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NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
The UK Soft Drinks Industry Levy (SDIL) (announced in March 2016; implemented in April 2018) aims to incentivise reformulation of soft drinks to reduce added sugar levels. The SDIL has been applauded as a policy success, and it has survived calls from parliamentarians for it to be repealed. We aimed to explore parliamentary reaction to the SDIL following its announcement until two years post-implementation in order to understand how health policy can become established and resilient to opposition.
Design:
Searches of Hansard for parliamentary debate transcripts that discussed the SDIL retrieved 186 transcripts, with 160 included after screening. Five stages of Applied Thematic Analysis were conducted: familiarisation and creation of initial codebooks; independent second coding; codebook finalisation through team consensus; final coding of the dataset to the complete codebook; and theme finalisation through team consensus.
Setting:
The United Kingdom Parliament
Participants:
N/A
Results:
Between the announcement (16/03/2016) – royal assent (26/04/2017), two themes were identified 1: SDIL welcomed cross-party 2: SDIL a good start but not enough. Between royal assent – implementation (5/04/2018), one theme was identified 3: The SDIL worked – what next? The final theme identified from implementation until 16/03/2020 was 4: Moving on from the SDIL.
Conclusions:
After the announcement, the SDIL had cross-party support and was recognised to have encouraged reformulation prior to implementation. Lessons for governments indicate that the combination of cross-party support and a policy’s documented success in achieving its aim can help cement the resilience of it to opposition and threats of repeal.
Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies, and industry. A broad spectrum of studies use real-world data (RWD) to produce RWE, ranging from randomized trials with outcomes assessed using RWD to fully observational studies. Yet, many proposals for generating RWE lack sufficient detail, and many analyses of RWD suffer from implausible assumptions, other methodological flaws, or inappropriate interpretations. The Causal Roadmap is an explicit, itemized, iterative process that guides investigators to prespecify study design and analysis plans; it addresses a wide range of guidance within a single framework. By supporting the transparent evaluation of causal assumptions and facilitating objective comparisons of design and analysis choices based on prespecified criteria, the Roadmap can help investigators to evaluate the quality of evidence that a given study is likely to produce, specify a study to generate high-quality RWE, and communicate effectively with regulatory agencies and other stakeholders. This paper aims to disseminate and extend the Causal Roadmap framework for use by clinical and translational researchers; three companion papers demonstrate applications of the Causal Roadmap for specific use cases.
We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings.
Design and setting:
This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures.
Results:
Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases.
Conclusion:
SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
The herbicides that inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) are primarily used for weed control in corn, barley, oat, rice, sorghum, sugarcane, and wheat production fields in the United States. The objectives of this review were to summarize 1) the history of HPPD-inhibitor herbicides and their use in the United States; 2) HPPD-inhibitor resistant weeds, their mechanism of resistance, and management; 3) interaction of HPPD-inhibitor herbicides with other herbicides; and 4) the future of HPPD-inhibitor-resistant crops. As of 2022, three broadleaf weeds (Palmer amaranth, waterhemp, and wild radish) have evolved resistance to the HPPD inhibitor. The predominance of metabolic resistance to HPPD inhibitor was found in aforementioned three weed species. Management of HPPD-inhibitor-resistant weeds can be accomplished using alternate herbicides such as glyphosate, glufosinate, 2,4-D, or dicamba; however, metabolic resistance poses a serious challenge, because the weeds may be cross-resistant to other herbicide sites of action, leading to limited herbicide options. An HPPD-inhibitor herbicide is commonly applied with a photosystem II (PS II) inhibitor to increase efficacy and weed control spectrum. The synergism with an HPPD inhibitor arises from depletion of plastoquinones, which allows increased binding of a PS II inhibitor to the D1 protein. New HPPD inhibitors from the azole carboxamides class are in development and expected to be available in the near future. HPPD-inhibitor-resistant crops have been developed through overexpression of a resistant bacterial HPPD enzyme in plants and the overexpression of transgenes for HPPD and a microbial gene that enhances the production of the HPPD substrate. Isoxaflutole-resistant soybean is commercially available, and it is expected that soybean resistant to other HPPD inhibitor herbicides such as mesotrione, stacked with resistance to other herbicides, will be available in the near future.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The naming of poetic predecessors within one’s own composition, often associated with a so-called Hellenistic aesthetic, has a less explored heritage going back to the sixth century BCE. This chapter traces the strategy in its earliest phases, especially as we find it within lyric poetry, from the reported statement by Stesichorus [fr. 168 Finglass] that the Shield of Heracles was indeed composed by Hesiod, to the Simonidean allusion to Homer as his forerunner in praise-poetry (fr.11.15–18), and on to Pindar’s complex and varied namings of Archilochus, Terpander, and the masters of hexameter verse. It offers a typology of three main functions of such naming (approbation, criticism, or the representation of conversational interaction), and then an in-depth analysis of two problematic issues: the generic affiliations of Stesichorean art, and the difficulties related to the Pindaric naming of Homer, in particular at Nemean 7.20–7. The device of naming a predecessor emerges as a sort of reception degree-zero, whereby previous verbal art is highlighted, distilled, and set up as a foil, while a new performative space is opened up for the presentation of one’s own innovative productions.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from $z = 0.35$ to 3; and a deep, high-redshift HI IM survey over 100 deg2 from $z = 3$ to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to $z \sim 3$ with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to $z = 6$. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
The aim of the 25 and Up (25Up) study was to assess a wide range of psychological and behavioral risk factors behind mental illness in a large cohort of Australian twins and their non-twin siblings. Participants had already been studied longitudinally from the age of 12 and most recently in the 19Up study (mean age = 26.1 years, SD = 4.1, range = 20–39). This subsequent wave follows up these twins several years later in life (mean age = 29.7 years, SD = 2.2, range = 22–44). The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). Data were collected between 2016 and 2018 from 2540 twins and their non-twin siblings (59% female, including 341 monozygotic complete twin-pairs, 415 dizygotic complete pairs and 1028 non-twin siblings and singletons). Participants were from South-East Queensland, Australia, and the sample was of predominantly European ancestry. The 25Up study collected information on 20 different mental disorders, including depression, anxiety, substance use, psychosis, bipolar and attention-deficit hyper-activity disorder, as well as general demographic information such as occupation, education level, number of children, self-perceived IQ and household environment. In this article, we describe the prevalence, comorbidities and age of onset for all 20 examined disorders. The 25Up study also assessed general and physical health, including physical activity, sleep patterns, eating behaviors, baldness, acne, migraines and allergies, as well as psychosocial items such as suicidality, perceived stress, loneliness, aggression, sleep–wake cycle, sexual identity and preferences, technology and internet use, traumatic life events, gambling and cyberbullying. In addition, 25Up assessed female health traits such as morning sickness, breastfeeding and endometriosis. Furthermore, given that the 25Up study is an extension of previous BLTS studies, 86% of participants have already been genotyped. This rich resource will enable the assessment of epidemiological risk factors, as well as the heritability and genetic correlations of mental conditions.
Poor social cognition is prevalent in schizophrenia spectrum disorders. Some authors argue that these effects are symptom-specific and that socio-cognitive difficulties (e.g. theory of mind) are strongly associated with thought disorder and symptoms of disorganisation.
Aims
The current review tests the strength of this association.
Method
We meta-analysed studies published between 1980 and 2016 that tested the association between social cognition and these symptoms in schizophrenia spectrum disorders.
Results
Our search (PsycINFO, MEDLINE and Web of Science) identified 123 studies (N = 9107). Overall effect size as r = −0.313, indicating a moderate association between symptoms and social cognition. Subanalyses yielded a moderate association between symptoms and theory of mind (r = −0.349) and emotion recognition (r = −0.334), but smaller effect sizes for social perception (r = −0.188), emotion regulation (r = −0.169) and attributional biases (r = −0.143).
Conclusions
The association is interpreted within models of communication that highlight the importance of mentalisation and processing of partner-specific cues in conversational alignment and grounding.