An assessment of the acute dietary exposure to glyphosate using deterministic and probabilistic methods.

Use of glyphosate in crop production can lead to residues of the active substance and related metabolites in food. Glyphosate has never been considered acutely toxic; however, in 2015 the European Food Safety Authority (EFSA) proposed an acute reference dose (ARfD). This differs from the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) who in 2016, in line with their existing position, concluded that an ARfD was not necessary for glyphosate. This paper makes a comprehensive assessment of short-term dietary exposure to glyphosate from potentially treated crops grown in the EU and imported third-country food sources. European Union and global deterministic models were used to make estimates of short-term dietary exposure (generally defined as up to 24 h). Estimates were refined using food-processing information, residues monitoring data, national dietary exposure models, and basic probabilistic approaches to estimating dietary exposure. Calculated exposures levels were compared to the ARfD, considered to be the amount of a substance that can be consumed in a single meal, or 24-h period, without appreciable health risk. Acute dietary intakes were <100% of the ARfD for all foodstuffs, except wild fungi, when calculated using the EFSA model. The model assumptions differ from those of the source model (German national model), resulting in the use of a higher variability factor. Intakes estimated with the German model represented only 18% of the ARfD. The impact of differing assumptions regarding variability and other input parameters is discussed. Probabilistic exposure estimates showed that the acute intake on no person-days exceeded 10% of the ARfD, even for the pessimistic scenario.

Topological properties of a self-assembled electrical network via ab initio calculation.

Interacting electrical conductors self-assemble to form tree like networks in the presence of applied voltages or currents. Experiments have shown that the degree distribution of the steady state networks are identical over a wide range of network sizes. In this work we develop a new model of the self-assembly process starting from the underlying physical interaction between conductors. In agreement with experimental results we find that for steady state networks, our model predicts that the fraction of endpoints is a constant of 0.252, and the fraction of branch points is 0.237. We find that our model predicts that these scaling properties also hold for the network during the approach to the steady state as well. In addition, we also reproduce the experimental distribution of nodes with a given Strahler number for all steady state networks studied.

An assessment of dietary exposure to glyphosate using refined deterministic and probabilistic methods.

Glyphosate is a herbicide used to control broad-leaved weeds. Some uses of glyphosate in crop production can lead to residues of the active substance and related metabolites in food. This paper uses data on residue levels, processing information and consumption patterns, to assess theoretical lifetime dietary exposure to glyphosate. Initial estimates were made assuming exposure to the highest permitted residue levels in foods. These intakes were then refined using median residue levels from trials, processing information, and monitoring data to achieve a more realistic estimate of exposure. Estimates were made using deterministic and probabilistic methods. Exposures were compared to the acceptable daily intake (ADI)-the amount of a substance that can be consumed daily without an appreciable health risk. Refined deterministic intakes for all consumers were at or below 2.1% of the ADI. Variations were due to cultural differences in consumption patterns and the level of aggregation of the dietary information in calculation models, which allows refinements for processing. Probabilistic exposure estimates ranged from 0.03% to 0.90% of the ADI, depending on whether optimistic or pessimistic assumptions were made in the calculations. Additional refinements would be possible if further data on processing and from residues monitoring programmes were available.

Stability and conductivity of self assembled wires in a transverse electric field.

Self assembling wire networks typically evolve to minimize the resistance across electrical contacts which are frequently used in a manner comparable to Hebbian learning. In this work, we demonstrate that electrical fields can also be used to cause an increase in the resistance of the wire network. We show that if such a wire is exposed to a transverse electric field, the wire is deformed in a way that depends on it's tensile strength. We measure the wire resistance as a function of transverse field for several field strengths and show that by deforming the wire, the amplitude of the resulting shape can be modified in a controllable fashion. At a critical value of the transverse field, we show that the wire loses stability. At this point we observe thresholding behavior in that the resistance increases abruptly to a maximum value and the wire is destroyed. This thresholding behavior suggests that self assembled wires may be manipulated via an transverse electric field and demonstrates that a mechanism exists for the destruction of undesirable connections.

The expression of ß3-adrenoceptor and muscarinic type 3 receptor immuno-reactivity in the major pelvic ganglion of the rat.

Bladder afferent outflow, linked to sensation, plays a critical role in bladder pathology: abnormal outflow results in altered sensation, leading to increased voiding frequency, urge and often incontinence. ß3-adrenoceptor agonists have been suggested to be beneficial in treating these symptoms. However, the absence of a significant sympathetic innervation of the detrusor and only a modest relaxation of bladder muscle by ß3 agonists has questioned the therapeutic site of action of ß3 agonists in the bladder. The present study was done to explore the possibility that ß3-adrenoceptors might be located in the pelvic plexus. Using the rat, where the pelvic plexus is located primarily within a single ganglion, the major pelvic ganglion (MPG), immuno-histochemical approaches were used to identify structures expressing ß3-adrenoceptor immuno-reactivity (ß3AR-IR). The only structures found to express ß3AR-IR were small-diameter tyrosine hydroxylase and vesicular mono-amine transporter immuno-reactive (TH-IR and vmat-IR) neurones. These neurones, found in clusters or singly on the periphery of the ganglion, or dispersed in smaller clumps throughout the MPG, are similar to the small intensely fluorescent (SIF) cells described previously. Not all small cells expressed ß3AR-IR. A population of the small cells were also immuno-reactive to the type 3 muscarinic receptor (M3R-IR) and the P2X3 purinergic receptor (P2X3-IR). Clumps of small cells were associated with calcitonin gene-related peptide immuno-reactive (CGRP-IR) nerve fibres (putative sensory fibres) and a small number were contacted by putative cholinergic nerves expressing immuno-reactivity to vesicular acetylcholine transporter (vacht-IR). These observations are consistent with the idea that small cells are interneurons and one of the components making up complex neural circuits within the MPG. The precise physiological role of these neural elements in the MPG is unknown. However, as one therapeutic action of ß3-adrenoceptor agonists is to modulate sensation, it is possible that these neural circuits may be involved in the regulation of afferent outflow and sensation.

Autoantibodies and associated T-cell responses to determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes.

B-cells influence T-cell reactivity by facilitating antigen presentation, but the role of autoantibody-secreting B-cells in regulating T-cell responses in Type 1 diabetes is poorly defined. The aims of this study were to characterise epitopes on the IA-2 autoantigen for three monoclonal antibodies from diabetic patients by amino acid substitutions of selected residues of IA-2, establish contributions of these epitopes to binding of serum antibodies in Type 1 diabetes and relate B- and T-cell responses to overlapping determinants on IA-2. The monoclonal antibodies recognised overlapping epitopes, with residues within the 831-860 region of IA-2 contributing to binding; substitution of Glu836 inhibited binding of all three antibodies. Monoclonal antibody Fab fragments and substitution of residues within the 831-836 region blocked serum antibody binding to an IA-2 643-937 construct. IL-10-secreting T-cells responding to peptides within the 831-860 region were detected by cytokine-specific ELISPOT in diabetic patients and responses to 841-860 peptide were associated with antibodies to the region of IA-2 recognised by the monoclonal antibodies. The study identifies a region of IA-2 frequently recognised by antibodies in Type 1 diabetes and demonstrates that these responses are associated with T-cells secreting IL-10 in response to a neighbouring determinant.

Children and young people with diabetes in Yorkshire: a population-based clinical audit of patient data 2005/2006.

AIMS: To provide a population-based clinical audit of children and young people with diabetes, reporting outcomes, including glycaemic control, for named individual units. METHODS: Clinical audit data on care processes and glycated haemoglobin (HbA(1c)) were collected for 1742 children and young people treated in 16 paediatric units in Yorkshire, from January 2005 to March 2006. The Yorkshire Register of Diabetes in Children and Young People provided information technology support and validation that enhanced data quality. Multi-level linear regression modelling investigated factors affecting glycaemic control. RESULTS: An HbA(1c) measure was recorded for 91.6% of patients. The National Institute for Clinical Excellence-recommended target level for HbA(1c) of < 7.5% was achieved for 14.7% of patients. HbA(1c) was positively associated with duration of diabetes and later age at diagnosis. Patients living in deprived areas had significantly poorer control compared with those from affluent areas. Significant between-unit variation in HbA(1c) was not reflected by any association with unit size. CONCLUSIONS: Our population-based clinical audit of children with diabetes is the product of an effective collaboration between those who deliver care and health services researchers. High levels of recording the key care process measuring diabetes control, compared with national figures, suggests collaboration has translated into improved services. The interesting association between poor diabetes control and higher deprivation is noteworthy and requires further investigation. Future audits require recording of clinical management and clinic structures, in addition to resources to record, assemble and analyse data.

A survey of measures used for the prevention of postoperative endophthalmitis after cataract surgery in the United Kingdom.

PURPOSE: This study investigates the current practice of United Kingdom (UK) ophthalmologists in perioperative antibiotic and antiseptic use in cataract surgery. MATERIALS AND METHODS: A telephone interview survey was conducted with ophthalmic staff at all ophthalmic training units in the UK in October and November 2005. RESULTS: The practices of a total of 800 consultants were ascertained. Preoperatively, 795 (99.4%) surgeons used povidone-iodine to prepare the skin. In all, 558 (69.8%) instilled 5 or 10% povidone-iodine in the conjunctival sac; 47 (5.9%) gave preoperative antibiotic eyedrops. Intraoperatively, intracameral antibiotics were given either as a bolus [80 (10.0%) intracameral cefuroxime, 29 (3.6%) intracameral vancomycin] or in the irrigating fluid [33 (4.1%) vancomycin]. 48 (6.0%) gave subconjunctival gentamycin only routinely, 531 (66.4%) gave subconjunctival cefuroxime, and 39 (4.9%) gave other subconjunctival antibiotics. A single dose of topical antibiotics was given by 134 (16.8%) surgeons. Postoperatively, 515 (64.4%) used a combination steroid and neomycin eyedrop, and 213 (26.6%) gave a separate steroid and chloramphenicol eyedrop. CONCLUSIONS: This study reveals wide variations in the choice and duration of antibiotics used by UK ophthalmologists. The predominant methods of intraoperative prophylaxis are subconjunctival cefuroxime and intracameral cefuroxime. Most surgeons used a neomycin eyedrop for postoperative prophylaxis.

Neuroanatomical correlates of memory deficits in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a multisystem syndrome classically associated with the occurrence of focal brain dysplasias. We used structural magnetic resonance imaging to test for neuroradiological abnormalities in TSC (tubers, white matter lesions, and subependymal nodules) and to explore the relationships between these lesions and computational morphometric abnormalities of gray and white matter distribution. We tested memory function in TSC and investigated the relationship between memory function and both morphometric variation and lesion load. Patients demonstrated deficits bilaterally in volume of subcortical gray matter regions including thalamus, basal ganglia, insula, and cerebellum, as well as white matter deficits bilaterally in intrahemispheric tracts. Morphometric deficits could not be explained as local effects of lesions. Patients demonstrated deficits in executive working memory and recall memory, sparing recognition. Structure-function mapping showed long-term and working memory function was positively correlated with gray matter density (in thalamus, caudate nucleus, and frontal cortex) but not with lesion load. The neuroanatomical endophenotype of TSC is more extensive than previously recognized and comprises abnormalities in the distribution of gray and white matter in addition to classical lesions. Normal intelligence quotient patients with TSC show a profile of long-term and working memory impairment that is related to gray matter deficits in thalamus and basal ganglia components of fronto-striatal circuits.

Insulin pump therapy in childhood diabetes-cost implications for Primary Care Trusts.

AIMS: Primary Care Trusts (PCTs) are now responsible for the planning and delivery of health-care services throughout England and Wales. As the 25 PCTs throughout Yorkshire are representative of the national distribution in terms of population structure and socio-economic status, we aimed to address the paucity of information describing the burden of childhood diabetes in primary care and to evaluate the cost implications of insulin pump therapy on individual PCTs. METHODS: We extracted information from a population-based register in Yorkshire, including 1952 patients diagnosed under the age of 15 years from 1990 to 2003. Each patient's postcode was linked to an individual PCT. Incidence rates (per 100 000 patient years) were derived and assessed for evidence of heterogeneity across PCTs and within Strategic Health Authorities (SHAs). RESULTS: Incidence rates were lower in West Yorkshire (19.1, 95% CI 18.0-20.2) than North-east Yorkshire (20.3, 18.9-21.6), although this difference was not significant (P = 0.20). No significant evidence of heterogeneity in incidence rates was observed across PCTs (P = 0.46). Ninety per cent of all PCTs would expect four to seven newly diagnosed children per year, corresponding to a single general practitioner (GP) referring an individual for diagnosis once every 15 years on average. Assuming 1% of current patients under the age of 15 years with diabetes were to move onto insulin pump therapy, this would impose an additional cost of pound400-1300 per year for each PCT. The average cost was 15% lower for PCTs in West Yorkshire than North and East Yorkshire. CONCLUSIONS: The additional resources required to pay for insulin pump therapy for a small proportion of the diabetes population would be minimal given the potential benefits to these patients of improved control and anticipated reduction in long-term morbidity.

Non-surgical management of live ectopic pregnancy with ultrasound-guided local injection: a case series.

OBJECTIVES: To describe a series of consecutive cases of live ectopic pregnancies managed with ultrasound-guided local injection of methotrexate (MTX) or potassium chloride (KCl). METHODS: Eighteen consecutive women with live and unruptured, tubal, cornual or cervical ectopic pregnancies referred to our unit for evaluation and management underwent risk-benefit counseling. Under transvaginal ultrasound guidance, puncture and injection of the ectopic pregnancy was performed using an automated puncture device. Either MTX or KCl was injected, producing immediate cessation of fetal cardiac activity. RESULTS: Of the 18 ectopic pregnancies, 10 were cervical, four were tubal and four were cornual. The mean initial beta-hCG level was 33 412 IU and the mean gestational age was 6 + 6 weeks. Ten ectopic gestational sacs were injected with KCl and eight were injected with MTX. There was no difference in time to resolution of the ectopic pregnancies between those injected with KCl and those with MTX. CONCLUSIONS: Unruptured live ectopic pregnancies of many types can be successfully managed without surgical intervention through local injection of KCl or MTX.

Endoscopic closure of fetal membrane defects: comparing iatrogenic versus spontaneous rupture cases.

OBJECTIVE: Currently, physicians manage preterm premature rupture of membranes (PPROM) by expectant management or termination of the gestation. A therapy aimed at sealing membranes would be optimal to maintain the pregnancy and achieve a normal neonate. Our objective was to compare an endoscopic technique for intrauterine closure of fetal membrane defects after both iatrogenic and spontaneous rupture of membranes. METHODS: Our technique was performed on four patients experiencing PPROM spontaneously and four patients after genetic amniocentesis. Intrauterine endoscopy allowed direct visualization of membrane defects. Rapid sequential injections of platelets, fibrin glue and powdered collagen slurry were administered at the site of the defect and of trocar placement. Sonography for amniotic fluid index, nitrazine and fern testing and pad count were performed after each procedure at three intervals: immediately post-procedure, and after 24 and 48 h. RESULTS: Eight patients underwent endoscopic intrauterine sealing of ruptured membranes between 16 and 24 weeks of gestation: four were spontaneous ruptures and four were ruptures post-amniocentesis. In the post-amniocentesis group, three patients delivered viable infants at 26, 32 and 34 weeks. In one patient, the membranes ruptured again 12 h after the sealing procedure and she decided to undergo termination of pregnancy. Of the four spontaneous rupture patients, two experienced preterm labor and delivery within 2 days of the procedure. One patient was diagnosed with fetal demise 12 h post-procedure, and one patient delivered a neonate at 31 weeks of gestation with severe respiratory distress syndrome. CONCLUSIONS: This technique for sealing ruptured membranes is effective after amniocentesis, but may not be of benefit with spontaneous rupture.

Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies.

OBJECTIVE: Hypofrontality is not a well-replicated finding in schizophrenia either at rest or under conditions of task activation. METHOD: Studies comparing whole brain and frontal blood flow/metabolism in schizophrenic patients and normal controls were pooled. Voxel-based studies were also combined to examine the pattern of prefrontal activation in schizophrenia. RESULTS: Whole brain flow/metabolism was reduced in schizophrenia to only a small extent. Resting and activation frontal flow/metabolism were both reduced with a medium effect size. Duration of illness significantly moderated resting hypofrontality, but the moderating effects of neuroleptic treatment were consistent with an influence on global flow/metabolism only. Pooling of voxel-based studies did not suggest an abnormal pattern of activation in schizophrenia. CONCLUSION: Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture.

Pregnancy-related thrombosis in a woman with congenital afibrinogenemia: a report of two successful pregnancies.

We managed two pregnancies in a woman with congenital afibrinogenemia with increasing amounts of cryoprecipitate to achieve a pre-infusion fibrinogen level of 60 mg/dL. The first pregnancy resulted in placental abruption at 36 weeks, in spite of recent cryoprecipitate infusion. Both placentas showed infarction. Post-partum ovarian and renal vein thromboses complicated the second pregnancy. Mean FVIII (344%) and vWF Antigen (323%) were elevated prior to cryoprecipitate infusion, with mean post-infusion levels of 367% and 363%. The clearance of fibrinogen after cryoprecipitate infusion increased during the course of pregnancy. A paradoxical prothrombotic state with embolization may play a role in the observed complications of pregnancy.

Dopaminergic effects on electrophysiological and functional MRI measures of human cortical stimulus-response power laws.

Power laws have been widely used to formulate relationships between objective intensity of stimulation and subjective intensity of sensation. We investigated the effects of dopaminergic drug treatment (sulpiride) on the relationship between somatosensory stimulus intensity and cortical response measured electrophysiologically by somatosensory-evoked potentials (SEP) and functional magnetic resonance imaging (fMRI). The intensity of stimulation was related by a simple power law to both electrophysiological and fMRI measures of cortical response, with overlapping confidence intervals for both power law exponents. Sulpiride did not modulate the power law exponent, but significantly attenuated the "gain" of both stimulus-response functions. Using path analysis we decomposed dopaminergic effects on fMRI data into an indirect component (16%), predictable by drug effects on SEP, and a direct component (84%), not explained electrophysiologically. Results indicate that sulpiride has comparable effects on power law parameters estimated from SEP and fMRI, but fMRI has superior sensitivity to detect drug effects on somatosensory cortical recruitment by graded stimulation.

Information dissemination and use: critical components in occupational safety and health.

BACKGROUND: Information dissemination is a mandated, but understudied, requirement of occupational and environmental health laws and voluntary initiatives. Research is needed on the factors that enhance and limit the development, transfer, and use of occupational safety and health information (OSH). Contemporary changes in the workforce, workplaces, and the nature of work will require new emphasis on the dissemination of information to foster prevention. METHODS: Legislative and regulatory requirements and voluntary initiatives for dissemination of OSH information were identified and assessed. Literature on information dissemination was reviewed to identify important issues and useful approaches. RESULTS: More than 20 sections of laws and regulations were identified that mandated dissemination of occupational and environmental safety and health information. A four-stage approach for tracking dissemination and considering the flow of information was delineated. Special areas of dissemination were identified: the information needs of the changing workforce, new and young workers; small businesses; and workers with difficulty in understanding or reading English. CONCLUSIONS: We offer a framework for dissemination of OSH information and underscore the need to focus on the extent to which decision-makers and others receive and use such information. More solid data are also needed on current investments in disseminating, diffusing and applying OSH information and on the utility of that information. Am. J. Ind. Med. 44:515-531, 2003. Published 2003 Wiley-Liss, Inc.

GABAergic inhibitory mechanisms for repetition-adaptivity in large-scale brain systems.

Molecular mechanisms for systems level adaptivity of brain activation are largely unknown but a key role for active inhibition by gamma-aminobutyric acid (GABA) is plausible. We used functional magnetic resonance imaging to contrast the modulatory effects on brain adaptivity to task repetition and task difficulty of two GABAergic drugs, lorazepam and flumazenil. In a working memory paradigm, occipitotemporal regions clearly demonstrated attenuation of activation as a function of within-session task repetition or practice in data acquired following placebo, but this spatiotemporal pattern of repetition adaptivity was abolished by both lorazepam and flumazenil. However, in other brain systems flumazenil enhanced repetition adaptivity compared to placebo: in frontal cortex, flumzenil induced attenuation of signal related to task repetition and in hippocampus it exaggerated normal enhancement of signal with repetition. In contrast, there were no significant effects of either flumazenil or lorazepam on areas of frontal cortex which normally demonstrated significant neurocognitive load response or adaptivity to task difficulty. We argue that repetition adaptivity of large-scale brain systems is regulated by GABAergic inhibitory mechanisms and that expression of repetition adaptivity in a given brain system may show an "inverted-U" form of relationship with pharmacologically manipulable levels of GABAergic inhibitory tone.

Type 2 and other forms of diabetes in 0-30 year olds: a hospital based study in Leeds, UK.

BACKGROUND AND AIMS: Following recent reports of increased numbers of adolescents being diagnosed with the adult or type 2 form of diabetes we aimed to describe the prevalence of both type 2 and other forms of diabetes in an urban population of children and young people in northern England. METHODS: A hospital based cross sectional study was performed in patients aged < or =30 years attending diabetic clinics in Leeds during the year 2000. RESULTS: A total of 677 subjects were identified, of whom 621 (92%) and 37 (5%) had type 1 and type 2 diabetes respectively. Four patients had confirmed maturity onset diabetes of the young, while the cause was uncertain for four. Median age of all patients was 22 years, with 396 (58%) aged 20-30; 32/37 patients with type 2 diabetes were aged 20-30. The prevalence of type 2 diabetes was 0.13 per 1000 overall, compared to 2.2 per 1000 for patients with type 1 diabetes. Of all type 2 diabetes patients, 24% were south Asian compared to 5% of the background population; 87% were categorised into the two least affluent tertiles of the Townsend score. This link with deprivation was not explained by the proportion of Asian patients across tertiles (approximately 25%). CONCLUSIONS: This study shows extremely low prevalence of type 2 diabetes in 10-19 year olds, but will provide a baseline for future comparisons. Overall, type 2 diabetes is seen more commonly in south Asians, and an association with deprivation is suggested.

Type 1 diabetes in Yorkshire, UK: time trends in 0-14 and 15-29-year-olds, age at onset and age-period-cohort modelling.

AIMS: To investigate whether the rising incidence of Type 1 diabetes in children is evident in young adults and determine whether age at onset has decreased over time. METHODS: Two geographically defined datasets from the population-based Yorkshire Diabetes Register were analysed: (i) 2718 children diagnosed under 15 years with Type 1 diabetes from 1978 to 2000 in Yorkshire; (ii) 631 young adults (15-29 years) diagnosed from 1991 to 1999 in West Yorkshire. Log-linear regression and age-period-cohort modelling evaluated changes in incidence over time and age at onset. RESULTS: Incidence rose steadily for 0-14-year-olds in Yorkshire with an average annual increase of 2.9%[95% confidence interval (CI) 2.0, 3.8]. In West Yorkshire between 1991 and 1999, the time trends for 0-14 and 15-29-year-olds were significantly different (P = 0.014). Stable rates in 15-29-year-olds contrasted with an average annual increase of 5.9% (95% CI 2.7, 9.2) for 0-14-year-olds. The mean age at onset fell from 9.2 to 8.4 years for 0-14-year-olds and from 16.0 to 14.6 years for 0-29-year-olds. Age-period-cohort modelling showed a statistically significant (P < 0.001) increased risk of developing diabetes was associated with decreasing age for those diagnosed more recently. CONCLUSIONS: A steady and continuing rise in the incidence of Type 1 diabetes over time is observed for children but not for young adults. In parallel, the age at onset is gradually decreasing and more recent birth cohorts are at increased risk. This overall pattern is consistent with the influence of an environmental agent that is gradually affecting children at younger and younger ages.

Trends in the incidence of childhood diabetes in south Asians and other children in Bradford, UK.

AIMS: To investigate incidence rates and time trends, over 21 years, of Type 1 diabetes in a migrant population of south Asian children in Bradford, UK. METHODS: Children (0-14 years) living in the city of Bradford and diagnosed with Type 1 diabetes were selected from a population-based region-wide register. Between 1978 and 1998, 289 new-onset cases were registered and classified as south Asian (Indian, Pakistani, Bangladeshi) or not, based on their full name using two different computer algorithms and visual inspection. RESULTS: Sixty-six children (22.8%) were designated as south Asian with 223 (77.2%) remaining. The overall age-sex standardized incidence for south Asian and non-south Asian children was 13.0 per 100,000 person years (95% confidence interval 9.9-16.2) and 12.9 (11.2-14.6), respectively. Rates were similar for south Asians at all ages, whereas for the mainly Caucasian children incidence differed significantly by age group (P < 0.001). An average annual increase in incidence of 4.3% (P = 0.001) was seen for all children compared with 6.5% in south Asians (P = 0.002) and 2.4% (P = 0.128) in non-south Asians. CONCLUSIONS: Children in south Asia have a low incidence of Type 1 diabetes but migrants to the UK have similar overall rates to the indigenous population. However, a more steeply rising incidence is seen in the south Asian population, and our data suggest that incidence in this group may eventually outstrip that of the non-south Asians. Genetic factors are unlikely to explain such a rapid change, implying an influence of environmental factors in disease aetiology. The similarity in rates by age group in the south Asian population is notable.