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Targeted drug development efforts in patients with CHD are needed to standardise care, improve outcomes, and limit adverse events in the post-operative period. To identify major gaps in knowledge that can be addressed by drug development efforts and provide a rationale for current clinical practice, this review evaluates the evidence behind the most common medication classes used in the post-operative care of children with CHD undergoing cardiac surgery with cardiopulmonary bypass.
We systematically searched PubMed and EMBASE from 2000 to 2019 using a controlled vocabulary and keywords related to diuretics, vasoactives, sedatives, analgesics, pulmonary vasodilators, coagulation system medications, antiarrhythmics, steroids, and other endocrine drugs. We included studies of drugs given post-operatively to children with CHD undergoing repair or palliation with cardiopulmonary bypass.
We identified a total of 127 studies with 51,573 total children across medication classes. Most studies were retrospective cohorts at single centres. There is significant age- and disease-related variability in drug disposition, efficacy, and safety.
In this study, we discovered major gaps in knowledge for each medication class and identified areas for future research. Advances in data collection through electronic health records, novel trial methods, and collaboration can aid drug development efforts in standardising care, improving outcomes, and limiting adverse events in the post-operative period.
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.
The systems ecology paradigm (SEP) emerged in the late 1960s at a time when societies throughout the world were beginning to recognize that our environment and natural resources were being threatened by their activities. Management practices in rangelands, forests, agricultural lands, wetlands, and waterways were inadequate to meet the challenges of deteriorating environments, many of which were caused by the practices themselves. Scientists recognized an immediate need was developing a knowledge base about how ecosystems function. That effort took nearly two decades (1980s) and concluded with the acceptance that humans were components of ecosystems, not just controllers and manipulators of lands and waters. While ecosystem science was being developed, management options based on ecosystem science were shifting dramatically toward practices supporting sustainability, resilience, ecosystem services, biodiversity, and local to global interconnections of ecosystems. Emerging from the new knowledge about how ecosystems function and the application of the systems ecology approach was the collaboration of scientists, managers, decision-makers, and stakeholders locally and globally. Today’s concepts of ecosystem management and related ideas, such as sustainable agriculture, ecosystem health and restoration, consequences of and adaptation to climate change, and many other important local to global challenges are a direct result of the SEP.
Emerging from the warehouse of knowledge about terrestrial ecosystem functioning and the application of the systems ecology paradigm, exemplified by the power of simulation modeling, tremendous strides have been made linking the interactions of the land, atmosphere, and water locally to globally. Through integration of ecosystem, atmospheric, soil, and more recently social science interactions, plausible scenarios and even reasonable predictions are now possible about the outcomes of human activities. The applications of that knowledge to the effects of changing climates, human-caused nitrogen enrichment of ecosystems, and altered UV-B radiation represent challenges addressed in this chapter. The primary linkages addressed are through the C, N, S, and H2O cycles, and UV-B radiation. Carbon dioxide exchanges between land and the atmosphere, N additions and losses to and from lands and waters, early studies of SO2 in grassland ecosystem, and the effects of UV-B radiation on ecosystems have been mainstays of research described in this chapter. This research knowledge has been used in international and national climate assessments, for example the IPCC, US National Climate Assessment, and Paris Climate Accord. Likewise, the knowledge has been used to develop concepts and technologies related to sustainable agriculture, C sequestration, and food security.
Colleges and universities around the world engaged diverse strategies during the COVID-19 pandemic. Baylor University, a community of ˜22,700 individuals, was 1 of the institutions which resumed and sustained operations. The key strategy was establishment of multidisciplinary teams to develop mitigation strategies and priority areas for action. This population-based team approach along with implementation of a “Swiss Cheese” risk mitigation model allowed small clusters to be rapidly addressed through testing, surveillance, tracing, isolation, and quarantine. These efforts were supported by health protocols including face coverings, social distancing, and compliance monitoring. As a result, activities were sustained from August 1 to December 8, 2020. There were 62,970 COVID-19 tests conducted with 1435 people testing positive for a positivity rate of 2.28%. A total of 1670 COVID-19 cases were identified with 235 self-reports. The mean number of tests per week was 3500 with approximately 80 of these positive (11/d). More than 60 student tracers were trained with over 120 personnel available to contact trace, at a ratio of 1 per 400 university members. The successes and lessons learned provide a framework and pathway for similar institutions to mitigate the ongoing impacts of COVID-19 and sustain operations during a global pandemic.
Nature has developed myriad ways for organisms to interact with their environment using light and electronic signals. Optical and electronic properties can be observed macroscopically by measuring light emission or electrical current, but are conferred at the molecular level by the arrangement of small biological molecules, specifically proteins. Here, we present a brief overview of the current uses of proteins for applications in optical and electronic materials. We provide the natural context for a range of light-emitting, light-receiving, and electronically conductive proteins, as well as demonstrate uses in biomaterials. Examples of how genetic engineering has been used to expand the range of functional properties of naturally occurring proteins are provided. We touch on how approaches to patterning and scaffolding optical and electronic proteins can be achieved using proteins with this inherent capability. While much research is still required to bring their use into the mainstream, optical and electronic proteins have the potential to create biomaterials with properties unmatched using conventional chemical synthesis.
We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19) was <0.5%, which suggests that early local public health interventions were successful. Although our protocol was resource intensive, it prevented exposures to healthcare team members.
Institutional deprivation in early childhood is associated with neuropsychological deficits in adolescence. Using 20-year follow-up data from a unique natural experiment – the large-scale adoption of children exposed to extreme deprivation in Romanian institutions in the 1980s –we examined, for the first time, whether such deficits are still present in adulthood and whether they are associated with deprivation-related symptoms of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).
Adult neuropsychological functioning was assessed across five domains (inhibitory control, emotion recognition, decision-making, prospective memory and IQ) in 70 previously institutionalized adoptees (mean age = 25.3, 50% female) and 22 non-deprived UK adoptees (comparison group, mean age = 24.6, 41% female). ADHD and ASD symptoms were assessed using parent-completed questionnaires.
Early institutionalization was associated with impaired performance on all tasks in adulthood. Prospective memory deficits persisted after controlling for IQ. ADHD and ASD symptoms were positively correlated. After controlling for ASD symptoms, ADHD symptoms remained associated with deficits in IQ, prospective memory, proactive inhibition, decision-making quality and emotion recognition. ASD symptoms were not independently associated with neuropsychological deficits when accounting for their overlap with ADHD symptoms. Multiple regression analysis revealed that the link between childhood deprivation and adult ADHD symptoms was statistically explained by deprivation-related differences in adult IQ and prospective memory.
These results represent some of the most compelling evidence to date of the enduring power of early, time-limited childhood adversity to impair long-term neuropsychological functioning across the lifespan – effects that are linked specifically to deprivation-related adult ADHD symptoms.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
Nearly 258 million ha (28%) of the United States is publicly owned land that is managed by federal government agencies. For example, the US Department of Agriculture's Forest Service (USFS) manages over 77 million ha of national forests and grasslands for the benefit of the American public. Given its legal directive to manage multiple uses, it is not surprising that conflicts arise among stakeholders over how this land should be used (Lansky, 1992). The USFS has much discretion in how land is managed, yet must often balance conflicting values of public use and benefit (Nie, 2004). As national priorities, social preferences and public awareness of national forest goods, services and values have changed over time, USFS managers have faced increased pressure to balance consumptive uses with the need for environmental protection. Competing stakeholder demands coupled with increased environmental risks (wildfires, tree diseases and insect epidemics) have resulted in an escalating conservation conflict that is manifested in administrative appeals, lawsuits and a growing distrust of the agency.
Over time, the USFS has embraced new directions and management paradigms to reduce conflict. Some of these have been ecosystem management, adaptive management and now collaborative management (e.g. Holling, 1978; Maser, 1988; Franklin, 1992; Boyce and Haney, 1997; Wondolleck and Yaffee, 2000; Brown et al., 2004). These approaches reflect changing societal values, political pressures and new scientific information.
A persistent conflict has been the logging of trees in national forests and related impacts on forest ecosystems (Lansky, 1992). The USFS’ timber sale programme has supported jobs and community stability through economic development. Logging has also been a mechanism to reduce the risk of wildfire by reducing tree density (fuel for fires) and vertical stand diversity (‘ladder’ fuels; North et al., 2009). However, logging can also negatively affect forest integrity, watershed quality, wildlife, aesthetic and spiritual values of forests (Satterfield, 2002; North et al., 2009).