125 research outputs found
Communicating effectiveness of intervention for chronic diseases: what single format can replace comprehensive information?
<p>Abstract</p> <p>Background</p> <p>There is uncertainty about how GPs should convey information about treatment effectiveness to their patients in the context of cardiovascular disease. Hence we study the concordance of decisions based on one of four single information formats for treatment effectiveness with subsequent decisions based on all four formats combined with a pictorial representation.</p> <p>Methods</p> <p>A randomized study comprising 1,169 subjects aged 40–59 in Odense, Denmark. Subjects were randomized to receive information in terms of absolute risk reduction (ARR), relative risk reduction (RRR), number needed to treat (NNT), or prolongation of life (POL) without heart attack, and were asked whether they would consent to treatment. Subsequently the same information was conveyed with all four formats jointly accompanied by a pictorial presentation of treatment effectiveness. Again, subjects should consider consent to treatment.</p> <p>Results</p> <p>After being informed about all four formats, 52%–79% of the respondents consented to treatment, depending on level of effectiveness and initial information format. Overall, ARR gave highest concordance, 94% (95% confidence interval (91%; 97%)) between initial and final decision, but ARR was not statistically superior to the other formats.</p> <p>Conclusion</p> <p>Decisions based on ARR had the best concordance with decisions based on all four formats and pictorial representation, but the difference in concordance between the four formats was small, and it is unclear whether respondents fully understood the information they received.</p
Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer
PTEN, a phosphoinositide-3-phosphatase, serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism. Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation, especially reactive carbonyl species, which are commonly occurring by-products of arachidonic acid peroxidation. Using MCF7 and HEK-293 cells, we report that several reactive aldehydes and ketones, e.g. electrophilic α,β-enals (acrolein, 4-hydroxy-2-nonenal) and α,β-enones (prostaglandin A2, Δ12-prostaglandin J2 and 15-deoxy-Δ-12,14-prostaglandin J2) covalently modify and inactivate cellular PTEN, with ensuing activation of PKB/Akt kinase; phosphorylation of Akt substrates; increased cell proliferation; and increased nuclear β-catenin signaling. Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation, oxidative stress, or aging
GABAA-Mediated Inhibition Modulates Stimulus-Specific Adaptation in the Inferior Colliculus
The ability to detect novel sounds in a complex acoustic context is crucial for survival. Neurons from midbrain through cortical levels adapt to repetitive stimuli, while maintaining responsiveness to rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). The site of origin and mechanism of SSA are currently unknown. We used microiontophoretic application of gabazine to examine the role of GABAA-mediated inhibition in SSA in the inferior colliculus, the midbrain center for auditory processing. We found that gabazine slowed down the process of adaptation to high probability stimuli but did not abolish it, with response magnitude and latency still depending on the probability of the stimulus. Blocking GABAA receptors increased the firing rate to high and low probability stimuli, but did not completely equalize the responses. Together, these findings suggest that GABAA-mediated inhibition acts as a gain control mechanism that enhances SSA by modifying the responsiveness of the neuron
Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies
The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes
Shedding Light on the Galaxy Luminosity Function
From as early as the 1930s, astronomers have tried to quantify the
statistical nature of the evolution and large-scale structure of galaxies by
studying their luminosity distribution as a function of redshift - known as the
galaxy luminosity function (LF). Accurately constructing the LF remains a
popular and yet tricky pursuit in modern observational cosmology where the
presence of observational selection effects due to e.g. detection thresholds in
apparent magnitude, colour, surface brightness or some combination thereof can
render any given galaxy survey incomplete and thus introduce bias into the LF.
Over the last seventy years there have been numerous sophisticated
statistical approaches devised to tackle these issues; all have advantages --
but not one is perfect. This review takes a broad historical look at the key
statistical tools that have been developed over this period, discussing their
relative merits and highlighting any significant extensions and modifications.
In addition, the more generalised methods that have emerged within the last few
years are examined. These methods propose a more rigorous statistical framework
within which to determine the LF compared to some of the more traditional
methods. I also look at how photometric redshift estimations are being
incorporated into the LF methodology as well as considering the construction of
bivariate LFs. Finally, I review the ongoing development of completeness
estimators which test some of the fundamental assumptions going into LF
estimators and can be powerful probes of any residual systematic effects
inherent magnitude-redshift data.Comment: 95 pages, 23 figures, 3 tables. Now published in The Astronomy &
Astrophysics Review. This version: bring in line with A&AR format
requirements, also minor typo corrections made, additional citations and
higher rez images adde
Advances in structure elucidation of small molecules using mass spectrometry
The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules
Authors’ Reply to Whitlock: Perispinal Etanercept for Post-Stroke Neurological and Cognitive Dysfunction: Scientific Rationale and Current Evidence
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