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.     

Levels of persistent organic pollutant and their predictors among young adults

Exposure to persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethane (p,p′-DDE), and hexachlorobenzene (HCB) continues to be of concern due to their ubiquitous distribution and high persistence. Current toxicant body burden is still a primary concern within the Akwesasne Mohawk Nation since other studies conducted within the community have shown relationships between these POPs and endocrine disruption.In this article we describe the levels of these toxicants in young adults of the Akwesasne Mohawk Nation between the ages of 17 and 21 years of age (mean age 18.1 years), and investigate potential influences of their current body burden. Seventeen congeners in fourteen chromatographic peaks were detected in 50% or more of the individuals sampled (geometric mean [GM] of the sum of these congeners = 0.43 ppb). Congeners 118, 138[+163 + 164] and 153 had the highest rate of detection (?98%) within the Akwesasne young adults. Of the other organochlorines, HCB (GM = 0.04 ppb) and p,p′-DDE (GM = 0.38 ppb) were found in 100% and 99% of the sample respectively.Significantly higher levels of PCBs were found among individuals who were breastfed as infants, were first born, or had consumed local fish within the past year. When compared to levels of p,p′-DDE, HCB, and 13 specific congeners reported by the CDC for youth between the ages of 12 and 19 years, the geometric means of several congeners (CBs 99, 105, 110, and 118) among the Akwesasne were higher than the reported CDC 90th percentile. In contrast, levels of CB 28 in Akwesasne young adults were ∼50% or less than those of the CDC cohort. p,p′-DDE and HCB levels were generally higher in the CDC cohort (GM of 0.516 and 0.065 ppb, respectively for Mohawks vs. 2.51 and 0.123, respectively, for CDC). Concentrations of non-persistent PCBs among this sample of Akwesasne young adults were higher than those reported by the CDC suggesting continued exposure, but lower than those associated with severe contamination.Additional research into the concentration trends of individual PCB congeners within Akwesasne youth and young adults is warranted to further improve our insight into the determinants and influences of organochlorine concentrations within members of the Akwesasne community.     

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).     

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.     

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.     

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.     

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.     

Biological responses to sediment remediation based on thin layer placement near a former pulp mill in Ward Cove, AK (USA)

In 2001, 28 acres of the bottom of Ward Cove, AK (USA) were remediated using thin layer placement, to enhance the natural recovery of contaminated sediments. The remediated areas were part of an 80-acre area of concern identified offshore from the site of a former sulfite pulp mill. The primary chemicals of concern were those commonly associated with organic enrichment near pulp mills: ammonia and 4-methylphenol. The primary remedial objectives were to reduce the toxicity of the contaminated sediments and to stimulate colonization of the remediated areas by benthic macroinvertebrates. In 2004, the initial monitoring event for the remediated areas was conducted, and included evaluations of physical/chemical sediment variables (i.e., total organic carbon, grain size distribution, ammonia, and 4-methylphenol), sediment toxicity (i.e., using the 10-day amphipod survival test with Eohaustorius estuarius), and in situ benthic macroinvertebrate communities. Results of the monitoring event showed that conditions in the remediated areas had improved considerably in the 3 years since thin layer placement had occurred. At most stations, concentrations of both ammonia and 4-methylphenol were very low, and amphipod survival was >or=90%. In addition, benthic macroinvertebrates appeared to be rapidly colonizing the remediated areas, based on evaluations of several community metrics (i.e., taxa richness, diversity, and dominance), as well as key indicator species of organic enrichment and associated transitional areas (i.e., primarily the polychaetes Capitella capitata and Nephtys cornuta, and the bivalve molluscs Axinopsida serricata and Parvilucina tenuisculpta). In general, colonization was consistent with the patterns identified for areas recovering from organic enrichment on the continental shelf of southern California and elsewhere. Based on these results, thin layer placement was considered successful in enhancing the natural recovery of the remediated sediments in Ward Cove.