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1.
J Anal Toxicol ; 42(7): e61-e64, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-29800291

ABSTRACT

A case of an elderly female with suspected paralytic shellfish poisoning (PSP) is presented. The patient shared a meal of recreationally-harvested shellfish with her family and soon began to experience nausea and weakness. She was taken to the local emergency department and then transported to a larger hospital in Anchorage where she was admitted to the intensive care unit with respiratory depression and shock. Her condition improved, and she was discharged from the hospital 6 days later. No others who shared the meal reported symptoms of PSP. A clam remaining from the meal was collected and analyzed for paralytic shellfish toxins (PST) by the Alaska Department of Environmental Conservation Environmental Health Laboratory; the clam tested positive for saxitoxin (STX; 277 µg/100 g), neosaxitoxin (NEO; 309 µg/100 g), multiple gonyautoxins (GTX; 576-2490 µg/100 g), decarbamoyl congeners (7.52-11.3 µg/100 g) and C-toxins (10.8-221 µg/100 g) using high-pressure liquid chromatography with post-column oxidation (AOAC Method 2011.02). Urine from the patient was submitted to Centers for Disease Control for analysis of selected PSTs and creatinine. STX (64.0 µg/g-creatinine), NEO (60.0 µg/g-creatinine) and GTX1-4 (492-4780 µg/g-creatinine) were identified in the urine using online solid phase extraction with HPLC and tandem mass spectrometry. This was the first time GTX were identified in urine of a PSP case from Alaska, highlighting the need to include all STX congeners in testing to protect the public's health through a better understand of PST toxicity, monitoring and prevention of exposures.


Subject(s)
Bivalvia/chemistry , Food Analysis/methods , Saxitoxin/analogs & derivatives , Shellfish Poisoning/urine , Animals , Chromatography, High Pressure Liquid , Female , Humans , Saxitoxin/urine , Shellfish Poisoning/diagnosis , Solid Phase Extraction , Tandem Mass Spectrometry , Urinalysis
2.
Br J Cancer ; 111(9): 1814-23, 2014 Oct 28.
Article in English | MEDLINE | ID: mdl-25051410

ABSTRACT

BACKGROUND: Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analyses relating to areas close to these nuclear installations by considering data from an additional 16 years of follow-up. METHODS: Cross-sectional analyses compared cancer incidence rates for 1963-2006 among those aged 0-24 years at diagnosis living in geographically specified areas around either Sellafield or Dounreay with general population rates. Cancer incidence for the period 1971-2006 among the cohort of Cumbrian births between 1950 and 2006 was compared to national incidence for 1971-2006 using person-years analysis. Cancer among those born in the postcode sector closest to Dounreay was compared with that among those born in the three adjoining postcode sectors. Analyses considered both cancer overall and ICD-O-3 defined diagnostic subgroups including leukaemia, central nervous system tumours and other malignancies. RESULTS: Apart from previously reported raised risks, no new significantly increased risks for cancer overall or any diagnostic subgroup were found among children or teenagers and young adults living around either nuclear installation. Individuals born close to the installations from 1950 to 2006 were not shown to be at any increased risk of cancer during the period 1971 to date. CONCLUSIONS: Analysis of recent data suggests that children, teenagers and young adults currently living close to Sellafield and Dounreay are not at an increased risk of developing cancer. Equally, there is no evidence of any increased cancer risk later in life among those resident in these areas at birth.


Subject(s)
Neoplasms, Radiation-Induced/epidemiology , Nuclear Reactors , Radioactive Fallout/adverse effects , Residence Characteristics , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Incidence , Infant , Infant, Newborn , Male , Neoplasms, Radiation-Induced/etiology , Prognosis , Risk Factors , United Kingdom/epidemiology , Young Adult
4.
Br J Cancer ; 108(6): 1273-9, 2013 Apr 02.
Article in English | MEDLINE | ID: mdl-23449361

ABSTRACT

BACKGROUND: Despite advances in the treatment of childhood cancer, some children continue to die from their disease. This study aimed to assess the impact of specialist paediatric palliative care services (SPPCSs) on the number of hospital admissions in children who subsequently died from cancer in Yorkshire, UK. METHODS: An extract of patients aged 0-19 years from the Yorkshire Specialist Register of Cancer in Children and Young People (YSRCCYP) diagnosed from 1990 to 2009 were linked to inpatient hospital episodes data and a SPPCS database. Deaths were included if they occurred before 31 August 2011. Differences in hospital admission patterns were assessed using negative binomial regression and presented as incidence rate ratios (IRRs). RESULTS: Of 2508 children on the YSRCCYP, 657 (26%) had died by the censoring date. A total of 211 children had been referred to the local SPPCS, of whom 182 (86%) had subsequently died. Referral to SPPCS was associated with a significant reduction in the rate of planned hospital admissions (IRR=0.60, 95% CI 0.43-0.85). Central nervous system tumours showed significant decreases for all planned and emergency admissions compared with all other diagnostic groups. CONCLUSION: Referral to SPPCS significantly reduced the number of planned hospital admissions for children and young people with cancer before their death, which are often integral to paediatric oncology treatment regimens. Overall, our findings show that SPPCS have a role in reducing hospital admissions during end of life care of paediatric cancer patients with potential personal, social and economic benefits.


Subject(s)
Hospitalization/statistics & numerical data , Neoplasms/therapy , Palliative Care , Patient Admission/statistics & numerical data , Referral and Consultation , Specialization/statistics & numerical data , Terminal Care , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Prognosis , Young Adult
5.
Cancer Epidemiol ; 36(1): e13-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21908244

ABSTRACT

INTRODUCTION: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults. METHODS: Subjects (n=3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan-Meier estimation and Cox regression. RESULTS: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR)=1.75; 95% confidence interval (CI)=1.11-2.76) and lymphoma (HR=2.05; 95% CI=1.09-3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR=0.50; 95% CI=0.28-0.89). This was independent of socioeconomic deprivation. CONCLUSION: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services.


Subject(s)
Neoplasms/mortality , Adolescent , Adult , Asia/ethnology , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Neoplasms/epidemiology , Neoplasms/ethnology , Survival Analysis , United Kingdom/epidemiology , Young Adult
6.
Ann Oncol ; 23(4): 1053-60, 2012 Apr.
Article in English | MEDLINE | ID: mdl-21828376

ABSTRACT

BACKGROUND: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. METHODS: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]. RESULTS: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01). CONCLUSIONS: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.


Subject(s)
Carcinoma, Squamous Cell/etiology , Head and Neck Neoplasms/etiology , Adult , Aspirin/adverse effects , Aspirin/therapeutic use , Candidiasis/complications , Case-Control Studies , Disease Susceptibility , Europe , Heartburn/complications , Herpesviridae Infections/complications , Humans , Laryngopharyngeal Reflux/complications , Middle Aged , Odds Ratio , Risk Factors , Warts/complications , Young Adult
7.
Article in English | MEDLINE | ID: mdl-21462017

ABSTRACT

Deoxynivalenol (DON) is a ubiquitous contaminant of cereal crops in temperate regions of the world. It causes growth faltering and immune suppression in animals. Limited information is available on DON exposure in UK subpopulations. The objective of this study was to provide DON exposure assessment in a subset of pregnant women scheduled for an elective caesarean in a large multi-ethnic mother/infant birth cohort from Bradford, UK. Women aged 16-44 years (n = 85) provided a urine sample for DON analysis in the last trimester of pregnancy, and concurrently completed a food-frequency questionnaire (FFQ). The urinary DON biomarker was detected in all measured samples (geometric mean (GM) = 10.3 ng DON mg(-1) creatinine, range = 0.5-116.7 ng mg(-1)). Levels were higher in women classified as South Asian in origin (GM: 15.2 ng mg(-1); 95% CI = 10.7-21.5 ng mg(-1)) compared with non-South Asians (GM = 8.6 ng mg(-1); 95% CI = 6.6-11.8 ng mg(-1)), p = 0.02). Estimated DON intake from FFQ data and typical levels of DON contamination of food suggest that this was mainly due to higher levels of exposure from bread, particularly daily intake of DON from chapattis in South Asians (estimated mean = 2.4 µg day(-1); 95% CI = 1.2, 3.7 µg day(-1)) compared with non-South Asians (estimated mean = 0.2 µg day(-1); 95% CI = 0-0.4 µg day(-1)), p < 0.001. This is the first biomarker demonstration of DON exposure in pregnant women, and several urinary DON levels were the highest ever recorded in any study. A larger survey within this birth cohort is warranted to investigate any potential risk to mothers and their babies, from DON exposure during pregnancy.


Subject(s)
Food Contamination , Trichothecenes/urine , Asian People , Biomarkers , Cohort Studies , Feeding Behavior , Female , Humans , Pregnancy , United Kingdom
8.
Diabet Med ; 28(12): 1508-13, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21838766

ABSTRACT

AIMS: Incidence of Type 1 diabetes in children is increasing worldwide. Earlier studies suggest that UK south Asian immigrants develop similar rates to the overall UK population, although incidence is lower in their country of origin. This study examines incidence rate trends of childhood Type 1 diabetes in Yorkshire 1978-2007, focusing on differences between south Asians and non-south Asians. METHODS: Data from the population-based Yorkshire Register of Diabetes in Children and Young People were used to estimate incidence (per 100,000 childhood population < 15 years per year) of Type 1 diabetes, stratified by sex, age and ethnicity validated using two name-recognition programs. Age-sex standardized rates were calculated for 1978-2007 and assessed by ethnic-group and deprivation for 1990-2007. We used Poisson regression to assess incidence trends and predict rates until 2020. RESULTS: From 1978-2007, 3912 children were diagnosed. Overall incidence was 18.1 per 100,000 childhood population (< 15 years) per year (95% CI17.6-18.7) and increased significantly over time: 13.2 (1978-1987) to 17.3 (1988-1997) to 24.2 (1998-2007). Average annual percentage change was 2.8% (2.5-3.2). Incidence for non-south Asians (21.5; 20.7-22.4) was significantly higher than for south Asians (14.7; 12.4-17.1). Average annual percentage change increased significantly over 18 years (1990-2007) in non-south Asians (3.4%; 2.7-4.2) compared with a non-significant rise of 1.5% (-1.5 to 4.6) in south Asians. Deprivation score did not affect overall incidence. CONCLUSIONS: Type 1 diabetes incidence rose almost uniformly for non-south Asians, but not for south Asians, contrary to previous studies. Overall rates are predicted to rise by 52% from 2007 to 2020 to 39.0 per 100,000 per year.


Subject(s)
Asian People/statistics & numerical data , Diabetes Mellitus, Type 1/epidemiology , White People/statistics & numerical data , Adolescent , Adult , Age Distribution , Age Factors , Age of Onset , Child , Child, Preschool , Diabetes Mellitus, Type 1/ethnology , England/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Registries , Socioeconomic Factors , Young Adult
9.
Br J Cancer ; 103(11): 1749-54, 2010 Nov 23.
Article in English | MEDLINE | ID: mdl-20959829

ABSTRACT

BACKGROUND: No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide. METHODS: A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33,731 women aged 35-69 years from the UK Women's Cohort Study followed up for a median of 11 years. RESULTS: In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 µg day(-1), 95% CI: 0.98-1.18, P(trend)=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0-1.3, P(trend)=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9-1.1, P(trend)=0.99). CONCLUSIONS: There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.


Subject(s)
Acrylamide/adverse effects , Breast Neoplasms/chemically induced , Acrylamide/administration & dosage , Adult , Aged , Cohort Studies , Diet , Female , Humans , Middle Aged , Prospective Studies , Risk , United Kingdom
10.
Br J Cancer ; 103(9): 1448-52, 2010 Oct 26.
Article in English | MEDLINE | ID: mdl-20842119

ABSTRACT

BACKGROUND: Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer. METHODS: Subjects aged 0-29 years, diagnosed between 1990 and 2005 in the former Yorkshire Regional Health Authority, were included in the analysis. Ethnicity (south Asian or not) was assigned using name analysis program and Hospital Episode Statistics data. Differences in incidence (per 1,000,000 person-years) rates and trends were analysed using joinpoint and Poisson regression analysis. RESULTS: Overall cancer incidence was similar for south Asians (12.1, 95% CI: 10.7-13.5; n=275) and non-south Asians (12.6, 95% CI: 12.2-13.1; n=3259). Annual incidence rates increased significantly by 1.9% per year on average (95% CI: 1.2-2.6%), especially for south Asians (7.0%; 95% CI: 4.2-9.9%). CONCLUSION: If present trends continue, the higher rate of increase seen among south Asians aged 0-29 years in Yorkshire will result in three times higher cancer incidence than non-south Asians by 2020.


Subject(s)
Neoplasms/ethnology , Neoplasms/epidemiology , Adolescent , Adult , Asia , Child , Child, Preschool , Female , Humans , Incidence , Infant , Infant, Newborn , Male , United Kingdom
11.
Eur J Epidemiol ; 25(3): 173-82, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20143252

ABSTRACT

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.


Subject(s)
Head and Neck Neoplasms/etiology , Social Mobility , Adult , Aged , Aged, 80 and over , Europe/epidemiology , Head and Neck Neoplasms/epidemiology , Humans , Interviews as Topic , Male , Middle Aged , Risk Assessment , Social Class , Surveys and Questionnaires , Young Adult
12.
Arch Dis Child ; 95(2): 89-93, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19897465

ABSTRACT

OBJECTIVE: To provide new epidemiological evidence base of information on models of hospice care for children and young adults. DESIGN: Retrospective cohort study of children referred to a hospice. SETTING: Martin House Children's and Young Person's Hospice in Boston Spa, North Yorkshire, UK. PARTICIPANTS: All children who had been referred for care at Martin House Children's Hospice since it opened in August 1987, until May 2008. MAIN OUTCOME MEASURES: Demographic profiles and survival times overall and by diagnostic group classified by the Association of Children's Palliative Care (ACT) Diagnostic Categories, calculated using the Kaplan- Meier and log rank pair-wise methodology. RESULTS: Over a 20-year period, 1554 children aged from birth to 19 years were referred to Martin House, of whom 89.5% (mean age 7.45 years) were accepted. The deprivation profile, referral source and distribution of diagnoses of these children have changed over time with recently increasing numbers of non-progressive disorders (ACT category 4). The ethnicity profile has changed with an increase in the numbers of South Asian children. The overall mean survival time was 5.6 years (95% CI 5.1 to 6.1) but this differed by ACT category. Diagnostic category was significantly associated with differing survival patterns. CONCLUSIONS: There are a disproportionate number of children from areas of higher deprivation being referred for palliative care services. There has been a recent increase in the number of children from South Asian families being referred to palliative care services in Yorkshire. Survival times for children and young people receiving care from a hospice can vary from hours and days to more than 20 years.


Subject(s)
Child Health Services/statistics & numerical data , Hospice Care/statistics & numerical data , Palliative Care/statistics & numerical data , Adolescent , Age Factors , Child , Child Health Services/trends , Child, Preschool , England , Ethnicity/statistics & numerical data , Female , Hospice Care/trends , Humans , Infant , Infant, Newborn , Male , Palliative Care/trends , Patient Selection , Poverty Areas , Referral and Consultation/statistics & numerical data , Referral and Consultation/trends , Retrospective Studies , Sex Factors , Survival Analysis , Young Adult
13.
Eur J Cancer ; 46(3): 588-98, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19857956

ABSTRACT

INTRODUCTION: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet. PATIENTS AND METHODS: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression. RESULTS: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community). CONCLUSION: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet.


Subject(s)
Head and Neck Neoplasms/etiology , Adult , Aged , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Case-Control Studies , Diet/statistics & numerical data , Educational Status , Europe/epidemiology , Female , Fruit , Head and Neck Neoplasms/epidemiology , Humans , Life Style , Male , Middle Aged , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , Social Class , Socioeconomic Factors , Vegetables
14.
Pharmacol Biochem Behav ; 94(2): 305-11, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19772870

ABSTRACT

Repeated-acquisition procedures that include performance controls for effects not specific to acquisition permit the assessment of drug effects on learning on a within-subject, within-session basis. Despite the advantages of this methodology, few studies have examined effects of psychomotor stimulants on repeated acquisition in rodents. The purpose of the present study was to investigate the effects of methylenedioxymethamphetamine (MDMA, 0.3-10mg/kg), methamphetamine (MA, 0.1-3mg/kg) and methylphenidate (MPD,1-17 mg/kg) using repeated-acquisition procedures with performance controls in rats using a touch-screen apparatus. Rats were presented a 2x3 array of stimuli using a computer touch-screen and nose-pokes to target locations within the array were reinforced. In the acquisition component, the correct location changed across sessions, whereas during the performance component, the correct location was constant across sessions. All three drugs reduced accuracy of responding to target locations in a dose-dependent fashion. None of the compounds enhanced learning at any dose. MPD and MA produced significant disruptions of acquisition accuracy only at doses that also disrupted performance, but the 3mg/kg dose of MDMA impaired acquisition of target responding without affecting performance. The selective impairment of acquisition found in the present study adds to the evidence of learning and memory disruption produced by acute MDMA administration and raise questions about the mechanisms for these actions.


Subject(s)
Methamphetamine/pharmacology , Methylphenidate/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Psychomotor Performance/drug effects , Reinforcement Schedule , Animals , Dose-Response Relationship, Drug , Male , Psychomotor Performance/physiology , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , Reaction Time/physiology , Time Factors
15.
J Autoimmun ; 33(2): 147-54, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19447008

ABSTRACT

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.


Subject(s)
Autoantibodies/immunology , Autoantigens/immunology , Diabetes Mellitus, Type 1/immunology , Epitopes, T-Lymphocyte/immunology , Receptor-Like Protein Tyrosine Phosphatases, Class 8/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Amino Acid Substitution , Antibodies, Monoclonal/immunology , Child , Epitopes, T-Lymphocyte/genetics , Female , Humans , Infant , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Interleukin-10/biosynthesis , Interleukin-10/immunology , Male , Receptor-Like Protein Tyrosine Phosphatases, Class 8/genetics , T-Lymphocytes/metabolism , Young Adult
16.
Occup Environ Med ; 66(9): 619-27, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19383596

ABSTRACT

BACKGROUND: Occupational exposure to extremely low frequency (ELF) magnetic fields (MF) in the UK general population is poorly documented. AIMS: To assess levels of occupational exposure to ELF MF in the UK and evaluate the use of a rigid job-exposure matrix (JEM) to assign exposures to subjects in the UK Adult Brain Tumour Study (UKABTS). METHODS: Personal ELF MF measurements were carried out. Exposure traces were divided into occupational, travel and elsewhere periods, under differing exposure metrics. Exposure was classified by Standard Occupational Classification (2000), Standard Industrial Classification (1997), and a combined occupation-industry classification. Statistical analyses (mixed effects model) determined the contribution of occupational exposure to the 24 h cumulative exposure and the contribution of occupation and industry to total variance. RESULTS: Data were obtained from 317 individuals, comprising UKABTS subjects (n = 192), occupational proxies for UKABTS subjects (n = 101) and "interest" readings (n = 24). 236 individuals provided occupational data covering 117 different occupations. Average exposure was significantly higher at work than at home. Elevated average occupational exposure was found for welding trades, printers, telephonists and filing and other records assistants. The discrimination of a rigid JEM based on occupation can be improved by linking the classification with industry and by the use of contextual information. CONCLUSIONS: This report substantially expands information on adult exposure to ELF MF in the UK. The accuracy of exposure assessments based solely on job codes is improved by linking with either industry code or contextual knowledge of equipment and of power lines or substations in the work environment.


Subject(s)
Brain Neoplasms/etiology , Electromagnetic Fields , Neoplasms, Radiation-Induced/etiology , Occupational Diseases/etiology , Occupational Exposure/analysis , Adult , Brain Neoplasms/epidemiology , Case-Control Studies , England/epidemiology , Environmental Monitoring/methods , Epidemiological Monitoring , Humans , Models, Statistical , Neoplasms, Radiation-Induced/epidemiology , Occupational Diseases/epidemiology , Occupational Exposure/adverse effects , Occupations/statistics & numerical data , Radiation Dosage , Radiometry/methods , Travel
17.
Br J Cancer ; 100(1): 188-93, 2009 Jan 13.
Article in English | MEDLINE | ID: mdl-19127271

ABSTRACT

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0-14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981-2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27-2.99) for osteosarcoma, 1.90 (1.58-2.21) for Ewing sarcoma and 0.21 (0.11-0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6-5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981-2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91-0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98-1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.


Subject(s)
Bone Neoplasms/epidemiology , Adolescent , Bone Neoplasms/mortality , Child , Child, Preschool , England/epidemiology , Female , Humans , Incidence , Infant , Infant, Newborn , Male , Osteosarcoma/epidemiology , Proportional Hazards Models , Sarcoma, Ewing/epidemiology , Survival Rate
18.
Cancer Causes Control ; 20(2): 129-36, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18766446

ABSTRACT

Little is known regarding the aetiology of central nervous system tumors in children. Recent studies have speculated on a potential infectious aetiology, but no clear associations have been found. This article uses parent reported questionnaire data from the UK Childhood Cancer Study (UKCCS), a population-based case-control study, to examine the relationship between the infectious exposure in the first year of life and the likelihood of developing a CNS tumor. The variables representing infectious exposure were social contact (including social contact with other infants and attendance at informal and formal day care), sharing a bedroom with another child, birth order, and exposure to a school-age child within the home. Children reported to have had no social contact with other infants in the first year of life displayed an increased risk of developing a CNS tumor when compared to those who had (OR 1.37, 95% CI 1.08-1.75). This effect was most prominent in the primitive neuroectodermal tumor/medulloblastoma subgroup (OR 1.78, 95% CI 1.12-2.83). Those who had attended informal (OR 0.86, 95% CI 0.68-1.09) or formal day care (OR 0.93, 95% CI 0.68-1.26) showed slightly non-statistically significant reduced risks when compared to those reporting social contact only. No association with any of the other variables was observed. Overall, the inconsistent findings by variable and tumor subtype suggest that an early exposure to infections is not strongly implicated in the aetiology of CNS tumors. However, the effect for social contact outside the home, particularly for PNET/medulloblastomas warrants further investigation.


Subject(s)
Central Nervous System Neoplasms/epidemiology , Central Nervous System Neoplasms/microbiology , Day Care, Medical , Environmental Exposure , Family , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Risk Factors
19.
Arch Dis Child ; 94(3): 210-5, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19106117

ABSTRACT

OBJECTIVE: The purpose of this work was to investigate the incidence rate for admission and mortality of children receiving paediatric intensive care in relation to socioeconomic status and ethnicity in England and Wales. DESIGN: National cohort of sequential hospital admissions. SETTING: Twenty nine paediatric intensive care units in England and Wales. PARTICIPANTS: All children aged under 16 years admitted to paediatric intensive care in the 4 years 2004-2007. MAIN OUTCOME MEASURES: Incidence rates for admission and odds ratios (OR) for risk-adjusted mortality by an area based measure of deprivation (Townsend score) and ethnic group (south Asian vs non-south Asian determined using two-name analysis algorithms). RESULTS: The incidence for south Asian children was higher than that of non-south Asian children (138 vs 95/100,000, incidence rate ratio 1.36, 95% CI 1.32 to 1.40). The age-sex standardised incidence for children admitted to paediatric intensive care ranged from 69/100,000 in the least deprived fifth of the population to 124/100,000 in the most deprived fifth. The risk-adjusted OR for mortality for south Asian children was 1.36 (95% CI 1.18 to 1.57) overall, rising to 2.40 (95% CI 1.40 to 4.10) in the least deprived fifth of the population when a statistical interaction term for deprivation was included. CONCLUSIONS: In England and Wales, the admission rate to paediatric intensive care is higher for children from more deprived areas and 36% higher for children from the south Asian population. Risk-adjusted mortality increases in south Asian children as deprivation decreases.


Subject(s)
Critical Illness/epidemiology , Adolescent , Age Distribution , Asian People/statistics & numerical data , Child , Child, Preschool , England/epidemiology , Epidemiologic Methods , Female , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Intensive Care Units/statistics & numerical data , Male , Poverty Areas , Sex Distribution , Socioeconomic Factors , Wales/epidemiology
20.
Diabet Med ; 25(11): 1276-82, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19046216

ABSTRACT

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.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin/drug effects , Adolescent , Adult , Child , Child, Preschool , Clinical Audit , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , England/epidemiology , Female , Humans , Hypoglycemic Agents/therapeutic use , Infant , Male , Registries/statistics & numerical data , Risk Factors , Self Care/standards , Socioeconomic Factors , Young Adult
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