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This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.
PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.
After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental “concern” (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77–15.80; GDM OR 3.96, 95% CI 1.55–10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05–6.98; GDM OR 2.54, 95% CI 1.17–5.54) domains, as well as increased “risk” (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85–15.39; GDM OR 4.86, 95% CI 1.95–12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11–0.69) after adjustment for maternal hyperglycemia.
Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.
Despite the numerous advantages of central venous catheters (CVCs), they have been associated with a variety of complications. Surveillance for mechanical complications of CVCs is not routine, so the true incidence and impact of this adverse patient outcome remains unclear.
Setting and methods:
Prospectively collected CVC data on mechanical complications were reviewed from a centralized database for all in-hospital patient days at our tertiary-care hospital from January 2001 to June 2016 in patients aged <19 years. Patient demographics, CVC characteristics, and rates of mechanical complications per 1,000 days of catheter use were described.
In total, 8,747 CVCs were placed in 5,743 patients during the study period, which captured 780,448 catheter days. The overall mechanical complication rate was 6.1 per 1,000 catheter days (95% confidence interval [CI], 5.9–6.3). The highest complication rates were in nontunneled lines; this was consistent throughout the 15-year study period. Also, 521 CVCs (∼6%) were removed due to mechanical complications before therapy termination. Catheters with tip location in the superior vena cava or right atrium had the fewest complications.
Mechanical complications of CVCs are a common and significant event in the pediatric population. We propose that CVC-associated mechanical complications become a routinely reported patient safety outcome.
Given the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.
Participants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV−/Binge+ (n = 23), HIV+/Binge− (n = 55), HIV−/Binge− (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.
HIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV−/Binge− participants (p’s < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p’s > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV−/Binge− participants (p’s < .05).
Results showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.
Questions remain regarding whether genetic influences on early life psychopathology overlap with cognition and show developmental variation.
Using data from 9,421 individuals aged 8–21 from the Philadelphia Neurodevelopmental Cohort, factors of psychopathology were generated using a bifactor model of item-level data from a psychiatric interview. Five orthogonal factors were generated: anxious-misery (mood and anxiety), externalizing (attention deficit hyperactivity and conduct disorder), fear (phobias), psychosis-spectrum, and a general factor. Genetic analyses were conducted on a subsample of 4,662 individuals of European American ancestry. A genetic relatedness matrix was used to estimate heritability of these factors, and genetic correlations with executive function, episodic memory, complex reasoning, social cognition, motor speed, and general cognitive ability. Gene × Age analyses determined whether genetic influences on these factors show developmental variation.
Externalizing was heritable (h2 = 0.46, p = 1 × 10−6), but not anxious-misery (h2 = 0.09, p = 0.183), fear (h2 = 0.04, p = 0.337), psychosis-spectrum (h2 = 0.00, p = 0.494), or general psychopathology (h2 = 0.21, p = 0.040). Externalizing showed genetic overlap with face memory (ρg = −0.412, p = 0.004), verbal reasoning (ρg = −0.485, p = 0.001), spatial reasoning (ρg = −0.426, p = 0.010), motor speed (ρg = 0.659, p = 1x10−4), verbal knowledge (ρg = −0.314, p = 0.002), and general cognitive ability (g)(ρg = −0.394, p = 0.002). Gene × Age analyses revealed decreasing genetic variance (γg = −0.146, p = 0.004) and increasing environmental variance (γe = 0.059, p = 0.009) on externalizing.
Cognitive impairment may be a useful endophenotype of externalizing psychopathology and, therefore, help elucidate its pathophysiological underpinnings. Decreasing genetic variance suggests that gene discovery efforts may be more fruitful in children than adolescents or young adults.
Catheter ablation is a safe and effective therapy for the treatment of supraventricular tachycardia in children. Current improvements in technology have allowed progressive reduction in radiation exposure associated with the procedure. To assess the impact of three-dimensional mapping, we compared acute procedural results collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to published results from the Prospective Assessment after Pediatric Cardiac Ablation study.
Inclusion and exclusion criteria from the Prospective Assessment after Pediatric Cardiac Ablation study were used as guidelines to select patient data from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry to compare acute procedural outcomes between cohorts. Outcomes assessed include procedural and fluoroscopy exposure times, success rates of procedure, and complications.
In 786 ablation procedures, targeting 498 accessory pathways and 288 atrioventricular nodal reentrant tachycardia substrates, average procedural time (156.5 versus 206.7 minutes, p < 0.01), and fluoroscopy time (1.2 versus 38.3 minutes, p < 0.01) were significantly shorter in the study group. Success rates for the various substrates were similar except for manifest accessory pathways which had a significantly higher success rate in the study group (96.4% versus 93.0%, p < 0.01). Major complication rates were significantly lower in the study group (0.3% versus 1.6%, p < 0.01).
In a large, multicentre study, three-dimensional systems show favourable improvements in clinical outcomes in children undergoing catheter ablation of supraventricular tachycardia compared to the traditional fluoroscopic approach. Further improvements are anticipated as technology advances.
Ecosystem modeling, a pillar of the systems ecology paradigm (SEP), addresses questions such as, how much carbon and nitrogen are cycled within ecological sites, landscapes, or indeed the earth system? Or how are human activities modifying these flows? Modeling, when coupled with field and laboratory studies, represents the essence of the SEP in that they embody accumulated knowledge and generate hypotheses to test understanding of ecosystem processes and behavior. Initially, ecosystem models were primarily used to improve our understanding about how biophysical aspects of ecosystems operate. However, current ecosystem models are widely used to make accurate predictions about how large-scale phenomena such as climate change and management practices impact ecosystem dynamics and assess potential effects of these changes on economic activity and policy making. In sum, ecosystem models embedded in the SEP remain our best mechanism to integrate diverse types of knowledge regarding how the earth system functions and to make quantitative predictions that can be confronted with observations of reality. Modeling efforts discussed are the Century ecosystem model, DayCent ecosystem model, Grassland Ecosystem Model ELM, food web models, Savanna model, agent-based and coupled systems modeling, and Bayesian modeling.
ABSTRACT IMPACT: The knowledge acquired from my research can inform the development of early diagnostic methods for HIV-associated neurocognitive disorders. OBJECTIVES/GOALS: In the era of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains high but the neural mechanisms are unclear. We examined whether older people with HIV (PWH) with minimal cognitive impairment have reduced functional connectivity in frontostriatal circuits compared to controls. METHODS/STUDY POPULATION: 99 PWH (mean age 56.6 years, 75% male, 62% Black, mean duration of HIV-infection 26.2 years ±9.3, 90% viral load <50 copies, 98% on stable cART) and 38 demographically-comparable controls (mean age 54.5 years, 71% male, 58% Black) participated in a cross-sectional study. A 7-domain neuropsychological battery and an Activities of Daily Living index were used to determine HAND diagnoses: 32 PWH met criteria for asymptomatic to mild HAND. Motor skill was assessed using the Grooved Pegboard Test by measuring performance speed. Structural MRI and resting-state functional MRI were collected. Seed-to-voxel analyses were conducted using 4 distinct regions in the striatum as seed regions. We used a voxel threshold of p<0.001 and cluster threshold of p<0.05 (FDR-corrected) after controlling for demographic variables. RESULTS/ANTICIPATED RESULTS: Compared to controls, PWH had lower resting state functional connectivity between the default mode region of the striatum (i.e., medial caudate) and bilateral superior frontal gyrus, supplementary motor cortex and paracingulate gyrus (p<0.05; cluster size: 567 voxels). Also, compared to controls, PWH had reduced resting state functional connectivity between the motor division of the striatum (i.e., posterior putamen) and anterior cingulate cortex and left supplementary motor cortex (p<0.05, cluster size: 405 voxels). Performance speed on the Grooved Pegboard motor test negatively correlated with functional connectivity between the motor region of the striatum and supplementary motor frontal regions in all participants (Spearman’s rho=-0.18, p=0.04). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results support the hypothesis that frontostriatal abnormalities are widely present in PWH and might play a key role in HAND development. Our data suggest that dysfunction within the frontostriatal circuits may be involved in motor impairment in PWH, and ongoing inflammation may contribute to motor impairment and frontostriatal injury.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
OBJECTIVES/GOALS: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. This study examined the relationship between CD4 nadir and brain atrophy. METHODS/STUDY POPULATION: Fifty-nine people with HIV participated in the cross-sectional study (mean age, 56.5 ± 5.8; age range, 41-69; 15 females; 46 African-Americans). High resolution structural MRI images were obtained using a 3T Siemens scanner. From a comprehensive 7-domain neuropsychological test battery, a global deficit score (GDS) and HAND diagnoses were determined for each participant. The correlation between CD4 nadir (the lowest ever lymphocyte CD4 count) and cortical thickness was investigated using a vertex-wise non-parametric approach with a conservative statistical threshold of p < 0.05 (FWE-corrected). RESULTS/ANTICIPATED RESULTS: Out of the 59 participants, 12 met standard Frascati criteria for asymptomatic neurocognitive impairment (ANI) and two met the criteria for mild neurocognitive disorder (MND). Across all participants, low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions. Higher GDS (indicating worse global neurocognitive function) was associated with bilateral frontal cortical thinning, and the association largely persisted in the subset of participants who did not meet HAND criteria. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. This spatial profile might contribute to the prevalence/phenotypes of HAND in the cART era, such as the frequently observed deficits in the executive domain.
Fungi have co-existed with animals and plants throughout the whole of the evolutionary time since these three groups of higher organisms originally separated from one another. Living together closely for this length of time has given rise to many cooperative ventures. We have already seen how many fungi have combined with plants as partners in mutually beneficial relationships such as mycorrhizas and lichens. In these symbiotic, or mutualistic, associations the partners each gain something from the partnership so that the association is more successful than either organism alone. The organisms concerned (often two but sometimes more) live in such close proximity to each other that their cells may intermingle and may even contribute to the formation of joint tissues, as they do in the lichen thallus, which is one of the most ancient mutualistic associations of all and found in some of the most inhospitable environments.
Wikipedia points out that ‘biodiversity’ is a new portmanteau word made up from ‘biology’ and ‘diversity’ that probably arrived in the English language in 1985. Wikipedia defines ‘biodiversity’ as ‘the variation of taxonomic life forms within a given ecosystem, biome or for the entire Earth.
The mysterious world of fungi is once again unearthed in this expansive second edition. This textbook provides readers with an all-embracing view of the kingdom fungi, ranging in scope from ecology and evolution, diversity and taxonomy, cell biology and biochemistry, to genetics and genomics, biotechnology and bioinformatics. Adopting a unique systems biology approach - and using explanatory figures and colour illustrations - the authors emphasise the diverse interactions between fungi and other organisms. They outline how recent advances in molecular techniques and computational biology have fundamentally changed our understanding of fungal biology, and have updated chapters and references throughout the book in light of this. This is a fascinating and accessible guide, which will appeal to a broad readership - from aspiring mycologists at undergraduate and graduate level to those studying related disciplines. Online resources are hosted on a complementary website.
Fungal biomass is a high-quality food source because it contains a good content of protein (typically 20–30% crude protein as a percentage of dry matter), which contains all the amino acids that are essential to human and animal nutrition. Add characteristically low-fat content to the protein, a chitinous wall as a source of dietary fibre, useful vitamin content, especially of B vitamins, and carbohydrate in the form of glycogen and a good food source can be considered an ideal food. Judging from archaeological and similar finds, mushrooms, toadstools and bracket fungi have been used by humans since before recorded history for both food and medicinal purposes.
This chapter considers the evolutionary origins and phylogenetics of fungi. We present these against the background of global evolution in the hope of improving appreciation of the timescales involved.
Fungi make crucial contributions to all ecosystems because of their abilities as decomposers. One of the most important kingdom-specific characteristics of fungi is that they obtain their nutrients by external digestion of substrates. In the real world though there is some digestion of inorganic substrates (see ), the bulk of the substrates that fungi recycle are the remains of animals and, most particularly, plants. In this chapter we give an account of the ways in which fungal hyphae obtain, absorb, metabolise, reprocess and redistribute nutrients.
Interactions with plants dominate the rest of the chapter. We describe all types of mycorrhiza: arbuscular (AM) endomycorrhizas, ericoid endomycorrhizas, arbutoid endomycorrhizas, monotropoid endomycorrhizas, orchidaceous endomycorrhizas, ectomycorrhizas and ectendomycorrhizas. The effects of mycorrhizas and their commercial applications, and the impact of environmental and climate changes are also discussed. Finally, we introduce lichens, endophytes and epiphytes.