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Prenatal choline is a key nutrient, like folic acid and vitamin D, for fetal brain development and subsequent mental function. We sought to determine whether effects of higher maternal plasma choline concentrations on childhood attention and social problems, found in an initial clinical trial of choline supplementation, are observed in a second cohort.
Of 183 mothers enrolled from an urban safety net hospital clinic, 162 complied with gestational assessments and brought their newborns for study at 1 month of age; 83 continued assessments through 4 years of age. Effects of maternal 16 weeks of gestation plasma choline concentrations ⩾7.07 μM, 1 s.d. below the mean level obtained with supplementation in the previous trial, were compared to lower levels. The Attention Problems and Withdrawn Syndrome scales on Child Behavior Checklist 1½–5 were the principal outcomes.
Higher maternal plasma choline was associated with lower mean Attention Problems percentiles in children, and for male children, with lower Withdrawn percentiles. Higher plasma choline concentrations also reduced Attention Problems percentiles for children of mothers who used cannabis during gestation as well as children of mothers who had gestational infection.
Prenatal choline's positive associations with early childhood behaviors are found in a second, more diverse cohort. Increases in attention problems and social withdrawal in early childhood are associated with later mental illnesses including attention deficit disorder and schizophrenia. Choline concentrations in the pregnant women in this study replicate other research findings suggesting that most pregnant women do not have adequate choline in their diets.
Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.
Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age.
Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring.
The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
This study investigated whether higher maternal choline levels mitigate effects of marijuana on fetal brain development. Choline transported into the amniotic fluid from the mother activates α7-nicotinic acetylcholine receptors on fetal cerebro-cortical inhibitory neurons, whose development is impeded by cannabis blockade of their cannabinoid-1(CB1) receptors.
Marijuana use was assessed during pregnancy from women who later brought their newborns for study. Mothers were informed about choline and other nutrients, but not specifically for marijuana use. Maternal serum choline was measured at 16 weeks gestation.
Marijuana use for the first 10 weeks gestation or more by 15% of mothers decreased newborns' inhibition of evoked potentials to repeated sounds (d’ = 0.55, p < 0.05). This effect was ameliorated if women had higher gestational choline (rs = −0.50, p = 0.011). At 3 months of age, children whose mothers continued marijuana use through their 10th gestational week or more had poorer self-regulation (d’ = −0.79, p < 0.05). This effect was also ameliorated if mothers had higher gestational choline (rs = 0.54, p = 0.013). Maternal choline levels correlated with the children's improved duration of attention, cuddliness, and bonding with parents.
Prenatal marijuana use adversely affects fetal brain development and subsequent behavioral self-regulation, a precursor to later, more serious problems in childhood. Stopping marijuana use before 10 weeks gestational age prevented these effects. Many mothers refuse to cease use because of familiarity with marijuana and belief in its safety. Higher maternal choline mitigates some of marijuana's adverse effects on the fetus.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Background: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal. Methods: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists. Results: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system. Conclusions: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.
The ‘religious right’ came to prominence in the US during the late 1970s by campaigning on ‘social issues’ and encouraging many fundamentalist and evangelical Christians to get involved in politics. However, the fact that it clashed with ‘born again’ President Jimmy Carter over tax breaks for religious schools believed to be discriminatory, together with its illiberal stances on many issues, meant that it was characterized as an extremist movement. I argue that this assessment is oversimplified. First, many Christian schools were not racially discriminatory, and their defenders resented being labelled as racists. Secondly, few historians have recognized that the Christians involved in the religious right were among the most secularized of their kind. The religious right was often mistakenly categorized alongside earlier American Christian political movements that had displayed extremist and anti-democratic tendencies. The Carter administration's records and oft-ignored religious right ephemeral literature partly substantiate the movement's contention that it was defensive rather than theocratic in nature. One of my conclusions is that more attention must be paid to the subtle nuances of the political and theological views of religious right leaders, because the confusion surrounding the religious right is partly a function of its leaders harbouring internally inconsistent views.
As this conference has attested to, cosmology is a rapidly maturing field, currently experiencing a very healthy and vigorous confrontation between theory and experiment. This rapid progress in many different areas of cosmology has not removed the longstanding interest in measuring many of the fundamental cosmological parameters - rather, the increasingly detailed predictions of current theory highlight the critical importance of independently, accurately measuring the cosmological parameters which define the basic model for the dynamical evolution of the Universe. I present here the final results of the Hubble Space Telescope (HST) Key Project to measure the Hubble constant, summarizing our method, the results and the uncertainties. The Key Project results are based on a Cepheid calibration of several secondary distance methods applied over the range of about 60 to 400 Mpc. Based on the Key Project Cepheid calibration and its application to five secondary methods (type Ia supernovae, the Tully-Fisher relation, surface brightness fluctuations, type II supernovae, and the fundamental plane for elliptical galaxies), a combined value of H0 = 72 ± 8 km/sec/Mpc is obtained. Comparing to current estimates of the ages of Galactic globular clusters, an age conflict is avoided for this high a value of H0 if we live in a Λ-dominated (or other form of dark energy) universe.
Abnormalities during a smooth pursuit eye movement task (SPEM)
are common in schizophrenic patients and their relatives. This
study assessed various components of SPEM performance in
first-degree unaffected relatives of schizophrenic patients.
One hundred individuals with schizophrenia, 137 unaffected
first-degree relatives, and 69 normal controls completed a
16.7°/s SPEM task. Smooth pursuit gain, catch-up saccades
(CUS), large anticipatory saccades, and leading saccades (LS)
were identified. Groups were compared with parametric and admixture
analyses. Schizophrenic patients performed more poorly than
unaffected relatives and normals on gain, CUS, and LS. Unaffected
relatives were more frequently impaired than normals only on
gain and LS. Relatives of childhood-onset and adult-onset probands
had similar impairments. Gain and frequency of leading saccades
may be genetic endophenotypes in childhood-onset and adult-onset
Scholars of Middle Eastern studies in the last decade often were preoccupied with two major problems. First, the democratization that has spread over most of the globe seems to have missed the Middle East. Second, there appears to be a growing gap between international relations and comparative politics theory, on the one hand, and Middle East studies, on the other. In seeking to explain why, some point to the highly politicized scholarship that can still be found in Middle East studies. Others argue that the theorists simply have not tried hard enough to fit the special nature of the Middle East into their theoretical models, or that Middle Eastern scholars have not tried hard enough to deal with theory. Two of the three books under review, by Hansen and Heydemann, do a great deal to narrow the gap between theory and reality in the Middle East. The book by Niblock is an example of the kind of highly politicized scholarship that is still found too often in Middle Eastern studies.
In an outgrowth of his doctoral dissertation, Talal Nizameddin, now a lecturer at Haigazian
University in Beirut, discusses the evolution of Russian foreign policy toward the Middle East
under Boris Yeltsin from the collapse of the Soviet Union in December 1991 until 1997. The
book, based in part on extensive interviews in Moscow, seeks to show how Russian policy
evolved from what the author describes as the “radical pro-West” view of Foreign
Minister Andrei Kozyrev in the early 1990s to the more nationalist view of Yevgeny Primakov in
the mid- to late 1990s. In general, Nizameddin succeeds in his task, although his failure to
evaluate critically some of the comments given to him by his interviewees in Moscow, such as
Vitaly Naumkin, and the clearly anti-United States and anti-Israel perspective with which the
book is written detract from the value of the study.
This book is a most welcome addition to the literature on Russian–Israeli relations. Although Yaacov Ro⊃i, in his study Soviet Decision Making in Practice: The USSR and Israel 1947–1954 (New Brunswick, N.J.: Transaction Books, 1980), covered the 1947–53 period thoroughly, and although there is an extensive body of literature on Russian policy toward Israel (and the rest of the Middle East) after the 1967 war, a gap has existed for many years in the scholarly coverage of Russian–Israeli relations from the death of Stalin in March 1953 until the June 1967 Six Day War. Yosef Govrin, a retired Israeli Foreign Office official who specialized in relations with the USSR, has gone a long way toward filling this gap. Having the advantage of access to the Israeli archives and internal political debates, Govrin presents a balanced picture of the Soviet–Israeli relationship, pointing out where, in his opinion, both Israel and the USSR made mistakes in developing their ties. He also goes into great detail on the question of Soviet Jewry (more than half of the book), noting how Israel's efforts to get the Soviet government to allow Jews to emigrate to Israel was a serious complicating factor in the relationship, although the primary cause for the USSR's breaking of diplomatic relations with Israel in June 1967 (Govrin was first secretary of the Israeli embassy in Moscow at the time) stemmed from Moscow's backing of the radical Ba⊃athist regime in Syria, which helped precipitate the 1967 war.