Performance of single-gene noninvasive prenatal testing for autosomal recessive conditions in a general population setting

Objective

Carrier screening with reflex to single-gene noninvasive prenatal testing (sgNIPT) is an alternative approach for identifying pregnancies at risk for inherited autosomal recessive conditions without the need for a sample from the reproductive partner. This study is the largest clinical validation of this approach in a general population setting.

Methods

The clinical performance of carrier screening with reflex to sgNIPT for cystic fibrosis, spinal muscular atrophy, alpha thalassemias, and beta hemoglobinopathies was assessed by collecting pregnancy outcome data on patients who underwent this testing and comparing the neonatal outcome to the assay-predicted fetal risk.

Results

Of 42,067 pregnant individuals who underwent screening, 7538 carriers (17.9%) had reflex sgNIPT, and neonatal or fetal outcomes were obtained for 528 cases, including 25 affected pregnancies. Outcomes demonstrated high concordance with sgNIPT, for example, all pregnancies with 9 in 10 personalized fetal risk results were affected (positive predictive value (PPV) of 100% for the sub-group) and the sgNIPT assay showed a sensitivity of 96.0% (95% CI: 79.65%–99.90%), specificity of 95.2% (95% CI: 92.98%–96.92%), average PPV of 50.0% (95% CI: 35.23%–64.77%), and negative predictive value (NPV) of 99.8% (95% CI: 98.84%–99.99%). The end-to-end performance of carrier screening with reflex to sgNIPT was calculated to have a sensitivity of 92.4% and specificity of 99.9%, which are unaffected by partner carrier screening or misattributed paternity unlike a traditional carrier screening workflow, which has a 35% sensitivity and a maximum of 25% PPV (1 in 4) in a real-life setting.

Conclusion

This study builds upon earlier findings to confirm that carrier testing with reflex to sgNIPT is highly accurate for general population screening. Given this high accuracy and an NPV of 99.8%, this workflow should be considered as an option for most of the general pregnant population. When the biological partner sample is unavailable, this workflow should be recommended as the first-line approach.     

A global community-sourced assessment of the state of conservation technology

Conservation technology holds the potential to vastly increase conservationists’ ability to understand and address critical environmental challenges, but systemic constraints appear to hamper its development and adoption. Understanding of these constraints and opportunities for advancement remains limited. We conducted a global online survey of 248 conservation technology users and developers to identify perceptions of existing tools’ current performance and potential impact, user and developer constraints, and key opportunities for growth. We also conducted focus groups with 45 leading experts to triangulate findings. The technologies with the highest perceived potential were machine learning and computer vision, eDNA and genomics, and networked sensors. A total of 95%, 94%, and 92% respondents, respectively, rated them as very helpful or game changers. The most pressing challenges affecting the field as a whole were competition for limited funding, duplication of efforts, and inadequate capacity building. A total of 76%, 67%, and 55% respondents, respectively, identified these as primary concerns. The key opportunities for growth identified in focus groups were increasing collaboration and information sharing, improving the interoperability of tools, and enhancing capacity for data analyses at scale. Some constraints appeared to disproportionately affect marginalized groups. Respondents in countries with developing economies were more likely to report being constrained by upfront costs, maintenance costs, and development funding (p = 0.048, odds ratio [OR] = 2.78; p = 0.005, OR = 4.23; p = 0.024, OR = 4.26), and female respondents were more likely to report being constrained by development funding and perceived technical skills (p = 0.027, OR = 3.98; p = 0.048, OR = 2.33). To our knowledge, this is the first attempt to formally capture the perspectives and needs of the global conservation technology community, providing foundational data that can serve as a benchmark to measure progress. We see tremendous potential for this community to further the vision they define, in which collaboration trumps competition; solutions are open, accessible, and interoperable; and user-friendly processing tools empower the rapid translation of data into conservation action. Article impact statement: Addressing financing, coordination, and capacity-building constraints is critical to the development and adoption of conservation technology.     

A Contingent Trip Model for Estimating Rail-trail Demand

The authors develop a contingent trip model to estimate the recreation demand for and value of a potential rail-trail site in north-east Georgia. The contingent trip model is an alternative to travel cost modelling useful for ex ante evaluation of proposed recreation resources or management alternatives. The authors estimate the empirical demand for trips using a negative binomial regression specification. Their findings indicate a per-trip consumer surplus ranging from US$18.46 to US$29.23 and a price elasticity of m 0.68. In aggregate, they estimate that the rail-trail would receive approximately 416 213 recreation visits per year by area households and account for a total consumer surplus in excess of US$7.5 million.     

Towards the characterisation of heavy metals in dredged canal sediments and an appreciation of 'availability': two examples from the UK.

Canal sediments can act as sinks for a wide range of contaminants including heavy metals from various sources (e.g. industrial and waste water discharges). Dredging of canals is required to maintain navigational depth and prevent flooding. The sediments removed from canals are often disposed of to land, being deposited either straight on to the banks of the canal or, in recent years, in licensed disposal sites. The aim of this work was to investigate the nature of dredged sediment-derived soils and the heavy metals present in them. Two disposal sites in the United Kingdom (UK) were investigated and soil samples taken. A variety of analytical techniques were used, including Aqua regia digestion and sequential extraction, in order to assess the concentrations and associations of metals present. Diethylene triaminepenta-acetic acid extracts, performed to illustrate plant-available metal concentrations, reveal that up to 40% of the total extracted metals were in an 'available' form. Variations in metal concentrations with depth in the soil cores show a significant correlation with total organic carbon content.     

Improving Technical Information Use: What Can Be Learnt from a Manager’s Perspective?

Conservation practice reportedly suffers from low use of technical information. Understanding of factors that affect the influence of technical information on management decision-making is limited. We sought to identify leverage points for improved technical information dissemination in the New South Wales Parks and Wildlife Service, Australia, given the significant recent investments in monitoring and evaluation that had been made. We did so by exploring the inter-relationships between factors affecting the influence of different information types on management decisions. Results indicate that managers have a high inclination toward adaptive behavior, given they operate in an information poor environment. The most influential types of information were those that enabled interaction between information provider and recipient (e.g., staff experience and expertise). An analysis of the concordance in individuals’ responses for different information types showed that neither accessibility nor organizational expectation of use was aligned with influence on decision-making. Alignment of responses also varied by work area. Raising expectations of information use or increasing access to particular types of information is therefore unlikely to result in an increase in influence on management decision-making. Rather than focussing on matching accessibility and expected use of particular information types, our results indicate that technical information uptake is best supported through existing peer networks tailored to specific work areas.     

Denning behaviour of the European badger (Meles meles) correlates with bovine tuberculosis infection status

Heterogeneities in behaviours of individuals may underpin important processes in evolutionary biology and ecology, including the spread of disease. Modelling approaches can sometimes fail to predict disease spread, which may partly be due to the number of unknown sources of variation in host behaviour. The European badger is a wildlife reservoir for bovine tuberculosis (bTB) in Britain and Ireland, and individual behaviour has been demonstrated to be an important factor in the spread of bTB among badgers and to cattle. Radio-telemetry devices were deployed on 40 badgers from eight groups to investigate patterns of den (sett) use in a high-density population, where each group had one or two main and three to eight outlier setts in their territory. Badgers were located at their setts for 28 days per season for 1 year to investigate how patterns differed between individuals. Denning behaviour may have a strong influence on contact patterns and the transmission of disease. We found significant heterogeneity, influenced by season, sex and age. Also, when controlling for these, bTB infection status interacting with season was highly correlated with sett use. Test-positive badgers spent more time away from their main sett than those that tested negative. We speculate that wider-ranging behaviour of test-positive animals may result in them contacting sources of infection more frequently and/or that their behaviour may be influenced by their disease status. Measures to control infectious diseases might be improved by targeting functional groups, specific areas or times of year that may contribute disproportionately to disease spread.     

Tree Structure and Diversity in Human-Impacted Littoral Forests, Madagascar

This research surveyed human-impacted littoral forests in southeastern Madagascar to determine (i) how forest structural features, indicative of human impact, are related to total, utilitarian, and endemic tree diversity; (ii) the distribution, abundance, and demographics of tree species groups (i.e., total, useful, endemic) across the landscape; and (iii) the amount of basal area available per human use category. We also use these data to consider issues of sustainable use and how human impact may influence littoral forest tree community composition across the landscape. Within 22 transects of 400 m² each, we recorded a total of 135 tree species and 2155 individuals. Seventy-nine species (58%) were utilitarian and 56 (42%) were nonutilitarian species. Of the 2155 individuals, 1827 (84%) trees were utilitarian species. We recorded 23 endemic species (17% of the total species) and 17 (74%) of these were utilitarian species. Basal area was significantly correlated with Shannon Weiner Index values for total (r = 0.64, P < 0.01), utilitarian (r = 0.58, P < 0.01), and endemic tree diversity (r = 0.85, P < 0.01). Basal area was significantly correlated with the Simpson’s index values for the endemic species (r = 0.74, P < 0.01). These correlations suggest that endemic tree species, of high global conservation value, may be the species group most influenced by changes in forest structure. Utilitarian species constituted 84% of the total basal area. The use category contributing the highest amount of basal area to the landscape was firewood. The results presented herein demonstrate that the landscape of southeastern Madagascar, commonly perceived as degraded, retains high value for both global conservation purposes and for local livelihoods. Thus, valuable opportunities may exist for developing conservation incentives that leverage both global and local conservation needs.     

Physical Modelling of Urban Roughness using Arrays of Regular Roughness Elements

The aerodynamic behaviour of large urbanagglomerations must be represented in increasingly greaterdetail, as large-scale numerical weather prediction and airpollution dispersion models are refined. The present studyprovides detailed measurements of the flow field in regulararrays of obstacles to obtain representative data on meanflow and turbulence statistics in urban-type areas. Obstacle arrays consisting of simple cubes and flat plateroughness commonly used in boundary layer simulations wereplaced in a simulated atmospheric boundary layer flow in ahydraulic flume. The scale factor was about 1:200 based onthe obstacle height (50 mm). The results show noappreciable `constant stress' region in the internalboundary layer above the buildings, since in any finite-length test array the boundary layer is always developing.However, if the RMS turbulence components are scaled by thelocal values of the shear stress, then there seems to be auniversal scaling, with _u/u_* = 2.1,_v/u_* = 1.65 and _w/u_* = 1.2. This greatly simplifies the parameterization of the first orderturbulence statistics in obstacle arrays. It was alsoobserved during the experiments that, compared to results inthe cube arrays, the turbulence kinetic energy and theReynolds stresses were almost doubled in the flat plateroughness arrays.     

Oviposition stimulants for the pipevine swallowtail butterfly,Battus philenor (Papilionidae), from anAristolochia host plant: Synergism between inositols,aristolochic acids and a monogalactosyl diglyceride

Aristolochia macrophylla (Lam.) is a major host of the pipevine swallowtail butterfly,Battus philenor (L.), in the eastern United States. The female butterflies use a synergistic mixture of inositols, acids and a lipid as oviposition cues in recognizing this plant on contact. The acids and lipid, all isolated from the Et₂O-CHCl₃ fraction of an alcoholic extract of fresh foliage, were identified as aristolochic acid I (1), aristolochic acid II (2) and 1,2-[di(9Z,12Z,15Z)-octadeca-9, 12, 15-trienoyl]-3-galactosyl-sn-glycerol (3). Identifications were facilitated by UV, MS (EI and FAB) and NMR (1D and 2D) spectral techniques and by analysis of the hydrolysis products of 3. The active inositols were identified as D-(+)-pinitol, reported previously, and sequoyitol. Though this is apparently the first report of oviposition responses to a diacyl glycerol glycoside by a phytophagous insect, responses to aristolochic acids and sequoyitol have been reported previously for anAristolochia-feeding swallowtail of a different genus in Japan. This indicates substantial evolutionary conservatism in chemical oviposition cues within the tribe Troidini.