Common polygenic risk for autism spectrum disorder (ASD) is associated with cognitive ability in the general population.

Cognitive impairment is common among individuals diagnosed with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been suggested that some aspects of intelligence are preserved or even superior in people with ASD compared with controls, but consistent evidence is lacking. Few studies have examined the genetic overlap between cognitive ability and ASD/ADHD. The aim of this study was to examine the polygenic overlap between ASD/ADHD and cognitive ability in individuals from the general population. Polygenic risk for ADHD and ASD was calculated from genome-wide association studies of ASD and ADHD conducted by the Psychiatric Genetics Consortium. Risk scores were created in three independent cohorts: Generation Scotland Scottish Family Health Study (GS:SFHS) (n=9863), the Lothian Birth Cohorts 1936 and 1921 (n=1522), and the Brisbane Adolescent Twin Sample (BATS) (n=921). We report that polygenic risk for ASD is positively correlated with general cognitive ability (beta=0.07, P=6 × 10(-7), r(2)=0.003), logical memory and verbal intelligence in GS:SFHS. This was replicated in BATS as a positive association with full-scale intelligent quotient (IQ) (beta=0.07, P=0.03, r(2)=0.005). We did not find consistent evidence that polygenic risk for ADHD was associated with cognitive function; however, a negative correlation with IQ at age 11 years (beta=-0.08, Z=-3.3, P=0.001) was observed in the Lothian Birth Cohorts. These findings are in individuals from the general population, suggesting that the relationship between genetic risk for ASD and intelligence is partly independent of clinical state. These data suggest that common genetic variation relevant for ASD influences general cognitive ability.

Maternal cardiac and obstetric performance in consecutive pregnancies in women with heart disease.

OBJECTIVE: Second pregnancies are usually less complicated than first pregnancies, and have a better outcome in terms of fetal growth. We studied a group of women with heart disease to assess whether their second pregnancy was less complicated and resulted in a larger baby. DESIGN: Retrospective case control study. SETTING: Tertiary referral academic obstetric unit. POPULATION: First and second pregnancies in 77 women with congenital and acquired heart disease and in 154 control women were identified. METHODS: Data were collected from medical and obstetric records. MAIN OUTCOME MEASURES: Cardiac complications, obstetric complications, intra-partum events, birthweight and perinatal complications. RESULTS: The rate of obstetric complication was greater in first pregnancies in both the heart disease and the control groups (38% versus 26%, cf. 20% versus 17%). In the heart disease group, the rate of cardiac complications was similar in first and second pregnancies (9% versus 6%). Overall, significantly more perinatal complications were seen in the heart disease group, with no significant difference between first and second pregnancies (36% versus 27%, cf. 14% versus 12%). Median birthweight was significantly higher in second pregnancies in the control group (3308 versus 3519 g P < 0.001), but not significantly different between pregnancies in the heart disease group (3014 versus 3133 g, P = 0.19). CONCLUSIONS: This case control study demonstrates that women with mild to moderate heart disease have similar pregnancy outcomes in consecutive pregnancies. However, while the median birthweight was higher in the control second pregnancies, it was not increased in the women with heart disease. TWEETABLE ABSTRACT: A study of women with heart disease to assess whether their second pregnancy was less complicated.

Genome-wide association study of Alzheimer's disease with psychotic symptoms.

Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWASs) to identify loci that (1) increase susceptibility to an AD and subsequent psychotic symptoms; or (2) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. In all, 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from Genetic and Environmental Risk in AD Consortium 1 (GERAD1), the National Institute on Aging Late-Onset Alzheimer's Disease (NIA-LOAD) family study and the University of Pittsburgh Alzheimer Disease Research Center (ADRC) GWASs. Unobserved genotypes were imputed to provide data on >1.8 million single-nucleotide polymorphisms (SNPs). Analyses in each data set were completed comparing (1) AD+P to AD-P cases, and (2) AD+P cases with controls (GERAD1, ADRC only). Aside from the apolipoprotein E (APOE) locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 × 10(-7); 'AD+PvControls' P=1.11 × 10(-4)). SNPs upstream of SLC2A9 (rs6834555, P=3.0 × 10(-7)) and within VSNL1 (rs4038131, P=5.9 × 10(-7)) showed strongest evidence for association with AD+P when compared with controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized.

Tetralogy of Fallot: maternal and neonatal outcomes.

We performed a retrospective cohort study of 26 pregnancies in 16 women with repaired tetralogy of Fallot (rTOF) delivering at the Chelsea and Westminster Hospital and compared them with 104 controls. The rate of antenatal complications was significantly higher in the rTOF group (30 cf. 13%). Use of epidural anaesthesia was higher (67 cf. 25%) in the rTOF group compared with controls, and the length of the second stage was shorter in both spontaneous and assisted deliveries. However, the mode of delivery and neonatal outcomes were similar in both groups. Mean birthweight centile was lower in the tetralogy of Fallot group, 26 versus 58 in the control group (P = 0.000001, Wilcoxon rank sum test). All women whose babies were <10th centile weight for gestational age had moderate to severe pulmonary regurgitation.

Nanotechnology--salvation or damnation for humans?

Nanotechnology is a term derived from the Greek word nanos, meaning dwarf. It is used to describe activities at the level of atoms and molecules. The application of this technology is aimed at controlling and manipulating the physical properties of materials with single molecule precision. Scientists use the technology to build working devices, systems and materials, molecule by molecule. This enables them to exploit the unique and powerful electrical, physical and chemical properties found at that scale. Nanotech holds the potential to revolutionise medicine, electronics and chemistry. Nanomedicine would facilitate the repair and improvement of the human body from the inside out, with a precision and delicacy far greater than the finest surgical instruments permit. Problem areas stemming from the technology include the following:- Who will benefit - just the rich or the poor as well? This paper will explore the role of law, ethics and suitable control mechanisms to limit the dangers and maximise the benefits of nanotechnology for society, especially in the field of medicine.

Calcification of the basal ganglia as a cause of levodopa-resistant parkinsonism.

We present a patient with levodopa-resistant parkinsonism due to basal ganglia calcification related to surgically-induced hypoparathyroidism. The calcification was seen on computerized axial tomography but not on skull x-rays. Such calcification should be looked for in all cases of levodopa-resistant parkinsonism, since it is possible that treatment of hypoparathyroidism may halt progression of the disease. This case with similar ones from the literature suggest that striatal disease itself can cause parkingonism and that the parkinsonism in such patients tends to be less responsive or nonresponsive to levodopa.

Is the foetal alcohol syndrome child protected by South African law?

It is scientifically indisputable that excessive use of alcohol or drugs during pregnancy causes defects in the children who are subsequently born to the abusing mothers. In the United States any legislative intervention by a state during the pregnancy would affect the rights of both the mother and the foetus. In order to remain within the bounds of constitutionality any maternal health legislation would have to strike a clear balance between the mother's rights to reproductive and familial privacy and bodily integrity guaranteed by the Fourteenth Amendment and the state's right to protect the foetus. This balance is currently achieved in terms of the framework set out by the Supreme Court in Roe v Wade 410 US 113 (1973). Although South African legislation cannot as yet be tested for its constitutionality the basic problem of balancing the rights of the mother, the foetus and the state remain the same. South Africa enjoys an advantage which the United States of America does not, viz the common-law remedies presented by the Aquilian action and the actio injuriarum. Only a person can be the bearer of rights and can thus invoke an action to protect those rights. It is thus necessary to determine whether the nasciturus fiction as enunciated in D 1.5.7 would enable a foetus (via a curator ad litem) to enforce rights against its mother. It is submitted that an extension of certain principles in the decisions of our Supreme Court in Christian League of Southern Africa v Rall 1981 (2) SA 821 (O), Wood v Ondangwa Tribal Authority 1975 (2) SA 294 (A) and Clark v Hurst NO 1992 (4) SA 630 (D) coupled to the nasciturus fiction are indicative of the fact that a foetus may enjoy protection against drug abuse by its mother prior to its birth.

Behaviour modification by genetic intervention--the law's response.

The Human Genome Initiative has stimulated research worldwide into mankind's genetic structure. It has led to identifying and understanding the function of many genes which cause illnesses, deformities, organ malfunctions and, more recently, behavioural aberrations. The science of gene therapy has developed in tandem and has initiated therapeutic treatment by the replacement of defective genes in humans. In the legal sphere guidelines for the application of gene therapy have been recommended by the Council of Europe, the United Kingdom, France, Denmark and the United States amongst others. South Africa has adopted the guidelines of the American National Institutes of Health. It is however submitted that third world countries such as South Africa have many other more basic health care problems on which to spend their limited resources despite having the technology to practise gene therapy.

The right to be born: surrogacy and the legal control of human fertility.

South African law, in common with many other legal systems, has exercised a strong measure of control over the fertility of its citizens via the sanction of illegitimacy and the prohibition of marriage (and hence legitimate children) between certain persons, e.g. those who fall within the so-called prohibited degrees of relationship. Until last year, when the Mixed Marriages Act was abolished, marriage across the colour line was prohibited in South Africa. The requirement of a valid consent by both prospective spouses in order to enter into marriage further excludes certain categories of persons from procreating legitimate children, e.g. the insane and mentally feeble, while the requirement of consummation will exclude certain categories of paraplegics from solemnizing a valid marriage. Age restrictions on marriages and the requirement of parental consent for minors are further factors limiting the individual's freedom to procreate. These restrictions have a well-established historical basis extending over many hundreds of years. They can be broadly categorised as having as their objective the preservation of the family unit. The above provisions were formulated at a time when the law never contemplated the spectacular advances in human biology that have produced the numerous artificial forms of conception, such as AID, IVF and surrogacy. The legislature, both in South Africa and elsewhere, at first adopted a neutral approach to this new fertility revolution and watched the courts struggle to adapt outmoded principles to the new technology. Legislation relating to AID and IVF eventually appeared in many jurisdictions; as a result of its delayed introduction public opinion had been educated to accept the new techniques and the legislation is by and large favourable to these new techniques. Not so, however, as far as surrogacy is concerned. South Africa, England and Australia have produced essentially negative legislation on this subject. Certain American states, however, have adopted progressive legislation accepting surrogacy. The merits of surrogacy are discussed and it is submitted that it should be condoned by the South African legislature under certain circumstances, as it can fall in the scope of furthering the interests of the family unit.

The impact of genetics on society: the law's response.

Technology has provided man with the ability to manipulate the genetic structure of the human race. The knowledge which geneticists have gained and will gain in future will raise numerous legal and ethical problems which will have to be debated and resolved within the parameters of the prevailing boni mores.

Artificial wombs: medical miracle, legal nightmare.

The fact that the development of the artificial uterus is nearing completion is a mixed blessing. It will provide numerous benefits within the field of pediatric medicine, such as ensuring normal development to term of extremely premature foetuses, but it will pose numerous problems which the law is ill-equipped to handle. The legislature will have to examine the current definition of 'parent' which is based on normal conception practices. It will also have to determine whether only married couples should have access to this technology and under which conditions.

Artificial reproduction and the family of the future.

The techniques of artificial reproduction have until fairly recently been geared to overcoming male sterility by means of AID and IPSI and female sterility by way of GIFT, VISPER and DIPI. The above techniques have concentrated on achieving conception either within or without the uterus. Gestation has always been completed in utero and the therapy was reserved for married couples. The above circumstances only required limited legal regulation and its effect on the family unit was minimal because the child was mostly conceived from the gametes of its parents New technologies which are looming on the horizon, however, threaten to change the concept of parent and family radically. I refer to the imminent perfection of the artificial uterus and the cloning of human cells. If these technologies are sanctioned, a child would be conceived from the cells of one parent only and will not be gestated within the mother's womb. How will society and the law react to these technologies? Will they regulate them or proscribe them? I will argue in favour of the former rather than the latter.

To clone or not to clone--whither the law?

The cloning of Dolly the lamb from adult cells by scientists at the Roslin Laboratories near Edinburgh in February 1997 has startled the world because it now opens the way to clone adult human beings. The reaction to Ian Wilmut's breakthrough has been instant and largely negative. Bills were rushed into both the US Senate and House of Representatives aimed at banning the cloning of human beings. Human cloning is premature at this stage, but there are many positive spin-offs of cloning in the field of genetic engineering, such as the production of human proteins such as blood clotting factors which aid in healing wounds. Progress by means of cloning can also be made into devising a cure for Parkinson's Disease amongst others. No lesser ethicist than John C. Fletcher of the University of Virginia foresees circumstances in which human cloning is acceptable e.g. to enable a couple to replace a dying child, to enable a couple, one of whom is infertile, to clone a child from either partner. Extensive regulation of cloning by the law is inevitable but, in doing so, the legislation should be careful not to outlaw research in this area which could be beneficial to mankind.

The role of the artificial uterus in embryo adoption and neonatal intensive care.

Embryo adoption is a way of having children for couples who wish to share a pregnancy experience but have neither eggs nor sperm to realise their dream. This type of situation could occur where the wife has had a hysterectomy, while her husband has an extremely low sperm count. The donors of embryos are usually couples who have completed their families. The artificial womb will duplicate the technology of a natural womb so as to enable the child to gestate and develop physically to maturity. This ability will enable the artificial womb to be used to rescue severely premature babies who would otherwise have died and allow them to develop normally to term. Legislation will be required to regulate situations where an entire pregnancy is sustained in an artificial uterus. Clarity as to parenthood in particular will need to be regulated.

A Multiple Indicators Multiple Causes (MIMIC) model of Behavioural and Psychological Symptoms in Dementia (BPSD).

INTRODUCTION: Although there is evidence for distinct behavioural sub-phenotypes in Alzheimer's disease (AD), their inter-relationships and the effect of clinical variables on their expression have been little investigated. METHODS: We have analysed a sample of 1850 probable AD patients from the UK and Greece with 10 item Neuropsychiatric Inventory (NPI) data. We applied a Multiple Indicators Multiple Causes (MIMIC) approach to investigate the effect of MMSE, disease duration, gender, age and age of onset on the structure of a four-factor model consisting of "psychosis", "moods", "agitation" and "behavioural dyscontrol". RESULTS: Specific clinical variables predicted the expression of individual factors. When the inter-relationship of factors is modelled, some previously significant associations are lost. For example, lower MMSE scores predict psychosis, agitation and behavioural dyscontrol factors, but psychosis and mood predict the agitation factor. Taking these associations into account MMSE scores did not predict agitation. CONCLUSIONS: The complexity of the inter-relations between symptoms, factors and clinical variables is efficiently captured by this MIMIC model.