Biogeography of Southern Ocean prokaryotes: a comparison of the Indian and Pacific sectors.

We investigated the Southern Ocean (SO) prokaryote community structure via zero-radius operational taxonomic unit (zOTU) libraries generated from 16S rRNA gene sequencing of 223 full water column profiles. Samples reveal the prokaryote diversity trend between discrete water masses across multiple depths and latitudes in Indian (71-99°E, summer) and Pacific (170-174°W, autumn-winter) sectors of the SO. At higher taxonomic levels (phylum-family) we observed water masses to harbour distinct communities across both sectors, but observed sectorial variations at lower taxonomic levels (genus-zOTU) and relative abundance shifts for key taxa such as Flavobacteria, SAR324/Marinimicrobia, Nitrosopumilus and Nitrosopelagicus at both epi- and bathy-abyssopelagic water masses. Common surface bacteria were abundant in several deep-water masses and vice-versa suggesting connectivity between surface and deep-water microbial assemblages. Bacteria from same-sector Antarctic Bottom Water samples showed patchy, high beta-diversity which did not correlate well with measured environmental parameters or geographical distance. Unconventional depth distribution patterns were observed for key archaeal groups: Crenarchaeota was found across all depths in the water column and persistent high relative abundances of common epipelagic archaeon Nitrosopelagicus was observed in deep-water masses. Our findings reveal substantial regional variability of SO prokaryote assemblages that we argue should be considered in wide-scale SO ecosystem microbial modelling.

Oceanographic boundaries constrain microbial diversity gradients in the South Pacific Ocean.

Marine microbes along with microeukaryotes are key regulators of oceanic biogeochemical pathways. Here we present a high-resolution (every 0.5° of latitude) dataset describing microbial pro- and eukaryotic richness in the surface and just below the thermocline along a 7,000-km transect from 66°S at the Antarctic ice edge to the equator in the South Pacific Ocean. The transect, conducted in austral winter, covered key oceanographic features including crossing of the polar front (PF), the subtropical front (STF), and the equatorial upwelling region. Our data indicate that temperature does not determine patterns of marine microbial richness, complementing the global model data from Ladau et al. [Ladau J, et al. (2013) ISME J 7:1669-1677]. Rather, NH4+, nanophytoplankton, and primary productivity were the main drivers for archaeal and bacterial richness. Eukaryote richness was highest in the least-productive ocean region, the tropical oligotrophic province. We also observed a unique diversity pattern in the South Pacific Ocean: a regional increase in archaeal and bacterial diversity between 10°S and the equator. Rapoport's rule describes the tendency for the latitudinal ranges of species to increase with latitude. Our data showed that the mean latitudinal ranges of archaea and bacteria decreased with latitude. We show that permanent oceanographic features, such as the STF and the equatorial upwelling, can have a significant influence on both alpha-diversity and beta-diversity of pro- and eukaryotes.

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.

Marfan syndrome and pregnancy: maternal and neonatal outcomes.

OBJECTIVE: To report outcomes in a recent series of pregnancies in women with Marfan syndrome (MFS). DESIGN: Retrospective case note review. SETTING: Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals). SAMPLE: Twenty-nine pregnancies in 21 women with MFS between 1995 and 2010. METHODS: Multidisciplinary review of case records. MAIN OUTCOME MEASURES: Maternal and neonatal mortality and morbidity of patients with MFS and healthy controls. RESULTS: There were no maternal deaths. Significant cardiac complications occurred in five pregnancies (17%): one woman experienced a type-A aortic dissection; two women required cardiac surgery within 6 months of delivery; and a further two women developed impaired left ventricular function during the pregnancy. Women with MFS were also more likely to have obstetric complications (OR 3.29, 95% CI 1.30-8.34), the most frequent of which was postpartum haemorrhage (OR 8.46, 95% CI 2.52-28.38). There were no perinatal deaths, although babies born to mothers with MFS were delivered significantly earlier than those born to the control group (median 39 versus 40 weeks of gestation, Mann-Whitney U-test, P = 0.04). These babies were also significantly more likely to be small for gestational age (24% in the MFS group versus 6% in the controls; OR 4.95, 95% CI 1.58-15.55). CONCLUSIONS: Pregnancy in women with MFS continues to be associated with significant rates of maternal, fetal, and neonatal complications. Effective pre-pregnancy counselling and meticulous surveillance during pregnancy, delivery, and the puerperium by an experienced multidisciplinary team are warranted for women with MFS.

Pulmonary hypertension and pregnancy--a review of 12 pregnancies in nine women.

OBJECTIVE: To report outcomes in a recent series of pregnancies in women with pulmonary hypertension (PH). DESIGN: Retrospective case note review. SETTING: Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals). SAMPLE: Twelve pregnancies in nine women with PH between 1995 and 2010. METHODS: Multidisciplinary review of case records. MAIN OUTCOME MEASURES: Maternal and neonatal mortality and morbidity. RESULTS: There were two maternal deaths (1995 and 1998), one related to pre-eclampsia and one to arrhythmia. Maternal morbidity included postpartum haemorrhage (five cases), and one post-caesarean evacuation of a wound haematoma. There were no perinatal deaths, nine live births and three first-trimester miscarriages. Mean birthweight was 2197 g, mean gestational age was 34 weeks (range 26-39), and mean birthweight centile was 36 (range 5-60). Five babies required admission to the neonatal intensive care unit, but were all eventually discharged home. All women were delivered by caesarean section (seven elective and two emergency deliveries), under general anaesthetic except for one emergency and one elective caesarean performed under regional block. CONCLUSIONS: Maternal and fetal outcomes for women with PH may be improving. However, the risk of maternal mortality remains significant, so that early and effective counselling about contraceptive options and pregnancy risks should continue to play a major role in the management of such women when they reach reproductive maturity.

Socioeconomic Disadvantage is Associated with Probable Sarcopenia in Community-Dwelling Older Adults: Findings from the English Longitudinal Study of Ageing.

BACKGROUND: Sarcopenia is characterized by the accelerated loss of muscle strength, mass, and function in aging. The disease is a major public health issue with emerging evidence of a disproportionate burden in areas of socioeconomic disadvantage. OBJECTIVES: To estimate the prevalence of probable sarcopenia overall, and according to Socioeconomic Position (SEP). To explore the association between markers of SEP and probable sarcopenia. DESIGN: Cross-sectional analysis of the English Longitudinal Study of Ageing data. SETTING: England, United Kingdom (UK). PARTICIPANTS: This study comprised 6,052 older adult participants from Wave 6 of the English Longitudinal Study of Ageing (ELSA) aged 60 years and older. MEASUREMENTS: Probable sarcopenia was identified by the EWGSOP2 guidelines as low hand grip strength (females <16kg and males <27kg) or poor chair rise test performance (completion of 5 chair rises >15 seconds). Socioeconomic position was defined by educational attainment and subjective social status (SSS). Weighted multivariable regression analysis was employed to identify determinants of probable sarcopenia. RESULTS: Over one-third of older adults met the criteria for probable sarcopenia (33.7%; weighted, 36.1%) in the study population of mean age 70.7 (SD 7.7) years. When examined by SEP, the prevalence of probable sarcopenia was over 2-fold higher in adults in the most vs the least disadvantaged SEP groups (47.0% vs 20.6%, respectively, p<0.001). Multivariable regression analysis identified disadvantaged SEP, as measured by educational attainment and SSS, as independent predictors of probable sarcopenia, along with older age, physical inactivity, underweight BMI, chronic conditions, osteoarthritis, and minority group ethnicity. CONCLUSIONS: Disadvantaged SEP was associated with an increased likelihood of probable sarcopenia when controlled for other known risk factors. The findings suggest a need and opportunity for sarcopenia prevention and treatment strategies to address socioeconomic disadvantage in policies and practice.

Metabolic pathways inferred from a bacterial marker gene illuminate ecological changes across South Pacific frontal boundaries.

Global oceanographic monitoring initiatives originally measured abiotic essential ocean variables but are currently incorporating biological and metagenomic sampling programs. There is, however, a large knowledge gap on how to infer bacterial functions, the information sought by biogeochemists, ecologists, and modelers, from the bacterial taxonomic information (produced by bacterial marker gene surveys). Here, we provide a correlative understanding of how a bacterial marker gene (16S rRNA) can be used to infer latitudinal trends for metabolic pathways in global monitoring campaigns. From a transect spanning 7000 km in the South Pacific Ocean we infer ten metabolic pathways from 16S rRNA gene sequences and 11 corresponding metagenome samples, which relate to metabolic processes of primary productivity, temperature-regulated thermodynamic effects, coping strategies for nutrient limitation, energy metabolism, and organic matter degradation. This study demonstrates that low-cost, high-throughput bacterial marker gene data, can be used to infer shifts in the metabolic strategies at the community scale.

Oceanographic Fronts Shape Phaeocystis Assemblages: A High-Resolution 18S rRNA Gene Survey From the Ice-Edge to the Equator of the South Pacific.

The cosmopolitan haptophyte Phaeocystis is recognized as a key contributor to marine biogeochemical cycling and important primary producer within polar marine environments. Yet, little is known about its solitary, non-colonial cell stages or its distribution during the colder, low-productivity seasons. We examined the biogeography of Phaeocystis along a high-resolution (0.5-degree latitudinal interval) transect from the Antarctic ice-edge to the equator of the South Pacific, in the austral autumn-winter. Using high-throughput 18S rRNA gene sequences with single nucleotide variable (zero-radius) operational taxonomic units (zOTUs) allowed us to explore the possibility of strain-level variation. From water samples within the upper water column, we show the presence of an abundant Phaeocystis assemblage that persisted during the colder months, contributing up to 9% of the microbial eukaryote community at high latitudes. The biogeography of Phaeocystis was strongly shaped by oceanographic boundaries, most prominently the polar and subantarctic fronts. Marked changes in dominant Phaeocystis antarctica zOTUs between different frontal zones support the concept that ecotypes may exist within the Phaeocystis assemblage. Our findings also show that the Phaeocystis assemblage did not abide by the classical latitudinal diversity gradient of increasing richness from the poles to the tropics; richness peaked at 30°S and declined to a minimum at 5°S. Another surprise was that P. globosa and P. cordata, previously thought to be restricted to the northern hemisphere, were detected at moderate abundances within the Southern Ocean. Our results emphasize the importance of oceanographic processes in shaping the biogeography of Phaeocystis and highlights the importance of genomics-based exploration of Phaeocystis, which have found the assemblage to be more complex than previously understood. The high winter relative abundance of the Phaeocystis assemblage suggests it could be involved in more complex ecological interactions during the less productive seasons, which should be considered in future studies to better understand the ecological role and strategies of this keystone species.

Ocular Manifestations of a Novel Proximal 19p13.3 Microdeletion.

Microdeletions at 19p13.3 are rarely reported in the medical literature with significant phenotypic variability. Among the reported cases, common clinical manifestations have included developmental delay, facial dysmorphism, and hypotonia. Herein we described a child with a de novo 19p13.3 microdeletion, proximal to the reported cases of 19p13.3 microdeletion/duplication, with ocular manifestations of bilateral ocular colobomata complicated with microphthalmos and cataract, associated with short stature. This case highlights the phenotypic heterogeneity of deletions in the 19p13.3 region.

Congenital Glaucoma: a Novel Ocular Manifestation of Hajdu-Cheney Syndrome.

Hajdu-Cheney Syndrome (HSC) is a rare multisystem disease in which the phenotype involves acro-osteolysis, severe osteoporosis, short stature, wormian bones, facial dysmorphism, central neurological abnormalities, cardiovascular defects, and polycystic kidneys. We describe an infant with severe manifestations of HCS in whom congenital glaucoma was a significant early feature, which has not been reported to date. HCS cases reported to date have involved truncating mutations in exon 34 of NOTCH2 upstream the PEST domain that lead to the development of a truncated and stable NOTCH2 protein which upregluates notch signaling. We describe a hitherto undescribed missense mutation that is predicted to be pathogenic, with functional characterization remaining to be performed. Serpentine fibula-polycystic kidney syndrome (SFPKS) is allelic to HCS and commonly associated with missense NOTCH2 mutations. Our patient provides new ophthalmological manifestations of HCS and provides insight into the potential role of notch signaling in the anterior chamber development.

Pre-pregnancy counseling for women with heart disease: A prospective study.

BACKGROUND: Women with cardiac disease and their infants are at a greater risk of mortality and morbidity during pregnancy. Expert groups recommend preconception counseling (PCC) for all women with cardiac disease so they are made aware of these risks. We have run a specialist maternal cardiac clinic since 1996. The aim of this study was to evaluate the experience of women who have received PCC within an established multidisciplinary tertiary clinic and to establish their views regarding the counseling they received. METHODS: Single centre prospective study using a patient questionnaire was given to women attending a specialist cardiac preconception counseling clinic from November 2015 to August 2016, with analysis of descriptive data and free text comments from the questionnaire responders. RESULTS: 40/65 returned patient questionnaires. Prior to the consultation fewer than half felt well informed regarding how their heart disease could impact upon pregnancy but a similar proportion felt nonetheless that they would be able to have a healthy pregnancy. Women reported two main areas of concerns, their own health (whether they would survive a pregnancy) and the health of their child. 15% of women reported that these concerns had prevented them from pursuing a pregnancy. Women reported high satisfaction rates with the clinic. CONCLUSIONS: There is an increasing demand for PCC services for women with cardiac disease; our study is the first attempt to determine both the acceptability and the impact of PCC from the patient perspective. Patients reported a high level of satisfaction with the service provided.

Transcatheter device closure of atrial septal defects in the elderly: technical considerations and short-term outcomes.

BACKGROUND: Device closure of an atrial septal defect (ASD) results in symptom-reduction, right heart remodelling and lower pulmonary artery pressures. However it is unclear if there is a chronological limit to these benefits and whether device closure is safe in elderly subjects. The aim of this study was, therefore, to assess the safety and efficacy of device closure in patients >60 years. METHODS: Retrospective study of Amplatzer Septal Occluder device closures from a single institution (May 1999-August 2002). RESULTS: Fifty subjects aged >60 years (range 60-85 years) had ASD device closure (27% of the total cohort). Defect size and shunt size were similar for both younger and older groups (2.2:1 in both groups, p=0.9) as were procedural duration, fluoroscopy time and device size deployed. Baseline right ventricular (RV) systolic pressure ((younger vs. older) 39 vs. 49 mmHg, p<0.001) and right ventricular size (45 vs. 51 mm, p<0.001) were greater in the older group. Following closure RV systolic pressure (49 vs. 45 mmHg, p<0.01) and RV size (51 vs. 44 mm, p=0.01) decreased in the older group. CONCLUSION: Device closure of an ASD can be performed safely in older patients. The right heart shows signs of remodelling even in elderly subjects.

Common long-term complications of adult congenital heart disease: avoid falling in a H.E.A.P.

Advances in cardiology and cardiac surgery have transformed the outlook for patients with congenital heart disease (CHD) so that currently 85% of neonates with CHD survive into adult life. Although early surgery has transformed the outcome of these patients, it has not been curative. Heart failure, endocarditis, arrhythmias and pulmonary hypertension are the most common long term complications of adults with CHD. Adults with CHD benefit from tertiary expert care and early recognition of long-term complications and timely management are essential. However, it is as important that primary care physicians and general adult cardiologists are able to recognise the signs and symptoms of such complications, raise the alarm, referring patients early to specialist adult congenital heart disease (ACHD) care, and provide initial care. In this paper, we provide an overview of the most commonly encountered long-term complications in ACHD and describe current state of the art management as provided in tertiary specialist centres.

Effects of sex steroid hormones on arginine vasopressin in intact and castrated male and female rats.

In the present study we have examined the effects of androgens and estrogens on circulating arginine vasopressin (AVP). Adult male Wistar rats had serum AVP levels of 0.4 microU/ml. Two weeks after bilateral castration, AVP rose to 2.6 microU/ml, but daily testosterone administration (100 microgram/100 g BW) to the castrate males prevented the AVP increase (0.8 microU/ml). During a normal estrous cycle, adult female Wistar rats had AVP values of 0.6 microU/ml during diestrus, 4.6 microU/ml on the morning of proestrus, 1.3 microU/ml on the afternoon or proestrus, and 1.5 microU/ml on the day of estrus. These changes in AVP paralleled the presumed changes in serum estradiol. Two weeks after bilateral ovariectomy of the adult female rats, AVP was 1.4 microU/ml but daily estradiol injections (100 microgram/100 g BW) to the castrate females produced a rise of serum AVP to 5.0 microU/ml. The results suggest an androgen inhibition and an estrogen stimulation of serum AVP levels.

Familial pattern of corticosteroids and their metabolism in adult human subjects--the Scottish Adult Twin Study.

Corticosteroids are important in the regulation of normal physiology and are key factors in regulating cardiovascular physiology and disease, the development of which is known to have a genetic component. However, there is little information on the extent to which plasma and urine steroid levels are determined by familial and genetic factors. We have examined basal and ACTH-stimulated plasma steroid levels and 24-h corticosteroid metabolite excretion rates in 146 pairs of adult twins [75 monozygotic (MZ); 71 dizygotic (DZ)]. Intraclass correlation coefficients were measured for all variables; several plasma steroid measurements were strongly related in both (MZ) and (DZ) twins, consistent with a familial pattern. These included basal levels of 11-deoxycortisol and aldosterone. ACTH-stimulated plasma aldosterone levels were also significantly correlated, to a significant degree, in both MZ and DZ twins. The index of 11beta-hydroxysteroid dehydrogenase activity (tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone) and of the more specific index of activity of the type 2 isoform of this enzyme (urine free cortisol/cortisone) also correlated, to a similar degree, in DZ and MZ twins. In contrast, for the basal and ACTH-stimulated plasma concentrations and 24-h urine excretion rates of several corticosteroids, there was evidence of significant heritability (H2), in that correlation in MZ twins was greater than in DZ. For example, basal plasma corticosterone concentrations (B) (H2 = 0.44), basal and stimulated 11-deoxycorticosterone concentrations (DOC) (H2 = 0.44 and 0.41, respectively), stimulated 11-deoxycortisol concentrations (H2 = 0.53), and the index of 11beta-hydroxylase activity DOC/B (H2 = 0.49) were all significantly heritable. For the urinary variables, 24-h tetrahydrodeoxycortisol (H2 = 0.59) and free aldosterone (H2 = 0.56) were significantly heritable. Our data provide the first evidence that plasma and urine levels of important glucocorticoids and mineralocorticoids show a strong familial pattern, and in some instances, there is evidence of a genetic component to this. This suggests that corticosteroids have a plausible role in essential hypertension that has a similar heritable component.

Hemodynamic and coronary effects of intravenous eletriptan, a 5HT1B/1D-receptor agonist.

OBJECTIVE: To investigate the systemic, pulmonary, and coronary artery effects of eletriptan, a new 5HT1B/1D-agonist in patients undergoing cardiac catheterization. METHODS: Ten patients (two men and eight women) without significant obstructive coronary artery disease were administered 3.33 microg/kg/min intravenous eletriptan after they were given a placebo infusion of 0.9% saline solution. Serial measurements of right heart and systemic pressures were taken at 5-minute intervals during placebo infusion, eletriptan infusion, and a 30-minute postinfusion period. Cardiac output by the thermodilution technique and coronary angiography were performed every 15 minutes. Quantitative coronary angiography was carried out to measure coronary artery dimensions. RESULTS: A small but statistically significant increase in occluded wedge pressure (7.4 versus 8.8 mm Hg; 95% confidence interval [CI], 0.74, 2.51; P < .01), right atrial pressure (5.3 versus 6.1 mm Hg; 95% CI, 0.0, 1.4; P < .05), and mean pulmonary artery pressure (13.2 versus 14.6 mm Hg; 95% CI, 0.0, 2.7; P = .05) was observed during the eletriptan infusion compared with placebo. A statistically significant increase in systemic vascular resistance (1256 versus 1519 dyne/sec/cm(-5); 95% CI, 126, 398; P < .01) and pulmonary vascular resistance (76.4 versus 100.8 dyne/sec/cm(-5); 95% CI, 1.9, 46.9; P < .05) was observed in the period after drug infusion. No overall effect was observed on the coronary arteries, although a segmental right coronary artery constriction developed in one patient, possibly as a result of catheter-induced spasm. CONCLUSIONS: Eletriptan, a 5HT1B/1D-agonist effective in migraine, causes no significant coronary artery constriction in patients without significant obstructive coronary artery disease. This finding may reflect a relative selectivity for the 5HT1D-receptor subtype.

Neuroanatomical substrates of late-life minor depression. A quantitative magnetic resonance imaging study.

OBJECTIVE: To examine the neuroanatomical correlates of late-life minor depression using magnetic resonance imaging. DESIGN: Cross-sectional quantitative magnetic resonance imaging study of elderly patients with minor depression and age-matched controls. SETTING: Patients and controls were recruited from the community through advertisements to the Section of Geriatric Psychiatry, University of Pennsylvania, Philadelphia. PARTICIPANTS: Our sample included 18 subjects diagnosed as having minor depression using the modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, research criteria and 31 controls without depression. Patients were free of other central nervous system disease and both groups had comparable degrees of medical comorbidity. MAIN OUTCOME MEASURES: All images were acquired on a 1.5-T scanner and absolute and normalized quantitative measures of global and focal brain and cerebrospinal fluid volumes were compared between groups. RESULTS: Prefrontal lobe volume was significantly smaller in the group with minor depression (P = .002) compared with controls after controlling for age, sex, and age by sex interactions. More global measures of brain and cerebrospinal fluid volumes were comparable in both groups. CONCLUSIONS: These data suggest that focal prefrontal atrophy may provide an important neuroanatomical substrate in late-life minor depression.

The determination of carotid intima medial thickness in adults--a population-based twin study.

INTRODUCTION: Although cardiovascular events are known to cluster in families it is unclear the extent to which atherosclerosis per se is genetically determined. The aim of this study was to assess the heritability of carotid intima media thickness (IMT) measurements, a surrogate marker of early atherosclerosis, using a population-based twin study methodology. METHODS: B-mode carotid artery ultrasound images were acquired on 264 twin subjects (142 monozygotic (MZ); mean age 54.3 years and 122 dizygotic (DZ); mean age 51.7 years). An estimate of genetic determination, heritability, was calculated for the IMT parameters before and after correction for confounding variables. RESULTS: An increased carotid IMT was associated with known cardiovascular risk factors (total cholesterol r=0.24, P<0.001 and systolic blood pressure r=0.42, P<0.001) and with a history of coronary events (0.79+/-0.12 vs. 0.72+/-0.14, P=0.01). Carotid IMT measurements demonstrated a familial influence (intra-class correlation of 0.54 for MZ vs. 0.39 for DZ) but no specific genetic determination (heritability estimate 0.31, P=0.15). CONCLUSION: Within a normal population carotid IMT is under a familial, but not genetic influence. The mechanism of genetic control over cardiovascular events may not be mediated through atherosclerotic load as measured by IMT.

Outcomes of transposition of the great arteries in the ear of atrial inflow correction.

OBJECTIVE: To examine long term morbidity and mortality following atrial inflow corrective procedures for transposition of the great arteries (TGA) and to investigate factors that influence morbidity and mortality. DESIGN: Retrospective cohort study from a single centre. SETTING: Cardiology and cardiothoracic surgical unit in a large tertiary referral centre. PATIENTS: All 130 patients who had TGA diagnosed between August 1972 and May 1988 and were considered suitable for atrial inflow correction; 109 of these underwent surgery (operative cohort: 84 Mustard operations and 25 Senning operations); 95 survived to hospital discharge (hospital surviving cohort). MAIN OUTCOME MEASURES: Death and cardiac events. RESULTS: There were relatively good long term results from atrial inflow correction for TGA with 5, 10, and 15 year survivals of 77.3%, 75.9%, and 71.3%. However, there was an appreciable incidence of late cardiac death and events, with 5, 10, and 15 year cardiac event-free survivals of 74.5%, 67.1%, and 39.6%. Supraventricular tachycardia was the only significant risk factor for late cardiac death (relative risk 8.72, 95% confidence interval, 2.86 to 26.64). Senning patients had better event-free survival (p = 0.04). CONCLUSIONS: Atrial inflow correction for TGA has a reasonably good 15 year survival (71.3%), but there is an appreciable incidence of late cardiac deaths and events (15 year event-free survival 39.6%). The Senning procedure is preferable to the Mustard procedure for cases unsuitable for arterial switching.