Molecular prenatal diagnosis: the impact of modern technologies

Originally prenatal diagnosis was confined to the diagnosis of metabolic disorders and depended on assaying enzyme levels in amniotic fluid. With the development of recombinant DNA technology, molecular diagnosis became possible for some genetic conditions late in the 1970s. Here we briefly review the history of molecular prenatal diagnostic testing, using Duchenne muscular dystrophy as an example, and describe how over the last 30 years we have moved from offering testing to a few affected individuals using techniques, such as Southern blotting to identify deletions, to more rapid and accurate PCR-based testing which identifies the precise change in dystrophin for a greater number of families. We discuss the potential for safer, earlier prenatal genetic diagnosis using cell free fetal DNA in maternal blood before concluding by speculating on how more recent techniques, such as next generation sequencing, might further impact on the potential for molecular prenatal testing. Progress is not without its challenges, and as cytogenetics and molecular genetics begin to unite into one, we foresee the main challenge will not be in identifying the genetic change, but rather in interpreting its significance, particularly in the prenatal setting where we frequently have no phenotype on which to base interpretation. Copyright © 2010 John Wiley & Sons, Ltd.     

Relationships between soil and runoff phosphorus in small Alberta watersheds

Field-scale relationships between soil test phosphorus (STP) and flow-weighted mean concentrations (FWMCs) of dissolved reactive phosphorus (DRP) and total phosphorus (TP) in runoff are essential for modeling phosphorus losses, but are lacking. The objectives of this study were (i) to determine the relationships between soil phosphorus (STP and degree of phosphorus saturation (DPS)) and runoff phosphorus (TP and DRP) from field-sized catchments under spring snowmelt and summer rainfall conditions, and (ii) to determine whether a variety of depths and spatial representations of STP improved the prediction of phosphorus losses. Runoff was monitored from eight field-scale microwatersheds (2 to 248 ha) for 3 yr. Soil test phosphorus was determined for three layers (0 to 2.5 cm, 0 to 5 cm, and 0 to 15 cm) in spring and fall and the DPS was determined for the surface layer. Average STP (0 to 15 cm) ranged from 3 to 512 mg kg(-1), and DPS (0 to 2.5 cm) ranged from 5 to 91%. Seasonal FWMCs ranged from 0.01 to 7.4 mg L(-1) DRP and from 0.1 to 8.0 mg L(-1) TP. Strong linear relationships (r2=0.87 to 0.89) were found between the site mean STP and the FWMCs of DRP and TP. The relationships had similar extraction coefficients, intercepts, and predictive power among all three soil layers. Extraction coefficients (0.013 to 0.014) were similar to those reported for other Alberta studies, but were greater than those reported for rainfall simulation studies. The curvilinear DPS relationship showed similar predictive ability to STP. The field-scale STP relationships derived from natural conditions in this study should provide the basis for modeling phosphorus in Alberta.     

Fetoscopic myelomeningocoele closure: Is the scientific evidence enough to challenge the gold standard for prenatal surgery?

Since the completion of the Management of Myelomeningocoele Study, maternal-fetal surgery for spina bifida has become a valid option for expecting parents. More recently, multiple groups are exploring a minimally invasive approach and recent outcomes have addressed many of the initial concerns with this approach. Based on a previously published framework, we attempt to delineate the developmental stage of the surgical techniques. Furthermore, we discuss the barriers of performing randomized controlled trials comparing two surgical interventions and suggest that data collection through registries is an alternative method to gather high-grade evidence.     

TREE RING RECONSTRUCTIONS OF STREAMFLOW FOR THREE CANADIAN PRAIRIE RIVERS1

ABSTRACT: Information regarding long term hydrological variability is critical for the effective management of surface water resources. In the Canadian Prairie region, growing dependence on major river systems for irrigation and other consumptive uses has resulted in an increasing vulnerability to hydrological drought and growing interprovincial tension. This study presents the first dendrochronological records of streamflow for Canadian Prairie rivers. We present 1,113‐year, 522‐year, and 325‐year reconstructions of total water year (October to September) streamflow for the North Saskatchewan, South Saskatchewan, and Saskatchewan Rivers, respectively. The reconstructions indicate relatively high flows during the 20th Century and provide evidence of past prolonged droughts. Low flows during the 1840s correspond with aridity that extended over much of the western United States. Similarly, an exceptional period of prolonged low flow conditions, approximately 900 A.D. to 1300 A.D., is coincident with evidence of sustained drought across central and western North America. The 16th Century megadrought of the western United States and Mexico, however, does not appear to have had a major impact on the Canadian rivers. The dendrohydrological records illustrate the risks involved if future water policy and infrastructure development in the Canadian Prairies are based solely on records of streamflow variability over the historical record.     

The European Union Solidarity Fund

This paper examines the legitimacy, viability and efficiency of the European Union Solidarity Fund by asking whether the Fund meets its stated purpose of providing solidarity within the EU, whether it is sufficiently capitalized and if it promotes disaster risk reduction in Europe. In examining these questions, we make use of ADAM models of disaster risks throughout Europe. We conclude that the Solidarity Fund falls short on all three counts, and we suggest possible alternatives. Most far-reaching, we explore whether the EUSF could support insurance systems in Europe by, among other possible activities, capitalizing national public-private insurance programs and providing support for government risk transfer. This would leverage the Fund’s capital and would overcome barriers to the provision of private and public sector insurance in uncertain catastrophe markets. It would also make insurance more affordable to Europe’s most vulnerable communities. Finally, it would reduce the disincentives for risk reduction inherent in post-disaster assistance.     

Cyclic AMP-dependent protein kinase: role in anoxia and freezing tolerance of the marine periwinkle Littorina littorea

A key regulatory mechanism underlying the switch between aerobic and anaerobic metabolism amongst anoxia-tolerant marine molluscs is reversible protein phosphorylation. To assess the role of cAMP-dependent protein kinase (PKA) in aerobic–anaerobic transitions, the effects of anoxia on the activity and subcellular distribution of PKA were assessed in foot and hepatopancreas of the marine periwinkle, Littorina littorea. Exposure to N₂ gas at 5 °C caused a rapid decline in the percentage of total enzyme present as the free catalytic subunit (PKAc) in both tissues; the percentage of PKAc fell from ∼30% in controls to 3% after 1 h anoxia and remained low over 72 h. Total PKA also fell by 30% after 72 h anoxia in hepatopancreas but rebounded during aerobic recovery. Freezing at −8 °C elicited parallel results for both percentage of PKAc and total PKA, suggesting that PKA responses to freezing were stimulated by the ischemia that develops when hemolymph freezes. Anoxia also led to a shift in PKA subcellular distribution in hepatopancreas (but not in foot), the percentage of total PKA activity associated with the nuclear fraction dropping from 25% in controls to 8% in 12 h anoxic snails with opposite changes in the cytosolic fraction. The catalytic subunit (PKAc) of foot PKA was purified to a final specific activity of 63.5 nmol phosphate transferred per minute per milligram protein. Enzyme properties included a molecular weight of 33 to 35 kDa, an activation energy from Arrhenius plots of 65.1 ± 4.8 kJ mol⁻¹, and substrate affinity constants of 151 ± 6 μM for the phosphate acceptor, Kemptide, and 72 ± 9 μM for Mg.ATP. Activity was strongly reduced by mammalian PKA inhibitors (H-89, PKA-I), by neutral chloride salts (I₅₀ values 165 to 210 mM) and by NaF (I₅₀ 62 mM). Reduced PKA activity under anoxic or freezing conditions would facilitate the observed suppression of the activities of numerous enzymes that are typically PKA-activated and thereby contribute to the overall anoxia-induced metabolic rate depression. Received: 19 November 1997 / Accepted: 30 September 1998     

Sovereign financial disaster risk management: The case of Mexico

In 2006, Mexico became the first transition country to transfer part of its public-sector natural catastrophe risk to the international reinsurance and capital markets. The Mexican case is of considerable interest to highly exposed transition and developing countries, many of which are considering similar transactions. Risk financing instruments can assure governments of sufficient post-disaster capital to provide emergency response, disaster relief to the affected population and repair public infrastructure. The costs of financial instruments, however, can greatly exceed expected losses, and for this reason it is important to closely examine their benefits and alternatives. This paper analyzes the Mexican case from the perspective of the risk cedent (the Ministry of Finance and Public Credit), which was informed by analyses provided by the International Institute for Applied Systems Analysis (IIASA). The rationale for a government to insure its contingent liabilities is presented along with the fiscal, legal and institutional context of the Mexican transaction. Using publicly available data, the paper scrutinizes the choice the authorities faced between two different risk-transfer instruments: reinsurance and a catastrophe bond. Making use of IIASA's catastrophe simulation model (CATSIM), this financial risk management decision is analyzed within the context of a public investment decision.