Development of a simulator for training of fetoscopic myelomeningocele surgery

Objective

To develop a realistic simulation model for laparotomy-assisted fetoscopic spina bifida aperta (SBa) surgery, to be used for training purposes and preoperative planning.

Methods

The predefined general requirement was a realistic model of an exteriorized uterus, allowing all neurosurgical steps of the intervention. The uterus was modelled using ultrasound and MRI images of a 25 weeks’ gravid uterus, consisting of flexible polyurethane foam coated with pigmented silicone. The fetal model, contained an opening on the dorsal side for a customizable spinal insert with all the aspects of a SBa, including a cele, placode, and myofascial and skin layer. The model was assessed in a series of validation experiments.

Results

Production costs are low, uterus and fetus are reusable. Placental localization and the level and size of the spinal defect are adjustable, enabling case-specific adaptations. All aspects of the simulator were scored close to realistic or higher for both appearance and functional capacities.

Conclusions

This innovative model provides an excellent training opportunity for centers that are starting a fetoscopic SBa repair program. It is the first simulation model with adjustable spinal defect and placental localisation. Further objective validation is required, but the potential for using this model in preoperative planning is promising.     

Congenital small bowel obstruction: Prenatal detection and outcome

Objective

To evaluate and compare the outcome of fetuses and neonates with congenital small bowel obstructions (SBO), evaluate the screening performance of prenatal ultrasound for SBO and identify possible risk factors for adverse outcomes.

Methods

All cases referred to the Amsterdam University Medical Centers between 2007 and 2021 for a prenatal suspected SBO, supplemented by cases of postnatal diagnosis of SBO, were included. The primary outcome was survival after 24 weeks of gestation until the first year of life.

Results

147 cases of SBO were included with a survival rate of 86.2% (119/138) after 24 weeks of gestation until the first year of age. Additional structural or chromosomal anomalies were found to have an increased risk of adverse outcomes. Intrauterine fetal demise occurred in 10/147 (6.8%) cases and 9/147 (6.1%) cases died during postnatal follow-up. The overall positive predictive value of all prenatally diagnosed cases was 91.5%. Surgical correction was performed in 123/128 (96.0%) of the live-born cases.

Conclusions

Congenital SBO has an overall favorable prognosis, but the outcome is negatively impacted by the possible presence of additional structural or chromosomal anomalies. Fetal monitoring in the early third trimester should be considered, since all cases of Intrauterine fetal demise occurred between 30 and 35 weeks of gestation.     

A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound

Objective

Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.

Methods

We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of ~3850 Online Mendelian Inheritance in Man (OMIM) genes.

Results

We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days.

Conclusion

Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.     

Improving ready biodegradability testing of fatty amine derivatives

This study assesses the biodegradation potential of a number of fatty amine derivatives in tests following the OECD guidelines for ready biodegradability. A number of methods are used to reduce toxicity and improve the bioavailability of the fatty amine derivatives in these tests. Alkyl-1,3-diaminopropanes and octadecyltrimethylammonium chloride are toxic to microorganisms at concentrations used in OECD ready biodegradability tests. The concentration of these fatty amine derivatives in the aqueous phase can be reduced by reacting humic, or lignosulphonic acids with the derivatives or through the addition of silica gel to the test bottles. Using these non-biodegradable substances, ready biodegradability test results were obtained with tallow-1,3-diaminopropane and octadecyltrimethylammonium chloride. Demonstration of the ready biodegradability of the water-insoluble dioctadecylamine under the prescribed standard conditions is almost impossible due to the limited bioavailability of this compound. However, ready biodegradability results were achieved by using very low initial test substance concentrations and by introducing an organic phase. The contents of the bottles used to assess the biodegradability of dioctadecylamine were always mixed. False negative biodegradability results obtained with the fatty amine derivatives studied are the result of toxic effects and/or limited bioavailability. The aids investigated therefore improve ready biodegradability testing.     

Temporal variability of groundwater chemistry in shallow and deep aquifers of Araihazar, Bangladesh

Samples were collected every 2-4 weeks from a set of 37 monitoring wells over a period of 2-3 years in Araihazar, Bangladesh, to evaluate the temporal variability of groundwater composition for As and other constituents. The monitoring wells are grouped in 6 nests and span the 5-91 m depth range. Concentrations of As, Ca, Fe, K, Mg, Mn, Na, P, and S were measured by high-resolution ICPMS with a precision of 5% or better; concentrations of Cl were measured by ion chromatography. In shallow wells <30 m deep, As and P concentrations generally varied by <30%, whereas concentrations of the major ions (Na, K, Mg, Ca and Cl) and the redox-sensitive elements (Fe, Mn, and S) varied over time by up to +/-90%. In wells tapping the deeper aquifers >30 m often below clay layers concentrations of groundwater As were much lower and varied by <10%. The concentrations of major cations also varied by <10% in these deep aquifers. In contrast, the concentration of redox-sensitive constituents Fe, S, and Mn in deep aquifers varied by up to 97% over time. Thus, strong decoupling between variations in As and Fe concentrations is evident in groundwaters from shallow and deep aquifers. Comparison of the time series data with groundwater ages determined by (3)H/(3)He and (14)C dating shows that large seasonal or inter-annual variations in major cation and chloride concentrations are restricted to shallow aquifers and groundwater recharged <5 years ago. There is no corresponding change in As concentrations despite having significant variations of redox sensitive constituents in these very young waters. This is attributed to chemical buffering due to rapid equilibrium between solute and solid As. At two sites where the As content of groundwater in existing shallow wells averages 102 microg/L (range: <5 to 648 microg/L; n=118) and 272 microg/L (range: 10 to 485 microg/L; n=65), respectively, a systematic long-term decline in As concentrations lends support to the notion that flushing may slowly deplete an aquifer of As. Shallow aquifer water with >5 years (3)H/(3)He age show a constant As:P molar ratio of 9.6 over time, suggesting common mechanisms of mobilization.     

Transport of Escherichia coli and solutes during waste water infiltration in an urban alluvial aquifer

Recharge of waste water in an unconsolidated poorly sorted alluvial aquifer is a complex process, both physically and hydrochemically. The aim of this paper is to analyse and conceptualise vertical transport mechanisms taking place in an urban area of extensive wastewater infiltration by analysing and combining the water balance, the microbial (Escherichia coli) mass balance, and the mass balance for dissolved solutes. For this, data on sediment characteristics (grain size, organic carbon, reactive iron, and calcite), groundwater levels, and concentrations of E. coli in groundwater and waste water were collected. In the laboratory, data on E. coli decay rate coefficients, and on bacteria retention characteristics of the sediment were collected via column experiments. The results indicated that shallow groundwater, at depths of 50 m below the surface, was contaminated with E. coli concentrations as high as 10(6) CFU/100 mL. In general, E. coli concentrations decreased only 3 log units from the point of infiltration to shallow groundwater. Concentrations were lower at greater depths in the aquifer. In laboratory columns of disturbed sediments, bacteria removal was 2-5 log units/0.5 cm column sediment. Because of the relatively high E. coli concentrations in the shallow aquifer, transport had likely taken place via a connected network of pores with a diameter large enough to allow bacterial transport instead of via the sediment matrix, which was inaccessible for bacteria, as was clear from the column experiments. The decay rate coefficient was determined from laboratory microcosms to be 0.15 d(-1). Assuming that decay in the aquifer was similar to decay in the laboratory, then the pore water flow velocity between the point of infiltration and shallow groundwater, coinciding with a concentration decrease of 3 log units, was 0.38 m/d, and therefore, transport in this connected network of pores was fast. According to the water balance of the alluvial aquifer, determined from transient groundwater modelling, groundwater flow in the aquifer was mainly in vertical downward direction, and therefore, the mass balance for dissolved solutes was simulated using a 1D transport model of a 200 m column of the Quaternary Alluvium aquifer. The model, constructed with PHREEQC, included dual porosity, and was able to adequately simulate removal of E. coli, cation-exchange, and nitrification. The added value of the use of E. coli in this study was the recognition of relatively fast transport velocities occurring in the aquifer, and the necessity to use the dual porosity concept to investigate vertical transport mechanisms. Therefore, in general and if possible, microbial mass balances should be considered more systematically as an integral part of transport studies.     

Organochlorine residue levels in livers of birds of prey from Spain: inter-species comparison in relation with diet and migratory patterns

Livers from 130 specimens corresponding to 18 species of raptors from Spain were analysed for persistent organochlorine (OC) residues. In all species, p,p'-DDE was the most abundant individual OC compound detected, with geometric means ranging from 61 to 40,086 ng/g ww. The geometric mean for summation operator PCB ranged from 225 to 9184 ng/g ww. Migration to Africa, south of Sahara, where p,p'-DDT is still in use, was not associated with higher liver concentrations of its metabolite, p,p'-DDE. The presence of birds in the diet of the species was an important species-specific factor determining the mean liver concentrations of p,p'-DDE and summation operator PCB. The effect of the diet on OC concentrations in liver is explained by the lower metabolising capacity of OC compounds in birds, especially for p,p'-DDE.     

Modelling assessment of regional groundwater contamination due to historic smelter emissions of heavy metals

Historic emissions from ore smelters typically cause regional soil contamination. We developed a modelling approach to assess the impact of such contamination on groundwater and surface water load, coupling unsaturated zone leaching modelling with 3D groundwater transport modelling. Both historic and predictive modelling were performed, using a mass balance approach for three different catchments in the vicinity of three smelters. The catchments differ in their hydrology and geochemistry. The historic modelling results indicate that leaching to groundwater is spatially very heterogeneous due to variation in soil characteristics, in particular soil pH. In the saturated zone, cadmium is becoming strongly retarded due to strong sorption at neutral pH, even though the reactivity of the sandy sediments is low. A comparison between two datasets (from 1990 to 2002) on shallow groundwater and modelled concentrations provided a useful verification on the level of statistics of "homogeneous areas" (areas with comparable land use, soil type and geohydrological situation) instead of comparison at individual locations. While at individual locations observations and the model varies up to two orders of magnitude, for homogeneous areas, medians and ranges of measured concentrations and the model results are similar. A sensitivity analysis on metal input loads, groundwater composition and sediment geochemistry reveals that the best available information scenario based on the median value of input parameters for the model predicts the range in observed concentrations very well. However, the model results are sensitive to the sediment contents of the reactive components (organic matter, clay minerals and iron oxides). Uncertainty in metal input loads and groundwater chemistry are of lesser importance. Predictive modelling reveals a remarkable difference in geochemical and hydrological controls on subsurface metal transport at catchment-scale. Whether the surface water load will peak within a few decades or continue to increase until after 2050 depends on the dominant land use functions in the areas, their hydrology and geochemical build-up.