A test of analog-based tools for quantitative prediction of large-scale fluvial architecture

Outcrop analogs are routinely used to constrain models of subsurface fluvial sedimentary architecture built through stochastic modeling or inter-well sandbody correlations. Correlability models are analog-based quantitative templates for guiding the well-to-well correlation of sand-bodies, whereas indicator variograms used as input to reservoir models can be parameterized from data collected from analogs, using existing empirical relationships. This study tests the value and limitations of adopting analog-informed correlability models and indicator-variogram models, and assesses the impact and significance of analog choice in subsurface workflows for characterizing fluvial reservoirs. A 3.2 km long architectural panel based on a Virtual Outcrop from the Cretaceous Blackhawk Formation (Wasatch Plateau, Utah, USA) has been used to test the methodologies: vertical 'dummy' wells have been constructed across the panel, and the intervening fluvial architecture has been predicted using correlability models and sequential indicator simulations. The correlability and indicator-variogram models employed to predict the outcrop architecture have been compiled using information drawn from an architectural database. These models relate to: (i) analogs that partially match with the Blackhawk Formation in terms of depositional setting, and (ii) empirical relationships relating statistics on depositional-element geometries and spatial relations to net-to-gross ratio, based on data from multiple fluvial systems of a variety of forms. The forecasting methods are assessed by quantifying the mismatch between predicted architecture and outcrop observations in terms of the correlability of channel complexes and static connectivity of channel deposits. Results highlight the effectiveness of correlability models as a check for the geologic realism of correlation panels, and the value of analog-informed indicator variograms as a valid alternative to variogram-model parameterization through geostatistical analysis of well data. This work has application in the definition of best-practice use of analogs in subsurface workflows; it provides insight into the typical degree of realism of analog-based predictions of reservoir architecture, as well as on the impact of analog choice, and draws attention to associated pitfalls

Type Ia Supernovae as Stellar Endpoints and Cosmological Tools

Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are being used to measure its properties. However, the nature of the SN Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now new large surveys are bringing about a paradigm shift --- we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modeling, breakthroughs in understanding all aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version. Shortened, update

The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star

The acceleration of the expansion of the universe, and the need for Dark Energy, were inferred from the observations of Type Ia supernovae (SNe Ia). There is consensus that SNe Ia are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that accrete matter from a companion star, although the nature of this companion remains uncertain. SNe Ia are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger -- they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass -- 1.4 solar masses. Here we show that the high redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar mass progenitor. Super-Chandrasekhar mass SNe Ia should preferentially occur in a young stellar population, so this may provide an explanation for the observed trend that overluminous SNe Ia only occur in young environments. Since this supernova does not obey the relations that allow them to be calibrated as standard candles, and since no counterparts have been found at low redshift, future cosmology studies will have to consider contamination from such events.Comment: 9 pages, 4 figures. To appear in Nature Sept. 21. Accompanying News & Views in same issue. Supplementary information available at www.nature.com/natur

Hydrogen-poor superluminous stellar explosions

Supernovae (SNe) are stellar explosions driven by gravitational or thermonuclear energy, observed as electromagnetic radiation emitted over weeks or more. In all known SNe, this radiation comes from internal energy deposited in the outflowing ejecta by either radioactive decay of freshly-synthesized elements (typically 56Ni), stored heat deposited by the explosion shock in the envelope of a supergiant star, or interaction between the SN debris and slowly-moving, hydrogen-rich circumstellar material. Here we report on a new class of luminous SNe whose observed properties cannot be explained by any of these known processes. These include four new SNe we have discovered, and two previously unexplained events (SN 2005ap; SCP 06F6) that we can now identify as members. These SNe are all ~10 times brighter than SNe Ia, do not show any trace of hydrogen, emit significant ultra-violet (UV) flux for extended periods of time, and have late-time decay rates which are inconsistent with radioactivity. Our data require that the observed radiation is emitted by hydrogen-free material distributed over a large radius (~10^15 cm) and expanding at high velocities (>10^4 km s^-1). These long-lived, UV-luminous events can be observed out to redshifts z>4 and offer an excellent opportunity to study star formation in, and the interstellar medium of, primitive distant galaxies.Comment: Accepted to Nature. Press embargoed until 2011 June 8, 18:00 U

Are BRCA1- and BRCA2-related breast cancers associated with increased mortality?

There has been contradictory evidence as to whether BRCA1 associated breast cancers have a poorer prognosis than non-BRCA1 cancers. In this issue of Breast Cancer Research Robson and colleagues provide further evidence for poorer survival in BRCA1 carriers and show that it could be attributed to failure to treat small node-negative grade 3 breast cancers with chemotherapy. There still remains little evidence for a survival difference for BRCA2 related breast cancers. Although the high contralateral breast cancer risk is confirmed by this study there is no real evidence for an increase in ipsilateral recurrence or new primary breast cancers in mutation carriers up to the 10-year point

Carboxypeptidase G2 rescue in patients with methotrexate intoxication and renal failure

The methotrexate (MTX) rescue agent carboxypeptidase G2 (CPDG2) rapidly hydrolyses MTX to the inactive metabolite DAMPA (4-[[2,4-diamino-6-(pteridinyl)methyl]-methylamino]-benzoic acid) and glutamate in patients with MTX-induced renal failure and delayed MTX excretion. DAMPA is thought to be an inactive metabolite of MTX because it is not an effective inhibitor of the MTX target enzyme dihydrofolate reductase. DAMPA is eliminated more rapidly than MTX in these patients, which suggests a nonrenal route of elimination. In a phase II study (May 1997–March 2002), CPDG2 was administered intravenously to 82 patients at a median dose of 50 U kg−1 (range 33–60 U kg−1). Eligible patients for this study had serum MTX concentrations of >10 μM at 36 h or >5 μM at 42 h after start of MTX infusion and documented renal failure (serum creatinine ⩾1.5 times the upper limit of normal). Immediately before CPDG2 administration, a median MTX serum level of 11.93 μM (range 0.52–901 μM) was documented. Carboxypeptidase G2 was given at a median of 52 h (range 25–178 h) following the start of an MTX infusion of 1–12 g m−2 4–36 h−1 and resulted in a rapid 97% (range 73–99%) reduction of the MTX serum level. Toxicity related to CPDG2 was not observed. Toxicity related to MTX was documented in about half the patients; four patients died despite CPDG2 administration due to severe myelosuppression and septic complications. In conclusion, administration of CPDG2 is a well-tolerated, safe and a very effective way of MTX elimination in delayed excretion due to renal failure

Predicted risks of radiogenic cardiac toxicity in two pediatric patients undergoing photon or proton radiotherapy

BACKGROUND: Hodgkin disease (HD) and medulloblastoma (MB) are common malignancies found in children and young adults, and radiotherapy is part of the standard treatment. It was reported that these patients who received radiation therapy have an increased risk of cardiovascular late effects. We compared the predicted risk of developing radiogenic cardiac toxicity after photon versus proton radiotherapies for a pediatric patient with HD and a pediatric patient with MB. METHODS: In the treatment plans, each patient’s heart was contoured in fine detail, including substructures of the pericardium and myocardium. Risk calculations took into account both therapeutic and stray radiation doses. We calculated the relative risk (RR) of cardiac toxicity using a linear risk model and the normal tissue complication probability (NTCP) values using relative seriality and Lyman models. Uncertainty analyses were also performed. RESULTS: The RR values of cardiac toxicity for the HD patient were 7.27 (proton) and 8.37 (photon), respectively; the RR values for the MB patient were 1.28 (proton) and 8.39 (photon), respectively. The predicted NTCP values for the HD patient were 2.17% (proton) and 2.67% (photon) for the myocardium, and were 2.11% (proton) and 1.92% (photon) for the whole heart. The predicted ratios of NTCP values (proton/photon) for the MB patient were much less than unity. Uncertainty analyses revealed that the predicted ratio of risk between proton and photon therapies was sensitive to uncertainties in the NTCP model parameters and the mean radiation weighting factor for neutrons, but was not sensitive to heart structure contours. The qualitative findings of the study were not sensitive to uncertainties in these factors. CONCLUSIONS: We conclude that proton and photon radiotherapies confer similar predicted risks of cardiac toxicity for the HD patient in this study, and that proton therapy reduced the predicted risk for the MB patient in this study

Two Earth-sized planets orbiting Kepler-20

Since the discovery of the first extrasolar giant planets around Sun-like stars, evolving observational capabilities have brought us closer to the detection of true Earth analogues. The size of an exoplanet can be determined when it periodically passes in front of (transits) its parent star, causing a decrease in starlight proportional to its radius. The smallest exoplanet hitherto discovered has a radius 1.42 times that of the Earth's radius (R Earth), and hence has 2.9 times its volume. Here we report the discovery of two planets, one Earth-sized (1.03R Earth) and the other smaller than the Earth (0.87R Earth), orbiting the star Kepler-20, which is already known to host three other, larger, transiting planets. The gravitational pull of the new planets on the parent star is too small to measure with current instrumentation. We apply a statistical method to show that the likelihood of the planetary interpretation of the transit signals is more than three orders of magnitude larger than that of the alternative hypothesis that the signals result from an eclipsing binary star. Theoretical considerations imply that these planets are rocky, with a composition of iron and silicate. The outer planet could have developed a thick water vapour atmosphere.Comment: Letter to Nature; Received 8 November; accepted 13 December 2011; Published online 20 December 201

Measuring care of the elderly: psychometric testing and modification of the Time in Care instrument for measurement of care needs in nursing homes

<p>Abstract</p> <p>Background</p> <p>Aging entails not only a decrease in the ability to be active, but also a trend toward increased dependence to sustain basic life functions. An important aspect for appropriately elucidating the individual's care needs is the ability to measure them both simply and reliably. Since 2006 a new version of the Time in Care needs (TIC-n) instrument (19-item version) has been explored and used in one additional municipality with the same structure as the one described in an earlier study.</p> <p>Methods</p> <p>The TIC-n assessment was conducted on a total of 1282 care recipients. Factor analysis (principal component) was applied to explore the construct validity of the TIC-n. Cronbach's alpha was calculated to test reliability and for each of the items remaining in the instrument after factor analysis, an inter-rater comparison was carried out on all recipients in both municipalities. Independently of each other, a weighted Kappa (K_w) was calculated. Results. The mean of each weighted Kappa (K_w) for the dimensions in the two municipalities was 0.75 and 0.76, respectively. Factor analysis showed that all 19 items had a factor loading of ≥ 0.40. Three factors (General Care, Medical Care and Cognitive Care) were created.</p> <p>Conclusion</p> <p>The TIC-n instrument has now been tested for validity and reliability in two municipalities with satisfactory results. However, TIC-n can not yet be used as a golden standard, but it can be recommended for use of measurement of individual care needs in municipal elderly care.</p

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care