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Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Background: Unwanted intrusive thoughts of intentionally harming one's infant (intrusive harm thoughts) are common distressing experiences among postpartum mothers and fathers. Aim: To understand infant crying as a stimulus for intrusive harm thoughts and associated emotional responses in prepartum and postpartum mothers and fathers in response to infant cry. Method: Following completion of self-report measures of negative mood and anger, prepartum (n = 48) and postpartum (n = 44) samples of mother and father pairs completed 10 minutes of listening to audio-recorded infant crying. Post-test questionnaires assessed harm thoughts, negative emotions, urges to comfort and flee, and thoughts of shaking as a soothing or coping strategy. Results: One quarter of prepartum and 44% of postpartum parents reported intrusive infant-related harm thoughts following crying. Mothers and fathers did not differ in the likelihood of reporting harm thoughts, nor in the number of thoughts reported. Women reported more internalizing emotions compared with men. Hostile emotions were stronger among postpartum parents, and parents reporting harm thoughts. All parents reported strong urges to comfort the infant. Urges to flee were stronger among parents who reported harm thoughts. The likelihood of using infant shaking as a soothing or coping strategy was minimally endorsed, albeit more strongly by fathers and parents who also reported harm thoughts. Conclusions: In response to crying, harm thoughts are common and are associated with hostile emotions, urges to flee, and increased thoughts of using infant shaking. Reassuringly, the number of participants considering infant shaking as a strategy for soothing or for coping with a crying infant was low.
Parent–child relationships have long-term effects on health, particularly later inflammation and depression. We hypothesized that these effects would be mediated by later romantic partner relationships and elevated stressors in young adulthood, helping promote chronic, low grade, inflammation as well as depressive symptoms, and driving their covariation. It has been proposed recently that youth experiencing harsher parenting may also develop a stronger association between inflammation and depressive symptoms in adulthood and altered effects of stressors on outcomes. In the current investigation, we test these ideas using an 18-year longitudinal study of N = 413 African American youth that provides assessment of the parent–child relationship (at age 10), pro-inflammatory cytokine profile and depressive symptoms (at age 28), and potential mediators in early young adulthood (assessed at ages 21 and 24). As predicted, the effect of harsher parent–child relationships (age 10) on pro-inflammatory state and increased depressive symptoms at age 28 were fully mediated through young adult stress and romantic partner relationships. In addition, beyond these mediated effects, parent–child relationships at age 10 moderated the concurrent association between inflammation and depressive symptoms, as well as the prospective association between romantic partner relationships and inflammation, and resulted in substantially different patterns of indirect effects from young adult mediators to outcomes. The results support theorizing that the association of depression and inflammation in young adulthood is conditional on earlier parenting, and suggest incorporating this perspective into models predicting long-term health outcomes.
Animal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.
A wide variety of X-ray spectral forms has been reported in BL Lac objects. Concave spectra, i.e. a steep soft X-ray spectrum with a flat high energy tail, have been reported in a few of the brightest BL Lacs (e.g Urry 1986). Conversely, convex spectra (steep hard X-rays, flat soft X-ray spectrum) have also been reported, sometimes in the same objects (Madejski 1985, Barr et al 1988, George et al 1988). The high energy tails have usually been invoked as a signature of synchrotron-self-Compton emission. Two conflicting interpretations of the convex spectra have been made. Urry et al (1986) suggest absorption by a partially ionised medium, probably intrinsic to the BL Lac object, following the identification of an Oxygen absorption trough in the Einstein OGS spectrum of PKS 2155-304 by Canizares and Kruper (1984). Conversely, Barr et al (1988) attribute the hard X-ray steepening to energy loss mechanisms operating on a synchrotron source.
With the changing distribution of infectious diseases, and an increase in the burden of non-communicable diseases, low- and middle-income countries, including those in Africa, will need to expand their health care capacities to effectively respond to these epidemiological transitions. The interrelated risk factors for chronic infectious and non-communicable diseases and the need for long-term disease management, argue for combined strategies to understand their underlying causes and to design strategies for effective prevention and long-term care. Through multidisciplinary research and implementation partnerships, we advocate an integrated approach for research and healthcare for chronic diseases in Africa.
This paper reports a case of achalasia in a 12-year-old girl who presented with stridor.
An otherwise healthy 12-year-old girl presented to the ENT clinic with an 18-month history of dysphagia and noisy breathing on eating. Flexible fibre-optic examination showed a normal larynx with normal vocal fold movements. Fibre-optic endoscopic evaluation of swallowing was normal initially, but biphasic stridor occurred after several swallows. Microlaryngoscopy, bronchoscopy and upper oesophagoscopy showed a dilated oesophagus with normal mucosa. Bronchoscopy showed tracheomalacia of the distal trachea, which reduced the airway by approximately 75 per cent. This was caused by posterior compression from redundant oesophageal mucosa with dilatation as a result of retained fluids. Videofluoroscopy suggested achalasia, which was confirmed by oesophageal manometry. Her symptoms improved following a Heller's myotomy.
This is the first paediatric case in the English literature of achalasia presenting with stridor. The condition was correctable with surgical intervention.
In humans, it has been demonstrated that the serotonin transporter linked polymorphic region (5-HTTLPR) genotype moderates risk in the face of adversity. One mechanism by which stress could interact with genotype is via epigenetic modifications. We wanted to examine whether stress interacted with genotype to predict binding of a histone 3 protein trimethylated at lysine 3 (H3K4me3) that marks active promoters. The brains (N = 61) of male rhesus macaques that had been reared in the presence or absence of stress were archived and the hippocampusi dissected. Chromatin immunoprecipitation was performed with an antibody against H3K4me3 followed by sequencing on a SolexaG2A. The effects of age, genotype (5-HTTLPR long/long vs. short), and stress exposure (peer-reared vs. mother-reared) on levels of H3K4me3 binding were determined. We found effects of age and stress exposure. There was a decline in H3K4me3 from preadolescence to postadolescence and lower levels in peer-reared monkeys and no effects of genotype. When we controlled for age, however, we found that there were effects of 5-HTTLPR genotype and rearing condition on H3K4me3 binding. In a larger sample, we observed that cerebrospinal fluid 5-hydroxyindoleacetic acid levels were subject to interactive effects among age, rearing history, and genotype. Genes containing both genetic selection and epigenetic regulation may be particularly important in stress adaptation and development. We find evidence for selection at the solute carrier family C6 member 4 gene and observe epigenetic reorganization according to genotype, stress, and age. These data suggest that developmental stage may moderate effects of stress and serotonin transporter genotype in the emergence of alternative adaptation strategies and in the vulnerability to developmental or psychiatric disorders.
Antipsychotic medications can contribute to neurocognitive and motor impairments, but specific links to individualized pharmacological treatment regimens are unclear. In 68 participants with stabilized first-episode psychosis (FEP), we investigated the links between neuropsychological functions and an established anticholinergic potency index and a new D2 antagonist potency index developed in our lab. Each participant's psychiatric medication regimen was converted into estimated receptor antagonist loads based upon specific medication dosage(s) and reported in vitro brain muscarinic cholinergic and D2 receptor antagonism. In addition to the global neuropsychological impairments of FEP participants, the findings supported the hypothesized links between receptor antagonist loads and specific deficits. Higher anticholinergic load was associated with poorer delayed verbal memory but was not related to motor functioning. In contrast, higher D2 load was associated with poorer motor functioning but not verbal memory. These selective antagonist load associations explained 19% of the variance in motor functioning and 17% of the variance in delayed verbal memory. Evidently, some of the neuropsychological impairments found in persons with FEP are selectively related to the specific pharmacodynamics and the dosing of their medication regimens. Moreover, these effects can be readily estimated from practical and inexpensive indices. (JINS, 2012, 18, 1–11)
The short allele of the serotonin transporter linked polymorphic region (5-HTTLPR) moderates the effects of stress on vulnerability to mood and anxiety disorders. The mechanism by which this occurs may relate to differential sensitivity to stressful life events. Here we explored whether 5-HTTLPR and sex affected behavioral responses to repeated maternal separation in infant rhesus macaques. Behaviors were collected during the acute (Day 1) and the chronic (Days 2–4) phases of the separation, and the effects of duration of separation (acute vs. chronic), genotype (long/long vs. short allele), and sex (male vs. female) on behavioral responses were analyzed across four successive separations. Males increased their levels of locomotion with repeated maternal separation, whereas females exhibited an increase in frequency of self-directed behavior, a measure of “depression-like” behavior. The short-allele predicted increased environmental exploration, particularly during the chronic phase of social separation, indicative of higher arousal. In addition, the short-allele carriers were more likely to increase their levels of self-directed behavior during the chronic phase of separation, as a function of repeated exposures. These findings suggest that the short allele may increase reactivity to repeated, chronic stressors, leaving them more vulnerable to affective psychopathology, with females particularly vulnerable.
Numerous studies have considered the benefits, and the disadvantages, of the Epworth Sleepiness Scale. Following an extensive literature review, we found that the evidence was inconclusive as regards the diagnostic efficacy of Epworth scoring for obstructive sleep apnoea syndrome. We undertook a retrospective study of 343 patients who underwent a sleep assessment over a 10-year period at the Monklands Hospital.
Analysis and results:
A total of 238 patients did not have sleep apnoea whereas 105 patients did. The mean Epworth score in patients with obstructive sleep apnoea syndrome was 10.94 (95 per cent confidence interval 9.46–11.42), and in the non-apnoeic group it was 7.73 (95 per cent confidence interval 7.04–8.41). Logistic regression and receiver operating characteristic curves were used to assess the predictive ability of Epworth scoring. The scores only explained 7–10 per cent of the variation in the probability of occurrence of obstructive sleep apnoea syndrome. The odds ratio for Epworth scoring was 1.118, and only 69 per cent of cases were correctly classified by the Scale.
The literature review suggested that the Epworth Sleepiness Scale is associated with a low effect size and/or low predictive value when correlated or regressed on the Apnoea–Hypopnoea Index or Respiratory Disturbance Index, thus limiting its value as a screening test. Our study concluded that the Epworth Scale is only marginally useful in predicting the occurrence of obstructive sleep apnoea syndrome. We believe that every patient with a direct or witnessed history of sleep apnoea with obstructive symptoms have some form of sleep assessment.
Whisker formation in pure Sn coatings on Cu conductors is a serious impediment to the development of Pb-free electronics manufacturing. Understanding whisker formation is complicated by the fact that it is the result of multiple materials kinetic processes including interdiffusion, intermetallic formation and stress generation We report preliminary studies of whisker growth kinetics and stress evolution aimed at developing a fundamental understanding of the whisker growth process. A proposed model of point defect mediated stress generation provides a simple picture of how the different processes are connected.
The future of the nuclear industry and its acceptance by public opinion depend to a large extent on the development of an acceptable solution for waste management and disposal. The long duration of the hazard presented by certain radionuclides found in nuclear wastes is certainly one of the reasons for public concern over definitive waste disposal.
In order to better understand the mechanics of metallization structures having very fine features, we performed in-situ, temperature-dependent X-ray strain measurements on Al-Cu films patterned into gratings with linewidths of 0.2-0.8μm, with and without a dielectric covering In comparison with earlier work on coarser structures, we find larger strains and less hysteresis, indicating an increased yield stress. The stress in unpassivated lines is almost independent of the linewidth. The slope of the stress/temperature curves for passivated lines increases with decreasing linewidth, so that the compressive stress at 500°C reaches 900MPa for the narrowest lines. The tensile stress at RT is smaller for the narrower lines, suggesting that these lines may not stress-void as much as wider ones. The significance of these results for stress voiding and electromigration will be discussed.