Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one ...of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.
THE DARK ENERGY CAMERA Flaugher, B.; Diehl, H. T.; Honscheid, K. ...
The Astronomical journal,
11/2015, Letnik:
150, Številka:
5
Journal Article
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ABSTRACT The Dark Energy Camera is a new imager with a 2 2 diameter field of view mounted at the prime focus of the Victor M. Blanco 4 m telescope on Cerro Tololo near La Serena, Chile. The camera ...was designed and constructed by the Dark Energy Survey Collaboration and meets or exceeds the stringent requirements designed for the wide-field and supernova surveys for which the collaboration uses it. The camera consists of a five-element optical corrector, seven filters, a shutter with a 60 cm aperture, and a charge-coupled device (CCD) focal plane of 250 m thick fully depleted CCDs cooled inside a vacuum Dewar. The 570 megapixel focal plane comprises 62 2k × 4k CCDs for imaging and 12 2k × 2k CCDs for guiding and focus. The CCDs have 15 m × 15 m pixels with a plate scale of 0 263 pixel−1. A hexapod system provides state-of-the-art focus and alignment capability. The camera is read out in 20 s with 6-9 electron readout noise. This paper provides a technical description of the camera's engineering, construction, installation, and current status.
We present results from a study of the photometric redshift performance of the Dark Energy Survey (DES), using the early data from a Science Verification period of observations in late 2012 and early ...2013 that provided science-quality images for almost 200 sq. deg. at the nominal depth of the survey. We assess the photometric redshift (photo-z) performance using about 15 000 galaxies with spectroscopic redshifts available from other surveys. These galaxies are used, in different configurations, as a calibration sample, and photo-z's are obtained and studied using most of the existing photo-z codes. A weighting method in a multidimensional colour-magnitude space is applied to the spectroscopic sample in order to evaluate the photo-z performance with sets that mimic the full DES photometric sample, which is on average significantly deeper than the calibration sample due to the limited depth of spectroscopic surveys. Empirical photo-z methods using, for instance, artificial neural networks or random forests, yield the best performance in the tests, achieving core photo-z resolutions ... ~ 0.08. Moreover, the results from most of the codes, including template-fitting methods, comfortably meet the DES requirements on photo-z performance, therefore, providing an excellent precedent for future DES data sets. (ProQuest: ... denotes formulae/symbols omitted.)
Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of ...hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.
Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disorder. Although molecular mechanisms remain elusive, deficits in autophagy have been associated with AMD. Here we show ...that deficiency of calcium and integrin binding protein 2 (CIB2) in mice, leads to age-related pathologies, including sub-retinal pigment epithelium (RPE) deposits, marked accumulation of drusen markers APOE, C3, Aβ, and esterified cholesterol, and impaired visual function, which can be rescued using exogenous retinoids. Cib2 mutant mice exhibit reduced lysosomal capacity and autophagic clearance, and increased mTORC1 signaling-a negative regulator of autophagy. We observe concordant molecular deficits in dry-AMD RPE/choroid post-mortem human tissues. Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to 'nucleotide empty' or inactive GDP-loaded Rheb. Upregulated mTORC1 signaling has been implicated in lymphangioleiomyomatosis (LAM) cancer. Over-expressing CIB2 in LAM patient-derived fibroblasts downregulates hyperactive mTORC1 signaling. Thus, our findings have significant implications for treatment of AMD and other mTORC1 hyperactivity-associated disorders.
Background: We previously reported results of the phase 2, multicenter PINNACLE study, which confirmed the substantial single-agent activity of bortezomib in patients with relapsed or refractory ...mantle cell lymphoma (MCL). Materials and methods: We report updated time-to-event data, in all patients and by response to treatment, after extended follow-up (median 26.4 months). Results: Median time to progression (TTP) was 6.7 months. Median time to next therapy (TTNT) was 7.4 months. Median overall survival (OS) was 23.5 months. In responding patients, median TTP was 12.4 months, median duration of response (DOR) was 9.2 months, median TTNT was 14.3 months, and median OS was 35.4 months. Patients achieving complete response had heterogeneous disease characteristics; among these patients, median TTP and DOR were not reached, and median OS was 36.0 months. One-year survival rate was 69% overall and 91% in responding patients. Median OS from diagnosis was 61.1 months, after median follow-up of 63.7 months. Activity was seen in patients with refractory disease and patients relapsing following high-intensity treatment. Toxicity was generally manageable. Conclusions: Single-agent bortezomib is associated with lengthy responses and notable survival in patients with relapsed or refractory MCL, with considerable TTP and TTNT in responding patients, suggesting substantial clinical benefit.
Essentials
How best to quantify thrombosis risk with peripherally inserted central catheters (PICC) is unknown.
Data from a registry were used to develop the Michigan Risk Score (MRS) for PICC ...thrombosis.
Five risk factors were associated with PICC thrombosis and used to develop a risk score.
MRS was predictive of the risk of PICC thrombosis and can be useful in clinical practice.
Summary
Background
Peripherally inserted central catheters (PICCs) are associated with upper extremity deep vein thrombosis (DVT). We developed a score to predict risk of PICC‐related thrombosis.
Methods
Using data from the Michigan Hospital Medicine Safety Consortium, image‐confirmed upper‐extremity DVT cases were identified. A logistic, mixed‐effects model with hospital‐specific random intercepts was used to identify factors associated with PICC‐DVT. Points were assigned to each predictor, stratifying patients into four classes of risk. Internal validation was performed by bootstrapping with assessment of calibration and discrimination of the model.
Results
Of 23 010 patients who received PICCs, 475 (2.1%) developed symptomatic PICC‐DVT. Risk factors associated with PICC‐DVT included: history of DVT; multi‐lumen PICC; active cancer; presence of another CVC when the PICC was placed; and white blood cell count greater than 12 000. Four risk classes were created based on thrombosis risk. Thrombosis rates were 0.9% for class I, 1.6% for class II, 2.7% for class III and 4.7% for class IV, with marginal predicted probabilities of 0.9% (0.7, 1.2), 1.5% (1.2, 1.9), 2.6% (2.2, 3.0) and 4.5% (3.7, 5.4) for classes I, II, III, and IV, respectively. The risk classification rule was strongly associated with PICC‐DVT, with odds ratios of 1.68 (95% CI, 1.19, 2.37), 2.90 (95% CI, 2.09, 4.01) and 5.20 (95% CI, 3.65, 7.42) for risk classes II, III and IV vs. risk class I, respectively.
Conclusion
The Michigan PICC‐DVT Risk Score offers a novel way to estimate risk of DVT associated with PICCs and can help inform appropriateness of PICC insertion.
We present an analysis of supernova light curves simulated for the upcoming Dark Energy Survey (DES) supernova search. The simulations employ a code suite that generates and fits realistic light ...curves in order to obtain distance modulus/redshift pairs that are passed to a cosmology fitter. We investigated several different survey strategies including field selection, supernova selection biases, and photometric redshift measurements. Using the results of this study, we chose a 30 deg super(2) search area in the griz filter set. We forecast (1) that this survey will provide a homogeneous sample of up to 4000 Type la supernovae in the redshift range 0.05 < z < 1.2 and (2) that the increased red efficiency of the DES camera will significantly improve high-redshift color measurements. The redshift of each supernova with an identified host galaxy will be obtained from spectroscopic observations of the host. A supernova spectrum will be obtained for a subset of the sample, which will be utilized for control studies. In addition, we have investigated the use of combined photometric redshifts taking into account data from both the host and supernova. We have investigated and estimated the likely contamination from core-collapse supernovae based on photometric identification, and have found that a Type Ia supernova sample purity of up to 98% is obtainable given specific assumptions. Furthermore, we present systematic uncertainties due to sample purity, photometric calibration, dust extinction priors, filter-centroid shifts, and inter-calibration. We conclude by estimating the uncertainty on the cosmological parameters that will be measured from the DES supernova data.
We measure the weak lensing masses and galaxy distributions of four massive galaxy clusters observed during the Science Verification phase of the Dark Energy Survey (DES). This pathfinder study is ...meant to (1) validate the Dark Energy Camera (DECam) imager for the task of measuring weak lensing shapes, and (2) utilize DECam's large field of view to map out the clusters and their environments over 90 arcmin. We conduct a series of rigorous tests on astrometry, photometry, image quality, point spread function (PSF) modelling, and shear measurement accuracy to single out flaws in the data and also to identify the optimal data processing steps and parameters. We find Science Verification data from DECam to be suitable for the lensing analysis described in this paper. The PSF is generally well behaved, but the modelling is rendered difficult by a flux-dependent PSF width and ellipticity. We employ photometric redshifts to distinguish between foreground and background galaxies, and a red-sequence cluster finder to provide cluster richness estimates and cluster–galaxy distributions. By fitting Navarro–Frenk–White profiles to the clusters in this study, we determine weak lensing masses that are in agreement with previous work. For Abell 3261, we provide the first estimates of redshift, weak lensing mass, and richness. In addition, the cluster–galaxy distributions indicate the presence of filamentary structures attached to 1E 0657−56 and RXC J2248.7−4431, stretching out as far as 1°(approximately 20 Mpc), showcasing the potential of DECam and DES for detailed studies of degree-scale features on the sky.
We present DES13S2cmm, the first spectroscopically-confirmed superluminous supernova (SLSN) from the Dark Energy Survey (DES). We briefly discuss the data and search algorithm used to find this event ...in the first year of DES operations, and outline the spectroscopic data obtained from the European Southern Observatory (ESO) Very Large Telescope to confirm its redshift (z = 0.663 ± 0.001 based on the host-galaxy emission lines) and likely spectral type (Type I). Using this redshift, we find
$M^{\rm peak}_U=-21.05^{+0.10}_{-0.09}$
for the peak, rest-frame U-band absolute magnitude, and find DES13S2cmm to be located in a faint, low-metallicity (sub-solar), low stellar-mass host galaxy (log (M/M⊙) = 9.3 ± 0.3), consistent with what is seen for other SLSNe-I. We compare the bolometric light curve of DES13S2cmm to 14 similarly well-observed SLSNe-I in the literature and find that it possesses one of the slowest declining tails (beyond +30 d rest-frame past peak), and is the faintest at peak. Moreover, we find the bolometric light curves of all SLSNe-I studied herein possess a dispersion of only 0.2–0.3 mag between +25 and +30 d after peak (rest frame) depending on redshift range studied; this could be important for ‘standardizing’ such supernovae, as is done with the more common Type Ia. We fit the bolometric light curve of DES13S2cmm with two competing models for SLSNe-I – the radioactive decay of 56Ni, and a magnetar – and find that while the magnetar is formally a better fit, neither model provides a compelling match to the data. Although we are unable to conclusively differentiate between these two physical models for this particular SLSN-I, further DES observations of more SLSNe-I should break this degeneracy, especially if the light curves of SLSNe-I can be observed beyond 100 d in the rest frame of the supernova.
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