What is the real “price” of more prenatal screening and fewer diagnostic procedures? Costs and trade-offs in the genomic era

Any screening approach, including with cell-free DNA, will have an inferior detection rate compared with 100% diagnostic testing with chromosomal microarrays. Cell-free DNA-based screening, however, should not be seen as a threat to informed choice or maximising the benefits of diagnostic testing. Screening methods have become so much better that more women are now comfortable relying on such screening and do not need the certainty of a diagnostic test. This has not lead to a decline in detection of fetal chromosome abnormalities—in fact, we are now seeing historically high yields from prenatal screening. There are both economic and ethical consequences of offering universal diagnostic testing and abandoning the presumption of a normal infant in otherwise uncomplicated pregnancies. However, for some women, comprehensive information and diagnostic accuracy are important. Offering these women all options, with a careful and comprehensive explanation of the risks and benefits of each, results in outcomes that are best aligned with woman's preferences while at the same time requiring fewer diagnostic tests and lowering costs. It is one of the primary challenges of the modern era of prenatal testing to ensure that women receive sufficient information on which to make informed decisions.     

Access to prenatal exome sequencing for fetal malformations: A qualitative landscape analysis in the US

Objective

There is increasing evidence supporting the clinical utility of next generation sequencing for identifying fetal genetic disorders. However, there are limited data on the demand for and accessibility of these tests, as well as payer coverage in the prenatal context. We sought to identify clinician perspectives on the utility of prenatal exome sequencing (ES) and on equitable access to genomic technologies for the care of pregnancies complicated by fetal structural anomalies.

Method

We conducted two focus group discussions and six interviews with a total of 13 clinicians (11 genetic counselors; 2 Maternal Fetal Medicine/Geneticists) from U.S. academic centers and community clinics.

Results

Participants strongly supported ES for prenatal diagnostic testing in pregnancies with fetal structural anomalies. Participants emphasized the value of prenatal ES as an opportunity for a continuum of care before, during, and after a pregnancy, not solely as informing decisions about abortions. Cost and coverage of the test was the main access barrier, and research was the main pathway to access ES in academic centers.

Conclusion

Further integrating the perspectives of additional key stakeholders are important for understanding clinical utility, developing policies and practices to address access barriers, and assuring equitable provision of prenatal diagnostic testing.     

Chemical characterization of synthetic soil from composting coal combustion and pharmaceutical by-products

Land application of coal combustion by-products (CCBs) mixed with solid organic wastes (SOWs), such as municipal sewage sludge, has become increasingly popular as a means of productively using what were once considered waste products. Although bulk chemical and physical properties of several of these CCB-SOW materials have been reported, detailed information about their synthesis and mineralogy of the CCB-SOW materials has not been reported. In this paper, chemical and mineralogical properties of a soil-like material obtained from composting a mixture of CCBs with a pharmaceutical fermentation by-product (FB) were investigated at the laboratory and field scale. All starting materials and products were characterized by X-ray diffraction (XRD), fourier transform infrared (FFIR) spectroscopy, and elemental analyses. The results showed that the FB was strongly bound to the CCBs and could not be removed by washing. Within 2 wk of the start of a composting study, there was a rapid drop in pH from 12 to 8, an increase in temperature to 70 degrees C, and a reduction in the dissolved oxygen content, attributed to the rapid establishment of a highly active microbial population. Composting produced a soil-like material with high levels of plant nutrients, a high nutrient retention capacity, and metal contents similar to median levels of those metals reported for soils. The levels of boron and soluble salts are such that sensitive plants may initially show toxicity symptoms. However, with adequate rainfall, leaching should rapidly remove most of the B and soluble salts. With care, the material produced is safe for use as a synthetic topsoil.     

Contribution of macroporosity to infiltration into a continuous corn no-tilled watershed: Implications for contaminant movement

Rainfall and runoff were measured for many years on small watersheds on 10–15% slopes in east-central Ohio. Surface runoff from watersheds used for corn (Zea mays L.) production was high with conventional tillage and very low with no-tillage. A 50-year storm produced 15 times more runoff from a plowed watershed than from a mulch-covered no-till watershed. Reduced runoff from the no-till surface resulted in increased percolation and enhanced the potential for transport of agricultural chemicals to the groundwater. The mulched surface of the no-till watershed also created a favorable environment for the deep burrowing earthworm, Lumbricus terrestris L., whose burrows can transmit water rapidly downward through the soil profile, thus contributing to the high infiltration rates.Open biopores and smaller structural pores were counted and measured to characterize the major flow paths of water movement in the no-till soil. Photos of horizontal surfaces at 2.5-, 7.5-, 15-, and 30 - cm depths and vertical faces of impregnated samples from the 1- and 5-cm depths were evaluated by image analysis. Number of pores was inversely proportional to pore diameter, however pores in the 0.05–1.0-mm diameter range accounted for less porosity than did those in the 1.0–5.0-mm range. The large pores were nearly vertical earthworm burrows and were continuously open from near the surface to the bedrock. Surface applications of lime increased subsoil pH in the no-till watershed but had little effect below the plow sole in the tilled watershed, suggesting that rapid movement of water in large pores can enhance chemical migration into the subsoil.     

Dynamics of P, Al, and Fe during High Discharge Episodic Acidification at the Bear Brook Watershed in Maine, U.S.A.

Phosphorus (P), aluminum (Al), and iron (Fe) stream chemistry were assessed for high discharge snowmelt events at the Bear Brook Watershed, Maine (BBWM) during December 2001 and February 2002 and compared with results from a January 1995 study of the same streams. The West Bear catchment has been subjected to artificial acidification since 1989. The East Bear catchment is the untreated reference. Total (acid soluble) Al, Fe, and P were positively correlated with discharge during the 2001–2002 events. However, dissolved P concentrations remained low (≤0.1 μmol L^-1) during high discharge events as pH decreased in both streams.For example, in 2001, total P concentration increased to 1.7 μmol L^-1 during the rising limb of the hydrograph in West Bear, approximately five times the value in East Bear. During the same event, in West Bear and East Bear dissolved Al concentrations increased to 21 and 6.3 μmol L^-1, respectively, while total Al concentrations increased to 166 and 30 μmol L^-1, respectively. Dissolved Fe concentrations remained ≤0.9 μmol L^-1 in both streams during all study events. However, total Fe concentrations in 2001 increased to 239 and 4.1 μmol L^-1 for West Bear and East Bear, respectively. Total Al and Fe declined parallel to total P after peaking during all study periods. Nearly all of the base cations were in dissolved form during the three events, indicating that total Al in West and East Bear Brooks is not associated with primary minerals such as feldspars. We conclude that particulate Al, Fe, and P are chemically linked during transport at high discharge in these episodically and chronically acidified streams.     

Population trend alters the effects of maternal dominance rank on lifetime reproductive success in yellow baboons (<Emphasis Type="Italic">Papio cynocephalus</Emphasis>)

We evaluated the association between dominance rank and lifetime reproductive success of 75 free-ranging female baboons in Mikumi National Park, Tanzania. Data were evaluated over a 22-year period that included a period of troop increase (1975–1987) associated with two troop splits in 1978 and 1979, followed by a precipitous population crash (1987–1996) where the troops successively fused back together in 1989 and 1994. Lifetime reproductive success was significantly greater for high- versus low-ranking females when examined across the entire study period. High-ranking females had a longer reproductive life span (7.4 vs 3.6 years after first birth), reached menarche earlier (4.6 vs 5.2 years), lived longer (12.0 vs 8.8 years), and had more offspring of both sexes (2.25 vs 1.33 for male offspring; 3.25 vs 0.94 for female offspring), with four times the number of offspring of each sex surviving to 4 years of age compared to low ranking females. Greater offspring production was associated with shorter interbirth intervals of dominant versus subordinate females (545 vs 723 days), partly owing to lower miscarriage rates (0.05 vs 0.2) and a shorter duration of lactation (244 vs 330 days). Rank effects were then partitioned by mothers experiencing the majority of their reproductive life prior to, versus during, the population decline. The majority of rank effects on measures of lifetime reproductive success were virtually eliminated for mothers reproducing during the troop decline, indicating that the considerable impacts of social status on lifetime reproductive success can be markedly altered by intrinsically and extrinsically mediated demographic events.Ramon Rhine is deceasedCommunicated by C. Nunn     

The MAGIC simulation of surface water acidification at, and first year results from, the Bear Brook Watershed Manipulation, Maine, USA

The catchments of East and West Bear Brooks, Maine, USA, have been hydrologically and chemically monitored for 3.5 years. Stream chemistries and hydrographs are similar. These clear water streams are low in ANC (0-70 microeq litre(-1)), with variations caused by changing concentrations of base cations, SO4, NO3 and Cl. The latter range between 90-120, 0-40 and 65-75 microeq litre(-1), respectively. The West Bear catchment is being treated with six applications per year of dry (NH4)2SO4 at 1800 eq ha(-1) year(-1). After one year of treatment, the response of the stream chemistry and the response modelled by MAGIC are similar. Retentions of NH4 and SO4 are nearly 100% and greater than 80%, respectively. The additional flux of SO4 is compensated principally by an increased Ca concentration. Episodes of high discharge in the treated catchment are now characterized by lower ANC and pH, and higher Al than prior to the manipulation. Concentrations of NO3 have increased about 10 microeq litre(-1) during the dormant season, presumably due to additional nitrification of N from NH4. Discharge-chemistry relationships indicate that changes in stream chemistry, except for NO3, are dominated by ion exchange reactions in the upper part of the soil profile.