Livestock microbial landscape patterns: Retail poultry microbiomes significantly vary by region and season.

Microbes play key roles in animal welfare and food safety but there is little understanding of whether microbiomes associated with livestock vary in space and time. Here we analysed the bacteria associated with the carcasses of the same breed of 28 poultry broiler flocks at different stages of processing across two climatically similar UK regions over two seasons with 16S metabarcode DNA sequencing. Numbers of taxa types did not differ by region, but did by season (P = 1.2 × 10-19), and numbers increased with factory processing, especially in summer. There was also a significant (P < 1 × 10-4) difference in the presences and abundances of taxa types by season, region and factory processing stage, and the signal for seasonal and regional differences remained highly significant on final retail products. This study therefore revealed that both season and region influence the types and abundances of taxa on retail poultry products. That poultry microbiomes differ in space and time should be considered when testing the efficacy of microbial management interventions designed to increase animal welfare and food safety: these may have differential effects on livestock depending on location and timing.

Cyclic vomiting syndrome is a prevalent and under-recognized condition in the gastroenterology outpatient clinic.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder (FGID) characterized by intermittent episodes of nausea and vomiting. Our aim was to report its prevalence and associated features. METHODS: Data concerning demographics, symptoms, and psychiatric comorbidity were collected. Symptoms compatible with CVS were classified as per Rome III criteria. We recorded whether a diagnosis of CVS was considered in patients after negative investigation. We compared demographics and association with other FGIDs in patients with and without CVS. KEY RESULTS: 920 of 1002 patients provided data. Of the 920 patients, 112 (12.2%) had symptoms compatible with CVS. Thirteen (11.6%) of these had an organic cause for their symptoms, but 99 patients (88.4%) were deemed to have CVS (prevalence=10.8%). Organic causes for symptoms compatible with CVS included gastroparesis, large hiatus hernia, achalasia, and small bowel obstruction. Only 39.4% of patients with CVS were asked about vomiting symptoms at their initial consultation, and a diagnosis of CVS was considered in only four (4.0%) of the 99 patients. CVS was associated with younger age, tobacco smoking, never having married, psychiatric comorbidity, and presence of symptoms compatible with other FGIDs (P≤.01). CONCLUSIONS AND INFERENCES: Prevalence of CVS in this outpatient gastroenterology adult population was 10.8%. Identified associations included younger age, tobacco smoking, psychiatric comorbidity, and symptoms compatible with other FGIDs. The condition was considered as a possible diagnosis in <5% of patients who met the diagnostic criteria.

Derivation and validation of a diagnostic test for irritable bowel syndrome using latent class analysis.

BACKGROUND: The accuracy of symptom-based diagnostic criteria for irritable bowel syndrome (IBS) is modest. AIMS: To derive and validate a new test that utilises latent class analysis. METHODS: Symptom, colonoscopy, and histology data were collected from 1981 patients and 360 patients in two cohorts referred to secondary care for investigation of their gastrointestinal symptoms in Canada and the UK, respectively. Latent class analysis was used to identify naturally occurring clusters in patient-reported symptoms in the Canadian dataset, and the latent class model derived from this was then applied to the UK dataset in order to validate it. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for the latent class models. RESULTS: In the Canadian cohort, the model had a sensitivity of 44.7% (95% CI 40.0-50.0) and a specificity of 85.3% (95% CI 83.4-87.0). Positive and negative LRs were 3.03 (95% CI 2.57-3.56) and 0.65 (95% CI 0.59-0.71) respectively. A maximum positive LR of 3.93 was achieved following construction of a receiver operating characteristic curve. The performance in the UK cohort was similar, with a sensitivity and specificity of 52.5% (95% CI 42.2-62.7) and 84.3% (95% CI 79.3-88.6), respectively. Positive and negative LRs were 3.35 (95% CI 2.38-4.70) and 0.56 (95% CI 0.45-0.68), respectively, with a maximum positive LR of 4.15. CONCLUSIONS: A diagnostic test for IBS, utilising patient-reported symptoms incorporated into a latent class model, performs as accurately as symptom-based criteria. It has potential for improvement via addition of clinical markers, such as coeliac serology and faecal calprotectin.

Systematic review with meta-analysis: the accuracy of diagnosing irritable bowel syndrome with symptoms, biomarkers and/or psychological markers.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex, heterogeneous disease which can be challenging to diagnose. No study has identified and assessed the accuracy of all available methods of diagnosing IBS. AIM: To conduct a systematic review of the literature to identify and assess accuracy of symptom-based diagnostic criteria, biomarkers, psychological markers or combinations thereof. METHODS: MEDLINE, EMBASE and EMBASE Classic were searched (until April 2015) to identify studies reporting accuracy of available methods to diagnose IBS in adult populations. Eligible studies assessed accuracy of these diagnostic tests against an accepted reference standard. Data were extracted to calculate positive and negative likelihood ratios, with 95% confidence intervals (CIs), of the diagnostic test utilised. Where more than one study used the same test, data were pooled in a meta-analysis. RESULTS: Twenty-two studies (7106 patients) were eligible. Positive and negative likelihood ratios of the current gold standard, the Rome III criteria, were 3.35 (95% CI: 2.97-3.79) and 0.39 (95% CI: 0.34-0.46), similar to other symptom-based criteria. Eleven biomarkers performed no better than symptom-based criteria. Psychological markers performed well in one study. Five different combinations were assessed. The best in terms of positive likelihood ratio was faecal calprotectin, intestinal permeability and Rome I criteria (26.4; 95% CI: 11.4-61.9), and in terms of negative likelihood ratio serum-based biomarkers and psychological markers (0.18; 95% CI: 0.12-0.25). CONCLUSIONS: Symptom-based diagnostic criteria, biomarkers and psychological markers performed modestly in predicting IBS. Combining symptoms with markers appears more effective, and may represent the way forward in the diagnosis of IBS.

Trends in the association between blood pressure and obesity in a Taiwanese population between 1996 and 2006.

In the last decades, the prevalence of obesity has increased in the Taiwanese population. This has the potential to impact on the risks of cardiovascular diseases and diabetes. This study investigated trends in the changes in several indices of obesity in the last decade, and the relationship between blood pressure (BP) and these obesity indices available in Mei-Jaw Corporation health-screening data from 1996/1998 to 2006. Three cross-sectional surveys among healthy individuals ages 20-59 years, in which 14,362 subjects examined in year 1996, 17,368 in 1998, and 28,524 in 2006, were included in the analysis. Body weight and height data were available from 1996, whereas %body fat, waist circumference and waist-hip ratio (Whratio) were only available from 1998 onwards. We found that the association between systolic BP and body weight, body mass index, %body fat, Whratio and waist became stronger for both men and women in 2006 than 1996 after adjustment for age, education level, alcohol intake, smoking and betel nut chewing. In contrast, non-obese people seemed to have lower diastolic BP in 2006 than in 1996. This trend is consistent irrespective of the index of obesity used. Among healthy individuals, the average values for the obesity indices increased in men but remained similar in women. However, in both men and women, the relationship between obesity and BP has changed. Further research is required to investigate the impact of these intriguing changes in the associations on the risk of cardiovascular diseases in the Taiwanese population.

Measuring placental transfusion for term births: weighing babies with cord intact.

OBJECTIVE: To estimate the volume and duration of placental transfusion at term. DESIGN: Prospective observational study. SETTING: Maternity unit in Bradford, UK. POPULATION: Twenty-six term births. METHODS: Babies were weighed with umbilical cord intact using digital scales that record an average weight every 2 seconds. Placental transfusion was calculated from the change in weight between birth and either cord clamping or when weighing stopped. Start and end weights were estimated using both a B-spline and inspection of graphs. Weight was converted to volume, 1 ml of blood weighing 1.05 g. MAIN OUTCOME MEASURES: Volume and duration of placental transfusion. RESULTS: Twenty-six babies were weighed. Start weights were difficult to determine because of artefacts in the data as the baby was placed on the scales and wrapped. The mean difference in weight was 116 g [95% confidence interval (CI), 72-160 g] using the B-spline and 87 g (95% CI, 64-110 g) using inspection. Converting this to the mean volume of placental transfusion gave 110 ml (95% CI, 69-152 ml) and 83 ml (95% CI, 61-106 ml), respectively. Placental transfusion was usually complete by 2 minutes, but sometimes continued for up to 5 minutes. Based on the B-spline, placental transfusion contributed 32 ml (95% CI, 30-33 ml) per kilogram of birth weight to blood volume, but 24 ml (95% CI, 19-32 ml) based on inspection. This equates to 40% (95% CI, 37-42%) and 30% (24-40%), respectively, of total potential blood volume. CONCLUSION: Inspection of the graphs probably underestimates placental transfusion. For term infants, placental transfusion contributes between one-third and one-quarter of total potential blood volume at birth.

Haplotype uncertainty in association studies.

Inferring haplotypes from genotype data is commonly undertaken in population genetic association studies. Within such studies the importance of accounting for uncertainty in the inference of haplotypes is well recognised. We investigate the effectiveness of correcting for uncertainty using simple methods based on the output provided by the PHASE haplotype inference methodology. In case-control analyses investigating non-Hodgkin lymphoma and haplotypes associated with immune regulation we find little effect of making adjustment for uncertainty in inferred haplotypes. Using simulation we introduce a higher degree of haplotype uncertainty than was present in our study data. The simulation represents two genetic loci, physically close on a chromosome, forming haplotypes. Considering a range of allele frequencies, degrees of linkage between the loci, and frequency of missing genotype data, we detail the characteristics of genetic regions which may be susceptible to the influence of haplotype uncertainty. Within our evaluation we find that bias is avoided by considering haplotype probabilities or using multiple imputation, provided that for each of these methods haplotypes are inferred separately for case and control populations; furthermore using multiple imputation provides the facility to incorporate haplotype uncertainty in the estimation of confidence intervals. We discuss the implications of our findings within the context of the complexity of haplotype inference for larger marker rich regions as would typically be encountered in genetic analyses.

Population mixing, childhood leukaemia, CNS tumours and other childhood cancers in Yorkshire.

We tested the hypothesis that variation in population mixing attributable to the diversity of migrants moving to an area is associated with the incidence of childhood leukaemia and other childhood cancers. An ecological analysis was performed on 954 children (<15 years) diagnosed with a malignancy between 1986 and 1996 in 532 electoral wards in Yorkshire, UK. Incidence rate ratios (IRR) were calculated for all childhood leukaemias (n=325), acute lymphoblastic leukaemia (ALL) (n=248), central nervous system (CNS) tumours (n=236) and other solid tumours (n=393) Incidence of all childhood leukaemias was significantly lower in areas of high (top decile) population mixing (IRR 0.72, 95% Confidence Interval (CI) 0.54-0.97) and higher in areas of low (bottom decile) population mixing (IRR 1.56, 95% CI 0.73-3.34), but similar patterns of incidence were not observed for central nervous system or other solid tumours. Population mixing may be a proxy for the range of infections circulating in a community and these results are consistent with the hypothesis that greater exposure to infections reduces the risk of developing childhood leukaemia by conferring efficient modulation of the immune system.

The importance of full participation: lessons from a national case-control study.

Differential participation between cases and controls can lead to biased estimates of risk. However, the effects of participation are often ignored. We report a detailed analysis of locations of residence for participants and non-participants in a large, national case-control study of childhood cancer in Great Britain, using the 1991 census. The initial selection of 7669 controls, taken from lists of those registered with a General Practitioner, was representative of the British population in respect to an areal-based index of material deprivation. However, parents of controls agreeing to participate were living in more affluent areas than initially selected controls and their matched 3838 cases. The three components of the deprivation index, persons unemployed, households not owning a car or their home were similarly associated with participation. Other census characteristics, such as proportion of flat dwellers and centrally heated households were also associated with control participation. Population density of the local area was not different between participating controls and their matched cases. However, initially selected controls lived in more urban areas than their cases. Such differences are not unique to this study, as they are an inevitable consequence of incomplete participation. The implications of these differences are discussed, in relation to the difficulty this imposes in the interpretation of studies of disease aetiology.

Leukaemia incidence near coastal features.

BACKGROUND: The aim of the study was to independently test the hypothesis that leukaemia incidence is higher in proximity to estuaries. METHODS: Electoral wards were classified as to whether they included estuarine, coastal or only inland features. Rates of different adult and childhood leukaemias were computed for each ward category; that is, acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) aged 0-79 and for all childhood leukaemias combined (aged 0-14). RESULTS: Poisson regression analysis controlling for the effects of sex, age, and socioeconomic and urban-rural status, showed no statistically significant differences in incidence between wards with different levels of estuarine classification. CONCLUSION: The hypothesis created from an earlier dataset that a link exists between leukaemia and residence near estuaries is not upheld.

Population mixing and childhood diabetes.

BACKGROUND: Exposure to infections, particularly in early life, may modify the risk of developing childhood diabetes. Population mixing, based on the number and diversity of incoming migrants to an area can be used as a proxy measure for exposure to infections. We tested the hypothesis that incidence of childhood Type 1 diabetes is higher in areas of low population mixing. METHODS: Children (<15 years) diagnosed with diabetes between 1986--1994 in Yorkshire, UK (n = 994) were analysed with demographic data and denominator populations from the 1991 UK Census. Population mixing was estimated separately for 'any age' (>1 year) and children (1--15 years) for each area, using the proportion of migrants and an index of diversity based on numbers and origins of migrants. Regression models calculated the effect of 'any age' and childhood population mixing on the incidence of diabetes, controlling for population density, ethnicity and proportion of migrants. RESULTS: Areas with low levels of population mixing of children (bottom decile), were significantly associated with higher incidence of childhood diabetes for 0-14 years (incidence rate ratio [IRR] = 1.46, 95% CI : 1.01--2.11). When stratified by age different effects were observed for childhood population mixing with raised IRR for ages 5-9 (2.23, 95% CI : 1.20--4.11) and 10-14 (1.47, 95% CI : 0.89--2.42), and decreased IRR for 0--4-year-olds (0.56, 95% CI : 0.17--1.82). CONCLUSION: The incidence of childhood diabetes is highest in areas where limited childhood population mixing occurs and the diversity of origins of incoming children is low; those over 4 years are at greatest risk. This is consistent with an infectious hypothesis where absence of stimulation to the developing immune system increases vulnerability to late infectious exposure, which may precipitate diabetes.

Large tables.

The traditional exploration of large contingency tables leads to multiple comparisons with the inherent generation of chance associations. To allow for this, a simple empirical Bayesian approach is used here to derive estimates of association 'shrunk' towards a global mean. Estimates are displayed on ordered normal plots, to allow visual detection of outliers, with the addition of 'guide rails', derived from simulation, to facilitate their detection. The methods, and the interpretation of results, are illustrated using a large table of occupations for cancer registrations in England and Wales for 1971-90.

Residential radon exposure and adult acute leukaemia.

Exposure to radioactive radon gas in homes, from natural sources, is an important public-health issue for many countries. We found no association between household exposure to radon and leukaemia in adults in the UK.

Early social mixing and childhood Type 1 diabetes mellitus: a case-control study in Yorkshire, UK.

AIMS: Evidence from animal models shows an increased risk of Type 1 diabetes mellitus associated with the absence of early life exposure to pathogens. To test this 'hygiene hypothesis', patterns of social mixing and infections in the first year of life and the risk of developing autoimmune diabetes in childhood were examined. METHODS: Personal interviews were conducted with the mothers of 220 children with Type 1 diabetes (0-15 years) and 433 age/sex matched controls from a population-based case control study in Yorkshire, UK. Social mixing including attendance at daycare, and infections occurring under 1 year of age were measures of exposure. Adjusted odds ratios (OR) were derived using conditional logistic regression. RESULTS: Frequency of attendance at daycare during the 1st year of life was inversely associated with childhood diabetes (OR 0.71, 95% confidence interval 0.51-1.00, P = 0.05), a finding not explained by mother's age, level of education or maternal diabetes. Increasing numbers of children in the daycare setting and numbers of sessions attended were significantly associated with increasing protection from diabetes. The strongest effect was observed in children with diabetes diagnosed aged 0-4 years. CONCLUSIONS: Social mixing through attendance at daycare in early infancy appears to confer protection against the development of childhood diabetes. This may be mediated through exposure to infectious agent(s) as a significant dose-response effect was evident with increasing numbers of child 'contacts'. These findings suggest early infectious exposure may play a role in the development of immunoregulatory mechanisms which protect against diabetes and further work is warranted.

Perinatal and neonatal determinants of childhood type 1 diabetes. A case-control study in Yorkshire, U.K.

OBJECTIVE: To identify environmental factors that exert their effect in the perinatal and neonatal period and influence the subsequent onset of insulin dependent (type 1) diabetes during childhood. RESEARCH DESIGN AND METHODS: A population-based case-control study of data abstracted from the hospital obstetric and neonatal records of 196 children with type 1 diabetes and 325 age- and sex-matched control subjects. Analysis of matched sets by conditional logistic regression was conducted for a range of perinatal and neonatal factors. RESULTS: A significantly raised risk was observed for illnesses in the neonatal period (OR 1.61, 95% CI 1.06-2.44), the majority of which were infections and respiratory difficulties. Exclusive breast feeding as the initial feeding method was significantly protective (OR 0.65, 95% CI 0.45-0.94). There were no significant associations with high- or low-birth weight, being firstborn or small-for-dates. All factors significant (5% level) for the entire dataset, that is, maternal age, type 1 diabetes in mothers, preeclampsia, delivery by cesarean section, neonatal illnesses, and initial breast feeding were modeled and the OR remained significant for all variables other than cesarean section. CONCLUSIONS: The findings are based on medical record data that cannot be subject to biased recall of mothers. Neonatal illnesses increased and initial breast feeding decreased the risk of childhood type 1 diabetes. Further determinants of risk are mothers with type 1 diabetes, older mothers, and preeclampsia during pregnancy.

Mortality and diabetes from a population based register in Yorkshire 1978-93.

OBJECTIVE: To investigate mortality of children diagnosed with insulin dependent diabetes mellitus (IDDM) and to identify common factors before death. DESIGN: Follow up of a population based cohort of children diagnosed with IDDM to ascertain deaths. SETTING: Children were diagnosed in Yorkshire but followed up throughout the United Kingdom. SUBJECTS: From the Yorkshire Children's Diabetes Register details of 1854 children aged 0-16 years (1978-93) were submitted to the NHS Central Register. MAIN OUTCOME MEASURE: Notification and causes of death. RESULTS: 98.3% of cases were traced and 26 deaths identified. Follow up ranged from 1-18 years (median 9.3 years), providing 17,350 person-years of IDDM. Fifteen deaths (58%) were attributed to diabetes or its complications; 11 (42%) were unrelated and included one suicide. For mortality from all causes, the standardised mortality ratio (SMR) of 247 (95% confidence interval (CI) 163 to 362) was significantly increased for those under 34 years. The largest number of deaths (n = 10) occurred in the 15-19 year age range, with an SMR of 442 (95% CI 209 to 802). Case note examination showed a clear tendency towards poor diabetic control, and worries over control were expressed before death by health care professionals. CONCLUSIONS: Despite advances in treatment, IDDM still carries an increased mortality for young people, particularly in the "transition" age range.