Early massive clusters and the bouncing coupled dark energy

The abundance of the most massive objects in the Universe at different epochs is a very sensitive probe of the cosmic background evolution and of the growth history of density perturbations, and could provide a powerful tool to distinguish between a cosmological constant and a dynamical dark energy field. In particular, the recent detection of very massive clusters of galaxies at high redshifts has attracted significant interest as a possible indication of a failure of the standard LCDM model. Several attempts have been made in order to explain such detections in the context of non-Gaussian scenarios or interacting dark energy models, showing that both these alternative cosmologies predict an enhanced number density of massive clusters at high redshifts, possibly alleviating the tension. However, all the models proposed so far also overpredict the abundance of massive clusters at the present epoch, and are therefore in contrast with observational bounds on the low-redshift halo mass function. In this paper we present for the first time a new class of interacting dark energy models that simultaneously account for an enhanced number density of massive clusters at high redshifts and for both the standard cluster abundance at the present time and the standard power spectrum normalization at CMB. The key feature of this new class of models is the "bounce" of the dark energy scalar field on the cosmological constant barrier at relatively recent epochs. We present the background and linear perturbations evolution of the model, showing that the standard amplitude of density perturbations is recovered both at CMB and at the present time, and we demonstrate by means of large N-body simulations that our scenario predicts an enhanced number of massive clusters at high redshifts without affecting the present halo abundance. (Abridged)Comment: 11 pages, 6 figures, 2 tables. Minor changes, references added. Accepted for publication in MNRA

Complex Portal 2022:New curation frontiers

International audienceThe Complex Portal (www.ebi.ac.uk/complexportal) is a manually curated, encyclopaedic database of macromolecular complexes with known function from a range of model organisms. It summarizes complex composition, topology and function along with links to a large range of domain-specific resources (i.e. wwPDB, EMDB and Reactome). Since the last update in 2019, we have produced a first draft complexome for Escherichia coli, maintained and updated that of Saccharomyces cerevisiae, added over 40 coronavirus complexes and increased the human complexome to over 1100 complexes that include approximately 200 complexes that act as targets for viral proteins or are part of the immune system. The display of protein features in ComplexViewer has been improved and the participant table is now colour-coordinated with the nodes in ComplexViewer. Community collaboration has expanded, for example by contributing to an analysis of putative transcription cofactors and providing data accessible to semantic web tools through Wikidata which is now populated with manually curated Complex Portal content through a new bot. Our data license is now CC0 to encourage data reuse. Users are encouraged to get in touch, provide us with feedback and send curation requests through the ‘Support’ link

KiDS-1000 Cosmology::constraints beyond flat ΛCDM

We present constraints on extensions to the standard cosmological model of a spatially flat Universe governed by general relativity, a cosmological constant (Λ), and cold dark matter (CDM) by varying the spatial curvature ΩK, the sum of the neutrino masses ∑mν, the dark energy equation of state parameter w, and the Hu-Sawicki f(R) gravity fR0 parameter. With the combined 3 × 2 pt measurements of cosmic shear from the Kilo-Degree Survey (KiDS-1000), galaxy clustering from the Baryon Oscillation Spectroscopic Survey (BOSS), and galaxy-galaxy lensing from the overlap between KiDS-1000, BOSS, and the spectroscopic 2-degree Field Lensing Survey, we find results that are fully consistent with a flat ΛCDM model with $\Omega_K=0.011^{+0.054}_{-0.057}$, ∑mν < 1.76 eV (95% CL), and $\mathit{w}=-0.99^{+0.11}_{-0.13}$. The fR0 parameter is unconstrained in our fully non-linear f(R) cosmic shear analysis. Considering three different model selection criteria, we find no clear preference for either the fiducial flat ΛCDM model or any of the considered extensions. In addition to extensions to the flat ΛCDM parameter space, we also explore restrictions to common subsets of the flat ΛCDM parameter space by fixing the amplitude of the primordial power spectrum to the Planck best-fit value, as well as adding external data from supernovae and lensing of the cosmic microwave background (CMB). Neither the beyond-ΛCDM models nor the imposed restrictions explored in this analysis are able to resolve the ∼3σ tension in S8 between the 3 × 2 pt constraints and the Planck temperature and polarisation data, with the exception of wCDM, where the S8 tension is resolved. The tension in the wCDM case persists, however, when considering the joint S8 − w parameter space. The joint flat ΛCDM CMB lensing and 3 × 2 pt analysis is found to yield tight constraints on $\Omega_{\mathrm{m}}=0.307^{+0.008}_{-0.013}$, $\sigma_8=0.769^{+0.022}_{-0.010}$, and $S_8=0.779^{+0.013}_{-0.013}$

Targeting Therapeutics to Bone by Conjugation with Bisphosphonates

Bisphosphonates target and bind avidly to the mineral (hydroxyapatite) found in bone. This targeting ability has been&nbsp;exploited to design and prepare bisphosphonate conjugate prodrugs to deliver a wide variety of drug molecules selectively&nbsp; to bones. It is important that conjugates be stable in the blood&nbsp;stream and that conjugate that is not taken up by bone is&nbsp;eliminated rapidly. The prodrugs should release active drug at a&nbsp;rate appropriate so as to provide efficacy. Radiolabelling is the&nbsp;best method to quantify and evaluate pharmacokinetics, tissue&nbsp;distribution, bone uptake and release of the active drug(s).&nbsp;Recent reports have described bisphosphonate conjugates&nbsp;derived from the antiresorptive drug, alendronic acid and&nbsp;anabolic prostanoid drugs that effectively deliver&nbsp;prostaglandins and prostaglandin EP4 receptor agonists to&nbsp;bone and show enhanced anabolic efficacy and tolerability&nbsp;compared to the drugs alone. These conjugate drugs can be&nbsp;dosed infrequently (weekly or bimonthly) whereas the free&nbsp;drugs must be dosed daily

Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries (Nature, (2022), 611, 7934, (115-123), 10.1038/s41586-022-05165-3)

In the version of this article initially published, the name of the PRECISE4Q Consortium was misspelled as “PRECISEQ” and has now been amended in the HTML and PDF versions of the article. Further, data in the first column of Supplementary Table 55 were mistakenly shifted and have been corrected in the file accompanying the HTML version of the article

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe