HIV-exposed, uninfected (EUN) babies born to HIV-infected mothers are examples of natural resistance to HIV infection. In this study, we evaluated the titer and neutralizing potential of gp41-specific maternal antibodies and their correlation with HIV transmission in HIV-infected mother-child pairs. Specific gp41-binding and -neutralizing antibodies were determined in a cohort of 74 first-time mother-child pairs, of whom 40 mothers were infected with HIV subtype C. Within the infected mother cohort, 16 babies were born infected and 24 were PCR negative and uninfected at birth (i.e., exposed but uninfected). Thirty-four HIV-uninfected and HIV-unexposed mother-child pairs were included as controls. All HIV-positive mothers and their newborns showed high IgG titers to linear epitopes within the HR1 region and to the membrane-proximal (MPER) domain of gp41; most sera also recognized the disulfide loop immunodominant epitope (IDE). Antibody titers to the gp41 epitopes were significantly lower in nontransmitting mothers (P < 0.01) and in the EUN babies (P < 0.005) than in HIV-positive mother-child pairs. Three domains of gp41, HR1, IDE, and MPER, elicited antibodies that were effectively transmitted to EUN babies. Moreover, in EUN babies, epitopes overlapping the 2F5 epitope (ELDKWAS), but not the 4E10 epitope, were neutralization targets in two out of four viruses tested. Our findings highlight important epitopes in gp41 that appear to be associated with exposure without infection and would be important to consider for vaccine design.

Molecular epidemiology studies have identified HLA-B*58:01 as a protective HIV allele. However, not all B*58:01-expressing persons exhibit slow HIV disease progression. We followed six HLA-B*58:01-positive, HIV subtype C-infected individuals for up to 31 months from the onset of infection and observed substantial variability in their clinical progression despite comparable total breadths of T cell responses. We therefore investigated additional immunological and virological factors that could explain their different disease trajectories. Cytotoxic T-lymphocyte (CTL) responses during acute infection predominantly targeted the TW10 and KF9 epitopes in p24Gag and Nef, respectively. Failure to target the TW10 epitope in one B*58:01-positive individual was associated with low CD4+ counts and rapid disease progression. Among those targeting TW10, escape mutations arose within 2 to 15 weeks of infection. Rapid escape was associated with preexisting compensatory mutations in the transmitted viruses, which were present at a high frequency (69%) in the study population. At 1 year postinfection, B*58:01-positive individuals who targeted and developed escape mutations in the TW10 epitope (n = 5) retained significantly higher CD4+ counts (P = 0.04), but not lower viral loads, than non-B*58:01-positive individuals (n = 17). The high population-level frequency of these compensatory mutations may be limiting the protective effect of the B*58:01 allele.

Background:

In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies.

Objective:

The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI.

Methods:

A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age- and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data.

Results:

A total of 25.8% of subjects (95% confidence interval [CI] 23.5–28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6–15.3), followed by visuospatial (11.0%; 9.4–13.0) and attention/executive ability impairment (10.1%; 8.6–11.9). Regarding cognitive profiles, 11.3% (9.7–13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0–9.9) as amnestic single-domain, 4.8% (3.8–6.1) as amnestic multiple-domain, and 1.3% (0.9–2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage.

Conclusions:

MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage.

GLOSSARY

= amnestic multiple-domain MCI;

= amnestic single-domain MCI;

= confidence interval;

= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;

= mild cognitive impairment;

= Mini-Mental State Examination;

= nonamnestic multiple-domain MCI;

= nonamnestic single-domain MCI;

= Parkinson disease;

= Parkinson's Disease Cognitive Rating Scale;

= Unified Parkinson's Disease Rating Scale.

In order to better understand the broad applicability of adenovirus (Ad) as a vector for human vaccine studies, we compared four adenovirus (Ad) vectors from families C (Ad human serotype 5 [HAdV-5; here referred to as AdHu5]), D (HAdV-26; here referred to as AdHu26), and E (simian serotypes SAdV-23 and SAdV-24; here referred to as chimpanzee serotypes 6 and 7 [AdC6 and AdC7, respectively]) of the Adenoviridae. Seroprevalence rates and titers of neutralizing antibodies to the two human-origin Ads were found to be higher than those reported previously, especially in countries of sub-Saharan Africa. Conversely, prevalence rates and titers to AdC6 and AdC7 were markedly lower. Healthy human adults from the United States had readily detectable circulating T cells recognizing Ad viruses, the levels of which in some individuals were unexpectedly high in response to AdHu26. The magnitude of T-cell responses to AdHu5 correlated with those to AdHu26, suggesting T-cell recognition of conserved epitopes. In mice, all of the different Ad vectors induced CD8+ T-cell responses that were comparable in their magnitudes and cytokine production profiles. Prime-boost regimens comparing different combinations of Ad vectors failed to indicate that the sequential use of Ad vectors from distinct families resulted in higher immune responses than the use of serologically distinct Ad vectors from the same family. Moreover, the transgene product-specific antibody responses induced by the AdHu26 and AdC vectors were markedly lower than those induced by the AdHu5 vector. AdHu26 vectors and, to a lesser extent, AdC vectors induced more potent Ad-neutralizing antibody responses. These results suggest that the potential of AdHu26 as a vaccine vector may suffer from limitations similar to those found for vectors based on other prevalent human Ads.

It is unresolved whether recently transmitted human immunodeficiency viruses (HIV) have genetic features that specifically favour their transmissibility. To identify potential “transmission signatures”, we compared 20 full-length HIV-1 subtype C genomes from primary infections, with 66 sampled from ethnically and geographically matched individuals with chronic infections. Controlling for recombination and phylogenetic relatedness, we identified 39 sites at which amino acid frequency spectra differed significantly between groups. These sites were predominantly located within Env, Pol and Gag (14/39, 9/39 and 6/39 respectively) and were significantly clustered (33/39) within known immunoreactive peptides. Within 6 months of infection we detected reversion-to-consensus mutations at 14 sites and potential CTL escape mutations at seven. Here we provide evidence that frequent reversion mutations probably allows the virus to recover replicative fitness which, together with immune escape driven by the HLA alleles of the new hosts, differentiate sequences from chronic infections from those sampled shortly after transmission.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and pediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac subspecialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Regulatory decisions and scientific statements regarding the management of attention-deficit hyperactivity disorder (ADHD) raise questions about the safety of medications and the appropriate pretreatment evaluation to determine suitability for treatment with medication. This is particularly true in the setting of known structural or functional heart disease. The present paper reviews the available data, including peer-reviewed literature, data from the United States Food and Drug Administration Web site on reported adverse reactions in children using stimulant medication, and Health Canada data on the same problem. A consensus-based guideline on appropriate assessment is provided, based on input from members of the Canadian Paediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry, with specific expertise and knowledge in the areas of both ADHD and paediatric cardiology. The present statement advocates a thorough history and physical examination before starting stimulant medications, with an emphasis on the identification of risk factors for sudden death, but does not routinely recommend electrocardiographic screening or cardiac sub-specialist consultation unless indicated by history or physical examination findings. A checklist for identifying children who are potentially at risk of sudden death (independent of ADHD or medications used to treat it) is provided. Although recommendations are based on the best evidence currently available, the committee further agrees that more research on this subject is necessary to optimize the approach to this common clinical scenario.

Les décisions en matière de réglementation et les documents scientifiques au sujet de la prise en charge du trouble de déficit de l’attention avec hyperactivité (TDAH) soulèvent des questions quant à l’innocuité des médicaments et à l’évaluation convenable à effectuer avant le traitement afin de déterminer la pertinence d’une pharmacothérapie. Ce constat est particulièrement vrai en présence de cardiopathies structurelles ou fonctionnelles. Le présent article contient l’analyse des données disponibles, y compris les publications révisées par des pairs, des données tirées du site Web de la Food and Drug Administration des États-Unis au sujet des réactions indésirables déclarées chez des enfants qui prennent des stimulants, ainsi que des données de Santé Canada sur le même problème. Des lignes directrices consensuelles sur l’évaluation pertinente sont proposées d’après l’apport des membres de la Société canadienne de pédiatrie, de la Société canadienne de cardiologie et de l’Académie canadienne de psychiatrie de l’enfant et de l’adolescent, qui possèdent notamment des compétences et des connaissances précises tant dans le secteur du TDAH que de la cardiologie pédiatrique. Le présent document de principes prône une anamnèse et un examen physique détaillés avant la prescription de stimulants et s’attarde sur le dépistage des facteurs de risque de mort subite, mais il ne contient pas de recommandations systématiques de dépistage électrocardiographique ou de consultations avec un spécialiste en cardiologie, à moins que les antécédents ou que l’examen physique ne le justifient. Le document contient un questionnaire pour repérer les enfants potentiellement vulnérables à une mort subite (quel que soit le type de TDAH ou les médicaments utilisés pour le traiter). Même si les recommandations dépendent des meilleures données probantes disponibles, le comité s’entend pour affirmer que d’autres recherches s’imposent pour optimiser l’approche de ce scénario clinique courant.

The LRRK2 G2019S mutation is the commonest genetic cause of Parkinson's disease (PD) identified to date, although estimates of its prevalence in idiopathic disease vary considerably. Our objectives were to determine G2019S mutation frequency in an unselected, community based cohort of idiopathic PD cases from the UK and to describe phenotypic characteristics among carriers. The mutation was present in two of 519 cases (0.4%) and none of 887 control individuals. The true prevalence of the mutation in idiopathic disease, its penetrance, and the phenotypic heterogeneity of associated cases have important implications for genetic screening in the clinical field.

This report examines the structure and function of ARHGAP4, a novel RhoGAP whose structural features make it ideally suited to regulate the cytoskeletal dynamics that control cell motility and axon outgrowth. Our studies show that ARHGAP4 inhibited the migration of NIH/3T3 cells and the outgrowth of hippocampal axons. ARHGAP4 contains an N-terminal FCH domain, a central GTPase activating (GAP) domain and a C-terminal SH3 domain. Our structure/function analyses show that the FCH domain appears to be important for spatially localizing ARHGAP4 to the leading edges of migrating NIH/3T3 cells and to axon growth cones. Our analyses also show that the GAP domain and C-terminus are necessary for ARHGAP4-mediated inhibition of cell and axon motility. These observations suggest that ARHGAP4 can act as a potent inhibitor of cell and axon motility when it is localized to the leading edge of motile cells and axons.

Olfactory ensheathing cells show promise in preclinical animal models as a cell transplantation therapy for repair of the injured spinal cord. This is a report of a clinical trial of autologous transplantation of olfactory ensheathing cells into the spinal cord in six patients with complete, thoracic paraplegia. We previously reported on the methods of surgery and transplantation and the safety aspects of the trial 1 year after transplantation. Here we address the overall design of the trial and the safety of the procedure, assessed during a period of 3 years following the transplantation surgery. All patients were assessed at entry into the trial and regularly during the period of the trial. Clinical assessments included medical, psychosocial, radiological and neurological, as well as specialized tests of neurological and functional deficits (standard American Spinal Injury Association and Functional Independence Measure assessments). Quantitative test included neurophysiological tests of sensory and motor function below the level of injury. The trial was a Phase I/IIa design whose main aim was to test the feasibility and safety of transplantation of autologous olfactory ensheathing cells into the injured spinal cord in human paraplegia. The design included a control group who did not receive surgery, otherwise closely matched to the transplant recipient group. This group acted as a control for the assessors, who were blind to the treatment status of the patients. The control group also provided the opportunity for preliminary assessment of the efficacy of the transplantation. There were no adverse findings 3 years after autologous transplantation of olfactory ensheathing cells into spinal cords injured at least 2 years prior to transplantation. The magnetic resonance images (MRIs) at 3 years showed no change from preoperative MRIs or intervening MRIs at 1 and 2 years, with no evidence of any tumour of introduced cells and no development of post-traumatic syringomyelia or other adverse radiological findings. There were no significant functional changes in any patients and no neuropathic pain. In one transplant recipient, there was an improvement over 3 segments in light touch and pin prick sensitivity bilaterally, anteriorly and posteriorly. We conclude that transplantation of autologous olfactory ensheathing cells into the injured spinal cord is feasible and is safe up to 3 years of post-implantation, however, this conclusion should be considered preliminary because of the small number of trial patients.

Cognitive deficits are very common in Parkinson's disease particularly for ‘executive functions’ associated with frontal cortico-striatal networks. Previous work has identified deficits in tasks that require attentional control like task-switching, and reward-based tasks like gambling or reversal learning. However, there is a complex relationship between the specific cognitive problems faced by an individual patient, their stage of disease and dopaminergic treatment. We used a bimodality continuous performance task during fMRI to examine how patients with Parkinson's disease represent the prospect of reward and switch between competing task rules accordingly. The task-switch was not separately cued but was based on the implicit reward relevance of spatial and verbal dimensions of successive compound stimuli. Nineteen patients were studied in relative ‘on’ and ‘off’ states, induced by dopaminergic medication withdrawal (Hoehn and Yahr stages 1–4). Patients were able to successfully complete the task and establish a bias to one or other dimension in order to gain reward. However the lateral prefrontal cortex and caudate nucleus showed a non-linear U-shape relationship between motor disease severity and regional brain activation. Dopaminergic treatment led to a shift in this U-shape function, supporting the hypothesis of differential neurodegeneration in separate motor and cognitive cortico–striato–thalamo–cortical circuits. In addition, anterior cingulate activation associated with reward expectation declined with more severe disease, whereas activation following actual rewards increased with more severe disease. This may facilitate a change in goal-directed behaviours from deferred predicted rewards to immediate actual rewards, particularly when on dopaminergic treatment. We discuss the implications for investigation and optimal treatment of this common condition at different stages of disease.

Parkinson's disease (PD) is associated with a loss of central dopaminergic pathways in the brain leading to an abnormality of movement, including saccades. In PD, analysis of saccadic latency distributions, rather than mean latencies, can provide much more information about how the neural decision process that precedes movement is affected by disease or medication. Subject to the constraints of intersubject variation and reproducibility, latency distribution may represent an attractive potential biomarker of PD. Here we report two studies that provide information about these parameters, and demonstrate a novel effect of dopamine on saccadic latency, implying that it influences the neural decision process itself. We performed a detailed cross-sectional study of saccadic latency distributions during a simple step task in 22 medicated patients and 27 age-matched controls. This revealed high intersubject variability and an overlap of PD and control distributions. A second study was undertaken on a different population specifically to investigate the effects of dopamine on saccadic latency distributions in 15 PD patients. l-dopa was found to prolong latency, although the magnitude of the effect varied between subjects. The implications of these observations for the use of saccadic latency distributions as a potential biomarker of PD are discussed, as are the effects of l-dopa on neural decision making, where it is postulated to increase the criterion level of evidence required before the decision to move is made.

Objective: To determine tolerability and symptom changes associated with the introduction of bisoprolol treatment in older patients with heart failure.

Design: Prospective observational cohort study.

Setting: Geriatric medicine outpatient department of a university hospital.

Patients: 51 patients (mean age 78 years, range 70–89 years) with stable symptomatic heart failure caused by left ventricular systolic dysfunction.

Interventions: Bisoprolol tablets, 1.25–10.0 mg.

Main outcome measures: Tolerability; changes in symptoms and exercise tolerance.

Results: 69% of patients tolerated bisoprolol. Mean tolerated dose was 7.6 mg. There was no change in symptoms or exercise capacity in those who tolerated bisoprolol. Perceived health status and symptoms of anxiety and depression improved during the titration period.

Conclusions: The rate of withdrawal from bisoprolol treatment in older patients with congestive heart failure was twice that previously reported in younger patients. The mean tolerated dose was similar to that found in trials reporting clinical efficacy. There was no evidence of a negative impact on symptoms or exercise capacity in patients who tolerated bisoprolol.

Insulin is neuroprotective in animal stroke models but its effects in acute stroke in humans are unknown. The Glucose Insulin in Stroke Trial (GIST-UK) is a randomised controlled trial investigating the benefits of maintaining euglycaemia in hyperglycaemic patients with acute stroke. Data are reported from a GIST-UK substudy which sought to determine the influence of glucose potassium insulin (GKI) infusion on blood pressure in acute stroke. All adult patients admitted to hospital with acute stroke with hyperglycaemia (plasma glucose 6.1-17 mmol/l) were potentially eligible. Randomised patients received either a GKI infusion (500 ml 10% glucose, 20 mmol potassium chloride, 16 units of insulin) or control therapy with 154 mmol/l (0.9%) saline at 100 ml/h for 24 hours. BM test strip glucose monitoring was performed 2 hourly, blood pressure monitoring 4hourly, and plasma glucose sampling 8 hourly. Insulin concentration in the GKI infusate was altered according to test strip values to maintain test strip values between 4-7 mmol/l in the GKI group. Neurological impairment was determined using the European stroke scale (ESS). 145 patients were studied (73 GKI, 72 control). Mean systolic blood pressure was significantly lower during GKI infusion between 4 hours and 24 hours except at 8 hours. Median total ESS scores improved significantly between admission and day 7 in the GKI group (p<0.001) although there was no significant difference in total ESS score between groups at day 7. The significant reduction of systolic blood pressure in acute stroke associated with GKI therapy was not associated with neurological deterioration and may have been beneficial.



Objective

To develop a renewed and innovative curricula for training and education in child and adolescent psychiatry career for track psychiatry trainees at the University of Ottawa.

Method

Faculty members who were graduates of multiple Canadian training programs, as well as current career child psychiatry trainees of the University of Ottawa program, summarized and reviewed their training and education experiences in a one day summit. This was integrated into overall directions cited by recent literature as well as positions of the Canadian Academy of Child and Adolescent Psychiatry.

Results

A template for new curricula was developed with new focus being placed on normal development, research methodology/evidence based medicine, emergency psychiatry, psychotherapy, and cultural competence.

Conclusions

Curricula renewal is essential, possible, and appropriate in order to produce a Child and Adolescent Psychiatrist who meets the needs of the Canadian public as defined in the CanMeds 2000 project of the RCPSC.

Betaretroviruses of sheep include two exogenous viruses, Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV), and a group of endogenous viruses known as enJSRVs. The exogenous JSRV and ENTV are the etiological agents of ovine pulmonary adenocarcinoma (OPA) and enzootic nasal tumor (ENT), respectively. Sheep affected by OPA or ENT do not show an appreciable antibody response to JSRV or ENTV. Consequently, it is conceivable that enJSRV expression in the fetal lamb tolerizes sheep to the related exogenous viruses. In this study, possible mechanisms of interference between the sheep exogenous and endogenous betaretroviruses were investigated. In situ hybridization detected enJSRV RNAs in lymphoid cells associated with the lamina propria of the small intestine and in the thymus of sheep fetuses. Low-level expression of enJSRVs was also detected in the lungs. In addition, expression of enJSRVs was found to block entry of the exogenous JSRV, presumably via mechanisms of receptor interference. Indeed, enJSRVs, like JSRV and ENTV, were found to utilize hyaluronidase-2 as a cellular receptor.

AIMS—To develop and validate a scale for the measurement of visual symptoms and functional disability due to cataract in older UK residents.
METHODS—In depth semistructured interviews were undertaken with 44 consecutive patients awaiting cataract surgery. Patients were asked to describe visual symptoms and problems with social functioning which were then incorporated into a questionnaire, the cataract symptom scale (CSS). The CSS was further examined in a cohort of 118 consecutive cataract patients awaiting surgery. Further assessments in these patients included visual acuity, visual function using an existing scale (the VF-14), activities of daily living, perceived health status, anxiety and depression, and a global assessment of how much patients felt their visual symptoms affected their daily life.
RESULTS—A 15 item scale was derived which was simple to administer to older patients and had a high internal consistency. The test-retest correlation coefficient for the total instrument score was r = 0.91 (p<0.0001). The CSS correlated well with the VF-14 and to a lesser extent with visual acuity in the better eye, activities of daily living, perceived health status, anxiety and depression, and the patients' global assessment of visual symptoms.
CONCLUSION—The CSS provides information regarding the symptomatic and functional status of older cataract patients resident in the UK which cannot be obtained by measurement of visual acuity alone.



The ovine genome contains 15 to 20 copies of endogenous retroviruses (enJSRVs) highly related to the oncogenic jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus. enJSRVs are highly expressed in the endometrial lumenal epithelia (LE) and glandular epithelia (GE) of the ovine uterus. The effects of neonatal age, estrous cycle, pregnancy, and progesterone on expression of enJSRVs in the ovine uterus were determined. Expression of enJSRV RNAs was absent from the uterus of ewes at birth, but enJSRV RNAs were expressed specifically in the LE and developing GE from postnatal day (PND) 7 to PND 56. In adult ewes, enJSRV RNAs were detected only in the epithelia of the uterine endometrium, as well as epithelia of the oviduct, cervix, and vagina. In cyclic ewes, endometrial enJSRV RNA abundance was lowest on day 1, increased 12-fold between days 1 and 13, and then decreased to day 15. In pregnant ewes, levels of endometrial enJSRV RNAs were high on day 11, increased to day 13, and then decreased to day 19. In day 17 and 19 conceptuses, enJSRV RNAs were also detected in binucleate cells of the trophectoderm. Immunoreactive JSRV capsid and envelope proteins were detected in the endometrial LE and GE, as well as in the binucleate cells of the conceptus. In transfection assays utilizing ovine endometrial LE cells, progesterone increased transcriptional activity of several enJSRV long terminal repeats. Collectively, these results indicate that transcription of enJSRVs in the endometrial epithelia of the ovine uterus is increased by progesterone and might support a role for enJSRVs in conceptus-endometrium interactions during the peri-implantation period and early placental morphogenesis.

Atrial fibrillation is an important and independent risk factor for cerebrovascular disease and vascular dementia. There is increasing evidence that atrial fibrillation is associated with an increased risk of asymptomatic or silent cerebral infarction and as a result may confer an increased risk of progressive cognitive impairment on a person. In this study we sought to determine whether this hypothesis could be explored in a prospective case controlled design. Twenty seven patients with non-valvular atrial fibrillation (NVAF) and no history of stroke, transient ischaemic attack, dementia, and thyrotoxicosis were compared with 54 age and sex matched controls in sinus rhythm. All cases underwent clinical examination, ECG, and psychological assessment using a battery of nine neuropsychological tests. Between group analysis and a comparison of mean test scores of paired controls with cases were undertaken. The presence of atrial fibrillation was consistently associated with poorer performances on all the subtests of the neuropsychological battery. There was no association between duration of atrial fibrillation and performance. These results provide evidence to justify further examination of the hypothesis in a larger prospective study to determine whether antithrombotic therapy may protect against cognitive decline in patients at maximal risk of silent cerebral ischaemia and associated cognitive decline.



AIM—To study the refractive status and corneal topography in Down's syndrome.
METHOD—A matched cohort subgroup of 50 individuals with Down's syndrome in the Manchester area aged 15-22 years was studied by refraction, corneal topography, A-scan biometry, slit lamp examination, and orthoptic examination.
RESULTS—(1) A linear relation was found between axial length and spherical equivalent refraction. There was no statistical relation between keratometry and the axial length. (2) 80% of the group had a hyperopic refraction (mean +2.46 D, range +0.5 to +7.5 D); 18% were myopic (mean −2.75 D, range −0.5 to −8.0 D); and 2% were emmetropic (within plus or minus 0.5 D of zero). The overall mean spherical equivalent refraction was +1.43 (SD 2.86) D. 63% of eyes could see 6/12 or better and 66% of the individuals had a binocular vision of 6/12 or better. (3) Corneal topography was generally of a regular "bow tie" pattern, but there was a high incidence of oblique cylinders. Mean cylinder strength was 1.14 (1.15) D. (4) The prevalence of overt keratoconus was 2%. 6% had corneal topography with inferior steepening which may be a preclinical keratoconic process.
CONCLUSIONS—In this cohort of late teenagers with Down's syndrome, emmetropisation has failed to occur in most individuals. In a similar aged group of non-disabled individuals one would expect about 83% emmetropic (plus or minus 0.25 D), 13% myopic, and 4% hyperopic. The wide spread of oblique cylinders and the small proportion of with the rule astigmatism is probably related to this failure of emmetropisation. The prevalence of 2% keratoconus in Down's syndrome compares with that found by other authors of between 5.5 and 15%. The 6% with inferior steepening on topography will be followed up over the next few years to see if there is any development of clinical keratoconus. Hence we will see if corneal topography is useful as a screening tool for preclinical keratoconus in this high risk group. 

 Keywords: Down's syndrome; emmetropisation; refraction; keratoconus

OBJECTIVES—To describe the natural recovery of visuospatial neglect in stroke patients and the distribution of errors made on cancellation tests using a standardised neuropsychological test battery.
METHOD—A prospective study of acute (< seven days) patients with right hemispheric stroke. Patients identified with visuospatial neglect were followed up for three months with monthly clinical and neuropsychological testing
RESULTS—There were 66 patients with acute right hemispheric stroke assessed of whom 27 (40.9%) had evidence of visuospatial neglect. Patients with neglect, on admission, had a mean behavioural inattention test (BIT) score of 56.3, range 10-126 (normal>129). Three of the subtests identified errors being made in both the right and left hemispaces. During follow up, recovery occurred across both hemispaces, maximal in the right hemispace. Recovery from visuospatial neglect was associated with improvement in function as assessed by the Barthel score. At the end of the study period only six (31.5%) patients had persisting evidence of neglect. On admission the best predictor of recovery of visuospatial neglect was the line cancellation test (Spearman's rank correlation r=−0.4217, p=0.028).
CONCLUSION—The demonstration of errors in both hemispaces has implications for the theory that neglect is a lateralised attentional problem and is important to recognise in planning the rehabilitation of stroke patients.