Development of Prognosis in Palliative care Study (PiPS) predictor models to improve prognostication in advanced cancer: prospective cohort study

OBJECTIVE: To develop a novel prognostic indicator for use in patients with advanced cancer that is significantly better than clinicians' estimates of survival. DESIGN: Prospective multicentre observational cohort study. SETTING: 18 palliative care services in the UK (including hospices, hospital support teams, and community teams). PARTICIPANTS: 1018 patients with locally advanced or metastatic cancer, no longer being treated for cancer, and recently referred to palliative care services. MAIN OUTCOME MEASURES: Performance of a composite model to predict whether patients were likely to survive for "days" (0-13 days), "weeks" (14-55 days), or "months+" (>55 days), compared with actual survival and clinicians' predictions. RESULTS: On multivariate analysis, 11 core variables (pulse rate, general health status, mental test score, performance status, presence of anorexia, presence of any site of metastatic disease, presence of liver metastases, C reactive protein, white blood count, platelet count, and urea) independently predicted both two week and two month survival. Four variables had prognostic significance only for two week survival (dyspnoea, dysphagia, bone metastases, and alanine transaminase), and eight variables had prognostic significance only for two month survival (primary breast cancer, male genital cancer, tiredness, loss of weight, lymphocyte count, neutrophil count, alkaline phosphatase, and albumin). Separate prognostic models were created for patients without (PiPS-A) or with (PiPS-B) blood results. The area under the curve for all models varied between 0.79 and 0.86. Absolute agreement between actual survival and PiPS predictions was 57.3% (after correction for over-optimism). The median survival across the PiPS-A categories was 5, 33, and 92 days and survival across PiPS-B categories was 7, 32, and 100.5 days. All models performed as well as, or better than, clinicians' estimates of survival. CONCLUSIONS: In patients with advanced cancer no longer being treated, a combination of clinical and laboratory variables can reliably predict two week and two month survival

MesobanK UK: an international mesothelioma bioresource.

Malignant pleural mesothelioma causes the greatest societal burden of all the asbestos-related diseases. Progress in better understanding tumour biology will be facilitated by the availability of quality-assured annotated tissue. MesobanK has been created to establish a bioresource of pleural mesothelioma tissue linked to detailed anonymised clinical data. When complete, the bioresource will comprise a 750-patient tissue microarray and prospectively collected tissue, blood and pleural fluid from 300 patients with mesothelioma. Twenty-six new cell lines have also been developed. MesobanK meets all appropriate ethical and regulatory procedures and has recently opened to requests for tissue and data.RCR and DMR are part funded by the Cambridge Biomedical Research Centre and the Cambridge Cancer Centre. RCR is also funded by the NIHR Clinical Research Network: Eastern.This is the final version of the article. It first appeared from BMJ via http://dx.doi.org/10.1136/thoraxjnl-2015-20749

Prospects for rapid deceleration of small molecules by optical bichromatic forces

We examine the prospects for utilizing the optical bichromatic force (BCF) to greatly enhance laser deceleration and cooling for near-cycling transitions in small molecules. We discuss the expected behavior of the BCF in near-cycling transitions with internal degeneracies, then consider the specific example of decelerating a beam of calcium monofluoride molecules. We have selected CaF as a prototype molecule both because it has an easily-accessible near-cycling transition, and because it is well-suited to studies of ultracold molecular physics and chemistry. We also report experimental verification of one of the key requirements, the production of large bichromatic forces in a multi-level system, by performing tests in an atomic beam of metastable helium.Comment: 11 pages, 6 figures, revised version, to be published in Physical Review

Membranous nephropathy in the UK Biobank

Background Despite MN being one of the most common causes of nephrotic syndrome worldwide, its biological and environmental determinants are poorly understood in large-part due to it being a rare disease. Making use of the UK Biobank, a unique resource holding a clinical dataset and stored DNA, serum and urine for ~500,000 participants, this study aims to address this gap in understanding. Methods The primary outcome was putative MN as defined by ICD-10 codes occurring in the UK Biobank. Univariate relative risk regression modelling was used to assess the associations between the incidence of MN and related phenotypes with sociodemographic, environmental exposures, and previously described increased-risk SNPs. Results 502,507 patients were included in the study of whom 100 were found to have a putative diagnosis of MN; 36 at baseline and 64 during the follow-up. Prevalence at baseline and last follow-up were 72 and 199 cases/million respectively. At baseline, as expected, the majority of those previously diagnosed with MN had proteinuria, and there was already evidence of proteinuria in patients diagnosed within the first 5 years of follow-up. The highest incidence rate for MN in patients was seen in those homozygous for the high-risk alleles (9.9/100,000 person-years). Conclusion It is feasible to putatively identify patients with MN in the UK Biobank and cases are still accumulating. This study shows the chronicity of disease with proteinuria present years before diagnosis. Genetics plays an important role in disease pathogenesis, with the at-risk group providing a potential population for recall

Bi-stable tunneling current through a molecular quantum dot

An exact solution is presented for tunneling through a negative-U d-fold degenerate molecular quantum dot weakly coupled to electrical leads. The tunnel current exhibits hysteresis if the level degeneracy of the negative-U dot is larger than two (d>2). Switching occurs in the voltage range V1 < V < V2 as a result of attractive electron correlations in the molecule, which open up a new conducting channel when the voltage is above the threshold bias voltage V2. Once this current has been established, the extra channel remains open as the voltage is reduced down to the lower threshold voltage V1. Possible realizations of the bi-stable molecular quantum dots are fullerenes, especially C60, and mixed-valence compounds.Comment: 5 pages, 1 figure. (v2) Figure updated to compare the current hysteresis for degeneracies d=4 and d>>1 of the level in the dot, minor corrections in the text. To appear in Phys. Rev.

On the Spiral Structure of the Milky Way Galaxy

We consider the possible pattern of the overall spiral structure of the Galaxy, using data on the distribution of neutral (atomic), molecular, and ionized hydrogen, on the base of the hypothesis of the spiral structure being symmetric, i.e. the assumption that spiral arms are translated into each other for a rotation around the galactic center by 180{\deg} (a two-arm pattern) or by 90{\deg} (a four-arm pattern). We demonstrate that, for the inner region, the observations are best represented with a four-arm scheme of the spiral pattern, associated with all-Galaxy spiral density waves. The basic position is that of the Carina arm, reliably determined from distances to HII regions and from HI and H2 radial velocities. This pattern is continued in the quadrants III and IV with weak outer HI arms; from their morphology, the Galaxy should be considered an asymmetric multi-arm spiral. The kneed shape of the outer arms that consist of straight segments can indicate that these arms are transient formations that appeared due to a gravitational instability in the gas disk. The distances between HI superclouds in the two arms that are the brightest in neutral hydrogen, the Carina arm and the Cygnus (Outer) arm, concentrate to two values, permitting to assume the presence of a regular magnetic field in these arms.Comment: 21 pages, 14 fugures; accepted for publication in Astronomichesky Journal (Astron. Rep.

Tracing spiral density waves in M81

We use SPITZER IRAC 3.6 and 4.5micron near infrared data from the Spitzer Infrared Nearby Galaxies Survey (SINGS), optical B, V and I and 2MASS Ks band data to produce mass surface density maps of M81. The IRAC 3.6 and 4.5micron data, whilst dominated by emission from old stellar populations, is corrected for small-scale contamination by young stars and PAH emission. The I band data are used to produce a mass surface density map by a B-V colour-correction, following the method of Bell and de Jong. We fit a bulge and exponential disc to each mass map, and subtract these components to reveal the non-axisymmetric mass surface density. From the residual mass maps we are able to extract the amplitude and phase of the density wave, using azimuthal profiles. The response of the gas is observed via dust emission in the 8micron IRAC band, allowing a comparison between the phase of the stellar density wave and gas shock. The relationship between this angular offset and radius suggests that the spiral structure is reasonably long lived and allows the position of corotation to be determined.Comment: 15 pages, 17 figures, accepted for publication in MNRA

Quantum computing with antiferromagnetic spin clusters

We show that a wide range of spin clusters with antiferromagnetic intracluster exchange interaction allows one to define a qubit. For these spin cluster qubits, initialization, quantum gate operation, and readout are possible using the same techniques as for single spins. Quantum gate operation for the spin cluster qubit does not require control over the intracluster exchange interaction. Electric and magnetic fields necessary to effect quantum gates need only be controlled on the length scale of the spin cluster rather than the scale for a single spin. Here, we calculate the energy gap separating the logical qubit states from the next excited state and the matrix elements which determine quantum gate operation times. We discuss spin cluster qubits formed by one- and two-dimensional arrays of s=1/2 spins as well as clusters formed by spins s>1/2. We illustrate the advantages of spin cluster qubits for various suggested implementations of spin qubits and analyze the scaling of decoherence time with spin cluster size.Comment: 15 pages, 7 figures; minor change

A cluster randomized trial of strategies to increase uptake amongst young women invited for their first cervical screen : The STRATEGIC trial

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NIHR Health Technology Assessment Programme (Project number 09/164/01). The funder had no involvement in the conduct of the trial. Full protocol can be accessed at http://www.nets.nihr.ac.uk/projects/hta/0916401.Peer reviewedPublisher PD