University of Hertfordshire

BACKGROUND: The Framework Method is becoming an increasingly popular approach to the management and analysis of qualitative data in health research. However, there is confusion about its potential application and limitations. DISCUSSION: The article discusses when it is appropriate to adopt the Framework Method and explains the procedure for using it in multi-disciplinary health research teams, or those that involve clinicians, patients and lay people. The stages of the method are illustrated using examples from a published study. SUMMARY: Used effectively, with the leadership of an experienced qualitative researcher, the Framework Method is a systematic and flexible approach to analysing qualitative data and is appropriate for use in research teams even where not all members have previous experience of conducting qualitative research.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Context. We present the early installment of the third Gaia data release, Gaia EDR3, consisting of astrometry and photometry for 1.8 billion sources brighter than magnitude 21, complemented with the list of radial velocities from Gaia DR2. Aims. A summary of the contents of Gaia EDR3 is presented, accompanied by a discussion on the differences with respect to Gaia DR2 and an overview of the main limitations which are present in the survey. Recommendations are made on the responsible use of Gaia EDR3 results. Methods. The raw data collected with the Gaia instruments during the first 34 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium and turned into this early third data release, which represents a major advance with respect to Gaia DR2 in terms of astrometric and photometric precision, accuracy, and homogeneity. Results. Gaia EDR3 contains celestial positions and the apparent brightness in G for approximately 1.8 billion sources. For 1.5 billion of those sources, parallaxes, proper motions, and the ( G BP − G RP ) colour are also available. The passbands for G , G BP , and G RP are provided as part of the release. For ease of use, the 7 million radial velocities from Gaia DR2 are included in this release, after the removal of a small number of spurious values. New radial velocities will appear as part of Gaia DR3. Finally, Gaia EDR3 represents an updated materialisation of the celestial reference frame (CRF) in the optical, the Gaia -CRF3, which is based solely on extragalactic sources. The creation of the source list for Gaia EDR3 includes enhancements that make it more robust with respect to high proper motion stars, and the disturbing effects of spurious and partially resolved sources. The source list is largely the same as that for Gaia DR2, but it does feature new sources and there are some notable changes. The source list will not change for Gaia DR3. Conclusions. Gaia EDR3 represents a significant advance over Gaia DR2, with parallax precisions increased by 30 per cent, proper motion precisions increased by a factor of 2, and the systematic errors in the astrometry suppressed by 30–40% for the parallaxes and by a factor ~2.5 for the proper motions. The photometry also features increased precision, but above all much better homogeneity across colour, magnitude, and celestial position. A single passband for G , G BP , and G RP is valid over the entire magnitude and colour range, with no systematics above the 1% level

Recent developments in the field of proteomics have revolutionized the way that proteins, and their contribution to cellular functions, are studied. The subsequent increased understanding of the mechanisms of cellular function and misfunction will have particular impact in the area of medical research, where disease processes will be better understood, many new (protein) therapeutic targets identified, and novel therapeutic agents developed. At the basic research level, phenotype will be explained in terms of cellular mechanisms.

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

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.

We describe the goals, design, and implementation of the UKIRT Infrared Deep Sky Survey (UKIDSS), a seven year sky survey which began in May 2005. It is a portfolio of five survey components covering various combinations of the filter set ZYJHK and H_2. The Large Area Survey, the Galactic Cluster Survey, and the Galactic Plane Survey cover approximately 7000 square degrees to a depth of K~18; the Deep Extragalactic Survey covers 35 square degrees to K~21, and the Ultra Deep Survey covers 0.77 square degrees to K~23. The prime aim of UKIDSS is to provide a long term astronomical legacy database; the design is however driven by a series of specific goals -- for example to find the nearest and faintest sub-stellar objects; to break the z=7 quasar barrier; to determine the epoch of re-ionisation; to determine the substellar mass function; to discover Population II brown dwarfs, if they exist; to measure the growth of structure from z=3 to the present day; to determine the epoch of spheroid formation; and to map the Milky Way through the dust, to several kpc. The data are being made available in a series of staged releases, the first of which (the "Early Data Release (EDR)") is described in Dye et al (2006). The data are immediately public to astronomers in all ESO member states, and available to the world after eighteen months. Before the formal survey began, UKIRT and the UKIDSS consortium collaborated in obtaining and analysing a series of small science verification (SV) projects to complete the commissioning of the camera. We show some results from these SV projects in order to demonstrate the likely power of the eventual complete survey.

Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.

The Spectral and Photometric Imaging REceiver (SPIRE), is the <i>Herschel<i/> Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 <i>μ<i/>m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194–671 <i>μ<i/>m (447–1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4´× 8´, observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6´. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the <i>Herschel<i/> cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5–2.

Why do growth rates differ? This paper surveys the recent empirical literature on economic growth, starting with a discussion of stylized facts, data problems, and statistical methods. Six research questions are emphasized, drawing on growth and convergence research. In answering these questions, the paper argues that efficiency has grown at different rates across countries, casting doubt on neoclassical models in which technology is a public good. The latter half of the paper rounds up a variety of findings before providing answers to all six questions, including a short summary of how differences in growth rates arise.

This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Despite a changing world in terms of data sharing, availability, and transparency, there are still major resource issues associated with collating datasets that will satisfy the requirements of comprehensive pesticide risk assessments, especially those undertaken at a regional or national scale. In 1996, a long-term project was initiated to begin collating and formatting pesticide data to eventually create a free-to-all repository of data that would provide a comprehensive transparent, harmonized, and managed extensive dataset for all types of pesticide risk assessments. Over the last 20 years, this database has been keeping pace with improving risk assessments, their associated data requirements, and the needs and expectations of database end users. In 2007, the Pesticide Properties DataBase (PPDB) was launched as a free-to-access website. Currently, the PPDB holds data for almost 2300 pesticide active substances and over 700 metabolites. For each substance around 300 parameters are stored, covering human health, environmental quality, and biodiversity risk assessments. With the approach of the twentieth anniversary of the database, this article seeks to elucidate the current data model, data sources, its validation, and quality control processes and describes a number of existing risk assessment applications that depend upon it.

BACKGROUND: Birth before 26 weeks of gestation is associated with a high prevalence of neurologic and developmental disabilities in the infant during the first two years of life. METHODS: We studied at the time of early school age children who had been born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland in 1995. Each child had been evaluated at 30 months of age. The children underwent standardized cognitive and neurologic assessments at six years of age. Disability was defined as severe (indicating dependence on caregivers), moderate, or mild according to predetermined criteria. RESULTS: Of 308 surviving children, 241 (78 percent) were assessed at a median age of six years and four months; 160 classmates delivered at full term served as a comparison group. Although the use of test reference norms showed that cognitive impairment (defined as results more than 2 SD below the mean) was present in 21 percent of the children born extremely preterm (as compared with 1 percent in the standardized data), this value rose to 41 percent when the results were compared with those for their classmates. The rates of severe, moderate, and mild disability were 22 percent, 24 percent, and 34 percent, respectively; disabling cerebral palsy was present in 30 children (12 percent). Among children with severe disability at 30 months of age, 86 percent still had moderate-to-severe disability at 6 years of age. In contrast, other disabilities at the age of 30 months were poorly predictive of developmental problems at 6 years of age. CONCLUSIONS: Among extremely preterm children, cognitive and neurologic impairment is common at school age. A comparison with their classroom peers indicates a level of impairment that is greater than is recognized with the use of standardized norms.

We present a comprehensive analysis of the relationship between star formation rate surface density, SigmaSFR, and gas surface density, Sigmagas, at sub-kpc resolution in a sample of 18 nearby galaxies. We use high-resolution H I data from The H I Nearby Galaxy Survey, CO data from HERACLES and the BIMA Survey of Nearby Galaxies, 24 mum data from the Spitzer Space Telescope, and UV data from the Galaxy Evolution Explorer. We target seven spiral galaxies and 11 late-type/dwarf galaxies and investigate how the star formation law differs between the H2 dominated centers of spiral galaxies, their H I dominated outskirts and the H I rich late-type/dwarf galaxies. We find that a Schmidt-type power law with index N = 1.0 ± 0.2 relates SigmaSFR and SigmaH2 across our sample of spiral galaxies, i.e., that H2 forms stars at a constant efficiency in spirals. The average molecular gas depletion time is ~2 × 109 years. The range of SigmaH2 over which we measure this relation is ~3-50 M sun pc 2, significantly lower than in starburst environments. We find the same results when performing a pixel-by-pixel analysis, averaging in radial bins, or when varying the star formation tracer used. We interpret the linear relation and constant depletion time as evidence that stars are forming in giant molecular clouds with approximately uniform properties and that SigmaH2 may be more a measure of the filling fraction of giant molecular clouds than changing conditions in the molecular gas. The relationship between total gas surface density (Sigmagas) and SigmaSFR varies dramatically among and within spiral galaxies. Most galaxies show little or no correlation between SigmaHI and SigmaSFR. As a result, the star formation efficiency (SFE), SigmaSFR/Sigmagas, varies strongly across our sample and within individual galaxies. We show that this variation is systematic and consistent with the SFE being set by local environmental factors: in spirals the SFE is a clear function of radius, while the dwarf galaxies in our sample display SFEs similar to those found in the outer optical disks of the spirals. We attribute the similarity to common environments (low density, low metallicity, H I dominated) and argue that shear (which is typically absent in dwarfs) cannot drive the SFE. In addition to a molecular Schmidt law, the other general feature of our sample is a sharp saturation of H I surface densities at SigmaHI ≈ 9 M sun pc 2 in both the spiral and dwarf galaxies. In the case of the spirals, we observe gas in excess of this limit to be molecular.

Development of the body plan is controlled by large networks of regulatory genes. A gene regulatory network that controls the specification of endoderm and mesoderm in the sea urchin embryo is summarized here. The network was derived from large-scale perturbation analyses, in combination with computational methodologies, genomic data, cis-regulatory analysis, and molecular embryology. The network contains over 40 genes at present, and each node can be directly verified at the DNA sequence level by cis-regulatory analysis. Its architecture reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time.

Polydimethylsiloxane (PDMS) elastomers are extensively used for soft lithographic replication of microstructures in microfluidic and micro-engineering applications. Elastomeric microstructures are commonly required to fulfil an explicit mechanical role and accordingly their mechanical properties can critically affect device performance. The mechanical properties of elastomers are known to vary with both curing and operational temperatures. However, even for the elastomer most commonly employed in microfluidic applications, Sylgard 184, only a very limited range of data exists regarding the variation in mechanical properties of bulk PDMS with curing temperature. We report an investigation of the variation in the mechanical properties of bulk Sylgard 184 with curing temperature, over the range 25 C to 200 C. PDMS samples for tensile and compressive testing were fabricated according to ASTM standards. Data obtained indicates variation in mechanical properties due to curing temperature for Young's modulus of 1.32-2.97 MPa, ultimate tensile strength of 3.51-7.65 MPa, compressive modulus of 117.8-186.9 MPa and ultimate compressive strength of 28.4-51.7 GPa in a range up to 40% strain and hardness of 44-54 Sh A .

We present "The HI Nearby Galaxy Survey (THINGS)", a high spectral (<=5.2 km/s) and spatial (~6") resolution survey of HI emission in 34 nearby galaxies obtained using the NRAO Very Large Array (VLA). The overarching scientific goal of THINGS is to investigate fundamental characteristics of the interstellar medium (ISM) related to galaxy morphology, star formation and mass distribution across the Hubble sequence. Unique characteristics of the THINGS database are the homogeneous sensitivity as well as spatial and velocity resolution of the HI data which is at the limit of what can be achieved with the VLA for a significant number of galaxies. A sample of 34 objects at distances 2<D<15Mpc (resulting in linear resolutions of ~100 to 500pc) are targeted in THINGS, covering a wide range of star formation rates (10^-3 to 6 M_sun/yr), total HI masses M_HI (0.01 to 14x10^9 M_sun), absolute luminosities M_B (-11.5 to -21.7 mag) and metallicities (7.5 to 9.2 in units of 12+log[O/H]). We describe the setup of the VLA observations, the data reduction procedures and the creation of the final THINGS data products. We present an atlas of the integrated HI maps, the velocity fields, the second moment (velocity dispersion) maps and individual channel maps of each THINGS galaxy. The THINGS data products are made publicly available through a dedicated webpage. Accompanying THINGS papers address issues such as the small-scale structure of the ISM, the (dark) matter distribution in THINGS galaxies, and the processes leading to star formation.

Abstract This paper documents the 16th data release (DR16) from the Sloan Digital Sky Surveys (SDSS), the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the Southern Hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey and new data from the SPectroscopic IDentification of ERosita Survey programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library “MaStar”). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).

Spectroscopic+photometric redshifts, stellar mass estimates, and rest-frame colors from the 3D-HST survey are combined with structural parameter measurements from CANDELS imaging to determine the galaxy size-mass distribution over the redshift range 0 &lt; z &lt; 3. Separating early- and late-type galaxies on the basis of star-formation activity, we confirm that early-type galaxies are on average smaller than late-type galaxies at all redshifts, and we find a significantly different rate of average size evolution at fixed galaxy mass, with fast evolution for the early-type population, R eff(1 + z) -1.48, and moderate evolution for the late-type population, R eff(1 + z)-0.75. The large sample size and dynamic range in both galaxy mass and redshift, in combination with the high fidelity of our measurements due to the extensive use of spectroscopic data, not only fortify previous results but also enable us to probe beyond simple average galaxy size measurements. At all redshifts the slope of the size-mass relation is shallow, , for late-type galaxies with stellar mass &gt;3 × 109 M , and steep, , for early-type galaxies with stellar mass &gt;2 × 1010 M . The intrinsic scatter is ≲0.2 dex for all galaxy types and redshifts. For late-type galaxies, the logarithmic size distribution is not symmetric but is skewed toward small sizes: at all redshifts and masses, a tail of small late-type galaxies exists that overlaps in size with the early-type galaxy population. The number density of massive (∼1011 M ), compact (R eff &lt; 2 kpc) early-type galaxies increases from z = 3 to z = 1.5-2 and then strongly decreases at later cosmic times.