Obesity, diabetes and their metabolic correlates in middle-aged adults with Down syndrome.

BACKGROUND: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile. METHODS: This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.7 ± 5.7 years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI < 18.5 kg/m2 ), normal (BMI 18.5-24.9 kg/m2 ), overweight (BMI 25-29.9 kg/m2 ) and obese (BMI ≥ 30 kg/m2 ). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c < 5.7%), pre-diabetes (HbA1c 5.7-6.4%) and diabetes (HbA1c ≥ 6.5%). We measured non-fasting lipids, hsCRP, insulin, adiponectin and leptin. RESULTS: The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre-diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non-HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P < 0.001). CONCLUSIONS: The only metabolic correlate of obesity in middle-aged adults with Down syndrome was high leptin levels. Our findings are limited by non-fasting laboratory tests but suggest that middle-aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome.

An improved method for detecting telomere size differences in T-lymphocyte interphases from older people with Down syndrome with and without mild cognitive impairment.

Telomere size (quantified by fluorescence intensity and physical lengths) in short-term T-lymphocyte cultures from adults with Down syndrome (DS) with and without mild cognitive impairment (MCI-DS) or dementia was compared. For these studies, dementia status was determined based on longitudinal assessments employing a battery of cognitive and functional assessments developed to distinguish adult-onset impairment from preexisting developmental disability. In the course of our studies using a MetaSystems Image Analyzer in combination with ISIS software and a Zeiss Axioskop 2, we found that Fluorescein isothiocyanate (FITC) telomere fluorescence referenced to chromosome 2-identified FITC probe fluorescence as a nontelomere standard (telomere/cen2 ratio) showed great promise as a biomarker of early decline associated with Alzheimer's disease (AD) in this high-risk population. We have now obtained a cen (2) CY3 probe that can clearly be distinguished from the blue-green FITC interphase telomere probe, providing a clear distinction between telomere and centromere fluorescence in both interphase and metaphase. We used FITC/CY3 light intensity ratios to compare telomere length in interphases in adults with DS with and without MCI-DS or dementia. Five age-matched female and five age-matched male pairs (n = 10) all showed clear evidence of telomere shortening associated with clinical progression of AD (P < 0.002 - P < 0.000001), with distributions of mean values for cases and controls showing no overlap. We also examined the time needed for microscopy using interphase versus metaphase fluorescence preparations. With interphase preparations, examination time was reduced by an order of magnitude compared with metaphase preparations, indicating that the methods employed herein have considerable practical promise for translation into broad diagnostic practice.

Our approach to changing the culture of caring for the acutely unwell patient at a large UK teaching hospital: A service improvement focus on Early Warning Scoring tools.

INTRODUCTION: Early Warning Scoring tools (EWS) play a major role in the detection of the deteriorating ward patient. EWS tools have been in place in Nottingham University Hospitals NHS Trust for over five years but compliance has been low. A service improvement project commenced across all admission wards in 2013, initiated through a financially driven CQUIN. Prior to the project, only one out of five clinical care targets set were achieved. STRATEGY: An established framework for service improvement was used to guide delivery. The approach has consisted of multi-faceted, inter-professional high impact interventions including ward delivered education, human factors training and clinician feedback, combined with regular performance audits. RESULTS: Since introduction of the service improvement team, consistent signs of improvement have been visible across the admission areas in four out of five of the clinical care targets. CONCLUSION: The first 12 months of the project has seen tangible benefits in patient care and staff experience. Personal feedback both to medical and nursing staff has been effective where a top-down approach may not have been.

The local metallicity of gadolinium doped compound semiconductors.

The local metallicities of Hf(0.97)Gd(0.03)O(2), Ga(0.97)Gd(0.03)N, Eu(0.97)Gd(0.04)O and EuO films were studied through a comparison of the findings from constant initial state spectroscopy using synchrotron light. Resonant enhancements, corresponding to the 4d → 4f transitions of Eu and Gd, were observed in some of the valence band photoemission features. The resonant photoemission intensity enhancements for the Gd 4f photoemission features are far stronger for the more insulating host systems than for the metallic system Eu(0.96)Gd(0.04)O. The evidence seems to suggest a correlation between the effective screening in the films and the resonant photoemission process.

Variation in inspiratory time and tidal volume with T-piece neonatal resuscitator: association with operator experience and distraction.

The most recent Neonatal Resuscitation Programme (NRP 5th edition) guidelines recognise the T-piece resuscitator (Neopuff) device as an acceptable method of administering a pre-selected peak inspiratory pressure (PIP) and positive end expiratory pressure (PEEP). While these are constant, other parameters are operator-dependent. Although in widespread clinical use, there is little published data on the use of the T-piece resuscitator in neonatal resuscitation. This study showed that despite fixed inflating pressures, less experienced operators used prolonged inspiratory times. Wide variation in mean airway pressure and tidal volume were seen in all operators.

Verbal intrusions precede memory decline in adults with Down syndrome.

BACKGROUND: Verbal intrusion errors are irrelevant responses made in the course of verbal memory retrieval or language production that have been associated with disruption of executive functions and the prefrontal cortex. They have been observed to occur more frequently both with normal aging and with neurodegenerative diseases such as Alzheimer's disease (AD). The purpose of this study was to longitudinally examine the production of verbal intrusions among middle-aged adults with Down syndrome (DS) and unspecified intellectual disability (ID) to determine whether producing verbal intrusions at one point in time was related to subsequent verbal memory performance. Because of the combination of a relative deficit in verbal working memory (WM), premature aging, and higher risk of AD among adults with DS, it was predicted that they would make more verbal intrusions than adults with unspecified ID. METHODS: Word List recall (WLR), the Selective Reminding Test (SRT), and the Cued Recall Test (CRT), were administered three times at 18-month intervals during a 3-year period. In Analysis 1, aetiology differences in making intrusion errors were examined. Twenty-three adults with unspecified ID in the moderate to mild range [time 1(T1) mean age = 47.2 years] and 42 adults with DS (T1 mean age = 44.3) participated. WLR is a serial WM task beginning at two word sequences and progressively increasing by one word every three trials. WLR intrusions were analysed because they were least likely to include 'educated guesses' because this test is not based on semantic categories. In Analysis 2, we only examined participants with DS. They were divided into two groups, 16 individuals who made at least one intrusion error at T1 (T1 mean age = 45.8) and 26 who did not (T1 mean age = 43.3). Longitudinal performance for these groups was analysed to determine whether the group that intruded at T1 did more poorly on subsequent memory tests. RESULTS: A higher proportion of responses comprised intrusions for the group with DS and a higher percentage of the participants with DS made at least one intrusion error when compared with participants with unspecified ID (74% and 44% respectively). Those participants with DS who made at least one intrusion error at T1 showed a subsequent decline in performance on both WLR and the SRT. CONCLUSIONS: The production of intrusion errors during a verbal WM task is a characteristic of middle-aged adults with DS. This suggests compromised executive function and control of inhibition within the verbal modality for this group. Further, verbal intrusions are a qualitative aspect of verbal processing that merit attention in considering the issue of deficiencies of language and verbal WM abilities among people with DS. Last, and perhaps most importantly, although not definitive diagnostically, an increase in verbal intrusions is a potentially noteworthy signal when evaluating the cognitive health of adults with DS.

Dementia of the Alzheimer's type and accelerated aging in Down syndrome.

This case study, of a woman with Down syndrome and dementia of the Alzheimer's type (DAT), follows the course of her decline over an 11-year period until death at age 57. Detailed neuropathological findings are also presented. This case illustrates features of premature aging that are typically associated with Down syndrome, and the progressive changes in memory and cognition that are usually associated with DAT. Although the subject's cardiovascular condition and thyroid disorder were treated, they may have contributed to the decline of her memory. This case shows the difficulty in diagnosing dementia in an individual with mental retardation who suffered comorbid episodes of depression and psychosis.

Sex differences in performance over 7 years on the Wechsler Intelligence Scale for Children--Revised among adults with intellectual disability.

BACKGROUND: The aim of this study was to explore changes related to sex differences on the Wechsler Intelligence Scale for Children - Revised (WISC-R) subtest performance over a 7-year interval in middle-aged adults with intellectual disability (ID). Cognitive sex differences have been extensively studied in the general population, but there are few reports concerning individuals with ID. Sex differences are of current relevance to actively debated issues such as cognitive changes during menopause and risk for Alzheimer's disease. Given that hormonal effects on cognition have been observed in the general population, particularly in areas such as visuospatial processing, and individuals with Down's syndrome (DS) have been reported to be hormonally and reproductively atypical, we analysed our data to allow for the possibility of an aetiology-specific profile of sex differences for these adults. METHODS: The WISC-R subtests were administered in a longitudinal study, as part of a more comprehensive test battery, at least twice within 7 years. Participants were 18 females with ID without DS [age at first test time (time 1): mean = 40.5; IQ: mean = 59.3], 10 males with ID without DS (age at time 1: mean = 42.4; IQ: mean = 59.4), 21 females with DS (age at time 1: mean = 37.9; IQ: mean = 51.6), and 21 males with DS (age at time 1: mean = 40.3; IQ: mean = 54.3). All participants were in the mild to moderate range of ID and were displaying no changes suggestive of early dementia. RESULTS: Females, regardless of aetiology of ID, exhibited a robust superiority on the coding subtest, which parallels the widely reported difference among adults in the general population. Additionally, there was a decline in overall performance during the 7-year study interval, particularly on the verbal subscale subtests, but there was no evidence of sex-differentiated decline. There were also marginal sex by aetiology interactions on the object assembly and block design subtests, suggesting that males with unspecified ID might perform better than their female peers, but among adults with DS, females might do better than males. CONCLUSIONS: This study supports the presence of cognitive sex differences in the population with ID as indicated by female superiority on the WISC-R coding subtest. Extending this observation to adults with ID has implications for explanations of female advantage on this task, which now have to account for its presence among individuals with a broader range of intellectual capabilities, more atypical developmental histories and more varied genotypes than previously considered. Trends towards sex by aetiology interactions on the two visuoconstructive subtests, while marginal, were sufficient to warrant continued consideration of the idea of a distinct profile of sex differences for adults with DS and to justify looking at the effects of sex separately within different aetiologies of ID.

Cued recall in early-stage dementia in adults with Down's syndrome.

BACKGROUND: Memory declines were evaluated with an adaptation of the Cued Recall Test (CRT) in 19 adults with Down's syndrome (DS) with mild or moderate intellectual disability (ID) who were at an early-stage of dementia of the Alzheimer type (DAT), and their performance was compared to peer groups of 75 adults with DS and 66 adults with ID without DS who were not suspected of functional declines. METHOD: The CRT consisted of a training period in which 12 items were presented, four at a time, with each item accompanied by a unique category cue. The testing phase consisted of three trials which generated two measures, a free recall score (FRS; spontaneous recall of the list of 12 items) and a total score (TS; FRS plus items recalled when the category cue was provided). RESULTS: It was found that a cut-off value of < or = 23 on the TS resulted in a sensitivity of 94.7% and a specificity of 93.9% with a positive predictive value of 81.9% when those individuals with DAT were compared to the participants with ID without DS. Eight of these individuals with DAT had relatively poor performance on the CRT compared to their healthy peers at a baseline when they were not suspected of functional declines, suggesting that memory declines can occur several years prior to the identification of DAT. In addition, 17 participants with DS without a diagnosis of DAT met the criterion for the cut-off score. Longitudinal data and converging measures indicated that there was the possibility that 15 of these individuals are in a 'pre-clinical' stage of decline. CONCLUSION: The usefulness of the CRT as a screening test for early memory deficits for this population needs to be confirmed by following these participants for an extended period of time and by studying an independent sample.

Changes in explicit memory associated with early dementia in adults with Down's syndrome.

BACKGROUND: A modified version of the Selective Reminding Test (SRT) (Buschke 1973) was used to examine the changes in memory that occur with early-stage dementia of the Alzheimer's type (DAT) in adults with intellectual disability (ID) and Down's syndrome (DS), and to compare these changes to those occurring with 'normal' ageing. METHOD: Hierarchical linear modelling analyses showed steep declines in the performance of participants who had met the criteria for the onset of DAT. Non-demented participants also showed declines in performance which were related to their age. However, the absolute magnitude of these declines was consistent with a 'normal' ageing pattern and not with undetected dementia. RESULTS: In analysing the specific memory components that are compromised, the present authors found that participants with early-stage DAT showed severely diminished long-term storage and retrieval processing abilities compared to their non-demented peers. Notably, these declines preceded other symptoms of dementia, in most cases by more than a full year and sometimes by as much as 3 years. CONCLUSIONS: Thus, the present results clearly confirm that memory processes are affected during early dementia in adults with DS, and that the SRT has promise as a clinical tool.

Gender and weight concerns in early and middle adolescence: links with well-being and family characteristics.

Studied sex and developmental differences in weight concerns in early and middle adolescence and links between concerns and adolescent well-being and family experiences. Participants were mothers, fathers, and older and younger siblings (Ms = 15 and 12.5 years, respectively) from 197, Caucasian, working-middle class, 2-parent families. Parents rated their gender role attitudes and adolescents rated their weight concerns, well-being, gender role orientations, and physical development. Girls reported more concerns than boys; body mass index (BMI) correlated with weight concerns for all youth. Controlling for BMI and pubertal status, weight concerns were linked to older girls' well-being; with physical characteristics controlled, mothers' gender attitudes explained older girls' weight concerns, and siblings' weight concerns explained those of older and younger girls and boys.

Conditions of sibling support in adolescence.

This study examined the nature and extent of adolescent siblings' supportive roles and the conditions under which siblings provide support to one another about familial and nonfamilial issues. Data were collected from 185 adolescent firstborn (M age = 16 years) and second born (M age = 13 years) sibling pairs. In home interviews, siblings reported on family experiences and psychosocial functioning during the past year. In a series of 7 evening telephone interviews, siblings reported on their shared daily activities. Findings suggested that both older and younger siblings view older siblings as sources of support about nonfamilial issues such as social and scholastic activities and that siblings assume equally supportive roles about familial issues. Further, the results suggested that family background characteristics, sibling relationship qualities, and adolescents' psychosocial functioning were linked to the nature and extent of sibling support.

The role of domiciliary nebulizers in managing patients with severe COPD.

The difficulty of assessing nebulizer responses in chronic obstructive pulmonary disease (COPD) has been demonstrated before. This study aims to re-examine both the role of domiciliary nebulizers in COPD and also bronchodilator (BD) assessment in individuals. In a double-blind, randomized, cross-over trial, 19 stable patients with severe COPD were given the following medication 6-hourly for 2-week periods: (1) nebulized salbutamol 2.5 mg with ipratropium 0.5 mg and placebo inhalers (MDI) with spacer; (2) placebo nebules and inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer; (3) inhaled salbutamol 400 microg with ipratropium 80 microg via MDI with spacer (but no placebo nebulized drugs). Both nebulized and MDI drugs produced highly significant improvements in forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), specific airways conductance, 6-min walking distance (6MWD) and residual volume. There were no significant differences between BD responses obtained after active nebulized and active MDI BDs. From the diary cards, 2 weeks of active nebulized BDs produced a slightly higher median peak expiratory flow (PEF) than active MDI BDs (236 and 219 l m(-1), respectively, P=0.01) and slightly less extra inhaler use (0.8 and 1.1 puffs, respectively, P<0.05) but no significant difference in dyspnoea or quality of life (QOL) scores. There were significant correlations between domiciliary PEF and acute BD-induced changes in FVC and 6MWD, and also between domiciliary dyspnoea scores and acute changes in both total lung capacity and 6MWD. In conclusion, nebulized medication conferred little clinical advantage over the regular use of inhalers with spacers in this group of patients with severe COPD. However, acute changes in total lung capacity, FVC and 6MWD may be useful predictors of the longer-term effects of nebulized BDs in individual patients.

Parental autonomy granting during adolescence: exploring gender differences in context.

This study investigated the ways in which 2 indicators of parental autonomy granting, adolescents' decision-making input and parental knowledge of adolescents' daily experiences, differed as a function of contextual factors (i.e., parents' gender role attitudes or sibling dyad sex composition) and boys' and girls' personal qualities (i.e., gender, pubertal status, developmental status, or birth order) in a sample of 194 families with firstborn (M = 15.0 years) and second-born (M = 12.5 years) adolescents. Firstborns were granted more autonomy than second borns, especially in families with firstborn girls and second-born boys. Girls in families marked by traditional maternal gender role attitudes were granted fewer autonomy opportunities. Postmenarcheal second-born girls were granted more opportunities for autonomy than were premenarcheal second-born girls, but only in families with less traditional maternal gender role attitudes.

Sibling influences on gender development in middle childhood and early adolescence: a longitudinal study.

The development of gender role qualities (attitudes, personality, leisure activities) from middle childhood to early adolescence was studied to determine whether siblings' gender role qualities predicted those of their sisters and brothers. Participants were 198 firstborn and second-born siblings (Ms = 10 years 9 months and 8 years 3 months, respectively, in Year 1) and their parents. Families were interviewed annually for 3 years. Firstborn siblings' qualities in Year 1 predicted second-born children's qualities in Year 3 when both parent and child qualities in Year 1 were controlled, a pattern consistent with a social learning model of sibling influence. Parental influence was more evident and sibling influence less evident in predicting firstborns' qualities; for firstborns, sibling influences suggested a de-identification process.

Free- time activities in middle childhood: links with adjustment in early adolescence.

This study assessed links between free-time activities in middle childhood (hobbies, sports, toys and games, outdoor play, reading, television viewing, and hanging out) and school grades, conduct, and depression symptoms both concurrently and 2 years later, in early adolescence. It also explored two mechanisms that might underlie activity-adjustment links: whether the social contexts of children's activities mediate these links, child effects explain these connections, or both. Participants were 198 children (M = 10.9 years, SD = .54 years) in Year 1, and their parents. In home interviews in Years 1 and 3 of the study, mothers rated children's conduct problems, children reported on their depression symptoms, and information was collected on school grades from report cards. In seven evening phone interviews, children reported on the time they spent in free-time activities during the day of the call and their companions in each activity. Links were found between the nature of children's free-time activities and their adjustment. The social contexts of free-time activities explained activity-adjustment links to a limited degree; with respect to child effects, evidence also suggested that better adjusted children became more involved in adaptive activities over time.