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Mikel Mikhail1, Keyvan Koushan2, Rajeshvar K Sharda2, Gloria Isaza2, Keith D Mann21Michael G DeGroote School of Medicine, 2Division of Ophthalmology, Department of Surgery, McMaster University, Hamilton, ON, CanadaPurpose: To report a case of aniridia in a pseudophakic patient following blunt trauma to the eye.Case report: The traumatized eye had cataract surgery through a 3.0 mm clear corneal incision 6 years prior to the incident. While there have been previous cases of traumatic aniridia in pseudophakic eyes, previous reports have all occurred closer to the time of the cataract surgery. We believe that the most likely mechanism of loss of iris tissue is through wound dehiscence, which would suggest the relative instability of clear corneal incisions several years postoperatively. The patient's visual acuity returned to 20/20 4 weeks post-trauma, with symptoms of glare which were managed by the use of a colored contact lens.Conclusion: The possibility of wound dehiscence should be recognized as an important clinical entity in the immediate postoperative period, but also several years following cataract surgery.Keywords: anirida, pseudophakia, cataract extraction, cataract, phacoemulsification, trauma

Research suggests parental ability to recognise when their child has overweight is limited. It is hypothesised that recognition of child overweight/obesity is fundamental to its prevention, acting as a potential barrier to parental action to improve their child's health-related behaviours and/or help seeking. The purpose of this study was to investigate the efficacy of an intervention (MapMe) to improve parental ability to correctly categorise their child as having overweight one-month post-intervention, and reduce child body mass index (BMI) z-score 12 months post-intervention. MapMe consists of body image scales of known child BMI and information on the consequences of childhood overweight, associated health-related behaviours and sources of support. We conducted a three-arm (paper-based MapMe, web-based MapMe and control) randomised control trial in fifteen English local authority areas with parents/guardians of 4-5- and 10-11-year-old children. Parental categorisation of child weight status was assessed using the question 'How would you describe your child's weight at the moment?' Response options were: underweight, healthy weight, overweight, and very overweight. Child weight status and BMI z-scores were calculated using objectively measured height and weight data and UK90 clinical thresholds. There was no difference in the percentage of parents correctly categorising their child as having overweight/very overweight ( n = 264: 41% control, 48% web-based, and 43% paper-based, p = 0.646). BMI z-scores were significantly reduced for the intervention group at 12 months post-intervention compared to controls ( n = 338, mean difference in BMI z-score change -0.11 (95% CI -0.202 to -0.020, p = 0.017). MapMe was associated with a decrease in BMI z-score 12 months post-intervention, although there was no direct evidence of improved parental ability to correctly categorise child overweight status. Further work is needed to replicate these findings in a larger sample of children, investigate mechanisms of action, and determine the use of MapMe as a public health initiative.

Purpose: Hearing loss is most prevalent among older adults, yet underestimated by patients, clinicians, and research communities. This study aimed to assess the accuracy of self-reported hearing difficulties among a group of adults aged 61-63 years, against audiometric measures., Method: The analysis used a sample ( N = 346) of the Newcastle Thousand Families Study birth cohort. Data from audiological examinations and self-reported hearing difficulties were used to compare subjective and objective hearing. Hearing aid use was also assessed., Results: Over 40% of the participants had some level of hearing loss ( n = 155, 44.8%), and 31% ( n = 133) of these reported having hearing problems during subjective assessment. Only 18 (10%) of those with objectively measured hearing loss reported using hearing aids., Conclusions: There was an inconsistency between measured and self-perceived hearing loss among adults aged 61-63 years in this cohort. The small number of hearing aid users in the cohort is a concern, in that people in this age group appear not to be getting the help they need. The data also add to the research evidence that people at this age underestimate their hearing loss.

Background: Early warning tools identify patients at risk of deterioration in hospitals. Electronic medical records in hospitals offer real-time data and the opportunity to automate early warning tools and provide real-time, dynamic risk estimates., Objective: This review describes published studies on the development, validation, and implementation of tools for predicting patient deterioration in general wards in hospitals., Methods: An electronic database search of peer reviewed journal papers from 2008-2020 identified studies reporting the use of tools and algorithms for predicting patient deterioration, defined by unplanned transfer to the intensive care unit, cardiac arrest, or death. Studies conducted solely in intensive care units, emergency departments, or single diagnosis patient groups were excluded., Results: A total of 46 publications were eligible for inclusion. These publications were heterogeneous in design, setting, and outcome measures. Most studies were retrospective studies using cohort data to develop, validate, or statistically evaluate prediction tools. The tools consisted of early warning, screening, or scoring systems based on physiologic data, as well as more complex algorithms developed to better represent real-time data, deal with complexities of longitudinal data, and warn of deterioration risk earlier. Only a few studies detailed the results of the implementation of deterioration warning tools., Conclusions: Despite relative progress in the development of algorithms to predict patient deterioration, the literature has not shown that the deployment or implementation of such algorithms is reproducibly associated with improvements in patient outcomes. Further work is needed to realize the potential of automated predictions and update dynamic risk estimates as part of an operational early warning system for inpatient deterioration., (©Kay D Mann, Norm M Good, Farhad Fatehi, Sankalp Khanna, Victoria Campbell, Roger Conway, Clair Sullivan, Andrew Staib, Christopher Joyce, David Cook. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 30.09.2021.)

Birth weight and early growth have been associated with later blood pressure. However, not all studies consistently find a significant reduction in blood pressure with an increase in birth weight. In addition, the relative importance of birth weight and of other lifestyle and environmental factors is often overlooked and the association is rarely studied in adolescents. We investigated early life predictors, including birth weight, of adolescent blood pressure in the Gateshead Millennium Study (GMS). The GMS is a cohort of 1029 individuals born in 1999-2000 in Gateshead in Northern England. Throughout infancy and early childhood, detailed information were collected, including birth weight and measures of height and weight. Assessments of 491 returning participants at age 12 years included measures of body mass and blood pressure. Linear regression and path analysis were used to determine predictors and their relative importance on blood pressure. Birth weight was not directly associated with blood pressure at the age of 12. However, after adjustment for contemporaneous body mass index (BMI), an inverse association of standardized birth weight on systolic blood pressure was significant. The relative importance of birth weight on later systolic blood pressure was smaller than other contemporaneous body measures (height and BMI). There was no independent association of birth weight on blood pressure seen in this adolescent population. Contemporaneous body measures have an important role to play. Lifestyle factors that influence body mass or size, such as diet and physical activity, where interventions are directed at early prevention of hypertension should be targeted.

Objectives: Refugees are most vulnerable to mental health problems of all migrant groups, and an understanding of the role of postdisplacement social factors in refugee emotional well-being can help to shape the future interventions for this group. We aimed to investigate the effect of social determinants, such as employment, language ability and accommodation, on mental health in refugees in the UK., Study Design: This prospective longitudinal cohort study was set in the UK. The study population of new UK refugees was drawn from an existing data set of the Longitudinal Survey of New Refugees (n = 5678), in which all new UK refugees (2005-2007) were sent a postal questionnaire at four time points across 2 years., Methods: Ordered logistic regression models were used to evaluate associations between social determinants and the dependent variables, emotional well-being or change in emotional well-being, using a question from the Short Form-36 Health Survey Questionnaire., Results: Refugees who were unemployed in the UK, could not speak English well or were unsatisfied with their accommodation had significantly higher odds of poorer emotional well-being in the cross-sectional analysis (P < 0.05 at all time points measured)., Conclusions: Postdisplacement social factors, including language ability, employment status and accommodation satisfaction, were important determinants of refugee emotional well-being. Changes in these social determinants have the potential to improve refugee mental health, making them legitimate, modifiable targets for important public health interventions. Accounting for this, further research into how to improve refugee well-being is crucial given the increase in refugee numbers around the developed world., (Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Parents tend to visually assess children to determine their weight status and typically underestimate child body size. A visual tool may aid parents to more accurately assess child weight status and so support strategies to reduce childhood overweight. Body image scales (BIS) are visual images of people ranging from underweight to overweight but none exist for children based on UK criteria. Our aim was to develop sex- and age-specific BIS for children, based on British growth reference (UK90) criteria., Methods: BIS were developed using 3D surface body scans of children, their associated weight status using UK90 criteria from height and weight measurements, and qualitative work with parents and health professionals., Results: Height, weight and 3D body scans were collected (211: 4-5 years; 177: 10-11 years). Overall, 12 qualitative sessions were held with 37 participants. Four BIS (4-5-year-old girls and boys, 10-11-year-old girls and boys) were developed., Conclusions: This study has created the first sex- and age-specific BIS, based on UK90 criteria. The BIS have potential for use in child overweight prevention and management strategies, and in future research. This study also provides a protocol for the development of further BIS appropriate to other age groups and ethnicities.

Background: Most evidence about what works in transitional care comes from small studies in single clinical specialties. We tested the hypothesis that exposures to nine recommended features of transitional healthcare were associated with better outcomes for young people with long-term conditions during transition from child-centred to adult-oriented health services., Methods: This is a longitudinal, observational cohort study in UK secondary care including 374 young people, aged 14-18.9 years at recruitment, with type 1 diabetes (n = 150), cerebral palsy (n = 106) or autism spectrum disorder with an associated mental health problem (n = 118). All were pre-transfer and without significant learning disability. We approached all young people attending five paediatric diabetes centres, all young people with autism spectrum disorder attending four mental health centres, and randomly selected young people from two population-based cerebral palsy registers. Participants received four home research visits, 1 year apart and 274 participants (73%) completed follow-up. Outcome measures were Warwick Edinburgh Mental Wellbeing Scale, Mind the Gap Scale (satisfaction with services), Rotterdam Transition Profile (Participation) and Autonomy in Appointments., Results: Exposure to recommended features was 61% for 'coordinated team', 53% for 'age-banded clinic', 48% for 'holistic life-skills training', 42% for 'promotion of health self-efficacy', 40% for 'meeting the adult team before transfer', 34% for 'appropriate parent involvement' and less than 30% for 'written transition plan', 'key worker' and 'transition manager for clinical team'. Three features were strongly associated with improved outcomes. (1) 'Appropriate parent involvement', example association with Wellbeing (b = 4.5, 95% CI 2.0-7.0, p = 0.001); (2) 'Promotion of health self-efficacy', example association with Satisfaction with Services (b = - 0.5, 95% CI - 0.9 to - 0.2, p = 0.006); (3) 'Meeting the adult team before transfer', example associations with Participation (arranging services and aids) (odds ratio 5.2, 95% CI 2.1-12.8, p < 0.001) and with Autonomy in Appointments (average 1.7 points higher, 95% CI 0.8-2.6, p < 0.001). There was slightly less recruitment of participants from areas with greater socioeconomic deprivation, though not with respect to family composition., Conclusions: Three features of transitional care were associated with improved outcomes. Results are likely to be generalisable because participants had three very different conditions, attending services at many UK sites. Results are relevant for clinicians as well as for commissioners and managers of health services. The challenge of introducing these three features across child and adult healthcare services, and the effects of doing so, should be assessed.

Aim: We hypothesized that participant well-being and satisfaction with services would be positively associated with a satisfactory clinical course during transition from child to adult health care., Methods: Some 150 young people with Type 1 diabetes mellitus from five diabetes units in England were recruited to a longitudinal study of transition. Each young person was visited at home four times by a research assistant; each visit was 1 year apart. Satisfaction with services (Mind the Gap; MTG) and mental well-being (Warwick-Edinburgh Mental Well-being Scale; WEMWBS) were captured. Change in HbA 1c , episodes of ketoacidosis, clinic and retinal screening attendance were used to assess clinical course. In total, 108 of 150 (72%) young people had sufficient data for analysis at visit 4., Results: Mean age at entry was 16 years. By visit 4, 81.5% had left paediatric healthcare services. Median HbA 1c increased significantly (P = 0.01) from 69 mmol/mol (8.5%) at baseline to 75 mmol/mol (9.0%) at visit 4. WEMWBS scores were comparable with those in the general population at baseline and were stable over the study period. MTG scores were also stable. By visit 4, some 32 individuals had a 'satisfactory' and 76 a 'suboptimal' clinical course. There were no significant differences in average WEMWBS and MTG scores between the clinical course groups (P = 0.96, 0.52 respectively); nor was there a significant difference in transfer status between the clinical course groups., Conclusions: The well-being of young people with diabetes and their satisfaction with transition services are not closely related to their clinical course. Investigating whether innovative psycho-educational interventions can improve the clinical course is a research priority., (© 2018 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: For young people with long-term conditions, transition from child to adult-oriented health services is a critical period which, if not managed well, may lead to poor outcomes. There are features of transition services which guidance and research suggest improve outcomes. We studied nine such features, calling them 'proposed beneficial features': age-banded clinic; meet adult team before transfer; promotion of health self-efficacy; written transition plan; appropriate parent involvement; key worker; coordinated team; holistic life-skills training; transition manager for clinical team. We aimed to describe the extent to which service providers offer these nine features, and to compare this with young people's reported experience of them., Methods: A longitudinal, mixed methods study followed 374 young people as their care moved from child to adult health services. Participants had type 1 diabetes, cerebral palsy or autism spectrum disorder with additional mental health difficulties. Data are reported from the first two visits, one year apart., Results: Three hundred four (81.3%) of the young people took part in the second visit (128 with diabetes, 91 with autism, 85 with cerebral palsy). Overall, the nine proposed beneficial features of transition services were poorly provided. Fewer than half of services stated they provided an age-banded clinic, written transition plan, transition manager for clinical team, a protocol for promotion of health self-efficacy, or holistic life-skills training. To varying degrees, young people reported that they had not experienced the features which services said they provided. For instance, the agreement for written transition plan, holistic life-skills training and key worker, was 30, 43 and 49% respectively. Agreement was better for appropriate parent involvement, age-banded clinic, promotion of health self-efficacy and coordinated team at 77, 77, 80 and 69% respectively. Variation in the meaning of the features as experienced by young people and families was evident from qualitative interviews and observations., Conclusions: UK services provide only some of the nine proposed beneficial features for supporting healthcare transition of young people with long term conditions. Observational studies or trials which examine the influence of features of transition services on outcomes should ensure that the experiences of young people and families are captured, and not rely on service specifications.

Observational evidence suggests that increased whole grain (WG) intake reduces the risks of many non-communicable diseases, such as CVD, type 2 diabetes, obesity and certain cancers. More recently, studies have shown that WG intake lowers all-cause and cause-specific mortality. Much of the reported evidence on risk reduction is from US and Scandinavian populations, where there are tangible WG dietary recommendations. At present there is no quantity-specific WG dietary recommendation in the UK, instead we are advised to choose WG or higher fibre versions. Despite recognition of WG as an important component of a healthy diet, monitoring of WG intake in the UK has been poor, with the latest intake assessment from data collected in 2000-2001 for adults and in 1997 for children. To update this information we examined WG intake in the National Diet and Nutrition Survey rolling programme 2008-2011 after developing our database of WG food composition, a key resource in determining WG intake accurately. The results showed median WG intakes remain low in both adults and children and below that of countries with quantity-specific guidance. We also found a reduction in C-reactive protein concentrations and leucocyte counts with increased WG intake, although no association with other markers of cardio-metabolic health. The recent recommendations by the UK Scientific Advisory Committee on Nutrition to increase dietary fibre intake will require a greater emphasis on consuming more WG. Specific recommendations on WG intake in the UK are warranted as is the development of public health policy to promote consumption of these important foods.

Background: Sedentary time (ST) has been reported to have a range of negative health effects in adults, however, the evidence for such effects among children and adolescents is sparse. The primary aim of the study was to examine associations between changes in sedentary behavior (time and fragmentation) and changes in adiposity across childhood and adolescence., Methods: Participants were recruited as part of the Gateshead Millennium Study. Measures were taken at age 7 (n=502), 9 (n=506), 12 (n=420) and 15 years (n=306). Participants wore an ActiGraph GT1M and accelerometer epochs were 'sedentary' when recorded counts were ⩽25 counts per 15 s. ST was calculated and fragmentation (SF) was assessed by calculating the number of sedentary bouts per sedentary hour. Associations of changes in ST and SF with changes in adiposity (body mass index (BMI), and fat mass index (FMI)) were examined using bivariate linear spline models., Results: Increasing ST by 1% per year was associated with an increase in BMI of 0.08 kg m -2 per year (95% CI: 0.06-0.10; P<0.001) and FMI of 0.15  kg m -2 per year (0.11-0.19; P<0.001). Change in SF was associated with BMI and FMI (P<0.001). An increase of 1 bout per sedentary hour per year (that is, sedentary time becoming more fragmented) was associated with an increase in BMI of 0.07  kg m -2 per year (0.06-0.09; P<0.001) and an increase in FMI of 0.14  kg m -2 per year (0.10-0.18; P<0.001) over the 8 years period. However, an increase in SF between 9-12 years was associated with a 0.09  kg m -2 per year decrease in BMI (-0.18-0.00; P=0.046) and 0.11  kg m -2 per year decrease in FMI (-0.22-0.00; P=0.049)., Conclusions: Increased ST and increased SF from 7-15 years were associated with increased adiposity. This is the first study to show age-specific associations between change in objectively measured sedentary behavior and adiposity after adjustment of moderate-to-vigorous-intensity physical activity in children and adolescents. The study suggests that, targeting sedentary behavior for obesity prevention may be most effective during periods in which we see large increases in ST.

This study aimed to assess the whole grain (WG) content of foods consumed in the UK which include ingredients that retain all three structural components of the grain, and contained ⩾10% WG. Dietary data from seven studies with 10,474 UK subjects were examined for foods containing WG. The WG content was then determined from ingredient lists, manufacturers' information and recipes. 372 food descriptors from nine food groups (4.4% of all food codes) contained ⩾10% WG. Of these 372 foods, 31.5% contained ⩾51%, 30.6% 25-50%, and 37.9% 10-24% WG dry matter as eaten. The relatively small number of WG foods identified in the total number of foods consumed confirms the low contribution of WG foods to the overall pattern of foods consumed in the UK. Since foods containing <51% WG accounted for the majority of WG food codes identified, recognising the importance of these foods to WG intake is essential., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: In many parts of the world policy and research interventions to modify sedentary behavior of children and adolescents are now being developed. However, the evidence to inform these interventions (e.g. how sedentary behavior changes across childhood and adolescence) is limited. This study aimed to assess longitudinal changes in sedentary behavior, and examine the degree of tracking of sedentary behavior from age 7y to 15y., Methods: Participants were part of the Gateshead Millennium Study cohort. Measures were made at age 7y (n = 507), 9y (n = 510), 12y (n = 425) and 15y (n = 310). Participants were asked to wear an ActiGraph GT1M and accelerometer epochs were defined as sedentary when recorded counts were ≤25 counts/15 s. Differences in sedentary time and sedentary fragmentation were examined using the Friedman test. Tracking was examined using Spearman's correlation coefficients and trajectories over time were assessed using multilevel linear spline modelling., Results: Median daily sedentary time increased from 51.3% of waking hours at 7y to 74.2% at 15y. Sedentary fragmentation decreased from 7y to 15y. The median number of breaks/hour decreased from 8.6 to 4.1 breaks/hour and the median bout duration at 50% of the cumulative sedentary time increased from 2.4 min to 6.4 min from 7y to 15y. Tracking of sedentary time and sedentary fragmentation was moderate from 7y to 15y however, the rate of change differed with the steepest increases/decreases seen between 9y and 12y., Conclusion: In this study, sedentary time was high and increased to almost 75% of waking hours at 15y. Sedentary behavior became substantially less fragmented as children grew older. The largest changes in sedentary time and sedentary fragmentation occurred between 9y to 12y, a period which spans the transition to secondary school. These results can be used to inform future interventions aiming to change sedentary behavior.

Epidemiological evidence suggests an inverse association between whole grain consumption and the risk of non-communicable diseases, such as CVD, type 2 diabetes, obesity and some cancers. A recent analysis of the National Diet and Nutrition Survey rolling programme (NDNS-RP) has shown lower intake of whole grain in the UK. It is important to understand whether the health benefits associated with whole grain intake are present at low levels of consumption. The present study aimed to investigate the association of whole grain intake with intakes of other foods, nutrients and markers of health (anthropometric and blood measures) in the NDNS-RP 2008-11, a representative dietary survey of UK households. A 4-d diet diary was completed by 3073 individuals. Anthropometric measures, blood pressure levels, and blood and urine samples were collected after diary completion. Individual whole grain intake was calculated with consumers categorised into tertiles of intake. Higher intake of whole grain was associated with significantly decreased leucocyte counts. Significantly higher concentrations of C-reactive protein were seen in adults in the lowest tertile of whole grain intake. No associations with the remaining health markers were seen, after adjustments for sex and age. Over 70% of this population did not consume the minimum recommend intake associated with disease risk reduction, which may explain small variation across health markers. Nutrient intakes in consumers compared with non-consumers were closer to dietary reference values, such as higher intakes of fibre, Mg and Fe, and lower intakes of Na, suggesting that higher intake of whole grain is associated with improved diet quality.

Increased whole grain intake has been shown to reduce the risk of many non-communicable diseases. Countries including the USA, Canada, Denmark and Australia have specific dietary guidelines on whole grain intake but others, including the UK, do not. Data from 1986/87 and 2000/01 have shown that whole grain intake is low and declining in British adults. The aim of the present study was to describe whole grain intakes in the most current dietary assessment of UK households using data from the National Diet and Nutrition Survey rolling programme 2008-11. In the present study, 4 d diet diaries were completed by 3073 individuals between 2008 and 2011, along with details of socio-economic status (SES). The median daily whole grain intake, calculated for each individual on a dry weight basis, was 20 g/d for adults and 13 g/d for children/teenagers. The corresponding energy-adjusted whole grain intake was 27 g/10 MJ per d for adults and 20 g/10 MJ per d for children/teenagers. Whole grain intake (absolute and energy-adjusted) increased with age, but was lowest in teenagers (13-17 years) and younger adults up to the age of 34 years. Of the total study population, 18% of adults and 15% of children/teenagers did not consume any whole-grain foods. Individuals from lower SES groups had a significantly lower whole grain intake than those from more advantaged classifications. The whole grain intake in the UK, although higher than in 2000/01, remains low and below that in the US and Danish recommendations in all age classes. Favourable pricing with increased availability of whole-grain foods and education may help to increase whole grain intake in countries without whole-grain recommendations. Teenagers and younger adults may need targeting to help increase whole grain consumption.

Background: Although a large number of previous studies suggest an association between birth weight and later blood pressure, others do not. Controversy surrounds the relative importance of these associations, in particular in relation to more modifiable factors in later life and whether the association would be seen in a, relatively disadvantaged, Indigenous population. The aim of this study, within the Aboriginal Birth Cohort study, was to examine the relative contributions and mediating pathways of birth weight, and later growth and lifestyle factors to variation in blood pressure at age 16-20 years., Methods: Detailed information was collected prospectively, including maternal smoking, birth weight, childhood BMI. At age 16-20 years, 451 underwent clinical examination, including the measurement of diastolic and systolic blood pressures. These data were analyzed using linear regression and path analyses, incorporating adjustment for potential confounders., Results: Increased BMI at age 18 years was significantly associated with both increasing systolic and diastolic blood pressures. BMI had the highest relative importance and mediated the effects from earlier in life, including birth weight. Being female and living in remote residence were also independently associated with a reduction in systolic blood pressure., Conclusion: Blood pressure in this cohort is primarily influenced by contemporaneous BMI, which in this population at this age is generally lower than that seen in non-Indigenous populations in developed countries. However, other factors, including birth weight, do appear to play a role that is mediated through later BMI.

Objectives: It is known that childhood hearing function can become impaired after the occurrence of specific infections. However, evidence on the effect of common childhood infections on adult hearing function is limited. The objective of the study was to identify whether associations exist between the occurrence of common childhood infections in a UK birth cohort and hearing function across different frequencies at age 61 to 63 years., Design: The Newcastle Thousand Families study is a birth cohort of all individuals born in May and June 1947 to mothers resident in Newcastle upon Tyne, United Kingdom. Of the original cohort members who had an audiometry test at age 61 to 63 years, 333 had data available on infections during their first year of life and 296 on infections up to their fifth year of life. These data were analyzed using linear regression in relation to adult hearing function across differing frequencies in isolation., Results: After adjustment for sex, overcrowding in the first year, having had an ear operation, and having worked in a loud environment, significant negative associations were identified between adult hearing and tonsillitis at 250 Hz (p = 0.013), 1 kHz (p = 0.018), 6 kHz (p = 0.012), and 8 kHz (p = 0.033); otorrhea at 4 kHz (p = 0.005), 6 kHz (p = 0.003), and 8 kHz (p = 0.002); bronchitis (two or more episodes) at 2 kHz (p = 0.001), 3 kHz (p = 0.005), 4 kHz (p = 0.009), 6 kHz (p < 0.001), and 8 kHz (p < 0.001); and the total number of severe respiratory infections in the first year at 2 kHz (p = 0.037), 3 kHz (p = 0.049), 4 kHz (p = 0.030), 6 kHz (p < 0.001), and 8 kHz (p = 0.006). That is, individuals who had tonsillitis, bronchitis (twice or more), otorrhea, or a severe respiratory infection (twice or more) in their first year of life were more likely to have impaired adult hearing function than those who did not have any infections in early life., Conclusion: The occurrence of some, but not all, childhood infections appears to have an effect on adult hearing function across different frequencies. Reducing the incidence of infectious diseases in early life may reduce subsequent incidence of hearing impairment among adults. However, further research in modern cohorts is needed to clarify the links between infectious childhood diseases and adult hearing function.

Background: In this study, we used data from Australia's Northern Territory to assess differences in self-reported smoking prevalence between the Indigenous and non-Indigenous populations. We also used urinary cotinine data to assess the validity of using self-reported smoking data in these populations., Methods: The Aboriginal Birth Cohort (ABC) is a prospective study of 686 Aboriginal babies born in Darwin 1987-90. The Top End Cohort (TEC) is a study of non-Indigenous adolescents, all born in Darwin 1987-91. In both studies, participants aged between 16 and 21 years, were asked whether they smoked. Urinary cotinine measurements were made from samples taken at the same visits., Results: Self-reported smoking prevalence was 68% in the ABC and 14% in the TEC. Among the self-reported non-smokers, the median cotinine levels were higher in the ABC (33 ng/ml) than in the TEC (5 ng/ml), with greater percentages of reported non-smokers in the under 50 ng/ml group in the TEC than in the ABC CONCLUSIONS: Prevalence of smoking was much higher in the ABC than in the TEC. The higher cotinine levels in ABC non-smokers may reflect an underestimated prevalence, but is also likely to reflect higher levels of passive smoking. A broader approach encompassing social, cultural and language factors with increased attention to smoking socialisation factors is required.

It has been suggested that in addition to genetic factors, fetal and post-natal growth influence cognition in early adulthood. However, most studies have been in developed populations, so it is unclear if the same findings would be seen in other, less developed, settings, and have used testing tools not applicable to an Australia Aboriginal population. This study investigated the relationships between cognitive function in early adulthood and birth weight and contemporary height. Simple reaction time (SRT), choice reaction time (CRT) and working memory (WM) were assessed using the CogState battery. A significant association was seen between birth weight and SRT in early adulthood, but not with the other two cognitive measures. Urban dwellers had significantly shorter SRT and CRT than their remote counterparts. Contemporary body mass index and maternal age were associated with CRT. Only fetal growth restriction was associated with WM, with greater WM in those with restricted growth. No associations were seen with contemporary height. These results suggest that fetal growth may be more important than the factors influencing post-natal growth in terms of cognition in early adulthood in this population, but that the associations may be inconsistent between cognitive outcomes. Further research is required to identify whether similar associations are seen in other, similar, populations and to assess why differences in cognitive outcome measures are seen.

Background: Musculoskeletal ultrasound has been found to be more sensitive than radiographs in detecting osteophytes. Our objective was to measure the prevalence of features of osteoarthritis (OA), in the dominant hand, knees and hips using ultrasound, within the Newcastle Thousand Families birth cohort., Methods: Participants were aged 61-63 (mean 63) years. Knee images were scored for presence of osteophytes and effusion. Hip images were scored for the presence of osteophytes and femoral head abnormality. The first carpometacarpal joint, metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints of the index finger (dominant hand) were imaged for osteophytes., Results: Among 311 participants, prevalence of osteophytes at the distal interphalangeal joint was 70% while it was 23%, 10% and 41% for index proximal interphalangeal and metacarpophalangeal and thumb base carpometacarpal joints respectively. Prevalence of knee osteophytes was 30%, hip OA was 41%. Prevalence of knee effusions was 24% (right) and 20% (left). Ultrasound evidence of generalised OA (48%) and isolated hand OA (31%) was common, compared to isolated hip or knee OA (5%) and both hip and knee OA (3%)., Conclusion: This is the first study to assess prevalence of ultrasound features of OA in a population-based sample. The higher prevalence of hand/hip OA, when compared to previous radiographic studies, supports the hypothesis that ultrasound is more sensitive than radiography in detecting OA, particularly for osteophytes.

Background: Helicobacter pylori infection is acquired in early childhood and persists for life (or until eradication treatment is taken). Seropositivity of H. pylori at age 49-51 years was assessed in relation to socio-economic deprivation in early life and the timing of other childhood infections common at that time., Methods: Prospectively collected socio-economic and morbidity data from the Newcastle Thousand Families study, a birth cohort established in 1947. H. pylori IgG seropositivity was assessed at 49-51 years and examined in relation to both whether the individual had been diagnosed with one of measles, mumps or chicken pox, and, if so, the age at first infection. This was done in logistic regression models, allowing adjustment for socio-economic status and housing quality in childhood., Results: Adult H. pylori status was strongly linked to disadvantaged socio-economic status in early life (p ≤ 0.002), unlike measles, mumps and chicken pox which showed no associations. Early measles infection was independently associated with H. pylori seropositivity (p = 0.01)., Conclusions: Of the four infectious diseases that we have studied, it appears that H. pylori differs from the others by the strength of association with socio economic deprivation in early childhood. Our findings further highlight the complex interaction between measles, childhood infections and other non-microbiological factors that occur within a whole population. These data suggest a strong association between H. pylori and deprivation and raise the possibility of an interaction between early measles exposure and increased risk of exposure to H. pylori infection.

Background: While current research priorities include investigations of age-related hearing loss, there are concerns regarding effects on childhood hearing, for example through increased personal headphone use. By utilising historical data, it is possible to assess what factors may have increased hearing problems in children in the past, and this may be used to inform current public health policies to protect children against hearing loss and in turn reduce the long-term burden on individuals and services that may possible evolve. The aim of this study was to investigate which factors in early life significantly impacted on hearing level in childhood using existing data from the Newcastle Thousand Families Study, a 1947 birth cohort., Methods: Data on early life factors, including growth, socio-economic status and illness, and hearing at age 14 years were collated for a representative subset of individuals from the cohort (n = 147). Factors were assessed using linear regression analysis to identify associations with hearing thresholds., Results: Males were found to have lower hearing thresholds at 250 Hz, 500 Hz and 1 kHz. Main analyses showed no associations between hearing thresholds and early life growth or socio-economic indicators. An increasing number of ear infections from birth to age 13 years was associated with hearing thresholds at 250Hz (p = 0.04) and 500Hz (p = 0.03), which remained true for females (p = 0.050), but not males (p = 0.213) in sex-specific analysis. Scarlet fever and bronchitis were associated with hearing thresholds at 8 kHz. After adjustment for all significant predictors at each frequency, results remained unchanged., Conclusions: We found no associations between childhood hearing thresholds and early life growth and socio-economic status. Consistent with other studies, we found associations between childhood infections and hearing thresholds. Current public health strategies aimed at reducing childhood infections may also have a beneficial effect upon childhood hearing.

Objective: To examine the relationships between birthweight, current size, and fasting glucose and fasting insulin levels in Aboriginal adolescents., Design, Participants and Setting: Longitudinal prospective study of a Northern Territory Aboriginal birth cohort of 686 Aboriginal babies born at the Royal Darwin Hospital between January 1987 and March 1990, and followed up between December 2006 and January 2008 in over 40 NT locations., Main Outcome Measures: Fasting insulin and glucose levels, adjusted for gestational age, sex and contemporary age., Results: Among the 134 participants with complete data, those with fetal growth restriction (FGR) or low birthweight (LBW) at birth were not overweight at 18 2013s. In these circumstances, birthweight showed a significant positively directed association with fasting glucose levels (P = 0.002). Current weight showed a significant and positively directed association with both fasting insulin (P < 0.001) and fasting glucose levels (P = 0.001), and current height showed a significant and positively directed association with insulin levels (P = 0.006)., Conclusions: Birthweight was only positively associated with fasting glucose levels, with no association with fasting insulin levels. The high-risk combination for type 2 diabetes of LBW or FGR with later overweight or obesity was rare in this adolescent Aboriginal population.

Background: It is suggested that impaired fetal growth can affect kidney development, resulting in fewer glomeruli being formed and reduced kidney function later in life. The aim of this study was to investigate early life variables in relation to adult kidney function, and compare these to the influence of later life variables., Methods: Detailed information was collected prospectively regarding 1,142 babies, born in 1947 in Newcastle upon Tyne. At the age of 63-64 years, 335 participants had serum creatinine successfully measured and completed a lifestyle questionnaire. These measurements were used to calculate their estimated glomerular filtration rate (eGFR)., Results: Body mass index (BMI) and being female were significantly negatively associated with eGFR. Birth weight was significantly positively associated with eGFR. In sex-specific analyses, BMI and cigarette smoking remained significant for males (n = 154), with a near significant association for birth weight, whereas none of the variables remained significant for females (n = 181)., Conclusions: The findings suggest that sex, size at birth and BMI may be important variables influencing adult kidney function. However, as only a small amount of variance in eGFR was explained by these variables, additional longitudinal studies would be beneficial for assessing lifecourse influences on kidney function.

Background: Despite marked improvements in childhood leukaemia survival, 20% still die within 5 years of diagnosis. The aim of this study was to evaluate the relationship between socioeconomic status, as assessed by paternal occupation at birth, and survival from childhood leukaemia in children, using data from the Northern Region Young Persons Malignant Disease Registry., Methods: All 1007 cases of leukaemia in children aged 0-14 years, diagnosed between 1968 and 2010 and registered with the Registry were studied. Paternal occupational social class at the time of the child's birth was obtained and analysed in relation to survival using Cox-proportional regression., Results: Compared with the most advantaged group (I/II), those in the middle group (IIIN/M) had a 68% increased risk of death, while those in the least advantaged group (IV/V) had 86% higher risk for acute lymphoblastic leukaemia. While the survival advantage of children in class I/II was apparent from the time of diagnosis, survival for children in groups IIIN/M and IV/V were comparable until 3-4 years after diagnosis, when they began to minimally diverge., Conclusion: The existence of such socioeconomic disparities cannot be attributed to accessibility to health care in the United Kingdom. Further research into the likely factors underlying these disparities is required.

Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome is caused by an activation mutation of glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme responsible for the reversible interconversion between glutamate and α-ketoglutarate. The syndrome presents clinically with hyperammonemia, significant episodic hypoglycemia, seizures, and frequent incidences of developmental and learning defects. Clinical research has implicated that although some of the developmental and neurological defects may be attributed to hypoglycemia, some characteristics cannot be ascribed to low glucose and as hyperammonemia is generally mild and asymptomatic, there exists the possibility that altered GDH1 activity within the brain leads to some clinical changes. GDH1 is allosterically regulated by many factors, and has been shown to be inhibited by the ADP-ribosyltransferase sirtuin 4 (SIRT4), a mitochondrially localized sirtuin. Here we show that SIRT4 is localized to mitochondria within the brain. SIRT4 is highly expressed in glial cells, specifically astrocytes, in the postnatal brain and in radial glia during embryogenesis. Furthermore, SIRT4 protein decreases in expression during development. We show that factors known to allosterically regulate GDH1 alter gliogenesis in CTX8 cells, a novel radial glial cell line. We find that SIRT4 and GDH1 overexpression play antagonistic roles in regulating gliogenesis and that a mutant variant of GDH1 found in HI/HA patients accelerates the development of glia from cultured radial glia cells., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives: We investigated the contributions of a range of factors from across life to variations in physical activity within the Newcastle Thousand Family's birth cohort., Methods: At age 49-51 years, 574 study members returned questionnaires, including details of physical activity (occupational, commuting, household and sport). Factor analysis of activity types produced two retained factor scores, 'sport' and 'other physical activity', analysed by path analysis., Results: More advantaged current social class, higher education level and not smoking were associated with increased sport activity, but not 'other physical activity'. Males had higher levels of occupational and lower levels of household activity than females. Smokers had increased work activity. Long-term illness was associated with lower activity across all types. Current social class and smoking showed the highest relative contribution for 'sport' and long-term illness for 'other physical activity'., Conclusion: Increasing activity in adults requires better understanding what the barriers to maintaining or taking on new levels of physical activity are, and long-term strategies and public health interventions need to be developed to engage adults in interesting, affordable and available activities.

Background: A decade ago it was reported that childhood cancer incidence was higher in boys than girls in many countries, particularly those with low gross domestic product (GDP) and high infant mortality rate. Research suggests that socio-economic and cultural factors are likely to be responsible. This study aimed to investigate the association between cancer registration rate sex ratios and economic, social and healthcare-related factors using recent data (1998-2002)., Methods: For 62 countries, childhood (0-15 years) cancer registration rate sex ratios were calculated from Cancer Incidence in Five Continents Vol IX, and economic, social and healthcare indicator data were collated., Results: Increased age standardised cancer registration rate sex ratio (M:F) was significantly associated with decreasing life expectancy (P=0.05), physician density (P=0.05), per capita health expenditure (P=0.05), GDP (P=0.01), education sex ratios (primary school enrolment sex ratio (P<0.01); secondary school enrolment sex ratio (P<0.01); adult literacy sex ratio (P<0.01)) and increasing proportion living on less than Int$1 per day (P=0.03)., Conclusion: The previously described cancer registration sex disparity remains, particularly, in countries with poor health system indicators and low female education rates. We suggest that girls with cancer continue to go undiagnosed and that incidence data, particularly in low- and middle-income countries, should continue to be interpreted with caution.

Objective: To compare three different techniques of obtaining informed patient consent and the relative acceptance rates for resident involvement in cataract surgery. The techniques differed with regards to physician-patient interaction, and how resident involvement was presented., Design: A retrospective cohort study in a tertiary care ophthalmology department with a recently established residency training program., Participants: 356 patients undergoing informed consent procedure for cataract surgery., Methods: Charts of all patients undergoing cataract surgery by 3 cataract surgeons from October 2009 to March 2010 were reviewed. Patient demographics, the documentation of a specific request for resident participation, and the patient response were recorded. Response rates were analyzed between the three different techniques/surgeons., Results: Consent to resident participation was found to range from 21% to 86%. Higher acceptance rates were associated with direct personal conversation between surgeon and patient., Conclusion: High acceptance rates for resident involvement in cataract surgery can be achieved with full disclosure of resident involvement to patients., (Copyright © 2012 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Telomere length is emerging as a potential factor in the pathogenesis of cardiovascular disease. We investigated whether birth weight, infant growth, childhood cognition and adult height, as well as a range of lifestyle, socio-economic and educational factors, were associated with white blood cell telomere length at age 49-51 years., Methods: The study included 318 members of the Newcastle Thousand Families Study, a prospectively followed birth cohort which includes all individuals born in Newcastle, England in May and June 1947, who attended for clinical examination at age 49-51 years, and had telomere length successfully measured using real-time PCR analyses of DNA extracted from peripheral blood mononuclear cells., Results: No association was found between birth weight and later telomere length. However, associations were seen with other factors from early life. Education level was the only predictor in males, while telomere length in females was associated with gestational age at birth, childhood growth and childhood IQ., Conclusions: While these findings may be due to chance, in particular where differing associations were seen between males and females, they do provide evidence of early life associations with telomere length much later in life. Our findings of sex differences in the education association may reflect the sex differences in achieved education levels in this generation where few women went to university regardless of their intelligence. Our findings do not support the concept of telomere length being on the pathway between very early growth and later disease risk.

Background: With a number of studies suggesting associations between early life influences and later chronic disease risk, it is suggested that associations between early growth and later physical activity (PA) may be a mediator. However, conflicting evidence exists for association between birth weight and childhood PA. In addition, it is important to know what other, potentially modifiable, factors may influence PA in children given its' association with childhood and later adiposity. We used the Gateshead Millennium Study (GMS) to identify predictors of childhood PA levels., Methods: The GMS is a cohort of 1029 infants born in 1999-2000 in Gateshead in northern England. Throughout infancy and early childhood, detailed information was collected. Assessments at age 9 years included body composition, objective measures of habitual PA and a range of lifestyle factors. Mean total volumes of PA (accelerometer count per minute, cpm) and moderate-vigorous intensity PA (MVPA), and the percentage of time spent in sedentary behaviour (%SB) were quantified and related to potential predictors using linear regression and path analysis., Results: Children aged 8-10 years were included. Significant differences were seen in all three outcome variables between sexes and season of measurement (p<0.001). Restricting children's access to television was associated with decreased MVPA. Increased paternal age was associated with significant increases in %SB (p = 0.02), but not MVPA or total PA. Increased time spent in out of school sports clubs was significantly associated with decreased %SB (p = 0.02). No significant associations were seen with birth weight., Conclusion: A range of factors, directly or indirectly, influenced PA and sedentary behaviour. However, associations differed between the different constructs of PA and %SB. Exploring further the sex differences in PA would appear to be useful, as would encouraging children to join out of school sports clubs.

Dense mammographic patterns are a strong predictor of breast cancer risk. Factors at differing stages of life have been linked to breast cancer risk, although rarely studied simultaneously. We aimed to investigate whether birth weight and factors later in life were associated with mammographic density in the Newcastle Thousand Families Study. The Study originally consisted of all 1142 babies born in May and June 1947 to mothers resident in Newcastle upon Tyne in Northern England. Detailed information was collected prospectively during childhood, including birth weight and socio-economic circumstances. At age 49-51 years, 574 study members completed a 'Health and Lifestyle' questionnaire. Of the 307 surviving women who returned these questionnaires, 199 returned a further questionnaire asking for details of routine mammographic screening, their reproductive and contraceptive history. Mammographic patterns were coded into Wolfe categories. This was analysed, by ordinal logistic regression, in relation to a range of variables at different stages of life. Increased standardised birth weight (odds ratio, OR 1.32 (95% CI 1.02-1.71) P = 0.03) was a significant independent predictor of higher density. Increasing body mass index (BMI) was predictive of lower density (OR 0.86 per Kg/m(2) (95% CI 0.81-0.92) P < 0.001), as was having reached menopause (OR, compared to pre- and peri-menopausal, 0.41 (95% CI 0.23-0.73) P = 0.002). Interactions were seen between menopausal status and both BMI and age at menarche (P = 0.06) on density, although for neither did the direction of association change. After adjustment for factors acting throughout life, we identified a significant association between standardised birth weight and density in adulthood, consistent with previous research suggesting that heavier babies have an increased risk of breast cancer in later life. We also confirmed associations between both BMI and menopausal status.

Central regulation of cardiac output via the sympathetic and parasympathetic branches of the autonomic nervous system allows the organism to respond to environmental changes. Sudden onset stimuli, startle stimuli, are useful probes to study central regulatory responses to the environment. In mammals, startle stimuli induce a transient bradycardia that habituates with repeated stimulation. Repeated presentation of the stimulus results in tachycardia. In this study, we investigate the behavioral regulation of heart rate in response to sudden stimuli in the zebrafish. Larval zebrafish show a stereotyped heart rate response to mild electrical shock. Naïve fish show a significant increase in interbeat interval that resolves in the 2 s following stimulation. This transient bradycardia decreases on repeated exposure to the stimulus. Following repeated stimulation, the fish become tachycardic within 1 min of stimulation. Both the transient bradycardia and following tachycardia responses are blocked with administration of the ganglionic blocker hexamethonium, demonstrating that these responses are mediated centrally. The transient bradycardia is blocked by the muscarinic antagonist atropine, suggesting that this response is mediated by the parasympathetic system, while the following tachycardia is specifically blocked by the beta-adrenergic antagonist propranolol, suggesting that this response is mediated by the sympathetic nervous system. Together, these results demonstrate that at the larval stage, zebrafish actively regulate cardiac output to changes in their environment using both the parasympathetic and sympathetic branches of the autonomic nervous system, a behavioral response that is markedly similar to that observed in mammals to similar sudden onset stimuli.