Does evidence support the high expectations placed in precision medicine? A bibliographic review

Background: Precision medicine is the Holy Grail of interventions that are tailored to a patient’s individual characteristics. However, conventional clinical trials are designed to find differences in averages, and interpreting these differences depends on untestable assumptions. Although only an ideal, a constant effect of treatment would facilitate individual management. A direct consequence of a constant effect is that the variance of the outcome measure would be the same in the treated and control arms. We reviewed the literature to explore the similarity of these variances as a foundation for examining whether and how often precision medicine is definitively required. Methods: We reviewed parallel clinical trials with numerical primary endpoints published in 2004, 2007, 2010 and 2013. We collected the baseline and final standard deviations of the main outcome measure. We assessed homoscedasticity by comparing the variance of the primary endpoint between arms through the outcome variance ratio (treated to control group). Results: The review provided 208 articles with enough information to conduct the analysis. One out of five studies (n = 40, 19.2%) had statistically different variances between groups, implying a non-constant-effect. The adjusted point estimate of the mean outcome variance ratio (treated to control group) is 0.89 (95% CI 0.81 to 0.97). Conclusions: The mean variance ratio is significantly lower than 1 and the lower variance was found more often in the intervention group than in the control group, suggesting it is more usual for treated patients to be stable. This observed reduction in variance might also imply that there could be a subgroup of less ill patients who derive no benefit from treatment. This would require further study as to whether the treatment effect outweighs the side effects as well as the economic costs. We have shown that there are ways to analyze the apparently unobservable constant effect

Decomposition and nutrient release of leguminous plants in coffee agroforestry systems.

Leguminous plants used as green manure are an important nutrient source for coffee plantations, especially for soils with low nutrient levels. Field experiments were conducted in the Zona da Mata of Minas Gerais State, Brazil to evaluate the decomposition and nutrient release rates of four leguminous species used as green manures (Arachis pintoi, Calopogonium mucunoides, Stizolobium aterrimum and Stylosanthes guianensis) in a coffee agroforestry system under two different climate conditions. The initial N contents in plant residues varied from 25.7 to 37.0 g kg-1 and P from 2.4 to 3.0 g kg-1. The lignin/N, lignin/polyphenol and(lignin+polyphenol)/N ratios were low in all residues studied. Mass loss rates were highest in the first 15 days, when 25 % of the residues were decomposed. From 15 to 30 days, the decomposition rate decreased on both farms. On the farm in Pedra Dourada (PD), the decomposition constant k increased in the order C. mucunoides < S. aterrimum < S. guianensis < A. pintoi. On the farm in Araponga (ARA), there was no difference in the decomposition rate among leguminous plants. The N release rates varied from 0.0036 to 0.0096 d-1. Around 32 % of the total N content in the plant material was released in the first 15 days. In ARA, the N concentration in the S. aterrimum residues was always significantly higher than in the other residues. At the end of 360 days, the N released was 78 % in ARA and 89 % in PD of the initial content. Phosphorus was the most rapidly released nutrient (k values from 0.0165 to 0.0394 d-1). Residue decomposition and nutrient release did not correlate with initial residue chemistry and biochemistry, but differences in climatic conditions between the two study sites modified the decomposition rate constants

The Athena X-IFU Instrument Simulator xifusim

International audienceWe present the instrument simulator xifusim developed for the X-ray Integral Field Unit X-IFU aboard the planned Athena mission. xifusim aims to be an accurate representation of the entire instrument, starting from a full simulation of the Transition-Edge Sensor (TES) array receiving impact photons unconstrained by the small signal limit. Its output current is then propagated through the entire readout chain, including multiplexing, amplification and the digital readout. The final output consists of triggered records, which can be post-processed to reconstruct the photon energies. The readout chain itself is separated into individual, modular blocks with several possible models for each, allowing the simulation of different readout schemes or models of varying physical accuracy at the expense of run time. New models are implemented as necessary to enable studies of the overall readout chain. Such studies are also facilitated by fine-grained control of the simulation output, including the internal state of intermediate simulation blocks. In addition to its modularity, xifusim also allows the manipulation of certain internal parameters during a run, enabling the simulation of readout chain characterization measurements, environmental drifts or various kinds of crosstalk

Model Fe-Al Steel with Exceptional Resistance to High Temperature Coarsening. Part II: Experimental Validation and Applications

In order to achieve a fine uniform grain-size distribution using the process of thin slab casting and directing rolling (TSCDR), it is necessary to control the grain-size prior to the onset of thermomechanical processing. In the companion paper, Model Fe-Al Steel with Exceptional Resistance to High Temperature Coarsening. Part I: Coarsening Mechanism and Particle Pinning Effects, a new steel composition which uses a small volume fraction of austenite particles to pin the growth of delta-ferrite grains at high temperature was proposed and grain growth was studied in reheated samples. This paper will focus on the development of a simple laboratory-scale setup to simulate thin-slab casting of the newly developed steel and demonstrate the potential for grain size control under industrial conditions. Steel bars with different diameters are briefly dipped into the molten steel to create a shell of solidified material. These are then cooled down to room temperature at different cooling rates. During cooling, the austenite particles nucleate along the delta-ferrite grain boundaries and greatly retard grain growth. With decreasing temperature, more austenite particles precipitate, and grain growth can be completely arrested in the holding furnace. Additional applications of the model alloy are discussed including grain-size control in the heat affected zone in welds and grain-growth resistance at high temperature