Amsterdam: planning and policy for the ideal city?

Is Amsterdam the “ideal city?” Many of the social, economic, and environmental problems facing Amsterdam are considerably less than those in cities in the USA, and in most cases, Western Europe. Amsterdam, at this moment in history, might be the world's greatest city because of its ability to ensure basic necessities, freedom, and creativity. Tolerance of drugs, sexual freedom, along with the integration of different races helps reduce many of the “social problems” faced by most cities. We have compared, on a per capita basis, differences between Amsterdam/Holland and the USA. The Netherlands is a tiny country, and comparisons are made on a city and per capita numbers at the national level. Our data show that Amsterdam has lower crime, murder, rape, drug usage (cocaine, marijuana), teenage pregnancy, diabetes, obesity, suicide, abortion rates, infant mortality, dependence on fossil fuels, and homelessness, and racial segregation is considerably less. People live longer because of Amsterdam's walkability and bike usage and access to parks. Indeed, the Netherlands leads both Western European and the USA in the proportion of trips made walking and bicycling, with significantly reduced car dependency. Ghettos are nearly non-existent compared with the segregation in the 1940s/1950s. Quality housing is supplied to everyone that gives pride of place compared with the stark, cold, and institutional “projects” provided by the US federal government. Amsterdam leads Western Europe by 35% in social housing, compared with runner-up UK, which has significantly less. The modernism of the 1960s where the poor were warehoused is nearly all gone. People living in Amsterdam seem more tolerant, secure, happier, and healthier compared with citizens in the USA. Great cities provide opportunities for all citizens to enhance their lives and ensure an unrivalled level of freedom. We demonstrate that social and environmental justice are tied together. Amsterdam is by no means perfect, but in comparison with many other democratic industrial cities, it is a far better place for citizens of all races, religions, and incomes.     

Identification of a case of maternal uniparental disomy of chromosome 10 associated with confined placental mosaicism

We report a case of maternal uniparental disomy of chromosome 10 discovered after chorionic villus sampling (CVS). Direct preparations revealed mosaic trisomy 10, while cultured CVS cells, as well as amniotic fluid cells, showed only a normal 46,XY complement. DNA analysis using microsatellite markers showed both chromosomes 10 to have been inherited from the mother. The pregnancy was complicated by polyhydramnios. A phenotypically normal male infant of appropriate size was delivered by Caesarean section at 41 weeks' gestation. Since only the direct preparations showed trisomy 10, this case illustrates the importance of CVS direct preparations in the detection of pregnancies at risk of uniparental disomy (UPD). Although the increased frequency of confined placental mosaicism (CPM) diagnosed when direct preparations are performed has been viewed negatively, identification of both CPM and UPD may have biological and clinical significance for a pregnancy. Even though only a single case of maternal disomy 10 is reported here, the apparently normal phenotype provides evidence that there are no major imprinted loci on chromosome 10 that affect in utero growth and development. However, other potential effects such as mental retardation will require long-term follow-up of this as well as additional cases.     

Noninvasive prenatal screening for patients with high body mass index: Evaluating the impact of a customized whole genome sequencing workflow on sensitivity and residual risk

Objective

Women with high body mass index (BMI) tend to have reduced fetal fraction (FF) during cell-free DNA-based noninvasive prenatal screening (NIPS), causing test failure rates up to 24.3% and prompting guidelines that recommend aneuploidy screening other than NIPS for patients with significant obesity. Because alternatives to NIPS are only preferable if they perform better, we compared the respective sensitivities at different BMI levels of traditional aneuploidy screening and a customized whole-genome sequencing NIPS.

Method

The relationship between FF, aneuploidy, and BMI was quantified from 58 105 patients screened with a customized NIPS that does not fail samples because of low FF alone. Expected analytical sensitivity as a function of aneuploidy and BMI (eg, trisomy 18 sensitivity when BMI = 35) was determined by scaling the BMI- and aneuploidy-specific FF distribution by the FF- and aneuploidy-specific sensitivity calculated from empirically informed simulations.

Results

Across all classes of obesity and assuming zero FF-related test failures, analytical sensitivity for the investigated NIPS exceeded that of traditional aneuploidy screening for trisomies 13, 18, and 21.

Conclusion

Relative to traditional aneuploidy screening, a customized NIPS with high accuracy at low FF and a low test-failure rate is a superior screening option for women with high BMI.     

Investigation into the genetics of fetal congenital lymphatic anomalies

Objective

Congenital lymphatic anomalies (LAs) arise due to defects in lymphatic development and often present in utero as pleural effusion, chylothorax, nuchal and soft tissue edema, ascites, or hydrops. Many LAs are caused by single nucleotide variants, which are not detected on routine prenatal testing.

Methods

Demographic data were compared between two subcohorts, those with clinically significant fetal edema (CSFE) and isolated fetal edema. A targeted variant analysis of LA genes was performed using American College of Medical Genetics criteria on whole exome sequencing (WES) data generated for 71 fetal edema cases who remained undiagnosed after standard workup.

Results

CSFE cases had poor outcomes, including preterm delivery, demise, and maternal preeclampsia. Pathogenic and likely pathogenic variants were identified in 7% (5/71) of cases, including variants in RASopathy genes, RASA1, SOS1, PTPN11, and a novel PIEZO1 variant. Variants of uncertain significance (VOUS) were identified in 45% (32/71) of cases. In CSFEs, VOUS were found in CELSR1, EPHB4, TIE1, PIEZO1, ITGA9, RASopathy genes, SOS1, SOS2, and RAF1.

Conclusions

WES identified pathogenic and likely pathogenic variants and VOUS in LA genes in 51% of fetal edema cases, supporting WES and expanded hydrops panels in cases of idiopathic fetal hydrops and fluid collections.     

Uptake and elimination of perchlorate in eastern mosquitofish

The purpose of this study was to investigate the uptake and elimination of perchlorate in eastern mosquitofish (Gambusia holbrooki). Fish were exposed to 0.1-1000 mg/l sodium perchlorate for 12h, 1, 2, 5, 10, and 30 days, and perchlorate was determined in whole body extracts. Perchlorate was not detected in mosquitofish exposed to the low concentrations of perchlorate (0, 0.1, and 1mg/l sodium perchlorate), regardless of the exposure time, whereas it was detected when fish were exposed to 10, 100, and 1000 mg/l. The tissue concentrations were approximately 10 times less than that in the water. There was no difference in the uptake of perchlorate depending upon the exposure time, however, a difference in perchlorate uptake depending upon the concentration of the exposure dose (P<0.001) was observed. Uptake (K(u)) and elimination (K(e)) rate constants were 0.09 l/mg day and 0.70 day(-1), respectively. The half-life (T1/2) of perchlorate was 0.99 day. Thus, it appears that perchlorate is rapidly taken up and eliminated in eastern mosquitofish. These results are critical and may be used to develop models of fate, effects, and transport of perchlorate in natural systems, as well as to assess ecological risk in affected ecosystems.     

Regional transport and urban contributions to fine particle concentrations in southeastern Canada

The impact of various atmospheric transport directions on ambient fine particle (PM2.5) concentrations at several sites in southeastern Canada was estimated (for May-September) using back-trajectory analysis. Three-day back trajectories (four per day) were paired with 6-hr average PM2.5 mass concentrations measured using tapered element oscillating microbalances (TEOM). PM2.5 concentrations at rural locations in the region were affected by nonlocal sources originating in both Canada and the United States. Comparison of sites revealed that, on average, the local contribution to total PM2.5 in the greater Toronto area (GTA) is approximately 30-35%. At each location, average PM2.5 concentrations under south/southwesterly flow conditions were 2-4 times higher than under the corresponding northerly flow conditions. The chemical composition of both urban and rural PM2.5 was determined during two separate 2-week spring/summer measurement campaigns. Components identified included SO4(2-) NO3-, NH4+, black carbon and organic carbon (OC), and trace elements. Higher particle mass at the urban Toronto site was composed of a higher proportion of all components. However, black carbon, NO3-, NaCl, and trace elements were found to be the most enriched over the rural/regional background levels.     

Effects of LATCH versus Available Seatbelt Installation of Rear Facing Child Restraint Systems on Head Injury Criteria for 6 Month Old Infants in Rear End Collisions

Objective: The Lower Anchor and Tethers for CHildren (LATCH) system was introduced in vehicles made after September 1, 2002 and intended to make installation of rear and forward-facing child safety seats easier. Due to the lack of rear impact testing of RFCRS required per the Federal Motor Vehicle Safety Standards (FMVSS), the purpose of this study was to explore the effects, if any, of installation method of RFCRS on the performance of commonly purchased makes and models of RFCRS. Specifically, we hypothesize that in a 48 km/h (29.8 MPH) rear-end collision, installation of RFCRS using the LATCH system will result in higher Head Injury Criteria (HIC) values when compared to using the available lap/shoulder seatbelt (Emergency Locking Retractor - ELR or Automatic Locking Retractor - ALR).

Methods: The test matrix included 36 rear impact sled tests conducted using 3 installation methods on 3 models of RFCRS: the Graco SnugRide® with and without the base, the Britax Chaperone with base-mounted anti-rebound bar, and the Evenflo Tribute®, a model of convertible rearward/forward facing restraint system used in the rearward facing mode. The seats were installed using the LATCH system, ELR lap/shoulder belts, or ALR lap/shoulder belts in seating positions 4 and 6 on a vehicle buck mounted to the sled test base. The infant seat and 6 month old CRABI anthropometric test device (ATD) installation methods were in accordance with standards set forth in the National Highway Traffic Safety Administration's (NHTSA) FMVSS No. 213, Child Restraint Systems. All tests were conducted on pneumatic controlled acceleration sled (HYGE, Inc., PA, USA) at 48 km/h.

Results: Installation of infant seat type RFCRS using the LATCH system resulted in higher HIC₁₅ values when compared to using the available lap/shoulder seatbelt (ELR or ALR). The mean HIC₁₅ values were most severe when infant seat type RFCRS were installed using LATCH (Graco SnugRide® HIC₁₅ = 394 and Britax Chaperone HIC₁₅ = 133) compared to using either ELR lap/shoulder belts (Graco SnugRide® HIC₁₅ = 218 and Britax Chaperone HIC₁₅ = 65) or ALR lap/shoulder belts (Graco SnugRide® HIC₁₅ = 194 and Britax Chaperone HIC₁₅ = 78). The installation method did not result in a statistically significant difference in HIC for the convertible type RFCRS (Evenflo Tribute®). In many of the tests, the ATD's head struck the seatback in which the RFCRS was installed. These head strikes resulted in the higher HIC₁₅ scores recorded throughout the testing.

Conclusions: The results of this study suggest that LATCH does not offer equal protection to lap/shoulder belts from head injuries in rear impacts when used with infant seat type RFCRS.