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Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.
To study the association between gastrointestinal colonization of carbapenemase-producing Enterobacteriaceae (CPE) and proton pump inhibitors (PPIs).
We analyzed 31,526 patients with prospective collection of fecal specimens for CPE screening: upon admission (targeted screening) and during hospitalization (opportunistic screening, safety net screening, and extensive contact tracing), in our healthcare network with 3,200 beds from July 1, 2011, through December 31, 2015. Specimens were collected at least once weekly during hospitalization for CPE carriers and subjected to broth enrichment culture and multiplex polymerase chain reaction.
Of 66,672 fecal specimens collected, 345 specimens (0.5%) from 100 patients (0.3%) had CPE. The number and prevalence (per 100,000 patient-days) of CPE increased from 2 (0.3) in 2012 to 63 (8.0) in 2015 (P<.001). Male sex (odds ratio, 1.91 [95% CI, 1.15–3.18], P=.013), presence of wound or drain (3.12 [1.70–5.71], P<.001), and use of cephalosporins (3.06 [1.42–6.59], P=.004), carbapenems (2.21 [1.10–4.48], P=.027), and PPIs (2.84 [1.72–4.71], P<.001) in the preceding 6 months were significant risk factors by multivariable analysis. Of 79 patients with serial fecal specimens, spontaneous clearance of CPE was noted in 57 (72.2%), with a median (range) of 30 (3–411) days. Comparing patients without use of antibiotics and PPIs, consumption of both antibiotics and PPIs after CPE identification was associated with later clearance of CPE (hazard ratio, 0.35 [95% CI, 0.17–0.73], P=.005).
Concomitant use of antibiotics and PPIs prolonged duration of gastrointestinal colonization by CPE.
Patients treated with intensity-modulated radiation therapy (IMRT) for head-and-neck cancer are often positioned supine on a carbon fibre board to which a thermoplastic mask is attached to immobilise the head and shoulders. For patients unable to tolerate a supine position, we developed a tilting board that accommodates a full-scale head-and-shoulder mask.
Materials and methods
Phantom measurements were obtained to confirm the dosimetric accuracy of our treatment planning system when using this board. A patient was simulated in the flat and tilted positions on the board. The two corresponding treatment plans were evaluated by comparing the target coverage and doses with organs at risk. The patient’s intra-fraction motion was quantified during his tilted treatments.
Phantom measurements confirmed the accuracy of the dosimetric calculations. The tilted plan met dosimetric standards for clinical acceptability. The intra-fraction motion of the patient in the tilted position was >3 mm in any direction.
The tilting board met clinical requirements for IMRT planning and delivery. Full-scale head-and-shoulder immobilisation was achieved in a more tolerable tilted position.
Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine–phosphate–guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine–phosphate–guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.
Computed tomography (CT) is an important tool in clinical diagnostic imaging enabling three-dimensional anatomic imaging at high spatial resolution with short scan times. However, X-ray attenuation differences in physiological fluids and soft tissues are relatively small, requiring the use of contrast agents to achieve sufficient imaging contrast. Recent advances in energy-sensitive X-ray detectors have made spectral (color) CT commercially feasible by unmixing the energy-dependent attenuation profile of different materials and will potentially enable molecular imaging in CT. In order to leverage these capabilities for diagnostic imaging, we are developing a spectral library of nanoparticle contrast agents with K-shell absorption edges spaced at least 10 keV apart. The objective of this study was to demonstrate the ability of spectral CT to simultaneously detect up to three different contrast agents and unmixed their signals to create color images. Gadolinium oxide (Gd), hafnium oxide (Hf) and gold (Au) were chosen due to exhibiting K-edges spaced 10-20 keV apart. Core-shell nanoparticles of each composition were synthesized by various methods to have a core diameter of 15-20 nm and were coated with a silica shell at least 2-4 nm in thickness to create a common platform for surface functionalization. The contrast agents were imaged in a soft tissue equivalent phantom using source-side method for spectral CT imaging. The source-side approach utilized monochromatic synchrotron radiation at the Argonne National Laboratory which, while not clinically applicable, served as a gold standard due to providing the highest spectral resolution. The nanoparticles designed for this study have broad applications in biomedical imaging due to their modular assembly, potential for enabling multi-modal detection, and surface functionalization with biomolecules (e.g., antibodies, peptides or enzymes) for active targeting.
Many countries face policy challenges related to the well-being of their aging populations, and China, with the world's largest aging population, is no different. Over the past 40 years, China has experienced demographic transition toward an “aging society.” According to the National Bureau of Statistics in China (NBSC), the number of people aged 60 years and older in China has risen to 185 million, with rural areas aging more rapidly during China's demographic transition (National Bureau of Statistics of China, 2013). In 1982, the proportion of population aged 60 years and older was 7.8% in rural China and 7.1% in urban China. However, by 2011 these proportions had risen to 12.6% and 15.4%, respectively, with a national average of 13.26% (National Bureau of Statistics of China, 2013). Difference between rural and urban areas in the proportion of the population aged 65 years and older in China has shown a similar trend over time. Rapid economic reforms since the 1980s, associated with increased rural-to-urban migration, especially the outflow of rural young population, have resulted in a larger proportion of elderly adults in rural areas (Cai et al., 2012; National Bureau of Statistics of China, 2013). These same social forces have resulted in relatively fewer people available to take care of the growing population of older adults as well. The “elderly dependency ratio” (the ratio of older adults in China to those in the population of working age) has increased from 8.0% in 1982 to 12.7% in 2012 (National Bureau of Statistics of China, 2013). The economic and social impact on caregiving will be profound.
On June 13, 2012, a group of key stakeholders, leaders, and national experts on tuberculosis (TB), occupational health, and laboratory science met in Atlanta, Georgia, to focus national discussion on the higher than expected positive results occurring among low-risk, unexposed healthcare workers undergoing serial testing with interferon-γ release assays (IGRAs). The objectives of the meeting were to present the latest clinical and operational research findings on the topic, to discuss evaluation and treatment algorithms that are emerging in the absence of national guidance, and to develop a consensus on the action steps needed to assist programs and physicians in the interpretation of serial testing IGRA results. This report summarizes its proceedings.
We implemented a direct-observer hand hygiene audit program that used trained observers, wireless data entry devices, and an intranet portal. We improved the reliability and utility of the data by standardizing audit processes, regularly retraining auditors, developing an audit guidance tool, and reporting weighted composite hand hygiene compliance scores.
Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness. We also compared the approach of estimating regional heritability based on the average heritability of vertices within the region to the more traditional region-of-interest (ROI)-based approach. The results suggested high heritability across the cortex for areal expansion and, to a slightly lesser degree, for cortical thickness. There was a great deal of genetic overlap between global and regional measures for surface area, so maps of region-specific genetic influences on surface area revealed more modest heritabilities. There was greater inter-regional variability in heritabilities when calculated using the traditional ROI-based approach compared to summarizing vertex-by-vertex heritabilities within regions. Discrepancies between the approaches were greatest in small regions and tended to be larger for surface area than for cortical thickness measures. Implications regarding brain phenotypes for future genetic association studies are discussed.
Replacement of retinal pigment epithelium (RPE) cells by transplantation is a potential treatment for some retinal degenerations. Here, we used a combination of invasive and noninvasive methods to characterize the structural and functional consequences of subretinal injection of RPE cells. Pigmented cells from primary cultures were injected into albino mice. Recovery was monitored over 8 weeks by fundus imaging, spectral domain optical coherence tomography (sdOCT), histology, and electroretinography (ERG). sdOCT showed that retinal reattachment was nearly complete by 1 week. ERG response amplitudes were reduced after injection, with cone-mediated function then recovering better than rod function. Photoreceptor cell loss was evident by sdOCT and histology, near the site of injection, and is likely to have been the main cause of incomplete recovery. With microscopy, injected cells were identified by the presence of apical melanosomes. They either established contact with Bruch’s membrane, and thus became part of the RPE monolayer, or were located on the apical surface of the host’s cells, resulting in apposition of the basal surface of the injected cell with the apical surface of the host cell and the formation of a series of desmosomal junctions. RPE cell density was not increased, indicating that the incorporation of an injected cell into the RPE monolayer was concomitant with the loss of a host cell. The transplanted and remaining host cells contained large vacuoles of ingested debris as well as lipofuscin-like granules, suggesting that they had scavenged the excess injected and host cells, and were stressed by the high digestive load. Therefore, although significant functional and structural recovery was observed, the consequences of this digestive stress may be a concern for longer-term health, especially where RPE cell transplantation is used to treat diseases that include lipofuscin accumulation as part of their pathology.
To evaluate the associations between sociodemographic and psychosocial characteristics and food label (FL) use in US adults.
Data from the 1994–1996 Continuing Survey of Food Intakes by Individuals and the Diet and Health Knowledge Survey were used. High socio-economic status (SES) was defined as >high school education and poverty–income ratio (PIR) >350 %, low SES as <high school level or PIR <130 %. Dietary intakes were assessed using 24 h recalls.
Metropolitan statistical area-central city, -suburban, and rural areas in the USA.
US adults (n 2797; 1460 men, 1337 women) aged 20–64 years.
Approximately 80 % of Americans reported using FL, including checking the nutrition panel, list of ingredients, short phrases, serving size, or health benefits. Only 26 % used all FL information. Compared with white women of higher SES, white men, black men and women with lower SES were 77–90 % less likely to use FL. Rural residents were 40 % less likely (OR = 0·60; 95 % CI 0·42, 0·86). Participants with good nutrition knowledge, perceptions and beliefs were twice as likely to check FL for nutrient content of foods (OR = 2·28; 95 % CI 1·53–3·40). Those who were unaware of diet–disease relationships were less likely to use FL (OR = 0·53; 95 % CI 0·32–0·85). Among overweight/obese Americans (BMI ≥ 25 kg/m2), those who perceived their weight ‘about right’ were 51 % less likely to use FL than those perceiving themselves as overweight.
Men, especially black men, women of low SES, rural residents and overweight Americans with inaccurate self-perception of body weight are less likely to use FL and should be targeted for increased intervention.
The Behavior Rating Inventory of Executive Function (BRIEF) is commonly used in the assessment of children and adolescents presenting with a wide range of concerns. It is unclear, however, whether the questionnaire is more closely related to general measures of behavioral disruption and impairment or to specific measures of executive function. In the present study, associations between the Behavioral Regulation Index and Metacognition Index of the BRIEF and cognitive, behavioral, and academic measures were examined in a sample of clinic-referred youth (n = 60) and healthy youth (n = 37) 6–15 years of age. Measures included ratings of inattentive and hyperactive-impulsive symptoms in youth, ratings of how well youth functioned in their everyday environments, youth’s scores on measures of reading and math, and youth’s scores on measures of inhibition, performance monitoring, and working memory. Although both BRIEF indices were strongly related to parent and teacher ratings of behavioral disruption and impairment, neither was associated with youth’s scores on the performance-based tasks of executive function. These findings support the use of the BRIEF as a clinical tool for assessing a broad range of concerns, but raise questions about the relation of the BRIEF to performance-based tasks that are commonly used to assess executive function. (JINS, 2010, 16, 495–505.)