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Geocoronal Solar Wind Charge Exchange (SWCX) is the process by which heavy ions from the solar wind undergo charge exchange with neutral hydrogen atoms from the Earth's exosphere, releasing photons at discrete energies characteristic of the solar wind ions. This paper investigates the solar wind types driving geocoronal SWCX. We find that during periods of time‐variable SWCX, higher fractions of every ion species are recorded by ACE compared to the averages. Notably, a subset of the slow solar wind characterized by a systematic lower temperature and higher proton flux is surprisingly effective for producing SWCX. Given the degradation of the solar wind composition spectrometer on ACE in 2011, we explore the capabilities of XMM‐Newton as an alternative sensor to monitor heavy ion composition in the solar wind. Unlike the distributions of other ion line fluxes analyzed, only OVIII, extracted via spectral analysis of XMM‐Newton observations, display patterns similar to the corresponding parent ion abundances from ACE O8+/p $\left({\mathrm{O}}^{\mathrm{8}+}/\mathrm{p}\right)$. Finally, we employ a Random Forest Classifier model to predict solar wind types based on literature results. When combining proton data with XMM‐Newton features, the model performance improves significantly, achieving a macro‐averaged F1 score of 0.80 (with a standard deviation of 0.06). Key Points: Variable solar wind charge exchange is associated with periods of outlier wind having increased solar wind proton fluxXMM‐Newton observes differences in solar wind charge exchange emission count rate during different solar wind typesThe distribution of the OVIII line flux from XMM‐Newton is similar to that of the ACE O8+/p ratio across different solar wind types [ABSTRACT FROM AUTHOR]

The Lunar Environment heliospheric X-ray Imager (LEXI) is a wide field-of-view soft X-ray telescope developed to study solar wind-magnetosphere coupling. LEXI is part of the Blue Ghost 1 mission comprised of 10 payloads to be deployed on the lunar surface. LEXI monitors the dayside magnetopause position and shape as a function of time by observing soft X-rays (0.1–2 keV) emitted from solar wind charge-exchange between exospheric neutrals and high charge-state solar wind plasma in the dayside magnetosheath. Measurements of the shape and position of the magnetopause are used to test temporal models of meso- and macro-scale magnetic reconnection. To image the boundary, LEXI employs lobster-eye optics to focus X-rays to a microchannel plate detector with a 9.1 × ∘ 9.1 ∘ field of view. [ABSTRACT FROM AUTHOR]

Surrounding the Milky Way (MW) is the circumgalactic medium (CGM), an extended reservoir of hot gas that has significant implications for the evolution of the MW. We used the HaloSat all-sky survey to study the CGM’s soft X-ray emission in order to better define its distribution and structure. We extend a previous HaloSat study of the southern CGM (Galactic latitude b < âˆ'30°) to include the northern CGM (b > 30°) and find evidence that at least two hot gas model components at different temperatures are required to produce the observed emission. The cooler component has a typical temperature of kT ∼0.18 keV, while the hotter component has a typical temperature of kT ∼0.7 keV. The emission measure in both the warm and hot components has a wide range (∼0.005â€"0.03, and ∼0.0005â€"0.004 cmâˆ'6 pc, respectively), indicating that the CGM is clumpy. A patch of relatively consistent CGM was found in the north, allowing for the CGM spectrum to be studied in finer detail using a stacked spectrum. The stacked spectrum is well described with a model including two hot gas components at temperatures of kT = 0.166 ± 0.005 keV and kT = 0.69 âˆ' 0.05 + 0.04 keV. As an alternative to adding a hot component, a neon-enhanced single-temperature model of the CGM was also tested and found to have worse fit statistics and poor residuals. [ABSTRACT FROM AUTHOR]

The Earth's magnetosheath and cusps emit soft X‐rays due to the charge exchange between highly charged solar wind ions and exospheric hydrogen atoms. The Lunar Environment Heliospheric X‐ray Imager and Solar wind Magnetosphere Ionosphere Link Explorer missions are scheduled to image the Earth's dayside magnetosphere system in soft X‐rays to investigate global‐scale magnetopause reconnection modes under varying solar wind conditions. The exospheric neutral hydrogen density distribution, especially the value of this density at the subsolar magnetopause is of particular interest for understanding X‐ray emissions near this boundary. This paper estimates the exospheric density during solar minimum using the X‐ray Multimirror Mission (XMM) astrophysics observatory. We selected an event on 12 November 2008 from the XMM data archive, which detects soft X‐rays of magnetosheath origin while solar wind and interplanetary magnetic field conditions are relatively constant. During the event the location of the magnetopause was measured in situ by the THEMIS mission, thus the location of the solar wind ions responsible for the magnetosheath emission is well constrained by observation. We estimated the exospheric density using the Open Geospace Global Circulation Model (OpenGGCM) and a spherically symmetric exosphere model. The ratio of the magnetosheath plasma flux between the OpenGGCM model and the THEMIS, was nearly 1, which means the magnetohydrodynamic model reasonably reproduces the magnetosheath plasma conditions. The OpenGGCM magnetosheath parameters were used to deconvolve soft X‐rays of exospheric origin from the XMM signal. The lower‐limit of the exospheric density of this solar minimum event is 36.8 ± 11.7 cm−3 at 10 RE subsolar location. Key Points: From 11 years of X‐ray Multimirror Mission‐Newton X‐ray observations, we identified 193 intervals that can be used to estimate the exospheric neutral densityWe derived a solar minimum exospheric neutral density from the 12 November 2008 event using a global MagnetoHydroDynamics model and a simplified exosphere modelThe density estimate is 36.8 cm−3 near the subsolar magnetopause and is likely a lower‐limit value [ABSTRACT FROM AUTHOR]

X-ray emission from solar wind charge exchange (SWCX) produced in interplanetary space contaminates every astrophysical observation, regardless of the line of sight. Unfortunately, the primary SWCX emission lines also happen to be important diagnostics of astrophysical plasmas. Models of SWCX emission are limited by two main uncertainties: the local solar wind fluxes along the line of sight and the charge exchange cross sections. The He cone, a localized density enhancement of helium neutrals, is the only heliospheric SWCX emission feature that is small enough and bright enough to be observationally isolated from the X-ray background and the broader SWCX emission. HaloSat, an X-ray CubeSat mission, has recently completed two series of specialized observations, near and far from the ecliptic plane, during two Earth transits of the He cone. These observations were used to test the predictions of an SWCX emission model against the emission observed at low ecliptic latitude, where the solar wind data are monitored, and at high ecliptic latitude, where the solar wind data are extrapolated. The measured SWCX emission for the set of observations near the ecliptic plane was consistent with the line intensities predicted by the model but underpredicted for the set of observations at high ecliptic latitude near the south ecliptic pole. Additionally, high-temperature Galactic halo emission components are reported for both spectral sets. [ABSTRACT FROM AUTHOR]

The Cusp Plasma Imaging detector (CuPID) Cube Satellite Observatory is a six‐unit Cube Satellite developed to study macroscale properties of dayside magnetopause reconnection. Reconnection will be studied through imaging spatial and temporal ion dispersion signatures in the magnetospheric cusps. As reconnection enables shocked solar wind plasma to enter the cusp, high charge state solar wind ions will charge‐exchange with Earth's neutral exosphere. This process generates soft X‐rays imaged by the spacecraft. CuPID is in a circular, highly inclined (97.6°), sun‐synchronous, low Earth orbit (550 km), where it views upward through the cusp from its low altitude footprint. The mission carries three science instruments, an energetic (>50 keV) radiation detector, a soft X‐ray (0.1–2 keV) imager, and a body‐mounted magnetometer. The soft X‐ray imager employs a novel, wide field‐of‐view (4.6°) slumped micropore optical element to focus X‐rays. The radiation detector uses collimated micro‐dosimeters with blocking foils to discriminate particle species. The three‐axis magnetometer is part of the attitude determination and control system and has been calibrated to provide scientifically useful data.Plain Language Summary: The Cusp Imaging Plasma Instrument Detector (CuPID) CubeSat Observatory is a small spacecraft designed to study soft X‐rays from space. These X‐rays will not penetrate the Earth's atmosphere, so an observer must make measurements from space, and CuPID will fly in a low altitude (550 km) polar orbit. The spacecraft will carry the first ever wide field‐of‐view soft X‐ray imager into orbit to make measurements of the Earth's space environment in soft X‐rays. Scientifically, soft X‐rays are useful as their intensity and dynamics in the Earth's polar cusps provide a proxy for the driving from the sun's solar wind. The spacecraft packs a modular set of avionics as well as soft X‐ray telescope and radiation sensor into a small 10 cm × 20 cm × 30 cm box. The self‐sustained mission will provide the first regular images of the Earth's magnetic field and space environment in soft X‐rays.Key Points: The Cusp Plasma Imaging detector (CuPID) Cube Satellite Observatory is a small satellite built to study soft X‐rays in spaceCuPID is a pioneering wide field‐of‐view soft X‐ray imager in orbitCuPID studies solar wind‐magnetosphere coupling and magnetopause reconnection [ABSTRACT FROM AUTHOR]

The LEXI and SMILE missions will provide soft X-ray images of the Earth's magnetosheath and cusps after their anticipated launch in 2023 and 2024, respectively. The IBEX mission showed the potential of an Energetic Neutral Atom (ENA) instrument to image dayside magnetosheath and cusps, albeit over the long hours required to raster an image with a single pixel imager. Thus, it is timely to discuss the two imaging techniques and relevant science topics. We simulate soft X-ray and low-ENA images that might be observed by a virtual spacecraft during two interesting solar wind scenarios: a southward turning of the interplanetary magnetic field and a sudden enhancement of the solar wind dynamic pressure. We employ the OpenGGCM global magnetohydrodynamics model and a simple exospheric neutral density model for these calculations. Both the magnetosheath and the cusps generate strong soft X-rays and ENA signals that can be used to extract the locations and motions of the bow shock and magnetopause. Magnetopause erosion corresponds closely to the enhancement of dayside reconnection rate obtained from the OpenGGCM model, indicating that images can be used to understand global-scale magnetopause reconnection. When dayside imagers are installed with high-ENA innermagnetosphere and FUV/UV aurora imagers, we can trace the solar wind energy flow from the bow shock to the magnetosphere and then to the ionosphere in a self-standing manner without relying upon other observatories. Soft X-ray and/or ENA imagers can also unveil the dayside exosphere density structure and its response to space weather. [ABSTRACT FROM AUTHOR]

The Cygnus Superbubble (CSB) is a region of soft X-ray emission approximately 13 degrees wide in the direction of the local spiral arm. Such a large region might be the result of strong stellar winds and supernovae from nearby stellar nurseries, or it could be the result of a single event—a hypernova. HaloSat observed four nonoverlapping 10 degree diameter fields in the CSB region over the 0.4-7 keV band. The CSB absorption and temperature was found to be consistent over all four fields, with a weighted average of 6.1 × 1021 cm−2 and 0.190 keV, respectively. These observations suggest that the CSB is a cohesive object with a singular origin. The total thermal energy for the CSB is estimated at 4 × 1052 erg, based upon a shell-like physical model of the CSB. Absorption and distance estimates to Cyg OB associations are examined. The CSB absorption is found to be most consistent with the absorption seen in Cyg OB1, implying that the CSB lies at a similar distance of 1.1–1.4 kpc. [ABSTRACT FROM AUTHOR]

We present HaloSat X-ray observations of the entirety of the bright X-ray emitting feature known as the North Polar Spur (NPS). The large field of view of HaloSat enabled coverage of the entire bright NPS in only 14 fields, which were each observed for ≈30,000 s. We find that the NPS fields are distinct in both brightness and spectral shape from the surrounding halo fields. We fit the NPS as two thermal components in ionization equilibrium with temperatures and. We note a temperature gradient in the NPS hot component with an inner arc temperature warmer than the outer arc. The emission measures we find for the cool component of the NPS is a factor of 3–5 greater than that of the hot component, which suggests that the bulk of the NPS material is in the ≈0.1 keV component. We evaluate distance estimates of 0.4 and 8.0 kpc for the NPS. Our findings suggest a preference for a distant NPS with an energy of ≈ 6 × 1054 erg, an age of ≈ 10 Myr, and pressures consistent with a 10μG magnetic field associated with the Fermi bubbles. The electron density ≈10 × 10−3 cm−3 is consistent with estimates for the shock region surrounding a Galactic-scale event. [ABSTRACT FROM AUTHOR]

One of the major and unfortunately unforeseen sources of background for the current generation of X-ray telescopes are few tens to hundreds of keV (soft) protons concentrated by the mirrors. One such telescope is the European Space Agency's (ESA) X-ray Multi-Mirror Mission (XMM-Newton). Its observing time lost due to background contamination is about 40%. This loss of observing time affects all the major broad science goals of this observatory, ranging from cosmology to astrophysics of neutron stars and black holes. The soft-proton background could dramatically impact future large X-ray missions such as the ESA planned Athena mission (http://www.the-athena-x-ray-observatory.eu/). Physical processes that trigger this background are still poorly understood. We use a machine learning (ML) approach to delineate related important parameters and to develop a model to predict the background contamination using 12 yr of XMM-Newton observations. As predictors we use the location of the satellite and solar and geomagnetic activity parameters. We revealed that the contamination is most strongly related to the distance in the southern direction, Z (XMM-Newton observations were in the southern hemisphere), the solar wind radial velocity, and the location on the magnetospheric magnetic field lines. We derived simple empirical models for the first two individual predictors and an ML model that utilizes an ensemble of the predictors (Extra-Trees Regressor) and gives better performance. Based on our analysis, future missions should minimize observations during times associated with high solar wind speed and avoid closed magnetic field lines, especially at the dusk flank region in the southern hemisphere. [ABSTRACT FROM AUTHOR]

Standardized identification of genotypes is necessary in animals that reproduce asexually and form large clonal populations such as coral. We developed a high-resolution hybridization-based genotype array coupled with an analysis workflow and database for the most speciose genus of coral, Acropora, and their symbionts. We designed the array to co-analyze host and symbionts based on bi-allelic single nucleotide polymorphisms (SNP) markers identified from genomic data of the two Caribbean Acropora species as well as their dominant dinoflagellate symbiont, Symbiodinium 'fitti'. SNPs were selected to resolve multi-locus genotypes of host (called genets) and symbionts (called strains), distinguish host populations and determine ancestry of coral hybrids between Caribbean acroporids. Pacific acroporids can also be genotyped using a subset of the SNP loci and additional markers enable the detection of symbionts belonging to the genera Breviolum, Cladocopium, and Durusdinium. Analytic tools to produce multi-locus genotypes of hosts based on these SNP markers were combined in a workflow called the Standard Tools for Acroporid Genotyping (STAG). The STAG workflow and database are contained within a customized Galaxy environment (https://coralsnp.science.psu.edu/galaxy/), which allows for consistent identification of host genet and symbiont strains and serves as a template for the development of arrays for additional coral genera. STAG data can be used to track temporal and spatial changes of sampled genets necessary for restoration planning and can be applied to downstream genomic analyses. Using STAG, we uncover bi-directional hybridization between and population structure within Caribbean acroporids and detect a cryptic Acroporid species in the Pacific. [ABSTRACT FROM AUTHOR]

Solar wind charge-exchange (SWCX) emission is present in every X-ray observation of an astrophysical object. The emission is problematic when one cannot remove the foreground by the simultaneous measurement of a nearby field. SWCX emission is a serious impediment to the study of the diffuse hot ISM, including the galactic halo, as its contribution to diagnostic emission lines is temporally variable. Modeling the SWCX emission, in order to remove it from our observations, has proven to be more difficult than originally anticipated. This work reviews our current understanding of SWCX emission, with special attention to all the components required for future modeling tools. Since, in the absence of such a tool, observing programs can still be constructed to minimize the effect of SWCX, mitigation strategies are discussed. Although some aspects of SWCX will be very difficult to characterize, progress continues on many fronts. [ABSTRACT FROM AUTHOR]

Background: Target selection for oncology is a crucial step in the successful development of therapeutics. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 editing of specific loci offers an alternative method to RNA interference and small molecule inhibitors for determining whether a cell line is dependent on a specific gene product for proliferation or survival. In our initial studies using CRISPR-Cas9 to verify the dependence on EZH2 activity for proliferation of a SMARCB1/SNF5/INI1 mutant malignant rhabdoid tumor (MRT) cell line, we noted that the initial reduction in proliferation was lost over time. We hypothesized that in the few cells that retain proliferative capacity, at least one allele of EZH2 remains functional. To verify this, we developed an assay to analyze 10s-100s of clonal cell populations for target gene disruption using restriction digest and fluorescent fragment length analyses. Results: Our results clearly show that in cell lines in which EZH2 is essential for proliferation, at least one potentially functional allele of EZH2 is retained in the clones that survive. Conclusion: This assay clearly indicates whether or not a specific gene is essential for survival and/or proliferation in a given cell line. Such data can aid the development of more robust therapeutics by increasing confidence in target selection. [ABSTRACT FROM AUTHOR]

Our purpose was to project and compare clinical and quality-adjusted life year (QALY) outcomes of adjuvant radiotherapy (ART) versus salvage RT (SRT) after radical prostatectomy for men with locally advanced prostate cancer. We constructed a Markov model to simulate the randomized studies of observation versus ART, assuming 75% of observation patients would receive SRT at PSA recurrence. Transition probabilities and utility inputs were drawn from randomized trials of ART and cohort studies of SRT. We projected 10-year PSA recurrence-free survival, metastasis-free survival and overall survival. We found that observation with selective SRT yielded slightly worse outcomes than ART for post-RT PSA recurrence-free survival (47 and 52%), metastasis-free survival (69 and 70%) and overall survival (72 and 73%). Findings were robust to sensitivity analyses. After adjusting for the disutility of RT, observation plus SRT yielded better QALYs at 10 years than ART (6.80 and 6.13 QALYs). Thus, observation plus SRT may be optimal for men likely to comply with surveillance who wish to minimize side effects of the treatment. These findings reflect outcomes for the average patient given the current level of evidence and are meant to help inform current decision-making as we await future clinical studies of comparative effectiveness. [ABSTRACT FROM AUTHOR]

We have performed an X-ray study of the nearby barred spiral galaxy NGC 1672, primarily to ascertain the effect of the bar on its nuclear activity. We use both Chandra and XMM-Newton observations to investigate its X-ray properties, together with supporting high-resolution optical imaging data from the Hubble Space Telescope (HST), infrared imaging from the Spitzer Space Telescope, and Australia Telescope Compact Array ground-based radio data. We detect 28 X-ray sources within the D25 area of the galaxy; many are spatially correlated with star formation in the bar and spiral arms, and two are identified as background galaxies in the HST images. Nine of the X-ray sources are ultraluminous X-ray sources, with the three brightest (Lx > 5 × 1039 erg s-1) located at the ends of the bar. With the spatial resolution of Chandra, we are able to show for the first time that NGC 1672 possesses a hard (Γ ~ 1.5) nuclear X-ray source with a 2-10 keV luminosity of 4 × 1038 erg s-1. This is surrounded by an X-ray-bright circumnuclear star-forming ring, comprised of point sources and hot gas, which dominates the 2-10 keV emission in the central region of the galaxy. The spatially resolved multiwavelength photometry indicates that the nuclear source is a low-luminosity active galactic nucleus (LLAGN), but with star formation activity close to the central black hole. A high-resolution multiwavelength survey is required to fully assess the impact of both large-scale bars and smaller-scale phenomena such as nuclear bars, rings, and nuclear spirals on the fueling of LLAGN. [ABSTRACT FROM AUTHOR]

Background: Faecal occult blood tests (FOBTs) are used for colorectal cancer (CRC) screening. We aimed to assess the sensitivity of an immunochemical FOBT for detecting advanced colorectal neoplasia in the left vs the right colon and to explore reasons for potential differences in site-specific test performance.Methods: We prospectively measured faecal occult blood levels by a quantitative immunochemical FOBT (RIDASCREEN) in 2310 average-risk subjects undergoing screening colonoscopy. We compared diagnostic performance for subjects with left- vs right-sided advanced neoplasia, as well as patient characteristics and adenoma characteristics that have been suggested to impact faecal haemoglobin levels.Results: Sensitivities for subjects with left- vs right-sided advanced neoplasia were 33% (95% confidence interval (CI), 26-41%) and 20% (CI, 11-31%) (P=0.04) at a specificity of 95% (overall sensitivity: 29%) and the areas under the receiver-operating characteristics curve were 0.71 (CI, 0.69-0.72) and 0.60 (CI, 0.58-0.63), respectively. Pedunculated shape was strikingly more common in participants with left- vs right-sided advanced neoplasia (47% vs 14%). In logistic regression analyses adjusted for site, pedunculated shape was statistically significantly associated with test sensitivity (P=0.04).Conclusions: The immunochemical FOBT in our study was more sensitive for detecting subjects with left- vs right-sided advanced colorectal neoplasia. Our findings may stimulate further diagnostic research in the field as well as modelling analyses to estimate the potential effect of site-specific test performance on the effectiveness of annual or biennial FOBT-based screening programmes, in particular with respect to protection from right-sided CRC. [ABSTRACT FROM AUTHOR]

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has proven efficacy in reducing the rate of coronary and cerebrovascular events in patients 75 years of age or younger with a history of myocardial infarction. However, in patients older than 75 years of age, the efficacy and potential cost-effectiveness of statins are unknown.Objective: To estimate the incremental cost-effectiveness of statin therapy compared with usual care in patients 75 to 84 years of age with previous myocardial infarction.Design: Cost-effectiveness analysis.Data Sources: Published data from cohort studies.Target Population: Patients 75 to 84 years of age with a history of myocardial infarction.Time Horizon: Lifetime.Perspective: Societal.Intervention: Statin therapy.Outcome Measures: Life expectancy, quality-adjusted life expectancy, and incremental cost-effectiveness.Results Of Base-case Analysis: The incremental cost-effectiveness of statin therapy compared with usual care in patients 75 to 84 years of age with previous myocardial infarction was $18800 per quality-adjusted life-year (QALY).Results Of Sensitivity Analysis: On the basis of a probabilistic sensitivity analysis, there is a 75% chance that statin therapy costs less than $39800 per QALY compared with usual care. If the cost of statin therapy and efficacy of statin therapy at reducing myocardial infarction were set to their most favorable values, statin therapy cost $5400 per QALY; if cost and efficacy were set to their least favorable values, statin therapy cost $97800 per QALY.Conclusions: The cost-effectiveness ratios of statin therapy in older patients with previous myocardial infarction are reasonable under a wide variety of assumptions about drug efficacy, drug cost, and rates of cardiac and cerebrovascular events. Pending results of randomized, controlled trials of secondary prevention in patients in this age group, statin therapy seems to be as cost-effective as many routinely accepted medical interventions in this setting. [ABSTRACT FROM AUTHOR]

Context: Women with BRCA1- or BRCA2-associated breast cancer are at increased risk for contralateral breast cancer and ovarian cancer and therefore may consider secondary cancer prevention strategies, such as prophylactic surgery and tamoxifen therapy. It is not proven to what extent these strategies reduce risk of second cancers in such patients.Objective: To examine the effect of tamoxifen therapy, bilateral prophylactic oophorectomy (PO), prophylactic contralateral mastectomy (PCM), and combinations of these strategies on life expectancy for women with unilateral breast cancer and a BRCA1 or BRCA2 gene mutation.Design and Setting: Decision analysis using a Markov model. Probabilities for developing contralateral breast cancer and ovarian cancer, dying from these cancers, dying from primary breast cancer, and the reduction in cancer incidence and mortality due to prophylactic surgeries and/or tamoxifen were estimated from published studies.Participants: Hypothetical breast cancer patients with BRCA1 or BRCA2 mutations facing decisions about secondary cancer prevention strategies.Interventions: Seven strategies, including 5 years of tamoxifen use, PO, PCM, and combinations of these strategies, compared with careful surveillance.Main Outcome Measures: Total and incremental life expectancy (LE) with each intervention strategy.Results: Depending on the assumed penetrance of the BRCA mutation, compared with surveillance alone, 30-year-old early-stage breast cancer patients with BRCA mutations gain in LE 0.4 to 1.3 years from tamoxifen therapy, 0.2 to 1.8 years from PO, and 0.6 to 2.1 years from PCM. The magnitude of these gains is least for women with low-penetrance mutations (assumed contralateral breast cancer risk of 24% and ovarian cancer risk of 6%) and greatest for those with high-penetrance mutations (assumed contralateral breast cancer risk of 65% and ovarian cancer risk of 40%.) Older age and poorer prognosis from primary breast cancer further attenuate these gains.Conclusions: Interventions to prevent second cancers, particularly PCM, may offer substantial LE gain for young women with BRCA-associated early-stage breast cancer. Estimates of LE gain may help women and their physicians consider the uncertainties, risks, and advantages of these interventions and lead to more informed choices about cancer prevention strategies. [ABSTRACT FROM AUTHOR]

Context: Expert panels and decision-analytic techniques are increasingly used to determine the appropriateness of medical interventions, but these 2 approaches use different methods to process evidence.Objective: To compare expert panel appropriateness ratings of coronary angiography after myocardial infarction (from the time of hospital discharge to 12 weeks after infarction) with the health gains and cost-effectiveness predicted by a decision-analytic model.Design: Comparison of the degree of importance of the clinical variables considered in expert panel appropriateness ratings vs a previously published decision-analytic model. Identification of 36 clinical scenarios from the expert panel that could be simulated by the decision-analytic model.Main Outcome Measures: Appropriateness score and appropriateness classification (expert panel) vs gain in quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (decision-analytic model).Results: The most important clinical variables were similar in the 2 approaches, with the exercise tolerance test result exerting the greatest leverage on strength of recommendation for angiography. Among the expert panel clinical scenarios considered to be appropriate for coronary angiography that could be simulated in the decision-analysis model, the median (interquartile range) health gain and incremental cost-effectiveness ratio were 0.59 (0.41-0.76) QALYs and $27000 ($23000-$35000) per QALY gained, respectively. Among the clinical scenarios that expert panels considered inappropriate, the corresponding medians (interquartile ranges) were 0.24 (0.19-0.34) QALYs and $54000 ($36000-$58000) per QALY gained. The Spearman rank correlation between appropriateness score and QALY gain was 0.58 (P<.001) and between appropriateness score and estimated incremental cost-effectiveness ratios was -0.66 (P<.001).Conclusions: For the 36 expert panel scenarios that could be simulated by the decision-analytic model, there was moderate to good agreement between the appropriateness score and both the health gain and the incremental cost-effectiveness ratio of coronary angiography compared with no angiography in the convalescent phase of acute myocardial infarction, but several scenarios judged as inappropriate by the expert panel approach had cost-effectiveness ratios comparable with many generally recommended medical interventions. Formal synthesis of expert judgment and decision modeling is warranted in future efforts at guideline development. [ABSTRACT FROM AUTHOR]

Context: Homosexual and bisexual men infected with human immunodeficiency virus (HIV) are at increased risk for human papillomavirus-related anal neoplasia and anal squamous cell carcinoma (SCC).Objective: To estimate the clinical benefits and cost-effectiveness of screening HIV-positive homosexual and bisexual men foranal squamous intraepithelial lesions (ASIL) and anal SCC.Design: Cost-effectiveness analysis performed from a societal perspective that used reference case recommendations from the Panel on Cost-Effectiveness in Health and Medicine. A state-transition Markov model was developed to calculate lifetime costs, life expectancy, and quality-adjusted life expectancy for no screening vs several screening strategies for ASIL and anal SCC using anal Papanicolaou (Pap) testing at different intervals. Values for incidence, progression, and regression of anal neoplasia; efficacy of screening and treatment; natural history of HIV; health-related quality of life; and costs were obtained from the literature.Setting and Participants: Hypothetical cohort of homosexual and bisexual HIV-positive men living in the United States.Main Outcome Measures: Life expectancy, quality-adjusted life expectancy, quality-adjusted years of life saved, lifetime costs, and incremental cost-effectiveness ratio.Results: Screening for ASIL increased quality-adjusted life expectancy at all stages of HIV disease. Screening with anal Pap tests every 2 years, beginning in early HIV disease (CD4 cell count >0.50 x 10(9)/L), resulted in a 2.7-month gain in quality-adjusted life expectancy for an incremental cost-effectiveness ratio of $13,000 per quality-adjusted life year saved. Screening with anal Pap tests yearly provided additional benefit at an incremental cost of $16,600 per quality-adjusted life year saved. If screening was not initiated until later in the course of HIV disease (CD4 cell count <0.50 x 10(9)/L), then yearly Pap test screening was preferred due to the greater amount of prevalent anal disease (cost-effectiveness ratio of less than $25,000 per quality-adjusted life year saved compared with no screening). Screening every 6 months provided little additional benefit over that of yearly screening. Results were most sensitive to the rate of progression of ASIL to anal SCC and the effectiveness of treatment of precancerous lesions.Conclusions: Screening HIV-positive homosexual and bisexual men for ASIL and anal SCC with anal Pap tests offers quality-adjusted life expectancy benefits at a cost comparable with other accepted clinical preventive interventions. [ABSTRACT FROM AUTHOR]

Background: Evaluation of acute chest pain is highly variable.Objective: To evaluate the cost-effectiveness of strategies using cardiac markers and noninvasive tests for myocardial ischemia.Design: Cost-effectiveness analysis.Data Sources: Prospective data from 1066 patients with chest pain and from the published literature.Target Population: Patients admitted with acute chest pain.Time Horizon: Lifetime.Perspective: Societal.Interventions: Creatine kinase (CK)-MB mass assay alone; CK-MB mass assay followed by cardiac troponin I assay if the CK-MB value is normal; CK-MB mass assay followed by troponin I assay if the CK-MB value is normal and electrocardiography shows ischemic changes; both CK-MB mass and troponin I assays; and troponin I assay alone. These strategies were evaluated alone or in combination with early exercise testing.Outcome Measures: Lifetime cost, life expectancy (in years), and incremental cost-effectiveness.Results Of Base-case Analysis: For patients 55 to 64 years of age, measurement of CK-MB mass followed by exercise testing in appropriate patients was the most competitive strategy ($43000 per year of life saved). Measurement of CK-MB mass followed by troponin I measurement had an incremental cost-effectiveness ratio of $47400 per year of life saved for patients 65 to 74 years of age; it was also the most cost-effective strategy when early exercise testing could not be performed, CK-MB values were normal, and ischemic changes were seen on electrocardiography.Results Of Sensitivity Analysis: Results were influenced by age, probability of myocardial infarction, and medical costs.Conclusions: Measurement of CK-MB mass plus early exercise testing is a cost-effective initial strategy for younger patients and those with a low to moderate probability of myocardial infarction. Troponin I measurement can be a cost-effective second test in higher-risk subsets of patients if the CK-MB level is normal and early exercise testing is not an option. [ABSTRACT FROM AUTHOR]

Background: New tests, such as magnetic resonance imaging (MRI) and electron-beam computed tomography (CT), are being developed for the diagnosis of coronary artery disease.Objective: To determine the conditions that a new test must meet to be a cost-effective alternative to established imaging tests.Design: Decision model and cost-effectiveness analysis.Data Sources: Literature review and meta-analysis.Target Population: 55-year-old men and 65-year-old women presenting with chest pain.Time Horizon: Lifetime of the patient.Perspective: Health care policy.Interventions: MRI, electron-beam CT, exercise echocardiography, exercise single-photon emission CT, and coronary angiography.Outcome Measures: Target sensitivity and specificity values for a new noninvasive test.Results Of Base-case Analysis: Assuming that society is willing to pay $75000 per quality-adjusted life-year (QALY) gained, a new test that costs $1000 would need a sensitivity of 94% and a specificity of 90% to be cost-effective.Results Of Sensitivity Analysis: Assuming that society is willing to pay $50000 per QALY gained, a new test that costs $1000 or more would never be cost-effective. For a test that costs $500, the sensitivity and specificity must each be 95%.Conclusions: New imaging techniques, such as MRI and electron-beam CT, must be relatively inexpensive and have excellent sensitivity and specificity to be cost-effective compared with other techniques for the diagnosis of coronary artery disease. Similar analyses in other areas of health care may help to focus the development of new diagnostic technology. [ABSTRACT FROM AUTHOR]