The varying role of the GP in the pathway between colonoscopy and surgery for colorectal cancer: a retrospective cohort study

Extent: 11p.Objectives: To describe general practitioner (GP) involvement in the treatment referral pathway for colorectal cancer (CRC) patients. Design: A retrospective cohort analysis of linked data. Setting: A population-based sample of CRC patients diagnosed from August 2004 to December 2007 in New South Wales, Australia, using the 45 and Up Study, cancer registry diagnosis records, inpatient hospital records and Medicare claims records. Participants: 407 CRC patients who had a colonoscopy followed by surgery. Primary outcome measures: Patterns of GP consultations between colonoscopy and surgery (ie, between diagnosis and treatment). We investigated whether consulting a GP presurgery was associated with time to surgery, postsurgical GP consultations or rectal cancer cases having surgery in a centre with radiotherapy facilities. Results: Of the 407 patients, 43% (n=175) had at least one GP consultation between colonoscopy and surgery. The median time from colonoscopy to surgery was 27 days for those with an intervening GP consultation and 15 days for those without the consultation. 55% (n=223) had a GP consultation up to 30 days postsurgery; it was more common in cases of patients who consulted a GP presurgery than for those who did not (65% and 47%, respectively, adjusted OR 2.71, 95% CI 1.50 to 4.89, p=0.001). Of the 142 rectal cancer cases, 23% (n=33) had their surgery in a centre with radiotherapy facilities, with no difference between those who did and did not consult a GP presurgery (21% and 25% respectively, adjusted OR 0.84, 95% CI 0.27 to 2.63, p=0.76). Conclusions: Consulting a GP between colonoscopy and surgery was associated with a longer interval between diagnosis and treatment, and with further GP consultations postsurgery, but for rectal cancer cases it was not associated with treatment in a centre with radiotherapy facilities. GPs might require a more defined and systematic approach to CRC management.David Goldsbury, Mark Harris, Shane Pascoe, Michael Barton, Ian Olver, Allan Spigelman, Justin Beilby, Craig Veitch, David Weller, Dianne L O'Connel

Six New Recycled Globular Cluster Pulsars Discovered with the Green Bank Telescope

We have completed sensitive searches for new pulsars in seven globular clusters using the Robert C. Byrd Green Bank Telescope, and have discovered six new recycled pulsars (four in NGC 6517 and two in M22), five of which are fully recycled millisecond pulsars with P < 10 ms. We report full timing solutions for all six new pulsars and provide estimates of their flux densities and spectral indices. None of the pulsars are detected in archival Chandra data down to L_X~10^32 erg/s for NGC 6517 and L_X~10^31 erg/s for M22. One of the millisecond pulsars in M22 appears to have a very low mass companion, and is likely a new "black widow". A second binary pulsar in NGC 6517 is in a long-period, mildly eccentric orbit. We are able to set some lower limits on the age of the system, and find that it may be less than a few hundred million years old, which would indicate recent pulsar recycling in NGC 6517. An isolated pulsar in NGC 6517 that lies about 20 core radii from the cluster center appears to have been ejected from the core by interacting with a massive binary. By analyzing the luminosity function of the pulsars in NGC 6517, we predict the cluster to harbor roughly a dozen pulsars. We use the observed period derivatives of three pulsars to set lower limits on the mass-to-light ratios in the cores of their host clusters, and find no evidence for large amounts of low-luminosity matter. We also discuss reasons for non-detections in some of the clusters we searched.Comment: 17 pages, 2 figure

The Gaia DR1 mass–radius relation for white dwarfs

The Gaia Data Release 1 (DR1) sample of white dwarf parallaxes is presented, including 6 directly observed degenerates and 46 white dwarfs in wide binaries. This data set is combined with spectroscopic atmospheric parameters to study the white dwarf mass-radius relationship (MRR). Gaia parallaxes and G magnitudes are used to derive model atmosphere dependent white dwarf radii, which can then be compared to the predictions of a theoretical MRR. We find a good agreement between Gaia DR1 parallaxes, published effective temperatures (Teff) and surface gravities (log g), and theoretical MRRs. As it was the case for Hipparcos, the precision of the data does not allow for the characterisation of hydrogen envelope masses. The uncertainties on the spectroscopic atmospheric parameters are found to dominate the error budget and current error estimates for well-known and bright white dwarfs may be slightly optimistic. With the much larger Gaia DR2 white dwarf sample it will be possible to explore the MRR over a much wider range of mass, Teff, and spectral types

The Peculiar Radial Distribution of Multiple Populations in the Massive Globular Cluster M80

We present a detailed analysis of the radial distribution of light-element multiple populations (LE-MPs) in the massive and dense globular cluster M80, based on a combination of UV and optical Hubble Space Telescope data. Surprisingly, we find that first-generation (FG) stars (FG) are significantly more centrally concentrated than extreme second-generation (SG) stars out to ∼2.5rhfrom the cluster center. To understand the origin of such peculiar behavior, we used a set of N-body simulations following the long-term dynamical evolution of LE-MPs. We find that, given the advanced dynamical state of the cluster, the observed difference does not depend on the primordial relative distributions of FG and SG stars. On the contrary, a difference of ∼0.05-0.10 Mobetween the average masses of the two subpopulations is needed to account for the observed radial distributions. We argue that such a mass difference might be the result of the higher He abundance of SG stars (of the order of ΔY ∼0.05-0.06) with respect to FG stars. Interestingly, we find that a similar He variation is necessary to reproduce the horizontal branch morphology of M80. These results demonstrate that differences in mass among LE-MPs, due to different He content, should be properly taken into account for a correct interpretation of their radial distribution, at least in dynamically evolved systems. © 2018. The American Astronomical Society. All rights reserved.

A multi-wavelength survey of NGC\,6752: X-ray counterparts, two new dwarf novae, and a core-collapsed radial profile

We present the results of a multi-wavelength (FUV to I-band) survey of the stellar populations of the globular cluster NGC 6752, using STIS, ACS and WFC3 on board the Hubble Space Telescope. We have confirmed that two previously identified CV candidates are, in fact, dwarf novae which underwent outbursts during our observations. We have also identified previously unknown optical counterparts to two X-ray sources. We estimate the position of the centre of the cluster, and show that the stellar density profile is not well described by a single King model, indicating that this cluster is in a core-collapsed or post-core collapse phase. The colour-magnitude diagram shows a well-populated horizontal branch, numerous blue stragglers and white dwarfs (WDs), as well as 87 sources in the gap region where we expect to find WD - main sequence binaries, including cataclysmic variables (CVs). The X-ray sources and WD binary systems are the most centrally concentrated populations, with dynamically estimated characteristic masses >1.1Msun and >0.8Msun, respectively.Comment: 17 pages, 11 figures, accepted for publication in MNRA

Monitoring Alzheimer Amyloid Peptide Aggregation by EPR

Plaques containing the aggregated β-Amyloid (Aβ) peptide in the brain are the main indicators of Alzheimer’s disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of Aβ. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue Aβ peptide variant containing an N-terminal cysteine (cys-Aβ) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Δ-pyrroline-3-methyl] methanethiosulfonate spin label (SL-Aβ). Fibril formation in solutions of pure SL-Aβ and of SL-Aβ mixed with Aβ was shown by Congo-red binding and electron microscopy. Continuous-wave 9 GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric Aβ, one to a multimer (8–15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation

Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles

A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling

Deciphering the Structure, Growth and Assembly of Amyloid-Like Fibrils Using High-Speed Atomic Force Microscopy

Formation of fibrillar structures of proteins that deposit into aggregates has been suggested to play a key role in various neurodegenerative diseases. However mechanisms and dynamics of fibrillization remains to be elucidated. We have previously established that lithostathine, a protein overexpressed in the pre-clinical stages of Alzheimer's disease and present in the pathognomonic lesions associated with this disease, form fibrillar aggregates after its N-terminal truncation. In this paper we visualized, using high-speed atomic force microscopy (HS-AFM), growth and assembly of lithostathine protofibrils under physiological conditions with a time resolution of one image/s. Real-time imaging highlighted a very high velocity of elongation. Formation of fibrils via protofibril lateral association and stacking was also monitored revealing a zipper-like mechanism of association. We also demonstrate that, like other amyloid ß peptides, two lithostathine protofibrils can associate to form helical fibrils. Another striking finding is the propensity of the end of a growing protofibril or fibril to associate with the edge of a second fibril, forming false branching point. Taken together this study provides new clues about fibrillization mechanism of amyloid proteins

Rapid Changes in Phospho-MAP/Tau Epitopes during Neuronal Stress: Cofilin-Actin Rods Primarily Recruit Microtubule Binding Domain Epitopes

Abnormal mitochondrial function is a widely reported contributor to neurodegenerative disease including Alzheimer's disease (AD), however, a mechanistic link between mitochondrial dysfunction and the initiation of neuropathology remains elusive. In AD, one of the earliest hallmark pathologies is neuropil threads comprising accumulated hyperphosphorylated microtubule-associated protein (MAP) tau in neurites. Rod-like aggregates of actin and its associated protein cofilin (AC rods) also occur in AD. Using a series of antibodies - AT270, AT8, AT100, S214, AT180, 12E8, S396, S404 and S422 - raised against different phosphoepitopes on tau, we characterize the pattern of expression and re-distribution in neurites of these phosphoepitope labels during mitochondrial inhibition. Employing chick primary neuron cultures, we demonstrate that epitopes recognized by the monoclonal antibody 12E8, are the only species rapidly recruited into AC rods. These results were recapitulated with the actin depolymerizing drug Latrunculin B, which induces AC rods and a concomitant increase in the 12E8 signal measured on Western blot. This suggests that AC rods may be one way in which MAP redistribution and phosphorylation is influenced in neurons during mitochondrial stress and potentially in the early pathogenesis of AD

Comparison of immature and mature bone marrow-derived dendritic cells by atomic force microscopy

A comparative study of immature and mature bone marrow-derived dendritic cells (BMDCs) was first performed through an atomic force microscope (AFM) to clarify differences of their nanostructure and adhesion force. AFM images revealed that the immature BMDCs treated by granulocyte macrophage-colony stimulating factor plus IL-4 mainly appeared round with smooth surface, whereas the mature BMDCs induced by lipopolysaccharide displayed an irregular shape with numerous pseudopodia or lamellapodia and ruffles on the cell membrane besides becoming larger, flatter, and longer. AFM quantitative analysis further showed that the surface roughness of the mature BMDCs greatly increased and that the adhesion force of them was fourfold more than that of the immature BMDCs. The nano-features of the mature BMDCs were supported by a high level of IL-12 produced from the mature BMDCs and high expression of MHC-II on the surface of them. These findings provide a new insight into the nanostructure of the immature and mature BMDCs