Bayesian comparison of cost-effectiveness of different clinical approaches to diagnose coronary artery disease

The objective of this study was to compare the cost-effectiveness of four clinical policies (policies I to IV) in the diagnosis of the presence or absence of coronary artery disease. A model based on Bayes' theorem and published clinical data was constructed to make these comparisons. Effectiveness was denned as either the number of patients with coronary disease diagnosed or as the number of quality-adjusted life years extended by therapy after the diagnosis of coronary disease.The following conclusions arise strictly from analysis of the model and may not necessarily be applicable to all situations. 1) As prevalence of coronary disease in the population increased, it caused a linear increase in cost per patient tested, but a hyperbolic decrease in cost per effect, that is, increased cost-effectiveness. Thus, cost-effectiveness of all policies (I to IV) was poor in populations with a prevalence of disease below 10%, for example, asymptomatic people with no risk factors. 2) Analysis of the model also indicates that at prevalences less than 80%, exercise thallium scintigraphy alone as a first test (policy II) is a more cost-effective initial test than is exercise electrocardiography alone as a first test (policy I) or exercise electrocardiography first combined with thallium imaging as a second test (policy IV). 3) Exercise electrocardiography before thallium imaging (policy IV) is more cost-effective than exercise electrocardiography alone (policy I) at prevalences less than 80%. 4) Noninvasive exercise testing before angiography (policies I, II and IV) is more cost-effective than using coronary angiography as the first and only test (policy III) at prevalences less than 80%. 5) Above a threshold value of prevalence of 80% (for example patients with typical angina), proceeding to angiography as the first test (policy III) was more cost-effective than initial noninvasive exercise tests (policies I, II and IV).One advantage of this quantitative model is that it estimates a threshold value of prevalence (80%) at which the rank order of policies changes. The model also allows substitution of different values for any variable as a way of accounting for the uncertainty inherent in the data. In conclusion, it is essential to consider the prevalence of disease when selecting the most cost-effective clinical approach to making a diagnosis

Rapid changes in meridional advection of Southern Ocean intermediate waters to the tropical Pacific during the last 30 kyr

The Southern Ocean is increasingly recognized as a key player in the general ocean thermohaline circulation and the global climate system during glacial–interglacial transitions. In particular, the advection of Southern Ocean intermediate waters (SOIW), like Antarctic Intermediate Water and Sub-Antarctic Mode Water, to the Eastern Equatorial Pacific (EEP), through a so-called “oceanic tunnelling” mechanism, is an important means for rapid transfer of climatic signals (such as heat, fresh water, salt, and chemical species) from high-to-low latitudes. However, information on how intermediate water advection rates changed in the past, and particularly during deglaciations, is fragmentary. We present new results for Nd isotopes (εNd) in cleaned foraminifera shells (Neogloboquadrina dutertrei) for the last 30 kyr at ODP Site 1240 in the EEP. N. dutertrei preferentially dwells in the lower thermocline, at the core of the Equatorial Undercurrent (EUC), and the εNd variability over time provides a record of the changes in the εNd of the EUC. Through mixing models we show that the EUC record is primarily controlled by changes in the volume transport of intermediate waters and not by Southern Ocean εNd changes. Southern Ocean signals in the EUC are stronger during colder intervals (Younger Dryas, last glacial maximum and Heinrich stadials 1 and 2), in agreement with tropical Atlantic intermediate water records. In addition, covariations between N. dutertrei δ13C, molecular biomarkers, and diatom productivity at Site 1240 confirm the intermediate water route as an important mechanism for the transfer of climate signals from high-to-low latitudes. Changes in the SOIW chemistry during the deglaciation are likely linked to the upwelling of ‘old’ deep waters in the Southern Ocean and subsequent export as intermediate waters, which are coeval with the atmospheric CO2 rise. Moreover, a comparison of multiple proxy records for the last 30 kyr indicates a latitudinal shift and/or a change in the convection depth of intermediate waters in the Southern Ocean prior to the onset of the deglaciation

Three‐Dimensional Micro‐Computed Tomographic Imaging of Alveolar Bone in Experimental Bone Loss or Repair

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142030/1/jper0273.pd

Development of a protocol to obtain the composition of terrigenous detritus in marine sediments -a pilot study from International Ocean Discovery Program Expedition 361

The geochemical and isotopic composition of terrigenous clays from marine sediments can provide important information on the sources and pathways of sediments. International Ocean Discovery Program Expedition 361 drilled sites along the eastern margin of southern Africa that potentially provide archives of rainfall on the continent as well as dispersal in the Agulhas Current. We used standard methods to remove carbonate and ferromanganese oxides and Stokes settling to isolate the clay fractions. In comparison to most previous studies that aimed to extract the detrital signal from marine sediments, we additionally applied a cation exchange wash using CsCl as a final step in the sample preparation. The motivation behind the extra step, not frequently applied, is to remove ions that are gained on the clay surface due to adsorption of authigenic trace metals in the ocean or during the leaching procedure. Either would alter the composition of the detrital fraction if no cation exchange was applied. Moreover, using CsCl will provide an additional measure of the cation exchange capacity (CEC) of the samples. However, no study so far has evaluated the potential and the limitations of such a targeted protocol for marine sediments. Here, we explore the effects of removing and replacing adsorbed cations on the clay surfaces with Cs+, conducting measurements of the chemical compositions, and radiogenic isotopes on a set of eight clay sample pairs. Both sets of samples underwent the same full leaching procedure except that one batch was treated with a final CsCl wash step. In this study, organic matter was not leached because sediments at IODP Site U1478 have relatively low organic content. However, in general, we recommend including that step in the leaching procedure. As expected, significant portions of elements with high concentrations in seawater were replaced by Cs+ (2SD 2.8%.) from the wash, including 75% of the sodium and approximately 25% of the calcium, 10% of the magnesium, and 8% of the potassium. Trace metals such as Sr and Nd, whose isotopes are used for provenance studies, are also found to be in lower concentrations in the samples after the exchange wash. The exchange wash affected the radiogenic isotope compositions of the samples. Neodymium isotope ratios are slightly less radiogenic in all the washed samples. Strontium and Pb isotopes showed significant deviations to either more or less radiogenic values in different samples. The radiogenic isotopes from the CsCl-treated fractions gave more consistent correlations with each other, and we suggest this treatment offers a superior measure of provenance. Although we observed changes in the isotope ratios, the general trend in the data and hence the overall provenance interpretations remained the same. However, the chemical compositions are significantly different. We conclude that a leaching protocol including a cation exchange wash (e.g. CsCl) is useful for revealing the terrestrial fingerprint. CEC could, with further calibration efforts, be useful as a terrestrial chemical weathering proxy

MicroRNA-26a Is Strongly Downregulated in Melanoma and Induces Cell Death through Repression of Silencer of Death Domains (SODD)

Melanoma is an aggressive cancer that metastasizes rapidly and is refractory to conventional chemotherapies. Identifying microRNAs (miRNAs) that are responsible for this pathogenesis is therefore a promising means of developing new therapies. We identified miR-26a through microarray and quantitative reverse-transcription–PCR (qRT-PCR) experiments as an miRNA that is strongly downregulated in melanoma cell lines as compared with primary melanocytes. Treatment of cell lines with miR-26a mimic caused significant and rapid cell death compared with a negative control in most melanoma cell lines tested. In surveying targets of miR-26a, we found that protein levels of SMAD1 (mothers against decapentaplegic homolog 1) and BAG-4/SODD were strongly decreased in sensitive cells treated with miR-26a mimic as compared with the control. The luciferase reporter assays further demonstrated that miR-26a can repress gene expression through the binding site in the 3′ untranslated region (3′UTR) of SODD (silencer of death domains). Knockdown of these proteins with small interfering RNA (siRNA) showed that SODD has an important role in protecting melanoma cells from apoptosis in most cell lines sensitive to miR-26a, whereas SMAD1 may have a minor role. Furthermore, transfecting cells with a miR-26a inhibitor increased SODD expression. Our findings indicate that miR-26a replacement is a potential therapeutic strategy for metastatic melanoma, and that SODD, in particular, is a potentially useful therapeutic target