Assessment of a non-invasive approach to pregnancy diagnosis in gray whales through drone-based photogrammetry and faecal hormone analysis

This project was supported by the NOAA National Marine Fisheries Service Office of Science and Technology, the Office of Naval Research Marine Mammals and Biology Program (no. N00014-20-1-2760), the Oregon State University Marine Mammal Institute and Oregon Sea Grant.Knowledge of baleen whales’ reproductive physiology is limited and requires long-term individual-based studies and innovative tools. We used 6 years of individual-level data on the Pacific Coast Feeding Group gray whales to evaluate the utility of faecal progesterone immunoassays and drone-based photogrammetry for pregnancy diagnosis. We explored the variability in faecal progesterone metabolites and body morphology relative to observed reproductive status and estimated the pregnancy probability for mature females of unknown reproductive status using normal mixture models. Individual females had higher faecal progesterone concentrations when pregnant than when presumed nonpregnant. Yet, at the population level, high overlap and variability in progesterone metabolite concentrations occurred between pregnant and non-pregnant groups, limiting this metric for accurate pregnancy diagnosis in gray whales. Alternatively, body width at 50% of the total body length (W50) correctly discriminated pregnant from non-pregnant females at individual and population levels, with high accuracy. Application of the model using W50 metric to mature females of unknown pregnancy status identified eight additional pregnancies with high confidence. Our findings highlight the utility of drone-based photogrammetry to non-invasively diagnose pregnancy in this group of gray whales, and the potential for improved data on reproductive rates for population management of baleen whales generally.Publisher PDFPeer reviewe

Redesign and commissioning of sexual health services in England – a qualitative study

Objectives Responsibility for the commissioning of sexual and reproductive health (SRH) services transferred from the National Health Service to local authorities in England in 2013. This transfer prompted many local authorities to undertake new procurements of these SRH services. This study was undertaken to capture some of the lessons learnt in order to inform future commissioning and system redesign. Study design A qualitative study was carried out involving semi-structured interviews. Methods Interviews were conducted with 13 local authority sexual health commissioners in Yorkshire and the Humber from 11 interviews. Thematic analysis was used to identify themes from transcripts of the interviews with the 13 participants. Results Key themes identified were as follows: the challenge and complexity to those new to clinical commissioning; the prerequisites of robust infrastructural inputs to undertake the process, including technical expertise, a dependable project team, with clarity over the timescales and the budget; the requirement for good governance, stakeholder engagement and successful management of relationships with the latter; and the need to focus on the outcomes, aiming for value for money and improved system performance. Conclusions Several key issues emerged from our study that significantly influenced the outcome of the redesign and commissioning process for sexual health services. An adapted model of the Donabedian evaluation framework was developed to provide a tool to inform future system redesign. Our model helps identify the key determinants for successful redesign in this context which is essential to both mitigate potential risks and maximize the likelihood of successful outcomes. Our model may have wider applications

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Tetraploid Wheat Landraces in the Mediterranean Basin: Taxonomy, Evolution and Genetic Diversity

The geographic distribution of genetic diversity and the population structure of tetraploid wheat landraces in the Mediterranean basin has received relatively little attention. This is complicated by the lack of consensus concerning the taxonomy of tetraploid wheats and by unresolved questions regarding the domestication and spread of naked wheats. These knowledge gaps hinder crop diversity conservation efforts and plant breeding programmes. We investigated genetic diversity and population structure in tetraploid wheats (wild emmer, emmer, rivet and durum) using nuclear and chloroplast simple sequence repeats, functional variations and insertion site-based polymorphisms. Emmer and wild emmer constitute a genetically distinct population from durum and rivet, the latter seeming to share a common gene pool. Our population structure and genetic diversity data suggest a dynamic history of introduction and extinction of genotypes in the Mediterranean fields

Trajectories of Early Adolescent Loneliness: Implications for Physical Health and Sleep

The current study examines the relationship between prolonged loneliness, physical health, and sleep among young adolescents (10–13 years; N = 1214; 53% girls). Loneliness was measured at 10, 12 and 13 years of age along with parent-reported health and sleep outcomes. Using growth mixture modelling, 6 distinct trajectories were identified: ‘low increasing to high loneliness’ (n = 23, 2%), ‘high reducing loneliness’ (n = 28, 3%), ‘medium stable loneliness’ (n = 60, 5%), ‘medium reducing loneliness’ (n = 185, 15%), ‘low increasing to medium loneliness’ (n = 165, 14%), and ‘low stable loneliness’ (n = 743, 61%). Further analyses found non-significant differences between the loneliness trajectories and parent-report health and sleep outcomes including visits to health professionals, perceived general health, and sleep quality. The current study offers an important contribution to the literature on loneliness and health. Results show that the relationship may not be evident in early adolescence when parent reports of children’s health are used. The current study highlights the importance of informant choice when reporting health. The implications of the findings for future empirical work are discussed

Protocol for creating a single, holistic and digitally implementable consensus clinical guideline for multiple multi-morbid conditions

Delivery of future healthcare information systems requires systems to support patients with multi-morbidity. Current approaches to computer interoperable guidelines typically consider only a single clinical guideline for a single condition. There is a need to establish a robust protocolized approach to the development of holistic consensus computer interoperable guidelines in the context of multi-morbidity. The presence of mild cognitive impairment (MCI) and dementia adds an additional challenge to the delivery of effective digital health solutions. CAREPATH proposes an ICT-based solution for the optimization of clinical practice in the treatment and management of multi-morbid older adults with mild cognitive impairment or mild dementia. In this manuscript, we present an evidence-based protocol for the development of a single computer interoperable holistic guideline for a collection of multi-morbid conditions. To the best of our knowledge, this is the first published protocol for the production of a consensus interoperable clinical guideline for people with multi-morbidity, with special focus on older adults with MCI or mild dementia. This addresses a still unmet need for such processes which are expected to play a central role for future integrated healthcare information systems

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

SummaryWe report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine