An approach to preimplantation diagnosis of β-thalassaemia

Using the polymerase chain reaction (PCR), it was possible to amplify a single copy fragment of the β-globin gene from 2–32 human embryonic cells obtained from arrested preimplantation embryos. For the detection of β-thalassaemia mutations, allele specific priming of the PCR using nested primers was employed using approximately 10 pg of DN A from individuals known to carry these mutations. This approach was successful in detecting the presence or absence of five Asian Indian β-thalassaemia mutations that were selected for this study. In spite of meticulous precautions against contamination, false-positive amplification was observed, a problem that will have to be overcome before this approach can be used in clinical practice.     

Prenatal diagnosis of 21-hydroxylase deficiency by rflp analysis of the 21-hydroxylase,complement C4, and HLA class II genes

In 19 pregnancies at risk for 21-hydroxylase deficiency (21OHD) in 18 families with at lea one affected child, prenatal diagnosis was performed by RFLP analysis using the enzymi Taq I and EcoRI and the DNA probes specific for the 21 OH genes, the closely linke complement C4 genes and the highly polymorphic HLA class II genes DRB, DQB, and DPI For fetal DNA analysis either chorionic villi or cultivated amniotic cells were used. In all 1 cases, a clear prenatal diagnosis was possible either with the 21OH probe alone or in mo cases, by combining the results of the different closely linked loci.     

Expanding multiple marker screening for Down's syndrome to include Edward'S syndrome

Information on maternal age and maternal serum alpha-fetoprotein, unconjugated oestriol (uE₃), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi-marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10–12 (67–80 per cent) cases with a false-positive rate of 0.3–0.6 per cent depending on the risk cut-off. A further case would have been detected as a result of screening for Down's syndrome alone. Similar results were obtained when the Edward's syndrome risk was based on uE₃ and hCG only. These data suggest that extending Down's syndrome screening to include Edward's syndrome risk will yield a high detection rate with only a small increase in the false-positive rate.     

Serum PAPP-A measurements in first-trimester screening for Down syndrome

Serum PAPP-A measurements taken from 254 women in the first trimester are reported. Eleven chromosomal abnormalities were detected. The mean serum PAPP-A levels in cases of Down syndrome were 0.44 MOM at 9 weeks gestation, 0.15 MOM at 10 weeks, and 0.29 MOM at 11 weeks. The PAPP-A level at 10 weeks was below those of pregnancies which aborted spontaneously. At 11 weeks, the pregnancies with Down syndrome recorded the lowest PAPP-A levels at that gestation. On this small sample, offering chorionic villus sampling to women with singleton pregnancies and a PAPP-A level below 0.3 MOM (approximately 6.5 per cent of this at-risk group) would have detected all the Down syndrome fetuses at 10 weeks and 50 per cent at 11 weeks without selecting those cases destined to abort. This suggests that serum PAPP-A should continue to be investigated as a potential first-trimester screening test for Down syndrome.     

Urban heat indicator map for climate adaptation planning

By 2050, 75 % of the world’s population will live in cities and the occurrence of heat wave events might have doubled. Mapping the climate and land use change impact for urban heat events should set the agenda for adaptation planning at the local scale. Literature on urban heat mapping does not reveal a clear indicator to visualise the urban heat impacts that includes consequences of land use and climate changes for planning purposes. This paper introduces a stepwise approach to develop a single complex indicator to map the urban heat impact for local climate adaptation planning processes. Information on climatic drivers and land use characteristics are combined and projected for future land use and climate change impacts. Next, several visualisation techniques are developed to investigate which techniques are most effective to visualise complex information with multiple variables in one visualisation. A usability test is performed to investigate how indicator and map meet the information and communication needs of policy makers. Our findings reveal that it is important to add information on future impacts to set the agenda for adaptation planning at the local scale. Applying cartographic techniques in a map series presentation has proven to be effective to map complex information in a single image and fulfil most of the identified information needs. Based on our finding, we introduce the information enrichment chain as a promising approach to support local adaptation planning.     

Identifying water resources management strategies in adaptation to climate change under uncertainty

In this study, an integrated simulation-based allocation modeling system (ISAMS) is developed for identifying water resources management strategies in response to climate change. The ISAMS incorporates global climate models (GCMs), a semi-distributed land use-based runoff process (SLURP) model, and a multistage interval-stochastic programming (MISP) approach within a general framework. The ISAMS can not only handle uncertainties expressed as probability distributions and interval values but also reveal climate change impacts on water resources allocation under different projections of GCMs. The ISAMS is then applied to the Kaidu-kongque watershed with cold arid characteristics in the Tarim River Basin (the largest inland watershed basin in China) for demonstrating its efficiency. Results reveal that different climate change models corresponding to various projections (e.g., precipitation and temperature) would lead to changed water resources allocation patterns. Variations in water availability and demand due to uncertainties could result in different water allocation targets and shortages. A variety of decision alternatives about water allocations adaptive to climate change are generated under combinations of different global climate models and ecological water release plans. These findings indicate that understanding the uncertainties in water resources system, building adaptive methods for generating sustainable water allocation patterns, and taking actions for mitigating water shortage problems are key adaptation strategies responding to climate change.     

Coxsackievirus B4 as a Causative Agent of Diabetes Mellitus Type 1: Is There a Role of Inefficiently Treated Drinking Water and Sewage in Virus Spreading?

This study proposed to detect the enterovirus (EV) infection in children with type 1 diabetes mellitus (T1D) and to assess the role of insufficiently treated water and sewage as sources of viral spreading. Three hundred and eighty-two serum specimens of children with T1D, one hundred serum specimens of children who did not suffer from T1D as control, and forty-eight water and sewage samples were screened for EV RNA using nested RT-PCR. The number of genome copies and infectious units of EVs in raw and treated sewage and water samples were investigated using real-time (RT)-PCR and plaque assay, respectively. T1D markers [Fasting blood glucose (FBG), HbA1c, and C-peptide], in addition to anti-Coxsackie A & B viruses (CVs A & B) IgG, were measured in control, T1D-negative EV (T1D–EV^?), and T1D-positive EV (T1D–EV⁺) children specimens. The prevalence of EV genome was significantly higher in diabetic children (26.2%, 100 out of 382) than the control children (0%, 0 out of 100). FBG and HbA1c in T1D–EV^? and T1D–EV⁺ children specimens were significantly higher than those in the control group, while c-peptide in T1D–EV^? and T1D–EV⁺ children specimens was significantly lower than that in the control (n = 100; p < 0.001). Positivity of anti-CVs A & B IgG was 70.7, 6.7, and 22.9% in T1D–EV⁺, T1D–EV^?, and control children specimens, respectively. The prevalence of EV genome in drinking water and treated sewage samples was 25 and 33.3%, respectively. The prevalence of EV infectious units in drinking water and treated sewage samples was 8.5 and 25%, respectively. Quantification assays were performed to assess the capabilities of both wastewater treatment plants (WWTPs) and water treatment plants (WTPs) to remove EV. The reduction of EV genome in Zenin WWTP ranged from 2 to 4 log₁₀, while the reduction of EV infectious units ranged from 1 to 4 log₁₀. The reduction of EV genome in El-Giza WTP ranged from 1 to 3 log₁₀, while the reduction of EV infectious units ranged from 1 to 2 log₁₀. This capability of reduction did not prevent the appearance of infectious EV in treated sewage and drinking water. Plaque purification was performed for isolation of separate EV isolates from treated and untreated water and sewage samples. Characterization of the EV amplicons by RT-PCR followed by sequencing of these isolates revealed high homology (97%) with human coxsackievirus B4 (CV B4) in 60% of the isolates, while the rest of the isolates belonged to poliovirus type 1 and type 2 vaccine strains. On the other hand, characterization of the EV amplicons by RT-PCR followed by sequencing for T1D–EV⁺ children specimens indicated that all samples contained CV B4 with the same sequence characterized in the environmental samples. CV B4-contaminated drinking water or treated sewage may play a role as a causative agent of T1D in children.