To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Longitudinal studies of first episode of psychosis (FEP) patients are critical to understanding the dynamic clinical factors influencing functional outcomes; negative symptoms and verbal memory (VM) deficits are two such factors that remain a therapeutic challenge. This study uses white-gray matter contrast at the inner edge of the cortex, in addition to cortical thickness, to probe changes in microstructure and their relation with negative symptoms and possible intersections with verbal memory.
T1-weighted images and clinical data were collected longitudinally for patients (N = 88) over a two-year period. Cognitive data were also collected at baseline. Relationships between baseline VM (immediate/delayed recall) and rate of change in two negative symptom dimensions, amotivation and expressivity, were assessed at the behavioral level, as well as at the level of brain structure.
VM, particularly immediate recall, was significantly and positively associated with a steeper rate of expressivity symptom decline (r = 0.32, q = 0.012). Significant interaction effects between baseline delayed recall and change in expressivity were uncovered in somatomotor regions bilaterally for both white-gray matter contrast and cortical thickness. Furthermore, interaction effects between immediate recall and change in expressivity on cortical thickness rates were uncovered across higher-order regions of the language processing network.
This study shows common neural correlates of language-related brain areas underlying expressivity and VM in FEP, suggesting deficits in these domains may be more linked to speech production rather than general cognitive capacity. Together, white-gray matter contrast and cortical thickness may optimally inform clinical investigations aiming to capture peri-cortical microstructural changes.
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.
This research explores media reporting of Indigenous students’ Programme for International Student Assessment (PISA) results in two national and 11 metropolitan Australian newspapers from 2001 to 2015. Of almost 300 articles on PISA, only 10 focused on reporting of Indigenous PISA results. While general or non-Indigenous PISA results featured in media reports, especially at the time of the publication of PISA results, there was overwhelming neglect of Indigenous results and the performance gap. A thematic analysis of articles showed mainstream PISA reporting had critical commentary which is not found in the Indigenous PISA articles. The three themes identified include: a lack of teacher quality in remote and rural schools; the debate on Gonski funding recommendations and the PISA achievement gap between Indigenous and non-Indigenous students. This study concluded the overwhelming neglect is linked to media bias, which continues to drive mainstream media coverage of Indigenous Australians.
OBJECTIVES/SPECIFIC AIMS: Cardiac radiation exposure following anti-cancer (CA) thoracic radiotherapy (RT) treatment increases risk of heart failure in a dose-dependent manner with a predominantly restrictive cardiomyopathy phenotype and is characterized by a diffuse fibrosis within the myocardium. The peak oxygen pulse (O2Pulse) determined at cardiopulmonary exercise testing (CPET) is the quotient of oxygen consumption (VO2) divided by the heart rate (HR) at peak exercise. Through deduction of the Fick equation (VO2 = cardiac output (CO) x arteriovenous oxygen difference) it provides a noninvasive estimate of the stroke volume response to exercise. Knowledge of the relationship between cardiac radiation dose and O2Pulse may provide mechanistic insight into the cardiac reserve of the CA survivor following thoracic RT. METHODS/STUDY POPULATION: Patients without a history of cardiovascular disease with a history of thoracic RT for CA treatment with significant incidental heart exposure (≥5 Gray (Gy) to ≥10% of the heart volume) underwent treadmill CPET to determine cardiorespiratory fitness and cardiac magnetic resonance (CMR) imaging to quantify central hemodynamics and for myocardial tissue characterization. The mean cardiac radiation dose (MCRD) and %volume of heart dose was determined from dose-volume histograms reflective of the dose contributions from all RT treatments for each patient. The oxygen pulse (milliliters (mL) of O2 per heart beat) was determined by dividing the absolute VO2 by the HR (beats per minute, bpm) at peak exercise and reported as %-predicted values to account for age and gender differences. Data are reported as number (%) or median (interquartile range). A stepwise multivariate linear regression model was created from significant univariate RT and CMR variables to determine independent predictors of %O2Pulse. RESULTS/ANTICIPATED RESULTS: Thirty patients (age = 63 [57-67] years, 18 [60%] female, 2.0 [0.1-28.7] years since completion of RT) underwent study procedures. The peak VO2=1376 mL·min-1 (62% of predicted) and peak HR = 150 (122-164) bpm resulted in a peak O2Pulse of 9.2 mL/beat (82% of predicted). The MCRD = 5.6 [3.7-17.8] Gy was inversely associated with %O2Pulse at univariate analysis (R = −0.514, p < .01), but was not retained at multivariate analysis. The CMR-derived CO ([4.9 (4.09-5.90) Liters/minute], β = +.374, p < .01), CMR-extracellular volume ([ECV, 26.9 (24.8-29.2)%], β = −.536, p < .01), and volume of the heart exposed to ≥30 Gy ([2.5 (0-15.0)Gy], (β = −.345, p = .01) were retained in the model (R2 = .709, F(3,19) = 15.438, p < .001) and were independent predictors of the %O2Pulse. DISCUSSION/SIGNIFICANCE OF IMPACT: In patients with significant heart exposure following RT, %O2Pulse (a surrogate of stroke volume response to exercise) is inversely associated with cardiac radiation dose and is related to central hemodynamics (CO) and markers of diffuse fibrosis (ECV).
The Institute of Health Economics offers a suite of analyses that provide developers an understanding of the expected commercial viability of an early stage health technology. In combination, these analyses form the Value-Engineered Translation framework. These methods incorporate innovative methods to manage uncertainty in early economic evaluations, in particular, moving beyond current stochastic assessments of headroom to account for inter-market variability in value hurdles, as well as incorporating social value premia considerations. An illustration of these methods is demonstrated using the example of a non-invasive diagnostic test (called DCRSHP) at an early stage of development, compared to current practice of cystoscopy in the diagnosis of bladder cancer.
Competing technologies were identified to inform the headroom assessment based on price and effectiveness. Then, a model-based cost-effectiveness analysis was undertaken incorporating headroom analysis, stochastic one-way sensitivity analysis, and value of information analysis using data from secondary sources.
Currently there are a number of non-invasive tests available, but none have sufficient test accuracy to be suitable for bladder cancer diagnosis alone. From the headroom analysis, DCRSHP can be priced at up to CAD 790 (i.e. USD 588) and still be cost-effective compared to the current practice of cystoscopy. Interestingly this price can be increased for patient groups that have lower levels of bladder cancer prevalence.
The requirements of economic evaluations depend on the stage of technology development, and analysis approaches must reflect this. The results here indicate that DCRSHP clears the value hurdle in terms of being cost-effective, and thus provides the opportunity to make a commercial return on future investment. Future analysis of DCRSHP could consider the cost drivers for development of the technology, including the regulatory pathways, costs associated with the intellectual asset management for the technology, and alternative manufacturing costs. All of which contribute to the research-to-practice continuum.
The financial system can be shown to be a complex adaptive system consisting primarily of a federation of systems and systems of systems. There are significant similarities between the characteristics of natural systems and financial systems suggesting that the type of analysis employed in understanding natural systems could have application in financial system analysis. Cladistics analysis has been used extensively for analysis of biological systems and has accordingly been used in the social sciences for some years but a rigorous justification for adopting the analysis has not been undertaken. This paper discusses the appropriateness of applying cladistics analysis to financial systems, and then considers the appropriate methodology to be adopted for analysis of different financial events.
Geochemical and related studies have been made of near-surface sediments from the River Clyde estuary and adjoining areas, extending from Glasgow to the N, and W as far as the Holy Loch on the W coast of Scotland, UK. Multibeam echosounder, sidescan sonar and shallow seismic data, taken with core information, indicate that a shallow layer of modern sediment, often less than a metre thick, rests on earlier glacial and post-glacial sediments. The offshore Quaternary history can be aligned with onshore sequences, with the recognition of buried drumlins, settlement of muds from quieter water, probably behind an ice dam, and later tidal delta deposits. The geochemistry of contaminants within the cores also indicates shallow contaminated sediments, often resting on pristine pre-industrial deposits at depths less than 1m. The distribution of different contaminants with depth in the sediment, such as Pb (and Pb isotopes), organics and radionuclides, allow chronologies of contamination from different sources to be suggested. Dating was also attempted using microfossils, radiocarbon and 210Pb, but with limited success. Some of the spatial distribution of contaminants in the surface sediments can be related to grain-size variations. Contaminants are highest, both in absolute terms and in enrichment relative to the natural background, in the urban and inner estuary and in the Holy Loch, reflecting the concentration of industrial activity.
The global banking system can be shown to be a Complex Adaptive System that exhibits phase transitions from time to time. These phase transitions can result in significant financial losses to the community that we estimate to be much more significant than losses occurring during “business as usual” periods. In this paper, we argue that the significant losses arising from phase transitions in the banking system requires a very different approach to regulation than the current Basel regime, and that there is a need to transition the Basel regime from a Federation of Systems to a System of Systems. We demonstrate that the World Health Organisation’s recent management system for pandemics is ideally suited for management of the global banking system and would have greater potential to control the phase transition losses than the current Basel system.
Operational risk events in banks include extreme events with significant losses being incurred and with substantial impact on share prices. A pooling arrangement between banks that would be able to reduce overall costs and reduce share price impacts would seem desirable, but one of the major inhibiting factors to establish the feasibility of such a pooling arrangement is that statistical models of these extreme events are difficult to build with any reliability. This paper uses both quantitative and qualitative analysis of operational risk losses for EU and US banks over the period 2008–2014 to establish the feasibility of creating a pooling arrangement between the banks and concludes that such an arrangement might be feasible but would require compulsory membership of the pool and capping of losses.
Our ALMA observations of HCO+ and HCN show such redshifted absorption toward an isolated core, BHR 71. Both lines show a similar redshifted absorption profile. We also found emissions of complex organic molecules (COMs) around 345 GHz from a compact region centered on the continuum source, which is barely resolved with a beam of 0″27, corresponding to ∼50 AU.
Starbursts are finite periods of intense star formation (SF) that can dramatically impact the evolutionary state of a galaxy. Recent results suggest that starbursts in dwarf galaxies last longer and are distributed over more of the galaxy than previously thought, with star formation efficiencies (SFEs) comparable to spiral galaxies, much higher than those typical of non-bursting dwarfs. This difference might be explainable if the starburst mode is externally triggered by gravitational interactions with other nearby systems. We present new, sensitive neutral hydrogen observations of 18 starburst dwarf galaxies, which are part of the STARburst IRregular Dwarf Survey (STARBIRDS) and each were mapped with the Green Bank Telescope (GBT) and/or Parkes Telescope in order to study the low surface brightness gas distributions, a common tracer for tidal interactions.
OBJECTIVES/SPECIFIC AIMS: The aims of this study are 2-fold: (1) to determine if maternal schistosomiasis affects maternal immunity to tetanus and/or transplacental transfer of antitetanus toxoid (TT) immunoglobulin G (IgG) from mother to infant and (2) determine the influence of maternal schistosomiasis on infant BCG vaccine immunogenicity. METHODS/STUDY POPULATION: The study will utilize blood samples from a historic cohort of 100 mother-infant pairs from Kisumu, Kenya, a schistosomiasis-endemic area. For the first aim, we will evaluate maternal schistosomal circulating anodic antigen, which has improved sensitivity and specificity to detect active schistosomiasis from serum, and antisoluble egg antigen IgG positivity compared with quantitative maternal anti-TT IgG at delivery and anti-TT IgG cord blood to maternal blood ratio (cord:maternal ratio). For the second aim, we will evaluate association between maternal schistosomiasis as detected by circulating anodic antigen and antisoluble egg antigen IgG at delivery and infant BCG-specific Th1-cytokine positive CD4+ cells at 10 weeks following BCG vaccination at birth. RESULTS/ANTICIPATED RESULTS: We hypothesize that active maternal schistosomiasis will be associated with decreased maternal anti-TT IgG and reduced efficiency of transplacental transfer, as measured by infant cord blood to maternal blood ratio of anti-TT IgG. We also expect that maternal schistosomiasis will be associated with decreased infant immunogenicity to BCG vaccine. DISCUSSION/SIGNIFICANCE OF IMPACT: This is a formative study on infant vaccine immunity using laboratory methodology not previously applied. Understanding infant immunity in the setting of maternal schistosomiasis will inform vaccination strategies and tailor vaccine development in schistosome-endemic areas such as Kenya, where neither TB nor neonatal tetanus have been eradicated. Additionally, our results will inform public health policies to consider integration of antischistosomal agents in antenatal care.
Heavy-tailed distributions have been observed for various financial risks and papers have observed that these heavy-tailed distributions are power law distributions. The breakdown of a power law distribution is also seen as an indicator of a tipping point being reached and a system then moves from stability through instability to a new equilibrium. In this paper, we analyse the distribution of operational risk losses in US banks, credit defaults in US corporates and market risk events in the US during the global financial crisis (GFC). We conclude that market risk and credit risk do not follow a power law distribution, and even though operational risk follows a power law distribution, there is a better distribution fit for operational risk. We also conclude that whilst there is evidence that credit defaults and market risks did reach a tipping point, operational risk losses did not. We conclude that the government intervention in the banking system during the GFC was a possible cause of banks avoiding a tipping point.
Grylloblatta campodeiformis campodeiformis Walker (Grylloblattodea: Grylloblattidae) was commonly collected during summer from trees killed by the mountain pine beetle, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae), in subalpine forests of Alberta, Canada. Gut content analysis revealed that the grylloblattids fed on subcortical invertebrates. This newly reported habitat association shows that this species is not limited to strictly alpine habitats and glacial margins, and thus may be more widespread and common than suggested by earlier reports.
The development of algorithms for agile science and autonomous exploration has been pursued in contexts ranging from spacecraft to planetary rovers to unmanned aerial vehicles to autonomous underwater vehicles. In situations where time, mission resources and communications are limited and the future state of the operating environment is unknown, the capability of a vehicle to dynamically respond to changing circumstances without human guidance can substantially improve science return. Such capabilities are difficult to achieve in practice, however, because they require intelligent reasoning to utilize limited resources in an inherently uncertain environment. Here we discuss the development, characterization and field performance of two algorithms for autonomously collecting water samples on VALKYRIE (Very deep Autonomous Laser-powered Kilowatt-class Yo-yoing Robotic Ice Explorer), a glacier-penetrating cryobot deployed to the Matanuska Glacier, Alaska (Mission Control location: 61°42′09.3″N 147°37′23.2″W). We show performance on par with human performance across a wide range of mission morphologies using simulated mission data, and demonstrate the effectiveness of the algorithms at autonomously collecting samples with high relative cell concentration during field operation. The development of such algorithms will help enable autonomous science operations in environments where constant real-time human supervision is impractical, such as penetration of ice sheets on Earth and high-priority planetary science targets like Europa.
OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
The East Asian–Australasian flyway contains some of the most threatened habitats in the world, with at least 155 waterbird species reliant on the tidal habitats it comprises. The black-faced spoonbill (Platalea minor) is an iconic endangered species distributed across the coast of East Asia. Its population suffered a severe decline into the 1990s, but extensive monitoring and conservation interventions have aided a substantial recovery of the species. We used a population viability analysis based on data collected over the past two decades in conjunction with species distribution models to project spatially explicit models of population change for the next 35 years. Over nearly all scenarios of habitat loss and climate change, the global spoonbill population was projected to increase in the short-term due to low population numbers likely well below current population carrying capacities. However, climate change and habitat loss together threaten the recovery of the spoonbill population such that, by 2050, population declines are apparent as a consequence of these cumulative impacts. These threats are also cryptic and represent a challenge to the conservation of species recovering from anthropogenic impacts; observed population increases can hide large reductions in habitat suitability that threaten the long-term viability of species.