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In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a “wet” person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.
This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.
We performed systematic review on 40 paired hospital and nursing home charts from a clinical trial to evaluate the fidelity of transitions of care among those discharged on antibiotics. We found that 30% of transitions included an inappropriate change to the patient’s antibiotic plan of care.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
The evidence underpinning the developmental origins of health and disease (DOHaD) is overwhelming. As the emphasis shifts more towards interventions and the translational strategies for disease prevention, it is important to capitalize on collaboration and knowledge sharing to maximize opportunities for discovery and replication. DOHaD meetings are facilitating this interaction. However, strategies to perpetuate focussed discussions and collaborations around and between conferences are more likely to facilitate the development of DOHaD research. For this reason, the DOHaD Society of Australia and New Zealand (DOHaD ANZ) has initiated themed Working Groups, which convened at the 2014–2015 conferences. This report introduces the DOHaD ANZ Working Groups and summarizes their plans and activities. One of the first Working Groups to form was the ActEarly birth cohort group, which is moving towards more translational goals. Reflecting growing emphasis on the impact of early life biodiversity – even before birth – we also have a Working Group titled Infection, inflammation and the microbiome. We have several Working Groups exploring other major non-cancerous disease outcomes over the lifespan, including Brain, behaviour and development and Obesity, cardiovascular and metabolic health. The Epigenetics and Animal Models Working Groups cut across all these areas and seeks to ensure interaction between researchers. Finally, we have a group focussed on ‘Translation, policy and communication’ which focusses on how we can best take the evidence we produce into the community to effect change. By coordinating and perpetuating DOHaD discussions in this way we aim to enhance DOHaD research in our region.
A K-band (18-25 GHz) reflected-wave ruby maser (Moore and Clauss 1979) has been borrowed from the National Radio Astronomy Observatory for radio astronomy use on the NASA 64-m antenna of the Deep Space Network at the Tidbinbilla Tracking Station, near Canberra. The purpose of the installation is to provide additional sensitive spectral line, continuum, and VLBI capabilities in the southern hemisphere. Previous measurements at 22.3 GHz (λ = 13.5 mm) determined that the Tidbinbilla 64-m antenna has a peak aperture efficiency of ˜22%, a well-behaved beam shape and consistent pointing (Fourikis and Jauncey 1979). Before installing the maser on the antenna a cooled (circulator) switch was added to provide a beam-switching capability, and a spectral line receiver following the maser was incorporated. The system was assembled and tested at JPL in late 1980 and installed at Tidbinbilla early in 1981. We give here a brief description and present some of the first line observations made in February and March 1981. Extensive line and continuum observations are planned with the present system and a program is under way to determine the telescope pointing characteristics.
During the American crisis of 1763–83, Edmund Burke was recognised, on both sides of the Atlantic, as ‘a friend of America’, primarily because of his determined efforts to seek a reconciliation between Britain and the American colonies on the question of taxation and his bitter criticisms of the efforts made by Lord North’s ministry to subdue the American rebellion by oppressive legislation and military aggression. Modern scholars, however, are divided over Burke’s response to the American crisis. Some maintain that Burke was well informed about American affairs, made vigorous and practical efforts to conciliate the American colonies, and played a leading role in attacking the war that Lord North’s ministry waged against the American rebels. Other scholars have argued that Burke never really fully appreciated the American position, wrongly believed that the root cause of the dispute was taxation, and used the war primarily to advance the interests of his own party. This chapter will explore the evidence that can be used to sustain these contrasting viewpoints and will suggest that he was aware of the contradictions in his position and strove to reconcile them.
Burke’s Knowledge of American Affairs
Among the many MPs who spoke or wrote on American affairs during twenty years of crisis, very few had any first-hand or deep knowledge of the situation in the American colonies. Only a tiny handful had been born in America or had spent substantial time in the colonies as merchants or landowners, civil administrators, or military officers. Burke himself never visited the American colonies, never corresponded regularly with any American Patriot during the crisis and never read widely in the American literature produced by the colonial critics of British policies. On the other hand, it is difficult to find many politicians of the period who made such an effort to educate themselves about American affairs as Burke did. Even before he entered parliament, Burke collaborated with his friend, William Burke, in producing a substantial Account of the European Settlements in America that was published in two volumes in 1757.
The Far-Infrared Radio Correlation (FRC) is the tightest and most universal correlation known among global parameters of galaxies. Here we present the results of our investigation of the 70 μm FRC of starforming galaxies in the Extended Chandra Deep Field South (ECDFS) out to z > 2. In order to quantify the evolution of the FRC we used both survival analysis and stacking techniques, which gave similar results. We also calculated the FRC using total infrared luminosity and rest-frame radio luminosity, qTIR, and find that qTIR is constant (within 0.22) over the redshift range 0 - 2. We see no evidence for evolution in the FRC at 70 μm, which is surprising given the many factors that are expected to change this ratio at high redshifts.
The French Revolution began with the astonishing events of 1789, but it has to be seen as an intense and profound process that changed and developed dramatically over the following decade and more. Its political and social experiments changed a great many aspects of French life, and these changes also had a major impact on all of France's neighbours, including Great Britain. The Revolution led to a bitter dispute across Europe about the French principles of ‘liberty, equality and fraternity’, and, because the French revolutionaries sought to export these principles to the rest of Europe, it helped to provoke a war that posed an enormous challenge to France and all its neighbours. The French Revolution and the French Revolutionary war were the most discussed issues in British politics and the British press. The Revolutionary debate of the 1790s in Britain had a profound influence on the political, religious and cultural life of the country, while the French war produced almost unprecedented economic and social strains, and forced Britain to make a huge military, naval and financial effort to counter French ambitions. For a great many Britons the 1790s were a decade of crisis that polarized British society into the friends and enemies of the French Revolutionary cause. To understand the nature of this crisis, we need to appreciate the ideological disputes in Britain about French Revolutionary principles, to explore how these disputes encouraged Britons to support or oppose these principles, and to examine how these disputes strengthened the party of government, and seriously undermined the opposition in Parliament.
We describe forests from three areas of Jamaica, all on White Limestone but with markedly different rainfall regimes. The areas are Hog House Hill in the north-east with lower montane rain forest at c. 450 m altitude with a rainfall of c. 4000 mm yr−1; Broom Hall in the centre of the island with evergreen seasonal forest at c. 670 m altitude and with a rainfall of c. 1600 mm yr−1 and a marked dry season; and Round Hill near the south coast with dry semi-evergreen forest at c. 300 m altitude with an irregularly distributed rainfall of c. 1000 mm yr−1. Species lists were made from c. 180 ha at Hog House Hill, c. 5 ha at Broom Hall and c. 50 ha at Round Hill, and detailed inventories made of five sample sites of c. 1000 m2, two at Hog House Hill, one at Broom Hall and two at Round Hill.
At Hog House Hill we listed 280 vascular plant species, including 118 species of trees and larger shrubs; at Broom Hall 247 and 135; at Round Hill 129 and 81. Species-area and species-individuals curves confirm that Broom Hall was richer in tree species than Hog House Hill. The wetter forests contain high proportions of species endemic to Jamaica: 40% of the total flora at Hog House Hill and 36% at Broom Hall. Canopy height decreased from c. 26–28 m at Hog House Hill to c. 13–24 m at Broom Hall to c. 8–15 m at Round Hill. Predominant leaf size decreased from mesophyll at Hog House Hill to notophyll at Broom Hall to microphyll at Round Hill.
Compared with forests on other Caribbean islands, the Jamaican forests appear to be as species-rich as any, but lower in stature than natural forest in Trinidad and Dominica. Continental Neotropical forests are both more species-rich and taller.
We search for massive and evolved galaxies at z ≥ 5 in the Great Observatories Origins Deep Survey (GOODS) southern field. Combining HST ACS, VLT ISAAC and Spitzer IRAC broad–band photometric data, we develop a color selection technique to identify candidates for being evolved galaxies at high redshifts. The color selection is primarily based on locating the Balmer–break using the K- and 3.6 μm bands. Stellar population synthesis models are fitted to the SEDs of these galaxies to identify the final sample. We find 11 candidates with photometric redshifts in the range 4.9 < z < 5.6, dominated by an old stellar population, with ages 0.2-1.0 Gyr, and stellar masses in the range (0.7 − 5) × 1011 M⊙. Most of the candidates have modest amounts of internal dust extinction. The majority of the stars in these galaxies were formed at z>9 and the current star formation activity is a few percent of the inferred initial star formation rate.
Hepatitis B carriers who acquired the infection perinatally die from hepatocellular carcinoma (HCC) and cirrhosis at high rates. Published cohort studies are largely limited to males and are too small to estimate the age-specific risk of death. We therefore used routinely collected Hong Kong data to estimate the risks. Deaths were partitioned between carriers and non-carriers, then current life table calculations determined life expectancy and probability of dying from HCC or cirrhosis. HCC is the dominant cause of death for male carriers in middle adulthood with a lifetime risk of 27% for HCC compared to 4% for females. Predicted life expectancy is 72 years for male carriers, compared to 79 years for non-carriers. Female carriers have a life expectancy of 81 years and non-carriers 83 years. This model probably applies to all southern Chinese populations and emigrants with similar life history, and other populations that acquired infection early in life.
An in vitro selection was designed to identify RNA-cleaving
ribozymes predisposed for function as a drug. The selection
scheme required the catalyst to be trans-acting with
phosphodiesterase activity targeting a fragment of the Kras mRNA
under simulated physiological conditions. To increase stabilization
against nucleases and to offer the potential for improved
functionality, modified sequence space was sampled by transcribing
with the following NTPs: 2′-F-ATP, 2′-F-UTP, or
2′-F-5-[(N-imidazole-4-acetyl)
propylamine]-UTP, 2′-NH2-CTP, and GTP.
Active motifs were identified and assessed for their modified
NMP and divalent metal dependence. The minimization of the
ribozyme's size and the ability to substitute 2′-OMe
for 2′-F and 2′-NH2 moieties yielded
the motif from these selections most suited for both nuclease
stability and therapeutic development. This motif requires only
two 2′-NH2-Cs and functions as a 36-mer. Its
substrate sequence requirements were determined to be
5′–Y-G-H–3′. Its half-life in human serum
is >100 h. In physiologically relevant magnesium concentrations
[∼1 mM] its kcat = 0.07
min−1, Km = 70 nM.
This report presents a novel nuclease stable ribozyme, designated
ZinzymeTM, possessing optimal activity in simulated
physiological conditions and ready for testing in a therapeutic
setting.
One current limitation of two-photon technology is the lack of optimized fluorochromes for Two-Photon Laser Scanning Microscopy (TPLSM). Recently, Albota et al. (1998) have reported the design and synthesis of a number of bis(styryl)benzene derivatives that have large fluorescence quantum yields and greater two-photon absoption cross sections than any of fluorochromes that are currently used for TPLSM. As a first step in understanding how such molecules could be used in biological experiments, we have tagged a donor-πdonor molecule with biotin. We have successfully used this dye to detect quail nuclei in 2- 4 day old fixed embryos that have been reacted with QCPN, a quail specific monoclonal antibody. We have observed that this molecule gives a very intense signal, among the most intense signals we have been able to measure in our immunoassay. In particular, the brightness was about a factor of four higher than Rhodamine B-labelled streptavidin (containing 3.3 moles of dye per streptavidin tetramer).