Defining core outcomes of reproductive genetic carrier screening: A Delphi survey of Australian and New Zealand stakeholders

Objective

Understanding the value, benefits and harms of health interventions is needed to inform best practice and ensure responsible implementation of new approaches to patient care. Such value is demonstrated through the assessment of outcomes; however, which outcomes are assessed is often highly varied across studies and can hinder the ability to draw robust conclusions. The Core Outcome Development for Carrier Screening study aims to understand the outcomes that can meaningfully capture the value of reproductive genetic carrier screening (RGCS).

Method

The authors report an iterative, two-round online Delphi survey of Australian and New Zealand stakeholders to determine the degree of consensus regarding the core outcomes of RGCS. Panellists ranked 83 outcomes according to their perceived importance on a nine-point Likert scale. Using the distribution of rankings, outcomes were grouped into tiers representative of their perceived level of importance and agreement between groups.

Results

The top tier outcomes represent those agreed to be critically important for all future studies of RGCS to assess and were used to define a preliminary core outcome set encompassing the domains (1) primary laboratory outcomes, (2) pregnancy outcomes, (3) resource use and, (4) perceived utility of RGCS.

Conclusion

These findings can guide the selection of meaningful outcomes in studies aiming to demonstrate the value of RGCS. A future international consensus process will expand on these findings and guide the inclusion of diverse perspectives across the range of settings in which RGCS is offered.     

OPTIMAL LONG-TERM SCHEDULING OF STORMWATER DRAINAGE REHABILITATION1

ABSTRACT: A mathematical model is developed to optimally schedule long-term stormwater infrastructure rehabilitation activities. The model is capable of considering multiple rehabilitation projects and is driven by overall cost eensiderations. Rehabilitation activities are scheduled based on perceived reliabilities and future deterioration expected within the specified planning horizon. Future growth within the stormwater drainage basin is incorporated using chance constraints that limit the likelihood that a stormwater discharge exceeds system conveyance capacity. Model structure and development are discussed, and a hypothetical example using a drainage network is presented.     

Neuere Ergebnisse der Mathematik

A short glance over recent progress in mathematical research. A more detailed account of the state of arts in the following domains of research: arithmetical progression (“Szemerédi-Furstenberg-Weiss-Saga”), Arrow's dictator theorem, classification of knots, inversion of the 2-sphere.     

Mercury-selenium-bromine imbalance in premature parturient California sea lions

High premature birth rates have been observed in the rookeries of the California sea lion Zalophus californianus since 1968. The reasons for the premature pupping are complex and, hence, not well understood, although leptospirosis infection and elevated PCB and DDT residues have been implicated. We were interested in determining what role trace and major elements played in these events. Livers and kidneys from 10 normal parturient and 10 premature parturient mothers and their pups were analyzed for Hg, Se, Br, Cd, Ag, Cu, Fe, Zn, Mn, K, Na, Ca, and Mg in order to detect differences that might exist between the two groups. A further objective was to establish how these elements varied in relation to each other in the normal and abnormal sea lions. Our results revealed that Hg, Se, Cd, and Br levels were significantly higher in the livers of the normal mothers and that these elements were all in balance (highly correlated) with each other. This was especially true for Hg, Se, and Br. In mothers with high concentrations of these elements (e.g. Hg greater than 800 g/g dry weight), atomic ratios of approximately 1Hg:1Se:1Br were observed. Atomic Se:Hg ratios were also near unity in the abnormal mothers; however, Br concentrations were always severely depressed in these individuals. Normal full-term pups had higher hepatic levels of Hg and Se, and near-perfect 1:1 Se:Hg atomic ratios were almost always observed. In contrast, the livers of the premature pups appeared to be deficient in Hg, and, consequently, elevated Se:Hg ratios were always found. In almost all cases, the premature pups had increased concentrations of Na, Ca, and Br. Levels of these elements were correlated with their Se:Hg ratios. Amounts of Mn and Cu were reduced in the premature pups and negatively correlated with Se:Hg ratios. The results suggest that balance between elements is of more importance than absolute concentration when the possible effects of toxic elements are considered. It also appears that bromine may be important in the detoxification process involving Se and Hg and perhaps Cd as well; i.e., every mother that had Br in balance with Hg, Cd, and Se had a normal pup, while every mother that lacked sufficient Br had a premature pup. The question of whether Hg detoxifies Se is also raised. All the normal pups had Se:Hg atomic ratios of less than 2.2, while all the premature pups had reduced Hg amounts and Se:Hg ratios above 3.4.     

Long-term population dynamics of seeded plants in invaded grasslands

In recent decades, dozens of studies have involved attempts to introduce native and desirable nonnative plant species into grasslands dominated by invasive weeds. The newly introduced plants have proved capable of establishing, but because they are rarely monitored for more than four years, it is unknown if they have a high likelihood of persisting and suppressing invaders for the long-term. Beyond invaded grasslands, this lack of long-term monitoring is a general problem plaguing efforts to reintroduce a range of taxa into a range of ecosystems. We introduced species from seed and then periodically measured plant abundances for nine years at one site and 15 years at a second site. To our knowledge, our 15-year data are the longest to date from a seeding experiment in invaded, never-cultivated grassland. At one site, three seeded grasses maintained high densities for three or more years, but then all or nearly all individuals died. At the second site, one grass performed similarly, but two other grasses proliferated and at least one greatly suppressed the dominant invader (Centaurea maculosa). In one study, our point estimate suggests that the seeded grass Thinopyrum intermedium reduced C. maculosa biomass by 93% 15 years after seeding. In some cases, data from three and fewer years after seeding falsely suggested that seeded species were capable of persisting within the invaded grassland. In other cases, data from as late as nine years after seeding falsely suggested seeded populations would not become large enough to suppress the invader. These results show that seeded species sometimes persist and suppress invaders for long periods, but short-term data cannot predict if, when, or where this will occur. Because short-term data are not predictive of long-term seeded species performances, additional long-term data are needed to identify effective practices, traits, and species for revegetating invaded grasslands.     

Ecological indicators of global climate change: A research framework

Large-scale environmental research efforts are conducted under frameworks that provide a common basis for evaluating research in many diverse fields. Such frameworks should be subjected to critical review to determine if they meet crucial expectations. In the case of the US Global Change Research Program, we perceive that most research follows a framework that we define as the predictive model framework. We believe this framework is insufficient for resolving the unprecedented predicaments posed by global change. We recommend a complementary framework, the system response framework, which directs research toward useful indicators of change rather than precise predictions. We further argue that, even if research is complementary and effective under the two frameworks, conclusive results prior to decisions should not be expected. The burden of proof must itself be a continuing topic of open discourse and inquiry.     

Bigger is not always better: offspring size does not predict growth or survival for seven ascidian species

The presumed trade-off between offspring size and quality predicted by life history theory is often invoked to explain the wide range of propagule sizes observed in animals and plants. This trade-off is broadly supported by intraspecific studies but has been difficult to test in an interspecific context, particularly in animals. We tested the fitness consequences of offspring size both intra- and interspecifically for seven species of ascidians (sessile, suspension-feeding, marine invertebrates) whose offspring volumes varied over three orders of magnitude. We measured two major components of fitness, juvenile growth rates and survival, in laboratory and field experiments encompassing several food conditions. Contrary to the predictions of life history theory, larger offspring size did not result in higher rates of growth or survival, and large offspring did not perform better under nutritional stress, either intraspecifically or interspecifically. In fact, two of the four species with small offspring grew rapidly enough to catch up in size to the species with large offspring in as little as eight weeks, under wild-type food conditions. Trade-offs between growth potential and defense may overwhelm and obscure any trade-offs between offspring size and survival or growth rate. While large initial size may still confer a competitive advantage, we failed to detect any consequences of interspecific variation in initial size. This implies that larger offspring in these species, far from being inherently superior in growth or survival, require compensation in other aspects of life history if reproductive effort is to be efficient. Our results suggest that the importance of initial offspring size is context dependent and often overestimated relative to other life history traits.     

Photocatalytic degradation of microcystin-LR in aqueous solutions

In this work, the photocatalytic degradation of aqueous microcystin-LR was studied using TiO₂ and ZnO as photocatalysts. The process was optimised and characterised at the bench scale (200 mL); both semiconductors exhibited a high degradation capacity at reaction times of 1 min (degradation greater than 95%). The transient species that were observed indicate that the degradation occurs via the multiple hydroxylation and elimination of the labile peptide residues of the molecule. When photocatalysis was applied in a continuous treatment system (20–50 L), the photocatalytic process exhibited a high degradation efficiency, which resulted in residual microcystin-LR concentrations that were less than 1 μg L^?1 (C₀ = 5 μg L^?1).