Neural correlates of social exchanges during the Prisoner's Dilemma game in depression.

BACKGROUND: Depression is a disabling disorder that significantly impacts on the interpersonal functioning of individuals. However, little is known about the neural substrates of such difficulties. In the last few years neuroeconomics, which combines imaging with multiplayer behavioural economic paradigms, has been used to study the neural substrates of normal and abnormal interpersonal interactions. METHOD: This study used functional magnetic resonance imaging to investigate neural activity in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic game, the Prisoner's Dilemma. In this game, the participant and a co-player independently choose either to cooperate or not cooperate with each other. RESULTS: Depressed participants reported higher levels of negative feelings (betrayal, guilt) during the game than did controls. Neural activation was compared between 'imbalanced' events [when one of the players cooperated and the other defected ('CD' and 'DC')] and 'draw' events [when both players either cooperated or defected ('CC' and 'DD')]. Participants preferentially activated the anterior insula and the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and regulation of emotions. Importantly, compared to controls depressed participants showed reduced activation in the left DLPFC, with the extent of signal reduction correlating with increased self-report feelings of guilt associated with DC outcomes. CONCLUSIONS: Our findings suggest that depression is associated with reduced activation of the DLPFC during social events that involve unreciprocated cooperation. This abnormality may underlie anomalies in cognitive control and top-down regulation of emotions during challenging social exchanges.

Identification and quantification of factors affecting neonatal immunological transfer in dairy calves in the UK.

The object of the study was to quantify the prevalence of failure of passive transfer in UK dairy farms and to identify variables that had a significant impact on the rate of immunological transfer. In a six-month study of 444 calvings from seven UK dairy farms, 26 per cent of calves failed to receive adequate immunoglobulin transfer as judged by a plasma total protein (pTP) concentration less than 5.6 g/dl. Colostrum immunoglobulin concentration, indirectly measured using Brix refractometry, showed wide variations with samples ranging from 10.3 to 34.7 Brix units. Thirty-seven per cent of samples were below the suggested cut-off Brix score for colostrum quality of 22 per cent. Potential associations between covariates and plasma protein concentration were investigated using multiple linear regression models. The covariate with the greatest impact on the pTP concentration was the farm on which the calf was born (P<0.05). A significant but small association was demonstrated between colostrum immunoglobulin concentration and calf pTP concentration (P<0.01). Multiple linear regression models suggested that the time of colostrum collection after calving, parity of the dam, and the individual farm were associated with the Brix measurements (P<0.05). This study suggested that veterinary review of colostrum protocols on farm with emphasis on prompt collection and dosing after calving remains a simple and effective measure to improve passive transfer and thus calf health on UK dairy farms.

Technical assessment of whole body angiography and cardiac function within a single MRI examination.

AIM: To evaluate a combined protocol for simultaneous cardiac MRI (CMR) and contrast-enhanced (CE) whole-body MR angiography (WB-MRA) techniques within a single examination. MATERIALS AND METHODS: Asymptomatic volunteers (n = 48) with low-moderate risk of cardiovascular disease (CVD) were recruited. The protocol was divided into four sections: (1) CMR of left ventricle (LV) structure and function; (2) CE-MRA of the head, neck, and thorax followed by the distal lower limbs; (3) CMR LV "late gadolinium enhancement" assessment; and (4) CE-MRA of the abdomen and pelvis followed by the proximal lower limbs. Multiple observers undertook the image analysis. RESULTS: For CMR, the mean ejection fraction (EF) was 67.3 ± 4.8% and mean left ventricular mass (LVM) was 100.3 ± 22.8 g. The intra-observer repeatability for EF ranged from 2.1-4.7% and from 9-12 g for LVM. Interobserver repeatability was 8.1% for EF and 19.1 g for LVM. No LV delayed myocardial enhancement was observed. For WB-MRA, some degree of luminal narrowing or stenosis was seen at 3.6% of the vessel segments (involving n = 29 of 48 volunteers) and interobserver radiological opinion was consistent in 96.7% of 1488 vessel segments assessed. CONCLUSION: Combined assessment of WB-MRA and CMR can be undertaken within a single examination on a clinical MRI system. The associated analysis techniques are repeatable and may be suitable for larger-scale cardiovascular MRI studies.

Abnormal brain responses to social fairness in depression: an fMRI study using the Ultimatum Game.

BACKGROUND: Depression is a prevalent disorder that significantly affects the social functioning and interpersonal relationships of individuals. This highlights the need for investigation of the neural mechanisms underlying these social difficulties. Investigation of social exchanges has traditionally been challenging as such interactions are difficult to quantify. Recently, however, neuroeconomic approaches that combine multiplayer behavioural economic paradigms and neuroimaging have provided a framework to operationalize and quantify the study of social interactions and the associated neural substrates. METHOD: We investigated brain activation using functional magnetic resonance imaging (fMRI) in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic paradigm, the Ultimatum Game (UG). In this task, participants accept or reject monetary offers from other players. RESULTS: In comparison to controls, depressed participants reported decreased levels of happiness in response to 'fair' offers. With increasing fairness of offers, controls activated the nucleus accumbens and the dorsal caudate, regions that have been reported to process social information and responses to rewards. By contrast, participants with depression failed to activate these regions with increasing fairness, with the lack of nucleus accumbens activation correlating with increased anhedonia symptoms. Depressed participants also showed a diminished response to increasing unfairness of offers in the medial occipital lobe. CONCLUSIONS: Our findings suggest that depressed individuals differ from healthy controls in the neural substrates involved with processing social information. In depression, the nucleus accumbens and dorsal caudate may underlie abnormalities in processing information linked to the fairness and rewarding aspects of other people's decisions.

'Back to sleep': the position in Oxfordshire and Northampton.

We examined hospital and domestic infant care practices in Oxfordshire and Northampton Health Districts to measure changes in prevalence of sudden infant death syndrome (SIDS) risk factors, and to evaluate a specific educational intervention restricted to Oxfordshire. We sent a postal questionnaire to 2781 parents of babies newly born in January 1992, July 1992 and January 1993 and achieved an 88% response rate. Overall, in hospital a relatively constant proportion (81%) slept on their sides and few prone, whereas at home 52% (but increasing) slept supine and 8% prone part or all of the time. Significant differences existed by district, both in hospital and at home, with more sleeping supine in Oxfordshire and more side-sleeping/propping in Northampton. First-time parents were more receptive to safety guidelines about sleeping position and several other risk factors also. We detected no modifying effect of the Oxfordshire advice. Professional practice can influence parental behaviour but general media coverage may produce the biggest effects.

Treatment of chronic recurrent multifocal osteomyelitis with interferon gamma.

Chronic recurrent multifocal osteomyelitis is characterized by recurrent episodes of painful swollen lesions of the bone and overlying skin with radiographic changes and an elevated sedimentation rate. It resembles infectious osteomyelitis but with negative findings on bacterial culture and no response to antibiotics. We treated a 13-year-old girl with interferon gamma for 3 months. She had 11 episodes of chronic recurrent multifocal osteomyelitis in 2 1/2 years before therapy and has had none in the 15 months since therapy, an outcome suggesting a favorable therapeutic response.

Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T.

Efficacy of the Haemophilus influenzae type b (Hib) conjugate vaccine PRP-T (Pasteur-Merieux) was evaluated in a controlled community intervention study in the Oxford region, UK. PRP-T was offered to infants from May 1, 1991 in three of the region's eight districts and from July 1, 1991, in a fourth district. It was given by separate injection in addition to the standard diphtheria, tetanus, and pertussis vaccine according to an accelerated 2, 3, and 4 month schedule without a booster dose in the second year of life. By October 1, 1992, more than 90% of infants in vaccine districts had received at least one dose of PRP-T. None of the infants given three doses had developed Hib infection, whereas 11 infections occurred in the control population (vaccine efficacy 100%, 95% CI 80-100%). Intention-to-treat analysis also showed a high estimate of efficacy for the vaccine (90%, 50-99%). Follow-up of study children until November 1, 1993, has shown only 1 vaccine failure in an infant, and no invasive infections in those older than 1 year (average age 22 months). PRP-T vaccine had high protective efficacy with an accelerated immunisation schedule. Furthermore, the vaccine appears to remain protective through the second year of life without a booster dose. These findings provide encouragement for use of PRP-T in the Expanded Programme of Immunisation.

Evaluation of a district growth screening programme: the Oxford Growth Study.

The Oxford district growth screening programme was established in 1988 as a community based survey of the heights of children at 3 and 4.5 years of age in a district of 550,000 people. The current birthrate is 7500 births/year and over the first three years of the study 20,338 children were screened in the community; the ascertainment ranged from 61-73.9% of the total expected. Mean height SD scores were significantly greater than the British standards; mean SD scores for boys and girls were 0.33 and 0.35 respectively at age 3, and 0.20 and 0.26 at 4.5 years. Altogether 260 (1.3%) of the total cohort were found to have heights < or = -2SD scores. The mean growth velocity of 2742 children measured at 3 and 4.5 years of age was similar to that of the national standards, 7.14 cm/year in boys and 7.21 cm/year in girls. Follow up data was available from 149 children whose heights were confirmed to be < or = -2SD scores. Of these 69 were already under the care of paediatricians. Thus far diagnoses in the 149 have included growth hormone deficiency (n = 2), Turner's syndrome (n = 2), Noonan's syndrome (n = 4), and emotional deprivation (n = 1). Ways in which ascertainment and detection of treatable causes of short stature could be improved are discussed and it is concluded that community growth screening is a useful part of the child health surveillance programme.

A comparison of height, weight and head circumference of primary school children living in deprived and non-deprived circumstances.

Heights, weights and head circumferences were obtained from two groups of primary school children: 1016 children from throughout Oxfordshire, a rural county with few areas of deprivation, and 219 children from an economically deprived part of the city of Newcastle on Tyne. Compared to Tanner and Whitehouse standards, Oxfordshire children were significantly taller, but not heavier, while the Newcastle children were significantly shorter and markedly lighter. Mean head circumference values were lower in the Newcastle than the Oxfordshire children. Existing national growth standards are outdated when applied to children in acceptably advantaged circumstances while impoverished children still fall below these standard in a pattern suggestive of under nutrition.

Immunogenicity and safety of PRP-T conjugate vaccine given according to the British accelerated immunisation schedule.

The immunogenicity and safety of a new Haemophilus influenzae type b conjugate vaccine, PRP-T, was studied in 107 infants from the Oxford district. The vaccine was given concurrently with diphtheria, pertussis, tetanus, and polio vaccines at 2, 3, and 4 months of age. Symptoms after immunisation were recorded by a parent. Sera were obtained before the first immunisation and at 5 months of age and the antibodies were measured by both radioimmunoassay and enzyme linked immunosorbent assay (ELISA). No serious adverse reactions were observed and there was no increase in the incidence of expected minor side effects. By radioimmunoassay, the geometric mean titre of serum anticapsular antibody increased from 0.09 micrograms/ml before immunisation to 5.01 micrograms/ml after three immunisations. Ninety eight per cent of children had antibody concentrations consistent with protection (greater than or equal to 0.15 micrograms/ml). IgG antibody concentrations measured by ELISA correlated well with total antibody concentrations measured by radioimmunoassay (r = 0.864). These results provide encouragement that routine immunisation against H influenzae type b at 2, 3, and 4 months of age, could prevent most cases of disease in children in the UK.

Immunogenicity of combined diphtheria, tetanus, and pertussis vaccine given at 2, 3, and 4 months versus 3, 5, and 9 months of age.

In the UK an accelerated schedule for immunisation against diphtheria, tetanus, and pertussis (injections at 2, 3, and 4 months of age) was introduced in 1990 to replace the more widely spaced schedule of 3, 5, and 9 months. There is concern, however, that the new schedule may be less immunogenic and therefore less protective than the old schedule. We have measured serum concentrations of antibodies against diphtheria, pertussis, and tetanus in infants immunised according to the two regimens. Both schedules resulted in protective concentrations of antibody against tetanus and diphtheria and in satisfactory antibody responses to three pertussis antigens (filamentous haemagglutinin, pertussis toxin, fimbriae). However, immunisation by the old schedule led to significantly higher antibody concentrations against both diphtheria and tetanus than did immunisation by the new schedule (p less than 0.01). In infants immunised with the new schedule, postimmunisation antibody concentrations against tetanus toxoid and against two pertussis antigens (pertussis toxin and fimbriae) were significantly lower in infants in whom preimmunisation (maternally derived) antibody concentrations were high (p less than 0.02). The findings suggest that with an accelerated immunisation schedule maternal antibodies can have an inhibitory effect on the responses to immunisation against tetanus and pertussis.

Are measurements of height made by health visitors sufficiently accurate for routine screening of growth?

To find out whether measurements of height made by health visitors are sufficiently accurate for use in routine screening of children we carried out an interobserver and intraobserver reliability study. Height measurements were made on a group of 10 children aged 3 years old and 10 aged 4.5 years old by two sets of four health visitors. They used a Microtoise or wall chart and the measurements were compared with those made by a trained auxologist with a Harpenden stadiometer. For a single assessment of height both pieces of equipment gave reasonably accurate results. In a child aged 3 years, with height measured on the Microtoise as 100 cm, the true height could be expected--with 95% probability--to lie between 99.2 cm-101.8 cm. At the age of 4.5 years, if the measurement was 110 cm, the child's true height could be expected to lie between 108.9 cm and 111.9 cm. The narrowest confidence interval for the growth rate from 3 to 4.5 years was achieved with the Microtoise, taking the mean of three measurements. We conclude that measurements made by health visitors are sufficiently accurate for routine screening of height, and the use of such measurements for the calculation of height velocity could be improved by more structured training.

Haemophilus influenzae type b conjugate vaccine trial in Oxford: implications for the United Kingdom.

The safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine was investigated in 103 infants immunised at 3, 5, and 9 months of age; the infants also received diphtheria, pertussis, and tetanus and polio vaccines. Side effects were compared with 99 matched infants receiving diphtheria, pertussis, and tetanus and polio vaccines only. No serious side effects were observed and the incidence of minor side effects was no greater in the recipients of H influenzae type b conjugate vaccine. Two doses of the vaccine (standard and low) were compared: geometric mean titres of serum anticapsular antibody rose from 0.11 microgram/ml before immunisation to 26.4 micrograms/ml after three immunisations with the standard dose and 14.6 micrograms/ml with the low dose. The geometric mean titre among 21 unimmunized infants at this age was 0.06 micrograms/ml. Both doses therefore generated antibody concentrations likely to be protective after three immunisations. There were no non-responders. Incorporation of an H influenzae type b conjugate vaccine into the primary immunisation schedule has the potential for preventing over 1000 cases of systemic H influenzae type b disease and 50 deaths each year in the United Kingdom.

Haemophilus influenzae type b disease in the Oxford region.

A prospective survey of children in the Oxford region identified 200 cases of systemic Haemophilus influenzae type b disease in the first three and a half years of the study. The annual incidence in children less than 5 years of age was 33.4/100,000. This represents a cumulative incidence of one systemic infection in 600 children before their 5th birthday. The mortality was 5.0%. The risk of H influenzae type b meningitis was one in 850 with a mortality of 5.6%, and substantial morbidity among survivors. From the total live birth rate, about 1300 cases of systemic H influenzae type b disease, over 900 cases of H influenzae type b meningitis, and 65 deaths would be predicted annually in children in the United Kingdom.