96 research outputs found
A fluorescent histone deacetylase (HDAC) inhibitor for cellular imaging
Fluorescence microscopy studies using 4-morpholinoscriptaid (4MS) demonstrated rapid cellular uptake of this scriptaid analogue into the cytoplasm but no nuclear penetration. As 4MS and scriptaid have the same in vitro activity against HDACs and KASUMI-1 cells; 4MS exemplifies a rational approach to subtly modify ‘profluorogenic’ substrates for intracellular studies
Valuing health states: is the MACBETH approach useful for valuing EQ-5D-3L health states?
Background
Quality Adjusted Life Years (QALYs) are a key outcome measure widely used within health technology assessment and health service research studies. QALYs combine quantity and quality of life, with quality of life calculations relying on the value of distinct health states. Such health states’ values capture the preferences of a population and have been typically built through numerical elicitation methods. Evidence points to these value scores being influenced by methods in use and individuals reporting cognitive difficulties in eliciting their preferences. Evidence from other areas has further suggested that individuals may prefer using distinct elicitation techniques and that this preference can be influenced by their numeracy. In this study we explore the use of the MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) non-numerical preference elicitation approach for health states’ evaluation.
Methods
A new protocol for preference elicitation based on MACBETH (only requiring qualitative judgments) was developed and tested within a web survey format. A sample of the Portuguese general population (n=243) valued 25 EQ-5D-3L health states with the MACBETH protocol and with a variant of the time trade-off (TTO) protocol, for comparison purposes and for understanding respondents’ preference for distinct protocols and differences in inconsistent evaluations. Respondents answered to a short numeracy test, and basic socio-economic information collected.
Results
Results show that the mean values derived from MACBETH and the TTO variant are strongly correlated; however, there are substantial differences for several health states’ values. Large and similar numbers of logical inconsistencies were found in respondents’ answers with both methods. Participants with higher levels of numeracy according to the test preferred expressing value judgments with MACBETH, while participants with lower levels were mostly indifferent to both methods. Higher correlations between MACBETH and TTO variant evaluations were observed for individuals with higher numeracy.
Conclusion
Results suggest that it is worth researching the use of non-numerical preference elicitation methods. Numeracy tests more appropriate for preference elicitation when no explicit considerations of uncertainty are made need to be explored and used. Further behavioural research is needed to fully understand the potential for using these methods in distinct settings (e.g. in different evaluation contexts and in face-to-face and non-face-to-face environments), as well as to explore the effect of literacy on assessments and on respondents’ preferences.UID/MULTI/4066/2016info:eu-repo/semantics/publishedVersio
PaLM 2 Technical Report
We introduce PaLM 2, a new state-of-the-art language model that has better
multilingual and reasoning capabilities and is more compute-efficient than its
predecessor PaLM. PaLM 2 is a Transformer-based model trained using a mixture
of objectives. Through extensive evaluations on English and multilingual
language, and reasoning tasks, we demonstrate that PaLM 2 has significantly
improved quality on downstream tasks across different model sizes, while
simultaneously exhibiting faster and more efficient inference compared to PaLM.
This improved efficiency enables broader deployment while also allowing the
model to respond faster, for a more natural pace of interaction. PaLM 2
demonstrates robust reasoning capabilities exemplified by large improvements
over PaLM on BIG-Bench and other reasoning tasks. PaLM 2 exhibits stable
performance on a suite of responsible AI evaluations, and enables
inference-time control over toxicity without additional overhead or impact on
other capabilities. Overall, PaLM 2 achieves state-of-the-art performance
across a diverse set of tasks and capabilities.
When discussing the PaLM 2 family, it is important to distinguish between
pre-trained models (of various sizes), fine-tuned variants of these models, and
the user-facing products that use these models. In particular, user-facing
products typically include additional pre- and post-processing steps.
Additionally, the underlying models may evolve over time. Therefore, one should
not expect the performance of user-facing products to exactly match the results
reported in this report
CMB-S4: Forecasting Constraints on Primordial Gravitational Waves
CMB-S4---the next-generation ground-based cosmic microwave background (CMB)
experiment---is set to significantly advance the sensitivity of CMB
measurements and enhance our understanding of the origin and evolution of the
Universe, from the highest energies at the dawn of time through the growth of
structure to the present day. Among the science cases pursued with CMB-S4, the
quest for detecting primordial gravitational waves is a central driver of the
experimental design. This work details the development of a forecasting
framework that includes a power-spectrum-based semi-analytic projection tool,
targeted explicitly towards optimizing constraints on the tensor-to-scalar
ratio, , in the presence of Galactic foregrounds and gravitational lensing
of the CMB. This framework is unique in its direct use of information from the
achieved performance of current Stage 2--3 CMB experiments to robustly forecast
the science reach of upcoming CMB-polarization endeavors. The methodology
allows for rapid iteration over experimental configurations and offers a
flexible way to optimize the design of future experiments given a desired
scientific goal. To form a closed-loop process, we couple this semi-analytic
tool with map-based validation studies, which allow for the injection of
additional complexity and verification of our forecasts with several
independent analysis methods. We document multiple rounds of forecasts for
CMB-S4 using this process and the resulting establishment of the current
reference design of the primordial gravitational-wave component of the Stage-4
experiment, optimized to achieve our science goals of detecting primordial
gravitational waves for at greater than , or, in the
absence of a detection, of reaching an upper limit of at CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note:
text overlap with arXiv:1907.0447
The Simons Observatory: Modeling Optical Systematics in the Large Aperture Telescope
We present geometrical and physical optics simulation results for the Simons
Observatory Large Aperture Telescope. This work was developed as part of the
general design process for the telescope; allowing us to evaluate the impact of
various design choices on performance metrics and potential systematic effects.
The primary goal of the simulations was to evaluate the final design of the
reflectors and the cold optics which are now being built. We describe
non-sequential ray tracing used to inform the design of the cold optics,
including absorbers internal to each optics tube. We discuss ray tracing
simulations of the telescope structure that allow us to determine geometries
that minimize detector loading and mitigate spurious near-field effects that
have not been resolved by the internal baffling. We also describe physical
optics simulations, performed over a range of frequencies and field locations,
that produce estimates of monochromatic far field beam patterns which in turn
are used to gauge general optical performance. Finally, we describe simulations
that shed light on beam sidelobes from panel gap diffraction.Comment: 15 pages, 13 figure
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
- …