All-in-one whole exome sequencing strategy with simultaneous copy number variant,single nucleotide variant and absence-of-heterozygosity analysis in fetuses with structural ultrasound anomalies: A 1-year experience

Objective

We performed a 1-year evaluation of a novel strategy of simultaneously analyzing single nucleotide variants (SNVs), copy number variants (CNVs) and copy-number-neutral Absence-of-Heterozygosity from Whole Exome Sequencing (WES) data for prenatal diagnosis of fetuses with ultrasound (US) anomalies and a non-causative QF-PCR result.

Methods

After invasive diagnostics, whole exome parent-offspring trio-sequencing with exome-wide CNV analysis was performed in pregnancies with fetal US anomalies and a non-causative QF-PCR result (WES-CNV). On request, additional SNV-analysis, restricted to (the) requested gene panel(s) only (with the option of whole exome SNV-analysis afterward) was performed simultaneously (WES-CNV/SNV) or as rapid SNV-re-analysis, following a normal CNV analysis.

Results

In total, 415 prenatal samples were included. Following a non-causative QF-PCR result, WES-CNV analysis was initially requested for 74.3% of the chorionic villus (CV) samples and 45% of the amniotic fluid (AF) samples. In case WES-CNV analysis did not reveal a causative aberration, SNV-re-analysis was requested in 41.7% of the CV samples and 17.5% of the AF samples. All initial analyses could be finished within 2 weeks after sampling. For SNV-re-analysis during pregnancy, turn-around-times (TATs) varied between one and 8 days.

Conclusion

We show a highly efficient all-in-one WES-based strategy, with short TATs, and the option of rapid SNV-re-analysis after a normal CNV result.     

In utero sonographic diagnosis of a communicating enteric duplication cyst in a giant omphalocele

Enteric duplications are rare lesions, and relatively few cases have been diagnosed prenatally. We present, to our knowledge, the first case of an associated communicating ileal duplication cyst in a huge omphalocele diagnosed prenatally. The prenatal ultrasound findings revealed four features of the cystic lesion including peristaltic movements of the cystic wall, communication between the cyst and normal bowel lumen, intra-cystic echogenic contents, and echogenic mesenteric tissue (fat) close to the cyst. These distinct characteristics helped us to make a firm in utero diagnosis. Copyright © 2001 John Wiley & Sons, Ltd.     

The influence of lipid and lifestyle factors upon correlations between highly prevalent organochlorine compounds in patients with exocrine pancreatic cancer

We aimed to analyse the influence of cholesterol and triglycerides, and of tobacco, coffee and alcohol consumption upon correlations between serum concentrations of organochlorine compounds (OCs) in patients with exocrine pancreatic cancer (EPC). Incident cases of EPC diagnosed in eastern Spain were prospectively identified (N=144). OCs were analysed by high-resolution gas chromatography with electron-capture detection. A strong correlation was observed between hexachlorobenzene (HCB) and beta-hexachlorocyclohexane (beta-HCH) (Spearman's rho=0.758). beta-HCH showed rho>0.4 with p,p'-DDT, p,p'-DDE, PCB138 and PCB153 (all p<0.001). Some correlations among compounds were slightly affected by tobacco, coffee or alcohol consumption. We observed a striking diversity of correlation patterns by strata of cholesterol and triglycerides. Most correlations were higher in the lowest category of triglycerides than in the lowest category of cholesterol. Most coefficients above 0.7 were seen in the lowest category of triglycerides (e.g., OC pairs p,p'-DDT and HCB, p,p'-DDT and beta-HCH, p,p'-DDE and beta-HCH, or HCB and beta-HCH). Correlations among OCs may be stronger when concentrations of triglycerides are low than when they are high. This is compatible with a dilution in the early phases of cancer and with a concentration effect as triglycerides become lower in the advanced phases of the disease.     

The anti-predator behaviour of wild white-handed gibbons (<Emphasis Type="Italic">Hylobates lar</Emphasis>)

Predation on gibbons is rarely observed in the wild. However, the gibbons' moderate body size and relatively small social groups suggest high vulnerability to predation. To assess the role of predation and to study their anti-predator behaviour, we presented visual predator models to nine groups of wild white-handed gibbons at Khao Yai National Park, Thailand. We measured subjects' immediate and delayed responses to four potential predators: tiger, clouded leopard, crested serpent eagle and reticulated python. Subjects reliably approached all four predators. In response to tigers and leopards, they additionally produced predator-specific songs and defecated copiously. In terms of delayed responses, distance between mated adults decreased, but only after exposure to the tiger model. In response to eagles and pythons, gibbons consistently vocalised, but this did not always include predator singing, and we found no long-term effects in overall activity or strata use. However, during 6 of 26 predator encounters, the gibbons produced songs with a structure that was intermediate between a duet song and a predator song more than 20 min after the predator encounter, indicating a long-term effect on their vocal behaviour. This study demonstrates that gibbons discriminate between different potential predators and respond to them with adaptive anti-predator behaviour, which include predator-specific vocal responses. We conclude that gibbons are not immune to predation and that terrestrial predators elicit consistent immediate and delayed anti-predation responses.     

Hydrological connectivity and <Emphasis Type="Italic">Burkholderia pseudomallei</Emphasis> prevalence in wetland environments: investigating rice-farming community’s risk of exposure to melioidosis in North-East Thailand

In our analysis of 136 water samples from wetland environments (rice paddies, natural wetland sites, man-made water bodies) in rural areas of North-East Thailand, Burkholderia pseudomallei was most prevalent in rice paddies (15 of the 30 positive sites). The high prevalence in the water of rice fields is indicative of the inherent vulnerability of farmers in rural agricultural areas in this area of Thailand and likely other locations in the tropics. Nearly all B. pseudomallei-positive sites were found within the vicinity of a large wetland associated with the Chi River, in the month of July 2014. Positive samples were found in water ranging in pH from 5.9 to 8.7, salinity ranging from 0.04 to 1.58 ppt, nitrate ranging from 0 to 10.8 ppm, and iron ranging from 0.003 to 1.519 ppm. Of these variables, only iron content was statistically higher in B. pseudomallei-positive versus B. pseudomallei-negative sites, suggesting that increasing concentrations of iron may encourage the growth of this bacterium, which is responsible for melioidosis. Our results, when combined with data from other published studies, support the notion that B. pseudomallei can exist in a wide range of environmental conditions. Thus, we argue that health safety education is a more appropriate means of addressing farmer vulnerability than chemical or physical alterations to fields at large scales. Further, it may be important to investigate melioidosis through transdisciplinary approaches that consider the complex social and ecological contexts in which the disease occurs.     

Particulate matter in the indoor and outdoor air of a gymnasium and a fronton

An indoor/outdoor monitoring programme of PM₁₀ was carried out in two sports venues (a fronton and a gymnasium). Levels always below 50 μg m^?3 were obtained in the fronton and outdoor air. Due to the climbing chalk and the constant process of resuspension, concentrations above 150 μg m^?3 were registered in the gymnasium. The chalk dust contributed to CO₃ ^2? concentrations of 32?±?9.4 μg m^?3 in this sports facility, which represented, on average, 18 % of the PM₁₀ mass. Here, the carbonate levels were 128 times higher than those registered outdoors. Much lower concentrations, around 1 μg m^?3, were measured in the fronton. The chalk dust is also responsible for the high Mg²⁺ concentrations in the gym (4.7?±?0.89 μg m^?3), unfolding a PM₁₀ mass fraction of 2.7 %. Total carbon accounted for almost 30 % of PM₁₀ in both indoor spaces. Aerosol size distributions were bimodal and revealed a clear dependence on physical activities and characteristics of the sports facilities. The use of climbing chalk in the gymnasium contributed significantly to the coarse mode. The average geometric mean diameter, geometric standard deviation and total number of coarse particles were 0.77 μm, 2.79 cm^?3 and 28 cm^?3, respectively.     

The influence of subordinate age on managerial actions: An attributional analysis

The present research examined the effects of employee age on managers attributions and actions toward subordinates. The major prediction was that managers attributions would mediate the effects of age on managerial actions. One-hundred and twenty-four undergraduate management students participated in a laboratory experiment in which subordinate age (30 versus 60 years) and performance (high versus low) were manipulated. A laboratory study was conducted so that subordinate credentials and performance levels could be controlled. Analyses indicated that poor performance by older subordinates was attributed more to stable factors than similar performance by younger subordinates. In addition, job simplification was rated as more appropriate and training was recommended as less appropriate for older subordinates. A series of hierarchical regression analyses indicated that the differences in managerial actions were a function of subjects' attributional patterns. Implications of the findings for practice and future research are discussed.     

Analysis of maternal serum alpha-fetoprotein and free beta human chorionic gonadotrophin in the first trimester: Implications for down's syndrome screening

The aim of this study was to determine the maternal population, pregnancy, serum alpha-fetoprotein (AFP) and free β subunit of human chorionic gonadotrophin (FβhCG) parameters in a large series of women attending prenatal clinics before 15 weeks' gestation and to assess the practical problems of population screening for Down's syndrome in the first trimester using these markers. Serum samples were collected from 8600 women attending prenatal clinic booking visits. Maternal serum AFP and FβhCG medians were calculated for each day of gestation (49–104 days), using both dates and ultrasound estimates of gestation. The effects of maternal weight, twin pregnancies, and threatened abortion on AFP and FβhCG levels were analysed. The median age of the population was 27.1 years and the median weight 62.1 kg. Twenty-six per cent of samples were collected before 70 days and 50 per cent before 78 days' gestation. Eighty-nine per cent of all samples had gestational estimates by dates, 60 per cent by ultrasound and 52 per cent by both dates and ultrasound. The AFP median was 5 kU/1 at 49 days, 5.9 kU/1 at 70 days, and 17.9 kU/1 at 100 days. The peak median FβhCG level was 66.4 ng/ml at 64 days, falling to 20.6 ng/ml at 100 days' gestation. Both AFP and FβhCG levels showed log Gaussian distributions but the standard deviation for AFP was 20 per cent greater than that found in the second trimester. AFP and FβhCG levels showed an inverse relationship with maternal weight and were increased in twin pregnancies (1.68 and 1.97 multiples of the median, respectively). AFP and FβhCG can be readily measured in a large screening population in the first trimester. Down's syndrome screening protocols based on these markers could be refined by the use of gestations in individual days but AFP is likely to be a less effective marker and detection rates are likely to be lower than in the second trimester. To realize the potential of first-trimester screening, more women should be encouraged to attend the prenatal clinic in early pregnancy and ultrasound dating should be carried out for all pregnancies at this stage.     

Trimethylamine abatement in algal-bacterial photobioreactors

Trimethylamine (TMA) is an odorous volatile organic compound emitted by industries. Algal-based biotechnologies have been proven as a feasible alternative for wastewater treatment, although their application to abate polluted air emissions is still scarce. This work comparatively assessed the removal of TMA in a conventional bacterial bubble column bioreactor (BC) and a novel algal-bacterial bubble column photobioreactor (PBC). The PBC exhibited a superior TMA abatement performance compared to the conventional BC. In this sense, the BC reached a removal efficiency (RE) and an elimination capacity (EC) of 78% and 12.1 g TMA m^?3 h^?1, respectively, while the PBC achieved a RE of 97% and a EC of 16.0 g TMA m^?3·h^?1 at an empty bed residence time (EBRT) of 2 min and a TMA concentration ~500 mg m^?3. The outstanding performance of the PBC allowed to reduce the operating EBRT to 1.5 and 1 min while maintaining high REs of 98 and 94% and ECs of 21.2 and 28.1 g m^?3·h^?1, respectively. Moreover, the PBC improved the quality of the gas and liquid effluents discharged, showing a net CO₂ consumption and decreasing by ~ 30% the total nitrogen concentration in the liquid effluent via biomass assimilation. A high specialization of the bacterial community was observed in the PBC, Mumia and Aquamicrobium sp. being the most abundant genus within the main phyla identified.

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