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Mono-2-ethylhexyl phthalate (MEHP) is the primary metabolite of the ubiquitous plasticizer and toxicant, di-2-ethylhexyl phthalate. MEHP exposure has been linked to abnormal development, increased oxidative stress, and metabolic syndrome in vertebrates. Nuclear factor, Erythroid 2 Like 2 (Nrf2), is a transcription factor that regulates gene expression in response to oxidative stress. We investigated the role of Nrf2a in larval steatosis following embryonic exposure to MEHP. Wild-type and nrf2a mutant (m) zebrafish embryos were exposed to 0 or 200 μg/l MEHP from 6 to either 96 (histology) or 120 hours post fertilization (hpf). At 120 hpf, exposures were ceased and fish were maintained in clean conditions until 15 days post fertilization (dpf). At 15 dpf, fish lengths and lipid content were examined, and the expression of genes involved in the antioxidant response and lipid processing was quantified. At 96 hpf, a subset of animals treated with MEHP had vacuolization in the liver. At 15 dpf, deficient Nrf2a signaling attenuated fish length by 7.7%. MEHP exposure increased hepatic steatosis and increased expression of peroxisome proliferator-activated receptor alpha target fabp1a1. Cumulatively, these data indicate that developmental exposure alone to MEHP may increase risk for hepatic steatosis and that Nrf2a does not play a major role in this phenotype.
Cardiac surgical interventions for children with trisomy 18 and trisomy 13 remain controversial, despite growing evidence that definitive cardiac repair prolongs survival. Understanding quality of life for survivors and their families therefore becomes crucial. Study objective was to generate a descriptive summary of parental perspectives on quality of life, family impact, functional status, and hopes for children with trisomy 18 and trisomy 13 who have undergone heart surgery.
A concurrent mixed method approach utilising PedsQL™ 4.0 Generic Core Parent Report for Toddlers or the PedsQL™ Infant Scale, PedsQL™ 2.0 Family Impact Module, Functional Status Scale, quality of life visual analogue scale, and narrative responses for 10 children whose families travelled out of state to access cardiac surgery denied to them in their home state due to genetic diagnoses.
Parents rated their child’s quality of life as 80/100, and their own quality of life as 78/100 using validated scales. Functional status was rated 11 by parents and 11.6 by providers (correlation 0.89). On quality of life visual analogue scale, all parents rated their child’s quality of life as “high” with mean response 92.7/100. Parental hopes were informed by realistic perspective on prognosis while striving to ensure their children had access to reaching their full potential. Qualitative analysis revealed a profound sense of the child’s relationality and valued life meaning.
Understanding parental motivations and perceptions on the child’s quality of life has potential to inform care teams in considering cardiac interventions for children with trisomy 18 and trisomy 13.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
In legal orders around the world, commitments to democracy, liberalism and constitutionalism are increasingly eroding. Although political and constitutional theorists often lament this trend, they invariably adopt frameworks that are indifferent to these commitments. My aims in this article are both critical and constructive. As a critical matter, I will expose the indifference of the leading political and constitutional theories to the emergence, maintenance and refinement of liberal democratic constitutional orders. As a constructive matter, I will draw on Immanuel Kant’s constitutional theory to explain why realizing such a form of governance is a public duty and why receding from it is a public wrong.
The Single Ventricle Reconstruction Trial randomised neonates with hypoplastic left heart syndrome to a shunt strategy but otherwise retained standard of care. We aimed to describe centre-level practice variation at Fontan completion.
Centre-level data are reported as median or median frequency across all centres and range of medians or frequencies across centres. Classification and regression tree analysis assessed the association of centre-level factors with length of stay and percentage of patients with prolonged pleural effusion (>7 days).
The median Fontan age (14 centres, 320 patients) was 3.1 years (range from 1.7 to 3.9), and the weight-for-age z-score was −0.56 (−1.35 + 0.44). Extra-cardiac Fontans were performed in 79% (4–100%) of patients at the 13 centres performing this procedure; lateral tunnels were performed in 32% (3–100%) at the 11 centres performing it. Deep hypothermic circulatory arrest (nine centres) ranged from 6 to 100%. Major complications occurred in 17% (7–33%). The length of stay was 9.5 days (9–12); 15% (6–33%) had prolonged pleural effusion. Centres with fewer patients (<6%) with prolonged pleural effusion and fewer (<41%) complications had a shorter length of stay (<10 days; sensitivity 1.0; specificity 0.71; area under the curve 0.96). Avoiding deep hypothermic circulatory arrest and higher weight-for-age z-score were associated with a lower percentage of patients with prolonged effusions (<9.5%; sensitivity 1.0; specificity = 0.86; area under the curve 0.98).
Fontan perioperative practices varied widely among study centres. Strategies to decrease the duration of pleural effusion and minimise complications may decrease the length of stay. Further research regarding deep hypothermic circulatory arrest is needed to understand its association with prolonged pleural effusion.
Weed control in corn traditionally has relied on atrazine as a foundational tool to control problematic weeds. However, the recent discovery of atrazine in aquifers and other water sources increases the likelihood of more strict restrictions on its use. Field-based research trials to find atrazine alternatives were conducted in 2017 and 2018 in Fayetteville, AR, by testing the tolerance of corn to PRE and POST applications of different photosystem II (PSII) inhibitors alone or in combination with mesotrione or S-metolachlor. All experiments were designed as a two-factor factorial, randomized complete block, with the two factors being (1) PSII-inhibiting herbicide and (2) the herbicide added to create the mixture. The PSII-inhibiting herbicides were prometryn, ametryn, simazine, fluometuron, metribuzin, linuron, diuron, atrazine, and propazine. The second factor consisted of either no additional herbicide, S-metolachlor, or mesotrione. Treatments were applied immediately after planting in the PRE experiments and to 30-cm–tall corn for the POST experiments. For the PRE study, low levels of injury (<15%) were observed at 14 and 28 d after application and corn height was negatively affected by the PSII-inhibiting herbicide applied. PRE-applied fluometuron- and ametryn-containing treatments consistently caused injury to corn, often exceeding 5%. Because of low injury levels caused by all treatments, crop density and yield did not differ from that of the nontreated plants. For the POST study, crop injury, relative height, and relative yield were affected by PSII-inhibiting herbicide and the herbicide added. Ametryn-, diuron-, linuron-, propazine-, and prometryn-containing treatments caused at least 25% injury to corn in at least 1 site-year. All PSII-inhibiting herbicides, except metribuzin and simazine when applied alone, caused yield loss in corn when compared with atrazine alone. Diuron-, linuron-, metribuzin-, and simazine-containing treatments applied PRE and metribuzin- and simazine-containing treatments applied POST should be investigated further as atrazine replacements.
Psychotic experiences (PEs) may be associated with injuries, but studies focusing specifically on low- and middle-income countries (LAMICs) are scarce. Thus, the current study examined the link between injuries and PEs in a large number of LAMICs.
Cross-sectional data were used from 242 952 individuals in 48 LAMICs that were collected during the World Health Survey in 2002–2004 to examine the association between traffic-related and other (non-traffic-related) forms of injury and PEs. Multivariable logistic regression analysis and meta-analysis were used to examine associations while controlling for a variety of covariates including depression.
In fully adjusted analyses, any injury [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.85–2.31], traffic injury (OR 1.84, 95% CI 1.53–2.21) and other injury (OR 2.09, 95% CI 1.84–2.37) were associated with higher odds for PEs. Results from a country-wise analysis showed that any injury was associated with significantly increased odds for PEs in 39 countries with the overall pooled OR estimated by meta-analysis being 2.46 (95% CI 2.22–2.74) with a moderate level of between-country heterogeneity (I2 = 56.3%). Similar results were observed across all country income levels (low, lower-middle and upper-middle).
Different types of injury are associated with PEs in LAMICs. Improving mental health systems and trauma capacity in LAMICs may be important for preventing injury-related negative mental health outcomes.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Perceived discrimination has been linked to psychotic experiences (PEs). However, as yet, information is lacking on the relationship between different forms of discrimination and PEs. This study examined this association in the English general population.
Nationally representative, cross-sectional data were analyzed from 7363 adults aged 16 and above that came from the Adult Psychiatric Morbidity Survey, 2007. Self-reported information was obtained on six forms of discrimination (ethnicity, sex, religious beliefs, age, physical health problems/disability, sexual orientation), while PEs were assessed with the Psychosis Screening Questionnaire (PSQ). Multivariable logistic regression analysis was used to assess associations.
In a fully adjusted logistic regression analysis, any discrimination was significantly associated with PEs (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.75–3.48). All individual forms of discrimination were significantly associated with PEs except sexual orientation. Multiple forms of discrimination were associated with higher odds for PEs in a monotonic fashion with those experiencing ≥ 3 forms of discrimination having over 5 times higher odds for any PE. In addition, experiencing any discrimination was associated with significantly increased odds for all individual forms of PE with ORs ranging from 2.16 (95%CI: 1.40–3.35) for strange experience to 3.36 (95%CI: 1.47–7.76) for auditory hallucination.
Different forms of discrimination are associated with PEs in the general population. As discrimination is common at the societal level, this highlights the importance of public policy and evidence-based interventions to reduce discrimination and improve population mental health.
Medical residents are an important group for antimicrobial stewardship programs (ASPs) to target with interventions aimed at improving antibiotic prescribing. In this study, we compared antimicrobial prescribing practices of 2 academic medical teams receiving different ASP training approaches along with a hospitalist control group.
Retrospective cohort study comparing guideline-concordant antibiotic prescribing for 3 common infections among a family medicine (FM) resident service, an internal medicine (IM) resident service, and hospitalists.
Community teaching hospital.
Adult patients admitted between July 1, 2016, and June 30, 2017, with a discharge diagnosis of pneumonia, cellulitis, and urinary tract infections were reviewed.
All 3 medical teams received identical baseline ASP education and daily antibiotic prescribing audit with feedback via clinical pharmacists. The FM resident service received an additional layer of targeted ASP intervention that included biweekly stewardship-focused rounds with an ASP physician and clinical pharmacist leadership. Guideline-concordant prescribing was assessed based on the institution’s ASP guidelines.
Of 1,572 patients, 295 (18.8%) were eligible for inclusion (FM, 96; IM, 69; hospitalist, 130). The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702). No differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). The FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001).
Adding dedicated stewardship-focused rounds into the graduate medical curriculum demonstrated increased guideline adherence specifically to duration of therapy recommendations.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.
Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.
Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).
Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.
Antipseudomonal carbapenems are an important target for antimicrobial stewardship programs. We evaluated the impact of formulary restriction and preauthorization on relative carbapenem use for medical and surgical intensive care units at a large, urban academic medical center using interrupted time-series analysis.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
Paediatric heart transplantation in Australia is centralised at The Royal Children’s Hospital, Melbourne. Survival to adulthood is improving but the ongoing need for complex medical therapy, surveillance, and potential for late complications continues to impact on quality of life. Quality of life in adults who underwent heart transplantation in childhood in Australia has not been assessed.
Cross-sectional quality of life data were collected from paediatric heart transplant survivors >18 years of age using Rand 36-Item Health Survey. Self-reported raw scores were transformed to a 0–100 scale with higher scores indicating better quality of life. Mean scores were compared to National Health Survey Short Form-36 Population Norms data using the independent sample t-test.
A total of 64 patients (64/151) who underwent transplantation at The Royal Children’s Hospital between 1988 and 2016 survived to adulthood. In total 51 patients (51/64, 80%) were alive at the time of the study and 27 (53%) responded with a mean age of 25 ± 6 years, being a median of 11 years (interquartile range 7–19) post-transplantation. Most self-reported quality of life subscale scores were not significantly different from the Australian normative population data. However, self-reported ‘General Health’ was significantly worse than normative data (p = 0.02). Overall, 93% (25/27) reported their general health as being the same or better compared to 1-year ago.
Adult survivors after paediatric heart transplantation in Australia report good quality of life in multiple domains and demonstrate independence in activities of daily living and employment. However, lifelong medical treatment may affect perceptions of general health.
To estimate the burden of Clostridium difficile infections (CDIs) due to interfacility patient sharing at regional and hospital levels.
Retrospective observational study.
We used data from the Healthcare Cost and Utilization Project California State Inpatient Database (2005–2011) to identify 26,878,498 admissions and 532,925 patient transfers. We constructed a weighted, directed network among the hospitals by defining an edge between 2 hospitals to be the monthly average number of patients discharged from one hospital and admitted to another on the same day. We then used a network autocorrelation model to study the effect of the patient sharing network on the monthly average number of CDI cases per hospital, and we estimated the proportion of CDI cases attributable to the network.
We found that 13% (95% confidence interval [CI], 7.6%–18%) of CDI cases were due to diffusion through the patient-sharing network. The network autocorrelation parameter was estimated at 5.0 (95% CI, 3.0–6.9). An increase in the number of patients transferred into and/or an increased CDI rate at the hospitals from which those patients originated led to an increase in the number of CDIs in the receiving hospital.
A minority but substantial burden of CDI infections are attributable to hospital transfers. A hospital’s infection control may thus be nontrivially influenced by its neighboring hospitals. This work adds to the growing body of evidence that intervention strategies designed to minimize HAIs should be done at the regional rather than local level.