Protocol for a longitudinal qualitative interview study: maintaining psychological well-being in advanced cancer - what can we learn from patients' and carers' own coping strategies?

IntroductionPeople with advanced cancer and their carers experience stress and uncertainty which affects the quality of life and physical and mental health. This study aims to understand how patients and carers recover or maintain psychological well-being by exploring the strategies employed to self-manage stress and uncertainty.Methods and analysisA longitudinal qualitative interview approach with 30 patients with advanced cancer and 30 associated family or informal carers allows the exploration of contexts, mechanisms and outcomes at an individual level. Two interviews, 4–12?weeks apart, will not only enable the exploration of individuals’ evolving coping strategies in response to changing contexts but also how patients’ and carers’ strategies inter-relate. Patient and Carer focus groups will then consider how the findings may be used in developing an intervention. Recruiting through two major tertiary cancer centres in the North West and using deliberately broad and inclusive criteria will enable the sample to capture demographic and experiential breadth.Ethics and disseminationThe research team will draw on their considerable experience to ensure that the study is sensitive to a patient and carer group, which may be considered vulnerable but still values being able to contribute its views. Public and patient involvement (PPI) is integral to the design and is evidenced by: a research advisory group incorporating patient and carers, prestudy consultations with the PPI group at one of the study sites and a user as the named applicant. The study team will use multiple methods to disseminate the findings to clinical, policy and academic audiences. A key element will be engaging health professionals in patient and carer ideas for promoting self-management of psychological well-being. The study has ethical approval from the North West Research Ethics Committee and the appropriate NHS governance clearance.RegistrationNational Institute for Health Research (NIHR) Clinical Studies Portfolio, UK Clinical Research Network (UKCRN) Study number 11725

Climatic forcing before, during, and after the 8.2 Kyr B.P. global cooling event

This paper attempts at full characterization of the unique global 8.2 Kyr B.P. cooling event. Significant atmospheric cooling started during 9.5-8.5 Kyr B.P. when the Sun was extremely quiet during three periods of ~ 50-100 years. The flood of melt water in the N. Atlantic from glacial lakes during the demise of the Laurentide ice sheet, starting at ~ 8.5 Kyr B.P., adds to the atmospheric cooling. Climatic forcing events occurred at 8.5 Kyr B.P., at 8.2 Kyr B.P. and finally at 8.06 Kyr B.P., leading to concurrent increases or decreases in the atmospheric Δ 14C levels, completely consistent with the climatic forcing proposed here

An experimental proposal to study collapse of the wave function in travelling-wave parametric amplifiers

The read-out of a microwave qubit state occurs using an amplification chain that enlarges the quantum state to a signal detectable with a classical measurement apparatus. However, at what point in this process did we really `measure' the quantum state? In order to investigate whether the `measurement' takes place in the amplification chain, we propose to construct a microwave interferometer that has a parametric amplifier added to each of its arms. Feeding the interferometer with single photons, the visibility depends on the gain of the amplifiers and whether a measurement collapse has taken place during the amplification process. We calculate the interference visibility as given by standard quantum mechanics as a function of gain, insertion loss and temperature and find a magnitude of $1/3$ in the limit of large gain without taking into account losses. This number reduces to $0.26$ in case the insertion loss of the amplifiers is $2.2$ dB at a temperature of $50$ mK. We show that if the wave function collapses within the interferometer, we will measure a reduced visibility compared to the prediction from standard quantum mechanics once this collapse process sets in.Comment: 21 pages and 23 figures (including appendices and subfigures). v4: Abstract and introduction rewritten and note on stochasticity of quantum state collapse added to section 6. v5: no content changes w.r.t. v

Identification of floodwater source areas in Nepal using SCIMAP‐Flood

Practical approaches for managing flooding from fluvial sources are moving away from mitigation solely at the point of impact and towards integrated catchment management. This considers the source areas, flow pathways of floodwaters and the locations and exposure to the risk of communities. For a field site in southern Nepal, we analyse catchment response to a range of simulated rainfall events, which when evaluated collectively can help guide potential flood management solutions. This is achieved through the adoption of SCIMAP-Flood, a decision support framework that works at the catchment-scale to identify critical source areas for floodwaters. The SCIMAP-Flood Fitted inverse modelling approach has been applied to the East Rapti catchment, Nepal. For multiple flood impact locations throughout the catchment, SCIMAP-Flood effectively identifies locations where flood management measures would have the most positive effects on risk reduction. The results show that the spatial targeting of mitigation measures in areas of irrigated and rainfed agriculture and the prevention of deforestation or removal of shrubland would be the most effective approaches. If these actions were in the upper catchment above Hetauda or upstream of Manahari they would have the most effective reduction in the flood peak

SUMSS: A Wide-Field Radio Imaging Survey of the Southern Sky. I. Science goals, survey design and instrumentation

The Molonglo Observatory Synthesis Telescope, operating at 843 MHz with a 5 square degree field of view, is carrying out a radio imaging survey of the sky south of declination -30 deg. This survey (the Sydney University Molonglo Sky Survey, or SUMSS) produces images with a resolution of 43" x 43" cosec(Dec.) and an rms noise level of about 1 mJy/beam. SUMSS is therefore similar in sensitivity and resolution to the northern NRAO VLA Sky Survey (NVSS; Condon et al. 1998). The survey is progressing at a rate of about 1000 square degrees per year, yielding individual and statistical data for many thousands of weak radio sources. This paper describes the main characteristics of the survey, and presents sample images from the first year of observation.Comment: 27 pages, 12 figures (figures 2, 8, 10 in jpg format); AJ, in pres

Wind measurements from an array of oceanographic moorings and from F/SMeteor during JASIN 1978

During the Joint Air-Sea Interaction (JASIN) experiment conducted in the northern Rockall Trough in the summer of 1978, oceanographic moorings with surface buoys carrying wind recorders were deployed in an array designed to investigate the variability of the near-surface wind field at scales of from 2 to 200 km. The wind records together with observations taken on board the research vessels participating in JASIN have provided ground truth measurements for the sea surface wind velocity sensors on the Seasat satellite. During most of the experiment the wind field was characterized by spatial scales large in comparison with the separations between the buoys. On several occasions, spatial differences associated with cold fronts were identified, and it was possible to track the passage of the front through the array. However, quantitative analysis of the variability of the wind field was complicated both by a lack of data due to mechanical failures of some instruments and by significant differences in the performance of the diverse types of wind recorders. Reevaluation of the instruments used in JASIN and recent comparison of some of these instruments with more conventional sets of wind sensors confirm the possibility that there is significant error in the JASIN wind measurements made from the buoys. In particular, the vector-averaging wind recorder on W2, which was one of the few instruments to recover a full length record and which was chosen during a Seasat-JASIN workshop as the JASIN standard, had performance characteristics that were among the most difficult to explain

Mean biases, variability, and trends in air–sea fluxes and sea surface temperature in the CCSM4

Author Posting. © American Meteorological Society, 2012. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 25 (2012): 7781–7801, doi:10.1175/JCLI-D-11-00442.1.Air–sea fluxes from the Community Climate System Model version 4 (CCSM4) are compared with the Coordinated Ocean-Ice Reference Experiment (CORE) dataset to assess present-day mean biases, variability errors, and late twentieth-century trend differences. CCSM4 is improved over the previous version, CCSM3, in both air–sea heat and freshwater fluxes in some regions; however, a large increase in net shortwave radiation into the ocean may contribute to an enhanced hydrological cycle. The authors provide a new baseline for assessment of flux variance at annual and interannual frequency bands in future model versions and contribute a new metric for assessing the coupling between the atmospheric and oceanic planetary boundary layer (PBL) schemes of any climate model. Maps of the ratio of CCSM4 variance to CORE reveal that variance on annual time scales has larger error than on interannual time scales and that different processes cause errors in mean, annual, and interannual frequency bands. Air temperature and specific humidity in the CCSM4 atmospheric boundary layer (ABL) follow the sea surface conditions much more closely than is found in CORE. Sensible and latent heat fluxes are less of a negative feedback to sea surface temperature warming in the CCSM4 than in the CORE data with the model’s PBL allowing for more heating of the ocean’s surface.The CESM project is supported by the National Science Foundation and the Office of Science (BER) of the U.S. Department of Energy. S. Stevensonwas supported byNASAGrantNNX09A020H and B. Fox-Kemper by Grants NSF 0934737 and NASA NNX09AF38G.2013-05-1

Intrapancreatic delivery of human umbilical cord blood aldehyde dehydrogenase-producing cells promotes islet regeneration

Aims/hypothesis We sought to investigate the stimulation of islet regeneration by transplanted human umbilical cord blood (UCB) cells purified according to high aldehyde dehydrogenase (ALDH) activity (ALDHhi), a conserved characteristic of multiple progenitor lineages. We hypothesised that direct intrapancreatic (iPan) delivery of ALDHhi progenitors would augment islet regeneration via timely and localised exposure to islet-regenerative stimuli. Methods Cells were purified from UCB based on flow cytometry for low ALDH activity (ALDHlo) vs ALDHhi. UCB ALDHlo or ALDHhi cells were compared for surface marker expression, as well as haematopoietic, endothelial and multipotent stromal progenitor content in vitro. UCB ALDHlo or ALDHhi cells were i.v. or iPan injected into streptozotocin-treated non-obese diabetic/severe combined immune-deficient mice temporally monitored for blood glucose, serum insulin and glucose tolerance. Human cell recruitment and survival in the pancreas, insulin content, islet-associated cell proliferation and islet vascularisation were documented in situ. Results UCB-derived ALDHhi cells were highly enriched for haematopoietic and endothelial progenitor frequency, and showed increased expression of progenitor and myeloid cell surface markers. Although i.v. transplantation of ALDHhi cells demonstrated low pancreas engraftment and only transient blood glucose lowering capacity, iPan injected ALDHhi cells reversed established hyperglycaemia, increased serum insulin and improved the response to a glucose challenge. iPan injected ALDHhi cells surrounded damaged islets at early time points and increased islet-associated cell proliferation, resulting in the recovery of beta cell mass. Conclusions/interpretation iPan delivery of UCB ALDHhi cells potentiated islet-associated cell proliferation, insulin production and islet revascularisation, resulting in the recovery of host islet function. Elucidation of the progenitor-specific pathways stimulated during islet regeneration may provide new approaches to promote islet expansion during diabetes. © Springer-Verlag 2012

Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches