and development opportunities in these fields. This paper also highlights the importance of incorporating prognostics and failure modes, mechanisms and effects analysis (FMMEA) in PEMFC to give them sustainable competitive advantage when compared with other non-clean energy solutions.

Hippocampal and prefrontal processing of network topology to simulate the future

Abstract: Topological networks lie at the heart of our cities and social milieu. However, it remains unclear how and when the brain processes topological structures to guide future behaviour during everyday life. Using fMRI in humans and a simulation of London (UK), here we show that, specifically when new streets are entered during navigation of the city, right posterior hippocampal activity indexes the change in the number of local topological connections available for future travel and right anterior hippocampal activity reflects global properties of the street entered. When forced detours require re-planning of the route to the goal, bilateral inferior lateral prefrontal activity scales with the planning demands of a breadth-first search of future paths. These results help shape models of how hippocampal and prefrontal regions support navigation, planning and future simulation.

Crystal structure of the GLP-1 receptor bound to a peptide agonist

Abstract: Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the molecular mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an α-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helices reveals hallmarks of an active conformation similar to that observed in class A receptors. Guided by this structural information, we design peptide agonists with potent in vivo activity in a mouse model of diabetes.

British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017.

Abstract: Decisions about the use of psychotropic medication in pregnancy are an ongoing challenge for clinicians and women with mental health problems, owing to the uncertainties around risks of the illness itself to mother and fetus/infant, effectiveness of medications in pregnancy and risks to the fetus/infant from in utero exposure or via breast milk. These consensus guidelines aim to provide pragmatic advice regarding these issues. They are divided into sections on risks of untreated illness in pregnancy; general principles of using drugs in the perinatal period; benefits and harms associated with individual drugs; and recommendations for the management of specific disorders.

When "Chems" Meet Sex: A Rising Phenomenon Called "ChemSex".

Abstract: Background The term "chemsex" was coined to indicate the voluntary intake of psychoactive and non psychoactive drugs in the context of recreational settings to facilitate and/or to enhance sexual intercourses mostly among men who have sex with other men (MSM). Objective The authors aimed to review the mechanisms of action, the toxicity and the pattern of use and abuse of substances involved in "chemsex" practice together with the sociocultural background underlying it and the health-related consequences that they may have. Results Gamma-hydroxybutyrate, gamma-butyrolactone,1,4-butanediol, mephedrone, methamphetamine, sildenafil, tadalafil, vardenafil and alkyl nitrites have been described in their role of "chemsex drugs" including pharmacological action and in their implication to impair capacities to chose sexual partners and consensual sex. Moreover, it has been demonstrated that sexual activity over protracted length of time under the influence of chemsex drugs can result in rectal trauma or penile abrasions and a significant increase of the risk of transmission of sexual transmitted diseases, especially in case of condomless intercourses, which are frequent in this context, representing therefore a serious health threat. Conclusion One of the major problems to establish health policy priority interventions for chemsex is the lack of available epidemiological data on the issue. Finally, social actions should be taken in order to break down the barriers that currently exist among chemsex drug users in accessing services, including the shame and stigma often associated with drug use. In conclusion, more specific resources to face high risks of infections and HIV transmission are required in bisexual and homosexual individuals having SUID: sex under the influence of drugs.

The Hi-GAL compact source catalogue – I. The physical properties of the clumps in the inner Galaxy (−71. ◦ 0 < ℓ < 67.◦ 0)

Abstract: Hi-GAL (Herschel InfraRed Galactic Plane Survey) is a large-scale survey of the Galactic plane, performed with Herschel in five infrared continuum bands between 70 and 500 μm. We present a band-merged catalogue of spatially matched sources and their properties derived from fits to the spectral energy distributions (SEDs) and heliocentric distances, based on the photometric catalogues presented in Molinari et al., covering the portion of Galactic plane −71∘.0 < l < 67∘.0. The band-merged catalogue contains 100 922 sources with a regular SED, 24 584 of which show a 70-μm counterpart and are thus considered protostellar, while the remainder are considered starless. Thanks to this huge number of sources, we are able to carry out a preliminary analysis of early stages of star formation, identifying the conditions that characterize different evolutionary phases on a statistically significant basis. We calculate surface densities to investigate the gravitational stability of clumps and their potential to form massive stars. We also explore evolutionary status metrics such as the dust temperature, luminosity and bolometric temperature, finding that these are higher in protostellar sources compared to pre-stellar ones. The surface density of sources follows an increasing trend as they evolve from pre-stellar to protostellar, but then it is found to decrease again in the majority of the most evolved clumps. Finally, we study the physical parameters of sources with respect to Galactic longitude and the association with spiral arms, finding only minor or no differences between the average evolutionary status of sources in the fourth and first Galactic quadrants, or between ‘on-arm’ and ‘interarm’ positions.

Opportunities for therapeutic antibodies directed at G-protein-coupled receptors

Abstract: G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands, from large proteins and proteases to small peptides, metabolites, neurotransmitters and ions. They are expressed on all cells in the body and have key roles in physiology and homeostasis. As such, GPCRs are one of the most important target classes for therapeutic drug discovery. The development of drugs targeting GPCRs has therapeutic value across a wide range of diseases, including cancer, immune and inflammatory disorders as well as neurological and metabolic diseases. The progress made by targeting GPCRs with antibody-based therapeutics, as well as technical hurdles to overcome, are presented and discussed in this Review. Antibody therapeutics targeting C-C chemokine receptor type 4 (CCR4), CCR5 and calcitonin gene-related peptide (CGRP) are used as illustrative clinical case studies.

Principles of robotics: regulating robots in the real world

Abstract: This paper proposes a set of five ethical principles, together with seven high-level messages, as a basis for responsible robotics. The Principles of Robotics were drafted in 2010 and published online in 2011. Since then the principles have influenced, and continue to influence, a number of initiatives in robot ethics but have not, to date, been formally published. This paper remedies that omission.

An ALMA Survey of Submillimeter Galaxies in the Extended Chandra Deep Field South: Spectroscopic Redshifts

Abstract: We present spectroscopic redshifts of {\text{}}{S}870μ {{m}} ≳ 2 mJy submillimeter galaxies (SMGs), which have been identified from the ALMA follow-up observations of 870 μm detected sources in the Extended Chandra Deep Field South (the ALMA-LESS survey). We derive spectroscopic redshifts for 52 SMGs, with a median of z = 2.4 ± 0.1. However, the distribution features a high-redshift tail, with ˜23% of the SMGs at z≥slant 3. Spectral diagnostics suggest that the SMGs are young starbursts, and the velocity offsets between the nebular emission and UV ISM absorption lines suggest that many are driving winds, with velocity offsets of up to 2000 km s-1. Using the spectroscopic redshifts and the extensive UV-to-radio photometry in this field, we produce optimized spectral energy distributions (SEDs) using Magphys, and use the SEDs to infer a median stellar mass of {M}\star = (6 ± 1)× 1010 M {}⊙ for our SMGs with spectroscopic redshift. By combining these stellar masses with the star formation rates (measured from the far-infrared SEDs), we show that SMGs (on average) lie a factor of ˜5 above the so-called “main sequence” at z˜ 2. We provide this library of 52 template fits with robust and uniquely well-sampled SEDs as a resource for future studies of SMGs, and also release the spectroscopic catalog of ˜2000 (mostly infrared-selected) galaxies targeted as part of the spectroscopic campaign.

Exploitation of endophytes for sustainable agricultural intensification.

Abstract: Intensive agriculture, which depends on unsustainable levels of agrochemical inputs, is environmentally harmful, and the expansion of these practices to meet future needs is not economically feasible. Other options should be considered to meet the global food security challenge. The plant microbiome has been linked to improved plant productivity and, in this microreview, we consider the endosphere – a subdivision of the plant microbiome. We suggest a new definition of microbial endophyte status, the need for synergy between fungal and bacterial endophyte research efforts, as well as potential strategies for endophyte application to agricultural systems.