Summary Background Total joint replacements for end-stage osteoarthritis of the hip and knee are cost-effective and demonstrate significant clinical improvement. However, robust population based ...lifetime-risk data for implant revision are not available to aid patient decision making, which is a particular problem in young patient groups deciding on best-timing for surgery. Methods We did implant survival analysis on all patients within the Clinical Practice Research Datalink who had undergone total hip replacement or total knee replacement. These data were adjusted for all-cause mortality with data from the Office for National Statistics and used to generate lifetime risks of revision surgery based on increasing age at the time of primary surgery. Findings We identified 63 158 patients who had undergone total hip replacement and 54 276 who had total knee replacement between Jan 1, 1991, and Aug 10, 2011, and followed up these patients to a maximum of 20 years. For total hip replacement, 10-year implant survival rate was 95·6% (95% CI 95·3–95·9) and 20-year rate was 85·0% (83·2–86·6). For total knee replacement, 10-year implant survival rate was 96·1% (95·8–96·4), and 20-year implant survival rate was 89·7% (87·5–91·5). The lifetime risk of requiring revision surgery in patients who had total hip replacement or total knee replacement over the age of 70 years was about 5% with no difference between sexes. For those who had surgery younger than 70 years, however, the lifetime risk of revision increased for younger patients, up to 35% (95% CI 30·9–39·1) for men in their early 50s, with large differences seen between male and female patients (15% lower for women in same age group). The median time to revision for patients who had surgery younger than age 60 was 4·4 years. Interpretation Our study used novel methodology to investigate and offer new insight into the importance of young age and risk of revision after total hip or knee replacement. Our evidence challenges the increasing trend for more total hip replacements and total knee replacements to be done in the younger patient group, and these data should be offered to patients as part of the shared decision making process.
Although platelet reactivity during P2Y12-inhibitors is associated with stent thrombosis (ST) and bleeding, standardized and clinically validated thresholds for accurate risk stratification after ...percutaneous coronary intervention (PCI) are lacking. We sought to determine the prognostic value of low platelet reactivity (LPR), optimal platelet reactivity (OPR), or high platelet reactivity (HPR) by applying uniform cut-off values for standardized devices.
Authors of studies published before January 2015, reporting associations between platelet reactivity, ST, and major bleeding were contacted for a collaborative analysis using consensus-defined, uniform cut-offs for standardized platelet function assays. Based on best available evidence for each device (exploratory studies), LPR-OPR-HPR categories were defined as <95, 95-208, and >208 PRU for VerifyNow, <19, 19-46, and >46 U for the Multiplate analyser and <16, 16-50, and >50% for VASP assay. Seventeen studies including 20 839 patients were used for the analysis; 97% were treated with clopidogrel and 3% with prasugrel. Patients with HPR had significantly higher risk for ST risk ratio (RR) and 95% CI: 2.73 (2.03-3.69), P < 0.00001, yet a slight reduction in bleeding RR: 0.84 (0.71-0.99), P = 0.04 compared with those with OPR. In contrast, patients with LPR had a higher risk for bleeding RR: 1.74 (1.47-2.06), P < 0.00001, without any further benefit in ST RR: 1.06 (0.68-1.65), P = 0.78 in contrast to OPR. Mortality was significantly higher in patients with HPR compared with other categories (P < 0.05). Validation cohorts (n = 14) confirmed all results of exploratory studies (n = 3).
Platelet reactivity assessment during thienopyridine-type P2Y12-inhibitors identifies PCI-treated patients at higher risk for mortality and ST (HPR) or at an elevated risk for bleeding (LPR).
The dwarf satellites of "giant" Milky Way (MW)-mass galaxies are our primary probes of low-mass dark matter halos. The number and velocities of the satellite galaxies of the MW and M31 initially ...puzzled galaxy formation theorists, but are now reproduced well by many models. Yet, are the MW's and M31's satellites representative? Were galaxy formation models "overfit"? These questions motivate deep searches for satellite galaxies outside the Local Group. We present a deep survey of the "classical" satellites (M ≥ 4 × 105 M ) of the MW-mass galaxy M94 out to a 150 kpc projected distance. We find only two satellites, each with M ∼ 106 M , compared with 6-12 such satellites in the four other MW-mass systems with comparable data (MW, M31, M81, and M101). Using a "standard" prescription for occupying dark matter halos (halos were taken from the fully hydrodynamical EAGLE simulation) with galaxies, we find that such a sparse satellite population occurs in <0.2% of MW-mass systems-a <1% probability among a sample of five (known systems + M94). In order to produce an M94-like system more frequently we make satellite galaxy formation much more stochastic than is currently predicted by dramatically increasing the slope and scatter of the stellar mass-halo mass (SMHM) relation. Surprisingly, the SMHM relation must be altered even for halos masses up to 1011 M -significantly above the mass scales predicted to have increased scatter from current hydrodynamical models. The sparse satellite population of this "lonely giant" thus advocates for an important modification to ideas of how the satellites around MW-mass galaxies form.
The addition of clopidogrel to aspirin treatment reduces ischemic events in a wide range of patients with cardiovascular disease. However, recurrent ischemic event occurrence during dual antiplatelet ...therapy, including stent thrombosis, remains a major concern. Platelet function measurements during clopidogrel treatment demonstrated a variable and overall modest level of P2Y12 inhibition. High on-treatment platelet reactivity to adenosine diphosphate (ADP) was observed in selected patients. Multiple studies have now demonstrated a clear association between high on-treatment platelet reactivity to ADP measured by multiple methods and adverse clinical event occurrence. However, the routine measurement of platelet reactivity has not been widely implemented and recommended in the guidelines. Reasons for the latter include: 1) a lack of consensus on the optimal method to quantify high on-treatment platelet reactivity and the cutoff value associated with clinical risk; and 2) limited data to support that alteration of therapy based on platelet function measurements actually improves outcomes. This review provides a consensus opinion on the definition of high on-treatment platelet reactivity to ADP based on various methods reported in the literature and proposes how this measurement may be used in the future care of patients.
Recent work has shown that Milky Way-mass galaxies display an incredible range of stellar halo properties, yet the origin of this diversity is unclear. The nearby galaxy M81-currently interacting ...with M82 and NGC 3077-sheds unique light on this problem. We present a Subaru Hyper Suprime-Cam survey of the resolved stellar populations around M81, revealing M81's stellar halo in never-before-seen detail. We resolve the halo to unprecedented V-band equivalent surface brightnesses of 33 mag arcsec −2 and produce the first-ever global stellar mass density map for a Milky Way-mass stellar halo outside of the Local Group. Using the minor axis, we confirm M81's halo as one of the lowest mass and metal poorest known (M 1.16 × 109M , Fe/H −1.2)-indicating a relatively quiet prior accretion history. Yet, our global halo census finds that tidally unbound material from M82 and NGC 3077 provides a substantial infusion of metal-rich material (M 5.4 × 108 M , Fe/H −0.9). We further show that, following the accretion of its massive satellite M82 (and the LMC-like NGC 3077), M81 will host one of the most massive and metal-rich stellar halos in the nearby universe. Thus, the saga of M81: following a passive history, M81's merger with M82 will completely transform its halo from a low-mass, anemic halo rivaling the Milky Way, to a metal-rich behemoth rivaled only by systems such as M31. This dramatic transformation indicates that the observed diversity in stellar halo properties is primarily driven by diversity in the largest mergers these galaxies have experienced.
Abstract
We have developed an automated quick data analysis system for data quality assurance (QA) for Hyper Suprime-Cam (HSC). The system was commissioned in 2012–2014, and has been offered for ...general observations, including the HSC Subaru Strategic Program, since 2014 March. The system provides observers with data quality information, such as seeing, sky background level, and sky transparency, based on quick analysis as data are acquired. Quick-look images and validation of image focus are also provided through an interactive web application. The system is responsible for the automatic extraction of QA information from acquired raw data into a database, to assist with observation planning, assess progress of all observing programs, and monitor long-term efficiency variations of the instrument and telescope. Enhancements of the system are being planned to facilitate final data analysis, to improve the HSC archive, and to provide legacy products for astronomical communities.
Organic photovoltaics (OPVs) promise cheap and flexible solar energy. Whereas light generates free charges in silicon photovoltaics, excitons are normally formed in organic semiconductors due to ...their low dielectric constants, and require molecular heterojunctions to split into charges. Recent record efficiency OPVs utilise the small molecule, Y6, and its analogues, which - unlike previous organic semiconductors - have low band-gaps and high dielectric constants. We show that, in Y6 films, these factors lead to intrinsic free charge generation without a heterojunction. Intensity-dependent spectroscopy reveals that 60-90% of excitons form free charges at AM1.5 light intensity. Bimolecular recombination, and hole traps constrain single component Y6 photovoltaics to low efficiencies, but recombination is reduced by small quantities of donor. Quantum-chemical calculations reveal strong coupling between exciton and CT states, and an intermolecular polarisation pattern that drives exciton dissociation. Our results challenge how current OPVs operate, and renew the possibility of efficient single-component OPVs.
Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key strategy to reduce platelet reactivity and to prevent thrombotic events in patients treated with percutaneous coronary ...intervention. In an earlier consensus document, we proposed cutoff values for high on-treatment platelet reactivity to adenosine diphosphate (ADP) associated with post–percutaneous coronary intervention ischemic events for various platelet function tests (PFTs). Updated American and European practice guidelines have issued a Class IIb recommendation for PFT to facilitate the choice of P2Y12 receptor inhibitor in selected high-risk patients treated with percutaneous coronary intervention, although routine testing is not recommended (Class III). Accumulated data from large studies underscore the importance of high on-treatment platelet reactivity to ADP as a prognostic risk factor. Recent prospective randomized trials of PFT did not demonstrate clinical benefit, thus questioning whether treatment modification based on the results of current PFT platforms can actually influence outcomes. However, there are major limitations associated with these randomized trials. In addition, recent data suggest that low on-treatment platelet reactivity to ADP is associated with a higher risk of bleeding. Therefore, a therapeutic window concept has been proposed for P2Y12 inhibitor therapy. In this updated consensus document, we review the available evidence addressing the relation of platelet reactivity to thrombotic and bleeding events. In addition, we propose cutoff values for high and low on-treatment platelet reactivity to ADP that might be used in future investigations of personalized antiplatelet therapy.
Abstract
We present an optically-selected cluster catalog from the Hyper Suprime-Cam (HSC) Subaru Strategic Program. The HSC images are sufficiently deep to detect cluster member galaxies down to ...M* ∼ 1010.2 M⊙ even at z ∼ 1, allowing a reliable cluster detection at such high redshifts. We apply the CAMIRA algorithm to the HSC Wide S16A dataset covering ∼232 deg2 to construct a catalog of 1921 clusters at redshift 0.1 < z < 1.1 and richness ${\skew7\hat{N}}_{\rm mem}>15$ that roughly corresponds to M200m ≳ 1014 h−1 M⊙. We confirm good cluster photometric redshift performance, with the bias and the scatter in Δz/(1 + z) being better than 0.005 and 0.01, respectively, over most of the redshift range. We compare our cluster catalog with large X-ray cluster catalogs from the XXL and XMM-LSS (the XMM Large Scale Structure) surveys and find good correlation between richness and X-ray properties.We also study the mis-centering effect from the distribution of offsets between optical and X-ray cluster centers. We confirm the high (>0.9) completeness and purity for high-mass clusters by analyzing mock galaxy catalogs.
Identifying genetic alterations that prime a cancer cell to respond to a particular therapeutic agent can facilitate the development of precision cancer medicines. Cancer cell-line (CCL) profiling of ...small-molecule sensitivity has emerged as an unbiased method to assess the relationships between genetic or cellular features of CCLs and small-molecule response. Here, we developed annotated cluster multidimensional enrichment analysis to explore the associations between groups of small molecules and groups of CCLs in a new, quantitative sensitivity dataset. This analysis reveals insights into small-molecule mechanisms of action, and genomic features that associate with CCL response to small-molecule treatment. We are able to recapitulate known relationships between FDA-approved therapies and cancer dependencies and to uncover new relationships, including for KRAS-mutant cancers and neuroblastoma. To enable the cancer community to explore these data, and to generate novel hypotheses, we created an updated version of the Cancer Therapeutic Response Portal (CTRP v2).
We present the largest CCL sensitivity dataset yet available, and an analysis method integrating information from multiple CCLs and multiple small molecules to identify CCL response predictors robustly. We updated the CTRP to enable the cancer research community to leverage these data and analyses.
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