How does cell-based non-invasive prenatal test (NIPT) perform against chorionic villus sampling and cell-free NIPT in detecting trisomies and copy number variations? A clinical study from Denmark

Objectives

We aimed to compare cell-based NIPT (cbNIPT) to chorionic villus sampling (CVS) and to examine the test characteristics of cbNIPT in the first clinical validation study of cbNIPT compared to cell-free NIPT (cfNIPT).

Material and Methods

Study 1: Women (N = 92) who accepted CVS were recruited for cbNIPT (53 normal and 39 abnormal). Samples were analyzed with chromosomal microarray (CMA). Study 2: Women (N = 282) who accepted cfNIPT were recruited for cbNIPT. cfNIPT was analyzed using sequencing and cbNIPT by CMA.

Results

Study 1: cbNIPT detected all aberrations (32/32) found in CVS: trisomies 13, 18 and 21 (23/23), pathogenic copy number variations (CNVs) (6/6) and sex chromosome aberrations (3/3). cbNIPT detected 3/8 cases of mosaicism in the placenta. Study 2: cbNIPT detected all trisomies found with cfNIPT (6/6) and had no false positive (0/246). One of the three CNVs called by cbNIPT was confirmed by CVS but was undetected by cfNIPT, two were false positives. cbNIPT detected mosaicism in five samples, of which two were not detected by cfNIPT. cbNIPT failed in 7.8% compared to 2.8% in cfNIPT.

Conclusion

Circulating trophoblasts in the maternal circulation provide the potential of screening for aneuploidies and pathogenic CNVs covering the entire fetal genome.     

Evaluation of carbon dioxide storage potential for the Bohai Basin,north-east China

The storage potential of selected sites within the Bohai Basin was assessed for the COACH project. The Gangdong oilfield is considered to have a small potential storage capacity (23 Mt) and to be possibly suitable for an enhanced oil recovery or small-scale storage pilot rather than large-scale storage. The Shengli oilfield province is considered to have a great potential storage capacity (472 Mt in eight selected fields), however, these fields, like those of the Gangdong oilfield province, are compartmentalised by faulting and stratigraphy and likely to be quite challenging for injection. Unmineable coal seams in the Kailuan mining area were also considered for storage, the estimated capacity is 504 Gt adsorbed onto the coal and 38,100 Mt void storage capacity. However, the coals have low porosity and permeability, so they would be expected to have poor injectivity. This is also an active mining area and so any storage site would have to be chosen carefully to avoid affecting future energy resources. The Huimin sub-basin within the Jiyang Depression was identified for consideration as an aquifer storage site; the Guantao Formation has good porosity and permeability in this region, and the regional-level storage capacity of these areas was estimated to be 0.7 Gt. The aquifers in the Huimin sub-basin appear promising for storage, however, less data are available than for the oilfields and the sealing formations are not directly proven to trap buoyant fluids, though in adjacent oilfield in the Shengli oilfield province, the Minghuazhen Formation forms a regional seal for the Guantao Formation.     

The burden of proof in trade disputes and the environment

The WTO leaves discretion over environmental policies to its members, but requests that a fundamental non-discrimination principle is respected: National Treatment (NT). The provision seeks to prevent protectionist use of domestic policy instruments, requesting that when an imported product is sufficiently similar to a domestic product, they are treated identically. WTO adjudicators will often face severe informational problems in environmental disputes. Important for the practical implementation of NT is therefore the allocation of the burden of proof (BoP). This paper highlights basic implications of the BoP for the occurrence of judicial errors, for the environment and for welfare, using a setting where NT serves its intended role of supporting negotiated tariff liberalization. The paper suggests that NT may indeed constrain environmental policies, but that this may be desirable from an efficiency point of view. Also, BoP rules that benefit the environment may not benefit global welfare, and conversely.     

A distributed modelling system for simulation of monthly runoff and nitrogen sources, loads and sinks for ungauged catchments in Denmark

We validated an existing physically based 3D MIKE SHE groundwater resource model (DK-model) at 175 Danish gauging stations covering different catchment sizes in order to calculate monthly water runoff in the 50% ungauged part of Denmark. Model performance was in most cases good (61% of gauging stations had a Nash-Sutcliffe (NS) coefficient >0.60) but nevertheless showed a large seasonal and georegion specific bias. Therefore, bias correction factors had to be developed before applying the DK-model simulations of runoff in the ungauged areas. Simulated monthly runoff from ungauged areas and the measured monthly runoff from 178 gauging stations were distributed to 2663 smaller Hydrological Units (ca. 15 km(2)) and linked with a new empirical model for flow-weighted monthly total nitrogen (TN) concentrations (R(2) = 0.43; P < 0.0001) developed based on 20 years of observations (1990-2009) in 83 small catchments for calculation of monthly gross diffuse TN-loads from HU's. Nitrogen retention was calculated in streams, lakes and wetlands utilising both lake specific models and rate coefficients to calculate N retention in surface water bodies. The whole model complex was linked in the DK-QN concept for simulation of monthly TN losses from point sources and diffuse sources, TN retention and resulting loadings to Danish coastal waters. The DK-QN model was validated in 118 gauged catchments and the model simulations had for >25% of the observations of monthly discharge weighted TN concentrations a NS larger than 0.26. Catchment specific monthly TN-loadings were modelled with a higher performance as 50% of the catchments had a NS greater than 0.75. The model concept allows calculation of N retention in streams, lakes and wetlands and the average annual model calculated N retention amounted to 21% of the modelled gross riverine TN loadings. The average annual gross TN loading to surface freshwater in Denmark derived from diffuse sources amounted to 97 000 tonnes N (91% of gross TN loadings) which is 54% of the total estimated N-leaching from the root zone on the Danish land area (212 000 tonnes N) during the period 1990-2009.     

How best to quantify soil seed banks in arid rangelands of the Nama Karoo?

Sampling design and three sample treatments prior the application of the seedling emergence method were tested in order to find the best method for seed bank quantification in arid Nama Karoo rangelands. I analyzed species composition and seed densities by contrasting undercanopy and open-matrix samples from two soil depths and by comparing the effects of cold-, heat-, and no stratification on germination rates of species in a greenhouse setting. The soil seed bank showed minimal similarity to the standing vegetation, with only 20 plant species germinated. Spatial distribution of seeds was highly heterogeneous. Nearly 90% of germinated seeds were located in 0- to 4-cm compared to >4- to 8-cm soil depth. Undercanopy seed banks contained significantly more species and seeds than open-matrix seed banks. Neither the number nor the diversity of seeds germinated differed significantly among the three treatments. Cold stratification tended to detect more species and seeds only at >4- to 8-cm soil depth. The results highlight the importance of spatial heterogeneity in the accurate evaluation of soil seed banks in the arid Nama Karoo and the importance of considering seasonal variability in the availability of readily germinable seeds. Data also suggest that sample pretreatment in germination trials may give little return for cost and effort, which emphasizes that it is more important to choose the sampling design most likely to give a representative number of seed bank species. Further studies are needed to analyze seed bank dynamics and species-specific germination requirements to promote recruitment of plant taxa underrepresented in the seed bank.     

Characterisation, dissemination and persistence of gentamicin resistant Escherichia coli from a Danish university hospital to the waste water environment

The aim of the study was to investigate the potential spread of gentamicin resistant (GEN(R)) Escherichia coli isolates or GEN(R) determinants from a Danish university hospital to the waste water environment. Waste water samples were collected monthly from the outlets of the hospital bed wards and the inlet of the related waste water treatment plant (WWTP) from October 2002 to August 2003. Waste water samples were also collected monthly from a residential area in the same period to be able to compare the prevalence of GEN(R)E. coli isolates from hospital related and residential waste water. The waste water isolates were compared to GEN(R)E. coli isolates obtained consecutively from September 2002 to September 2003 from patients mainly with urinary tract infections at the hospital with respect to Pulsed Field Gel Electrophoresis (PFGE) profiles. All isolates were investigated for GEN(R) mechanisms (aac(3)-II, aac(3)-IV, ant(2')-I, armA), phenotypic resistance pattern, and virulence genes (hlyA, chuA, sfaS, fogG, malX, traT, iutA, fyuA, iroN, cnf1) to investigate if the hospital and waste water could be reservoirs of antimicrobial resistance and virulence. The ability for GEN(R) determinants to transfer horizontally was investigated by mating experiments. A total of 38, 15, 21, and two GEN(R)E. coli were isolated from patients, the hospital outlets, the inlet of the WWTP, and the residential area, respectively. GEN(R)E. coli were more prevalent in waste water from the hospital and the WWTP than in waste water from the residential area. PFGE profiling revealed no spread of specific patient isolates to the waste water. The aac(3)-II gene was detected both in patient and waste water isolates. Furthermore horizontal transfer of the aac(3)-II gene of patient origin to a recipient was shown in vitro, indicating a potential spread of the gene from patient isolates to waste water isolates. Regardless of origin, most isolates exhibited multi-resistance and contained several virulence genes. In conclusion, our study showed a possible spread of aac(3)-II from the hospital to the waste water. Most of the GEN(R)E. coli isolates from both patients and waste water had a multi-resistant phenotype and contained virulence genes and should therefore be considered reservoirs of antimicrobial resistance and virulence genes.     

Natural and synthetic endocrine disrupting compounds (EDCs) in water, sediment and biota of a coastal lagoon

We report a survey on the occurrence and distribution of natural (17beta-estradiol, E2; estrone, E1) and synthetic (nonylphenol, NP; nonylphenol monoethoxylate carboxylate, NP1EC; bisphenol-A, BPA; benzophenone, BP; mestranol, MES; 17alpha-ethinylestradiol, EE2; diethylstilbestrol, DES) endocrine disrupting compounds (EDCs) in water, sediment and biota (Mediterranean mussel, Mytilus galloprovincialis) in the Venice lagoon, a highly urbanized coastal water ecosystem that receives both industrial and municipal wastewater effluents. The survey was preceded by the development of tailor made extraction and clean-up procedures for the simultaneous HPLC-ESI-MS determination of all examined EDCs in sediment and biota samples. Satisfactory extraction performances and method detection limits (MDLs) were obtained for almost all EDCs. Most of the selected compounds were found in water and sediment (concentration range: 2.8-211 ng/L, and 3.1-289 microg/kg, d.w., respectively), while only 17alpha-ethinylestradiol and nonylphenol were recorded in biota samples (conc. range: 7.2-240 ng/g, d.w.). 17beta-estradiol and ethinylestradiol contributed mostly to the water estradiol equivalent concentration (EEQ) (1.1-191 ng/L, average: 25 ng/L), while synthetic EDCs (17alpha-ethinylestradiol, diethylstilbestrol) were mainly responsible of the sediment EEQ (1.1-191 microg/kg, average: 71 microg/kg, d.w.). Whenever diethylstilbestrol was not recorded in the sediment, water EEQs were similar to sediment EEQs. A remarkable increase of nonylphenol was observed in sediments over the last decade.     

Global assessment of the non-equilibrium concept in rangelands

The non-equilibrium concept of rangeland dynamics predicts that the potential for grazing-induced degradation is low in rangelands with relatively variable precipitation. To date, evidence in support of the non-equilibrium concept has been inconsistent. Using a standardized protocol, including a newly developed global map of rainfall variability, we reviewed the incidence of degradation in relation to rainfall variability across 58 published studies. We distinguished between (1) zonal degradation (i.e., degradation independent of water and key resources), (2) degradation in the presence of key resources, and (3) degradation in the presence of water. For studies not affected by proximity to permanent water or key resources, we found strong support for the non-equilibrium concept for rangelands. Zonal degradation was absent at CV (coefficient of variation) values above 33%, which has been proposed as a critical threshold. Grazing degradation was almost entirely restricted to areas with relatively stable annual precipitation as expressed by a low CV, or to rangelands with key resources or water points nearby. To better understand rangeland dynamics, we recommend that future studies use globally comparable measures of degradation and rainfall variability. Our work underlines that rangelands with relatively stable rainfall patterns, and those with access to water or key resources, are potentially vulnerable to degradation. Grazing management in such areas should incorporate strategic rest periods. Such rest periods effectively mimic natural fluctuations in herbivore populations, which are a defining characteristic of non-degraded rangelands occurring under highly variable precipitation regimes.     

Native predators reduce harvest of reindeer by Sámi pastoralists

Contemporary efforts to protect biological diversity recognize the importance of sustaining traditional human livelihoods, particularly uses of the land that are compatible with intact landscapes and ecologically complete food webs. However, these efforts often confront conflicting goals. For example, conserving native predators may harm pastoralist economies because predators consume domestic livestock that sustain people. This potential conflict must be reconciled by policy, but such reconciliation requires a firm understanding of the effects of predators on the prey used by people. We used a long-term, large-scale database and Bayesian models to estimate the impacts of lynx (Lynx lynx), wolverine (Gulo gulo), and brown bear (Ursus arctos) on harvest of semi-domesticated reindeer (Rangifer tarandus) by Sami pastoralists in Sweden. The average annual harvest of reindeer averaged 25% of the population (95% credible interval = 19, 31). Annual harvest declined by 96.6 (31, 155) reindeer for each lynx family group (the surveyed segment of the lynx population) in a management unit and by 94.3 (20, 160) for each wolverine reproduction (the surveyed segment of the wolverine population). We failed to detect effects of predation by brown bear. The mechanism for effects of predation on harvest was reduced population growth rate. The rate of increase of reindeer populations declined with increasing abundance of lynx and wolverine. The density of reindeer, latitude, and weather indexed by the North Atlantic Oscillation also influenced reindeer population growth rate. We conclude that there is a biological basis for compensating the Sámi reindeer herders for predation on reindeer.