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This study demonstrates that the thickness of the target and its backing condition have a powerful effect on the development of a wave structure in impact welds. Conventional theories and experiments related to impact welds show that the impact angle and speed of the flyer have a controlling influence on the development of wave structure and jetting. These results imply that control of reflected stress waves can be effectively used to optimize welding conditions and expand the range of acceptable collision angle and speed for good welding. Impact welding and laser impact welding are a class of processes that can create solid-state welds, permitting the formation of strong and tough welds without the creation of significant heat affected zones, and can avoid the gross formation of intermetallic in dissimilar metal pairs. This study examined small-scale impact using a consistent launch condition for a 127 µm commercially pure titanium flyer impacted against commercially pure copper target with thicknesses between 127 µm and 1000 µm. Steel and acrylic backing layers were placed behind the target to change wave reflection characteristics. The launch conditions produced normal collision at about 900 m/s at the weld center, with decreasing impact speed and increasing angle moving toward the outer perimeter. The target thickness had a large effect on wave morphology, with the wave amplitude increasing with target thickness in both cases, peaking when target thickness is about twice flyer thickness, and then falling. The acrylic backing showed a consistently smaller unwelded central zone, indicating that impact welding is possible at a smaller angle in that case. Strength was measured in destructive tensile testing. Failure was controlled by the breakdown of the weaker of the two base metals over all thicknesses and backings. This demonstrates that laser impact welding is a robust method for joining dissimilar metals over a range of thicknesses.

BACKGROUND: Increased risk of various congenital anomalies has been reported to be associated with trihalomethane (THM) exposure in the water supply. OBJECTIVES: We conducted a registry-based study to determine the relationship between THM concentrations and the risk of congenital anomalies in England and Wales. METHODS: We obtained congenital anomaly data from the National Congenital Anomalies System, regional registries, and the national terminations registry; THM data were obtained from water companies. Total THM (< 30, 30 to < 60, > or =60 microg/L), total brominated exposure (< 10, 10 to < 20, > or =20 microg/L), and bromoform exposure (< 2, 2 to < 4, > or =4 microg/L) were modeled at the place of residence for the first trimester of pregnancy. We included 2,605,226 live births, stillbirths, and terminations with 22,828 cases of congenital anomalies. Analyses using fixed- and random-effects models were performed for broadly defined groups of anomalies (cleft palate/lip, abdominal wall, major cardiac, neural tube, urinary and respiratory defects), a more restricted set of anomalies with better ascertainment, and for isolated and multiple anomalies. Data were adjusted for sex, maternal age, and socioeconomic status. RESULTS: We found no statistically significant trends across exposure categories for either the broadly defined or more restricted sets of anomalies. For the restricted set of anomalies with isolated defects, there were significant (p < 0.05) excess risks in the high-exposure categories of total THMs for ventricular septal defects [odds ratio (OR) = 1.43; 95% confidence interval (CI), 1.00-2.04] and of bromoform for major cardiovascular defects and gastroschisis (OR = 1.18; 95% CI, 1.00-1.39; and OR = 1.38; 95% CI, 1.00-1.92, respectively). CONCLUSION: In this large national study we found little evidence for a relationship between THM concentrations in drinking water and risk of congenital anomalies. [ABSTRACT FROM AUTHOR]

The significance of status Between nations and across cultures, threats to the social status of an individual or group motivate retaliatory violence. History provides countless examples of such violence, committed at all levels of society. Whether orchestrated by individuals or governments, the perpetrators almost invariably justify the violence as a necessary response to an existential threat. “Cultures of honor” such as the Southeastern United States condone the use of violence to protect one’s reputation and, unsurprisingly, this region of America has consistently produced the highest levels of per capita violence in the entire country.Additionally, religious texts warn of the destructive power of “pride,” placing it with envy, greed, wrath, lust, gluttony and sloth as one of the Seven Deadly Sins. Our personal experiences with road rage, school bullies and office politics all provide a regular stream of anecdotal evidence of the inexplicably powerful emotions driving those whose status has been threatened. As a former mental health counselor, criminal prosecutor and gang task force coordinator in the Southeastern United States, this author has personally observed numerous examples of pride’s destructive influence. Deadly bar fights, domestic violence and street gang conflicts frequently ensue from seemingly trivial offenses to one’s status. In American cities,simply spray painting over a rival gang’s graffiti can lead to retaliation murder. In fact, gang retaliation plays out so consistently that when a gang entrenched neighborhood gets shot up, the police can usually predict which neighborhood they will respond to for the next shooting.

Abstract Background Environmental pollution as a cause of congenital anomalies is sometimes suspected because of clustering of anomalies in areas of higher exposure. This highlights questions around spatial heterogeneity (clustering) in congenital anomaly rates. If spatial variation is endemic, then any one specific cluster is less remarkable, though the presence of uncontrolled geographically clustered risk factors is suggested. If rates are relatively homogeneous across space other than around specific hazards, then evidence for these hazards causing the clusters is strengthened. We sought to estimate the extent of spatial heterogeneity in congenital anomaly rates in the United Kingdom. Methods The study population covered about one million births from five registers in Britain from 1991–1999. We estimated heterogeneity across four geographical levels: register area, hospital catchment, electoral ward, and enumeration district, using a negative binomial regression model. We also sought clusters using a circular scan statistic. Results Congenital anomaly rates clearly varied across register areas and hospital catchments (p < 0.001), but not below this level (p > 0.2). Adjusting for socioeconomic deprivation and maternal age made little difference to the extent of geographical variation for most congenital anomaly subtypes. The two most significant circular clusters (of four ano-rectal atresias and six congenital heart diseases) contained two or more siblings. Conclusion The variation in rates between registers and hospital catchment area may have resulted in part from differences in case ascertainment, and this should be taken into account in geographical epidemiological studies of environmental exposures. The absence of evidence for variation below this level should be interpreted cautiously in view of the low power of general heterogeneity tests. Nevertheless, the data suggest that strong localised clusters in congenital anomalies are uncommon, so clusters around specific putative environmental hazards are remarkable when observed. Negative binomial models applied at successive hierarchical levels provide an approach of intermediate complexity to characterising geographical heterogeneity.

Objective: To determine the outcome of antenatally suspected congenital cystic adenomatoid malformation of the lung (CCAM) over a 10 year period. Methods: This is a retrospective study of all babies diagnosed antenatally in the Prenatal Diagnosis Unit and delivered in Oxford between 1991 and 2001. Data were obtained from the Oxford Congenital Anomaly Register, theatre records, and histopathology reports. Results: Twenty eight cases of CCAM were diagnosed antenatally. Five pregnancies were terminated. Data are available on all 23 of the pregnancies that continued and resulted in two neonatal deaths and 21 surviving babies. Eleven of the 23 cases (48%) showed some regression of the lesion antenatally, and four of these cases appeared to resolve completely on prenatal ultrasound. Three of the 23 babies (13%) were symptomatic in the early neonatal period, and three developed symptoms shortly afterwards. Seventeen of the 23 babies (74%) were asymptomatic, of whom 12 had abnormalities on chest radiograph or computed tomography scan and had elective surgery. Two babies (8%) had completely normal postnatal imaging, and three had abnormalities which resolved in the first year of life. Seventeen of the 23 babies (74%) had surgery. Histology at surgery was heterogeneous. Of the 23 live births, all 21 survivors (91%) are well at follow up or have been discharged. Conclusions: All babies diagnosed antenatally with CCAM require postnatal imaging with computed tomography irrespective of signs of antenatal resolution. In asymptomatic infants, the recommendations are close follow up and elective surgery for persistent lesions within the first year of life. Histology at surgery was heterogeneous, and this should be considered when counselling parents. [ABSTRACT FROM AUTHOR]

The aim of this study is to quantify the prevalence and types of rare chromosome abnormalities (RCAs) in Europe for 2000-2006 inclusive, and to describe prenatal diagnosis rates and pregnancy outcome. Data held by the European Surveillance of Congenital Anomalies database were analysed on all the cases from 16 population-based registries in 11 European countries diagnosed prenatally or before 1 year of age, and delivered between 2000 and 2006. Cases were all unbalanced chromosome abnormalities and included live births, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. There were 10,323 cases with a chromosome abnormality, giving a total birth prevalence rate of 43.8/10,000 births. Of these, 7335 cases had trisomy 21,18 or 13, giving individual prevalence rates of 23.0, 5.9 and 2.3/10,000 births, respectively (53, 13 and 5% of all reported chromosome errors, respectively). In all, 473 cases (5%) had a sex chromosome trisomy, and 778 (8%) had 45,X, giving prevalence rates of 2.0 and 3.3/10,000 births, respectively. There were 1,737 RCA cases (17%), giving a prevalence of 7.4/10,000 births. These included triploidy, other trisomies, marker chromosomes, unbalanced translocations, deletions and duplications. There was a wide variation between the registers in both the overall prenatal diagnosis rate of RCA, an average of 65% (range 5-92%) and the prevalence of RCA (range 2.4-12.9/10,000 births). In all, 49% were liveborn. The data provide the prevalence of families currently requiring specialised genetic counselling services in the perinatal period for these conditions and, for some, long-term care.

This study aims to assess prevalence and pregnancy outcome for sex chromosome trisomies (SCTs) diagnosed prenatally or in the first year of life. Data held by the European Surveillance of Congenital Anomalies (EUROCAT) database on SCT cases delivered 2000-2005 from 19 population-based registries in 11 European countries covering 2.5 million births were analysed. Cases included were livebirths diagnosed to 1 year of age, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly (TOPFA). In all, 465 cases of SCT were diagnosed between 2000 and 2005, a prevalence of 1.88 per 10,000 births (95% CI 1.71-2.06). Prevalence of XXX, XXY and XYY were 0.54 (95% CI 0.46-0.64), 1.04 (95% CI 0.92-1.17) and 0.30 (95% CI 0.24-0.38), respectively. In all, 415 (89%) were prenatally diagnosed and 151 (36%) of these resulted in TOPFA. There was wide country variation in prevalence (0.19-5.36 per 1000), proportion prenatally diagnosed (50-100%) and proportion of prenatally diagnosed resulting in TOPFA (13-67%). Prevalence of prenatally diagnosed cases was higher in countries with high prenatal detection rates of Down syndrome. The EUROCAT prevalence rate for SCTs diagnosed prenatally or up to 1 year of age represents 12% of the prevalence expected from cytogenetic studies of newborn babies, as the majority of cases are never diagnosed or are diagnosed later in life. There is a wide variation between European countries in prevalence, prenatal detection and TOPFA proportions, related to differences in screening policies as well as organizational and cultural factors.

Objective: To provide current population-based prevalence and prenatal diagnosis rates (PND) for specified major congenital anomalies in England and Wales to enable monitoring of the Fetal Anomaly Screening Programme (FASP)., Design: Secondary analysis of prospectively collected registry data., Setting: Seven multiple-source, population-based congenital anomaly registers, members of the British Isles Network of Congenital Anomaly Registers (BINOCAR) in 2005 and 2006., Population: 2,883 births with congenital anomalies from a total of 601,545 live and stillbirths., Main Outcome Measures: PND and birth prevalence of selected congenital anomaly groups/subtypes (anencephaly, spina-bifida, serious cardiac, diaphragmatic hernia, gastroschisis, exomphalos, bilateral renal agenesis, lethal/severe skeletal dysplasia, cleft lip with or without cleft palate [CL + /- P])., Results: Of the selected anomaly groups, the most frequently reported were serious cardiac (14.1 per 10,000 births [95% CI 13.0-15.2]) and CL + /- P (9.7 per 10,000 births [8.9-10.5]); the least frequent were bilateral renal agenesis and lethal/severe skeletal dysplasia (< 1.5 per 10,000 births). The PND varied for different anomalies from 53.1% (95% CI 43.5-65.2) for serious cardiac anomalies to 99.6% (95% CI 97.9-100.0) for anencephaly. Least variation in PND rates was for anencephaly (range 98.9-100%) and gastroschisis (93.5-100%); greatest variation was for serious cardiac (43.5-65.2%) and lethal/severe skeletal dysplasias (50.0-100%)., Conclusions: BINOCAR registers can, uniquely, provide contemporary data on PND and birth prevalence rates to enable monitoring of the ultrasound component of FASP at a national and regional level, allowing comparisons between populations to be made, planning of resources facilitated and assistance for parents making informed decisions on whether to enter the screening programme.

Objectives: To investigate whether there is an association between risk of congenital anomaly and annual ward level exposure to air pollution in England during the 1990s., Methods: A geographical study was conducted across four regions of England using population-based congenital anomaly registers, 1991-1999. Exposure was measured as 1996 annual mean background sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)) and particulate matter (PM(10)) concentrations at census ward level (n=1474). Poisson regression, controlling for maternal age, area socioeconomic deprivation and hospital catchment area, was used to estimate relative risk for an increase in pollution from the 10th to the 90th centile., Results: For non-chromosomal anomalies combined, relative risks were 0.99 (95% CI 0.93 to 1.05) for SO(2), 0.97 (95% CI 0.84 to 1.11) for NO(2) and 0.89 (95% CI 0.75 to 1.07) for PM(10). For chromosomal anomalies, relative risks were 1.06 (95% CI 0.98 to 1.15) for SO(2), 1.11 (95% CI 0.95 to 1.30) for NO(2) and 1.18 (95% CI 0.97 to 1.42) for PM(10). Raised risks were found for tetralogy of Fallot and SO(2) (RR=1.38, 95% CI 1.07 to 1.79), NO(2) (RR=1.44, 95% CI 0.71 to 2.93) and PM(10) (RR=1.48, 95% CI 0.57 to 3.84), which is of interest in light of previously reported associations between this cardiac anomaly and other air pollutants., Conclusions: While air pollution in the 1990s did not lead to sustained geographical differences in the overall congenital anomaly rate in England, further research regarding specific anomalies is indicated.

The EUROCAT website www.eurocat-network.eu publishes prenatal detection rates for major congenital anomalies using data from European population-based congenital anomaly registers, covering 28% of the EU population as well as non-EU countries. Data are updated annually. This information can be useful for comparative purposes to clinicians and public health service managers involved in the antenatal care of pregnant women as well as those interested in perinatal epidemiology.

Objective: The objective of this study was to assess the maternal and prenatal ultrasound findings and outcome in pregnancies complicated by congenital myotonic dystrophy Type 1 (DM1)., Methods: A retrospective chart review of all patients with a diagnosis of DM1 and pregnancy presenting to the Oxford Radcliffe Hospital between 1990 and 2004 was undertaken. Obstetric case notes were reviewed and details of all pregnancies obtained. This included data on prenatal diagnostic tests and obstetric ultrasound scans performed as well as pregnancy complications and pregnancy outcome. Maternal and fetal CTG expansion size was also recorded where available. Maternal genetic case notes were reviewed for details of maternal grip myotonia., Results: Sixty pregnancies among 26 couples in which one of the parents was a carrier of DM1 were identified during the study period. These resulted in 36 (60%) pregnancies affected by congenital DM1 and 19 (31.7%) unaffected pregnancies. There were four miscarriages and one termination of pregnancy for non-medical reasons. Nineteen of the 36 affected pregnancies ended in termination following the antenatal diagnosis of congenital DM1 by either chorionic villus sampling (CVS) or amniocentesis. In the remaining 17 affected pregnancies (16 singleton and one twin) there was one miscarriage of an affected fetus with co-existing Down syndrome and eight perinatal deaths. The principal cause of perinatal death was respiratory failure in the early neonatal period. Antenatally noted clinical/sonographic abnormalities in these pregnancies included polyhydramnios (100%), talipes (26.6%) and borderline ventriculomegaly (13.3%). Uni- or bilateral talipes was noted at delivery in 10 of 16 (62.5%) neonates. Maternal grip myotonia was present in all but one of these cases., Conclusion: The antenatal findings of polyhydramnios and talipes should prompt a search for maternal grip myotonia. If present, definitive testing for congenital DM1 should be considered.

Objective: Firstly, to assess the completeness of ascertainment in the National Congenital Anomaly System (NCAS), the basis for congenital anomaly surveillance in England and Wales, and its variation by defect, geographical area, and socioeconomic deprivation. Secondly, to assess the impact of the lack of data on pregnancies terminated because of fetal anomaly., Design: Comparison of the NCAS with four local congenital anomaly registers in England., Setting: Four regions in England covering some 109,000 annual births., Participants: Cases of congenital anomalies registered in the NCAS (live births and stillbirths) and independently registered in the four local registers (live births, stillbirths, fetal losses from 20 weeks' gestation, and pregnancies terminated after prenatal diagnosis of fetal anomaly)., Main Outcome Measure: The ratio of cases identified by the national register to those in local registry files, calculated for different specified anomalies, for whole registry areas, and for hospital catchment areas within registry boundaries., Results: Ascertainment by the NCAS (compared with data from local registers, from which terminations of pregnancy were removed) was 40% (34% for chromosomal anomalies and 42% for non-chromosomal anomalies) and varied markedly by defect, by local register, and by hospital catchment area, but not by area deprivation. When terminations of pregnancy were included in the register data, ascertainment by NCAS was 27% (19% for chromosomal anomalies and 31% for non-chromosomal anomalies), and the geographical variation was of a similar magnitude., Conclusion: The surveillance of congenital anomalies in England is currently inadequate because ascertainment to the national register is low and non-uniform and because no data exist on termination of pregnancy resulting from prenatal diagnosis of fetal anomaly.

Objective: To study trends in termination of pregnancy for fetal anomaly over 10 years and to assess the contribution of autopsy to the final diagnosis and counselling after termination., Design: Retrospective study with cases from a congenital anomaly register and a defined unselected population., Data Sources: Pregnancies resulting in termination for fetal anomaly identified from the Oxford congenital anomaly register. Details about the prenatal diagnosis and autopsy findings were retrieved from case notes., Results: Of the 57 258 deliveries, 309 (0.5%) were terminated because of prenatally diagnosed abnormality. There were 129/29 086 (0.4%) terminations for fetal anomaly carried out in 1991-5 and 180/28 172 (0.6%) in 1996-2000. The percentage of fetuses that underwent autopsy fell from 84% to 67%. Autopsy was performed in 132 cases identified by ultrasound scan, with no evidence for abnormal karyotype. In 95 (72%) the autopsy confirmed the suspected diagnosis and did not add important further information, two cases were not classified, and in 35 (27%) the autopsy added information that led to a refinement of the risk of recurrence (reduced in 17, increased in 18); in 11 of these 18 cases it was increased to a one in four risk., Conclusions: Though there has been an increase in the rate of terminations of pregnancy for fetal anomaly, there has been a decline in the autopsy rate. When a prenatal diagnosis was based on the results of a scan only, the addition of information from an autopsy by a specialist paediatric pathologist provided important information that changed the estimated risk of recurrence in 27% of cases and in 8% this was to a higher (one in four) risk.

Objective: Evaluation of prenatal diagnosis of neural tube defects by ultrasound examination in unselected populations across Europe., Setting: Prenatal ultrasound units in areas that report to contributing congenital malformation registers., Methods: All cases with a suspected or confirmed neural tube defect and delivered within the 30 month study period were identified from 18 Congenital Malformation Registers from 11 European countries. Data on the pregnancy, prenatal scans, outcome of pregnancy, and information on different screening policies for each country were analysed., Results: 670766 deliveries occurred in the area covered by the registers during the study period. A neural tube defect was diagnosed at delivery in 542 cases. In 84% of these, the lesion was isolated (166 anencephaly, 252 spina bifida, 35 encephalocele). Of the 166 isolated cases with anencephaly, 96% were correctly identified prenatally; one was missed on scan, two were wrongly diagnosed, and four were not scanned (sensitivity 98%). 84% of the prenatal diagnoses were made before 24 weeks' gestation; 86% of isolated anencephalic pregnancies were terminated. Of the 252 cases of isolated spina bifida, 171 (68%) were correctly identified prenatally; 66% of these before 24 weeks' gestation. The diagnosis was missed on scan in 60 cases and 21 were not scanned (sensitivity 75%). The mean reduction in birth prevalence because of termination of pregnancy for spina bifida was 49% (range 6-100%). There was a wide variation between centres in prenatal detection rate (33-100%), termination of pregnancy of prenatally diagnosed cases (17-100%), and gestation both at diagnosis and termination of pregnancy., Conclusion: A high prenatal detection rate for anencephaly was reported by all registers. There is a large variation in prenatal detection and termination rates for spina bifida between centres, reflecting differences both in policy and culture.

Objectives: Various studies have identified psychosocial factors that may influence attitudes toward colon cancer gene testing. Whereas family history of colon cancer has been associated with interest in gene testing, this has not been examined extensively. We hypothesized that the strength of family history of colon cancer is associated with risk perception and willingness to undergo gene testing., Materials and Methods: We evaluated attitudes toward colon cancer gene testing among persons who had at least one first-degree relative with colon cancer. A total of 2680 at-risk relatives in 863 kindreds were identified and mailed an extensive survey regarding sociodemographic variables, family history, health behaviors and knowledge, and willingness to take a colon cancer gene test. A total of 56.6% of persons completed and returned surveys. We conducted a brief telephone survey of a random sample of 200 persons who did not respond to the mail survey., Results: The combined study sample of 1373 people was 42% male, had a mean age of 55 +/- 15 years, was 96% white, and had moderate-to-high SES. A total of 77.4% were very likely to take the gene test, and 92.4% were somewhat or very likely to take the gene test. A total of 78% of the sample perceived a higher colon cancer risk, although patterns of risk perception and worry differed significantly between mail survey and telephone survey respondents. More of the telephone survey respondents were also somewhat unlikely or very unlikely to take the gene test compared to the mail survey respondents (13.7% versus 6.9%). In the combined sample, concern about developing colon cancer and risk perception increased with number of relatives with colon cancer (P < 0.0001). Eight percent expressed no concern about developing colon cancer; 4.8% felt their chance of developing colon cancer was lower than others of the same age, sex, and race; and 3.3% felt that they were very unlikely to develop colon cancer in their lifetime. However, there was strong interest in gene testing regardless of the number of affected relatives, and persons with more affected relatives were generally willing to pay more for the gene test (up to $1000)., Conclusions: The strength of family history of colon cancer is associated with risk perception but not with willingness to undergo gene testing.

One hundred consecutive cases of confirmed anterior abdominal wall defect, identified prenatally in the Oxford Prenatal Diagnosis Unit over 11 years, were studied. Fifty nine per cent of cases were suspected omphaloceles and 41% suspected gastroschisis. Fifty four per cent of omphaloceles were accompanied by other defects compared with 5% of those with gastroschisis. Overall, 29% of fetuses with omphalocele had an abnormal karyotype, and of those with another abnormality identified on scan (excluding four cases with no karyotype performed), 54% had an abnormal karyotype. Of the 27 cases with suspected isolated omphalocele, 14 were live born, all of whom have survived. If the 11 whose parents opted for termination of pregnancy are excluded, survival to birth was 88%. Six of the suspected isolated omphaloceles have Beckwith Wiedemann syndrome (BWS). Eight (57%) of the live born babies with omphaloceles had major problems up to the age of 2, but only one (7%) has long term major problems. This child has BWS and is deaf. Of the 39 cases of suspected isolated gastroschisis, 33 (85%) pregnancies resulted in live birth and one in neonatal death after surgery. Survival rate (excluding terminated pregnancies) was 97%. Gastroschisis was associated with a younger maternal age than omphalocele (p < 0.001) and lower birthweight centile (p < 0.01). Fifteen per cent of the gastroschisis babies had major problems up to the age of 2 years and 12% long term developmental problems. Ninety three per cent of the omphalocele babies and 88% of those who had gastroschisis have no long term problems. Over the study period there have been major changes in scanning equipment and expertise. Since 1991 no woman with a suspected isolated lesion has opted for termination of pregnancy.

Meckel syndrome (MKS) is a lethal malformation syndrome characterised by posterior meningoencephalocele, polycystic kidneys, fibrotic changes of the liver, and polydactyly. We have previously shown a linkage to chromosome 17q in 17 Finnish Meckel families. In this study we have analysed one Italian, one Austrian (of Turkish origin) and three British MKS families (Caucasian, Pakistani, and Bangladeshi families) for linkage to the MKS locus on chromosome 17q22-q24. We did not observe co-segregation of the disease and marker haplotypes in the Austrian family or in the three British families, of which two represented classical MKS and one a slightly atypical MKS phenotype with longer survival of the patient. In the Italian family the affected and non-affected children did not share the same maternal chromosome and thus this family could represent the same allelic disease as the Finnish MKS families. These results suggest locus heterogeneity in Meckel syndrome--a feature previously suspected based on the highly variable clinical phenotype.

Comparison of the frequency of occurrence of restriction fragment length polymorphisms in control human DNAs and DNAs from infants dying from sudden infant death syndrome has indicated no significant difference in the case of restriction fragment length polymorphisms associated with the heat shock protein genes hsp70 and hsp90. A highly significant difference was detected, however, in the case of the specific restriction fragment length polymorphisms detected by an hsp60 gene probe in MspI digests.

Exposure of HeLa cells in monolayer culture to increasing concentrations of exogenously added H2O2 causes damage to cellular DNA. When the DNA is subsequently isolated from the non-apoptotic cells remaining in such cultures, evidence was obtained to suggest that the DNA damage elicited in intact cells was non-random and that certain nucleotide sequences associated with, or related to, the genes for heat shock protein 60 and catalase were more susceptible to damage than others. In contrast, these particular sequences were not specifically susceptible to damage when naked human DNA was exposed directly to H2O2 in vitro. On an overall comparative basis, sequences in the genes encoding catalase, alpha-1 antitrypsin and beta-actin appear more vulnerable to H2O2 in vivo, than sequences in H-ras and the P53 gene which seem surprisingly resistant.

Information on the outcome of pregnancy was collected on 92 fetuses with cystic hygroma or nuchal pad, identified prenatally. Forty three (47% of the total) were associated with abnormal karyotype. Twenty five (27%) had normal karyotype but an additional abnormality was identified on ultrasound scan. There were 10 liveborn babies in this group of whom seven had significant problems postnatally. In twenty four (26%) cases the cystic hygroma or nuchal pad was an isolated finding. Seventeen (89% of those in which the pregnancy was electively continued) were liveborn and reported to be normal. Those with a normal karyotype, no other anomaly identified on antenatal scan, and smaller non-septate lesions have a good prognosis.

Objective: To compare different screening policies for Down's syndrome across a broad range of outcomes, using decision analysis, with particular reference to the role of maternal serum testing., Design: A decision tree was used to combine data from local sources and the medical literature to predict the likely frequency of several outcomes. Sensitivity analyses were used to test the robustness of the conclusions drawn., Setting: Oxfordshire Health Authority., Main Outcome Measures: Live births with and without Down's syndrome; miscarriages with Down's syndrome; cases of Down's syndrome detected antenatally; amniocenteses performed (and associated miscarriages); direct NHS screening costs; number of women offered screening., Results: Screening policies for Down's syndrome that include serum testing can produce better population outcomes than programmes that do not. Each option for screening for Down's syndrome that we considered had significant drawbacks. In Oxfordshire, offering serum testing to women of all ages would prevent the birth of approximately one more baby with Down's syndrome per year than would a policy of screening for women aged 30 years or more. The cost of preventing this one extra Down's birth would be one or two normal babies lost after amniocentesis, 4500 blood tests for young women (with the associated anxiety and counselling), approximately 200 false positive serum test results and amniocenteses (with the associated anxiety and distress), and 90,000 pounds for the extra tests, counselling, and amniocenteses. Opinions are divided as to which policy is the better option for the population., Conclusions: Decision analysis is a useful tool for determining the likely consequences of different policy options across a broad range of outcomes. This focuses debate and decision making on outcomes of care, which in turn makes it clear that the choice of screening programme for Down's syndrome depends on the relative importance ascribed to the different outcomes. If individuals' values vary widely it may be impossible to find one screening policy that meets the needs of all pregnant women.

A previously healthy young primigravida suffered very severe pre-eclampsia and was delivered at 32 weeks gestation. The baby was growth retarded with dysmorphic features, and died aged 4 days. Chromosome analysis of the baby revealed partial trisomy 13 resulting from recombination within a maternal insertion of part of 13q into 3p. To date, the maternal insertion has been identified in a further three members of the family and may have contributed to a number of spontaneous abortions, stillbirths and neonatal deaths in other family members. The various possibilities for recombination and malsegregation are discussed. An association between pre-eclampsia and trisomy 13 has been reported previously. To our knowledge this present paper constitutes the first report of partial trisomy for 13q occurring with pre-eclampsia.

We have determined the parental origin of 50 cases of trisomy 18. In 48 cases the additional chromosome was maternal in origin, and in 2 cases it was paternal in origin. Seven cases, including both those with an additional paternal chromosome, appeared to be the result of postzygotic error. In contrast to the situation in nondisjunction involving chromosomes 21 and X, there was no evidence for nullochiasmate nondisjunction.

Seventy-two fetuses or neonates with non-immune hydrops were examined between 1983 and 1988. The commonest association was chromosome abnormality; 11 fetuses had a 45,X karyotype and 11 autosomal trisomy. Chromosome abnormality was suspected in a further 20 on necropsy findings but chromosome culture was not possible or unsuccessful. In 11 cases there was histological evidence of infection; seven babies had major structural anomalies and six affected fetuses were twins. In six (8%) the cause of hydrops was not determined compared with eight (16%) of cases examined between 1976 and 1982. Hydrops was diagnosed more frequently while the fetus was alive, before 20 weeks' gestation, and associated with chromosome anomaly than found previously.

We show that chromosome-mediated gene transfer can provide an enriched source of DNA markers for predetermined, subchromosomal regions of the human genome. Forty-four human DNA recombinants isolated from a HRAS1-selected chromosome-mediated gene transformant map exclusively to chromosome 11, with several sublocalizing to the Wilms tumor region at 11p13. We present a detailed molecular map of the deletion chromosomes 11 from five WAGR (Wilms tumor/aniridia/genitourinary abnormalities/mental retardation) syndrome patients, three of which are at the limits of cytogenetic resolution but shown here to be molecularly distinguishable and overlapping. We can define ten distinct regions of the short arm of chromosome 11, five of which subdivide band 11p13. We also map two independent 11p13 translocation breakpoints to within the smallest region of overlap defined by the WAGR deletions. The first comes from a patient with familial aniridia, and the second from a patient with Potter facies and genitourinary dysplasia. The close similarities in map location and affected cell lineage for Wilms tumor and genitourinary dysplasia suggest that they may be alternative manifestations of mutation at the same locus.

We used mitotic chromosomes isolated from a human EJ bladder carcinoma cell line for morphological transformation of mouse C127 cells. These chromosome-mediated transformants were analyzed for cotransfer of markers syntenic with c-Ha-ras-1 on human chromosome 11. We also used cloned, dispersed human DNA repeats, in a general mapping strategy, to quantitate the amounts and molecular state of human DNA transferred along with the activated c-Ha-ras-1 gene. In situ hybridization was used to visualize the physical state of the transfected human chromatin. The combined use of these various techniques revealed the occurrence of both chromosomal and DNA rearrangements. However, our analysis also demonstrated that, in general, very substantial lengths of DNA are transferred intact. Closely linked markers are likely to cosegregate. Therefore, these transformants should be invaluable sources for the complete molecular cloning of isolated fragments of the short arm of human chromosome 11.

Genes implicated in the development of Wilms' tumour (WT) and aniridia (AN2) have been localised to a sub-region of band p13 on chromosome 11 by molecular and cytogenetic characterisation of WAGR syndrome patients carrying variable constitutional deletions. Polymorphic markers for the region would be valuable for linkage analysis in the familial forms of both Wilms' tumour and aniridia, as well as for studying somatic rearrangements of chromosome 11 in a variety of tumour types. Here we describe the isolation and characterisation of three frequently polymorphic arbitrary DNA fragments that map proximal to the AN2 and WT loci.

We describe five individuals who have constitutional deletions of the short arm of one chromosome 11, including all or part of the band p13. All of these individuals suffer from aniridia; two have had a Wilms tumor removed. We have established lymphoblastoid cell lines from these and in three cases constructed somatic cell hybrids containing the deleted chromosome 11. Analysis of DNA from the cell lines and hybrids with a cloned cDNA probe has shown that the catalase gene is deleted in four of five patients. The catalase locus must be proximal to the Wilms and aniridia-related loci. We have not detected a deletion of the beta-globin or calcitonin genes in any of these individuals; we conclude these genes are likely to be outside the region 11p12-11p15.4. In addition, we have used monoclonal antibodies in fluorescence-activated cell sorting analysis to measure expression in the hybrids of two cell surface markers encoded by genes that map to the short arm of chromosome 11. The genes for both of these are deleted in two individuals but are present in the individual with the smallest deletion.

The plasma protease inhibitors control a wide variety of physiological functions including blood coagulation, complement activation and aspects of the inflammatory response. The inhibitors function by forming a 1:1 complex with a specific protease within the reactive centre region of the inhibitor. Little is known about the evolutionary relationships of these inhibitors. We report here the sequences of cDNAs which represent the C-terminal halves of the two major murine plasma protease inhibitors. One of these, murine alpha 1-antitrypsin, more appropriately called alpha 1-proteinase inhibitor (alpha 1-PI), has diverged from its human counterpart at a vital position in the reactive centre but this has not led to a physiologically significant change in function. Also, we have determined the partial sequence of a recently characterized protein termed contrapsin, which inhibits trypsin-like proteases. We show, surprisingly, that contrapsin is highly homologous to human alpha 1-antichymotrypsin, an inhibitor of chymotrypsin-like proteases. The reactive centre regions of these two inhibitors have diverged considerably, which may account for the differences in specificity. We propose that the genes for contrapsin and human alpha 1-antichymotrypsin are the descendents of a single gene that have evolved since rodent and primate divergence to encode proteins with different functions.