Col-OSSOS: The Distribution of Surface Classes in Neptune's Resonances

The distribution of surface classes of resonant trans-Neptunian objects (TNOs) provides constraints on the protoplanetesimal disk and giant planet migration. To better understand the surfaces of TNOs, the Colours of the Outer Solar System Origins Survey (Col-OSSOS) acquired multi-band photometry of 102 TNOs, and found that the surfaces of TNOs can be well described by two surface classifications, BrightIR and FaintIR. These classifications both include optically red members and are differentiated predominantly based on whether their near-infrared spectral slope is similar to their optical spectral slope. The vast majority of cold classical TNOs, with dynamically quiescent orbits, have the FaintIR surface classification, and we infer that TNOs in other dynamical classifications with FaintIR surfaces share a common origin with the cold classical TNOs. Comparison between the resonant populations and the possible parent populations of cold classical and dynamically excited TNOs reveal that the 3:2 has minimal contributions from the FaintIR class, which could be explained by the $\nu_8$ secular resonance clearing the region near the 3:2 before any sweeping capture occurred. Conversely, the fraction of FaintIR objects in the 4:3 resonance, 2:1 resonance, and the resonances within the cold classical belt, suggest that the FaintIR surface formed in the protoplanetary disk between 34.6 and 47 au, though the outer bound depends on the degree of resonance sweeping during migration. The presence and absence of the FaintIR surfaces in Neptune's resonances provides critical constraints for the history of Neptune's migration, the evolution of the $\nu_8$, and the surface class distribution in the initial planetesimal diskComment: 19 pages, 8 figures. in Press at PS

Long Covid in adults discharged from UK hospitals after Covid-19 : a prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Funding: This work is supported by grants from: the National Institute for Health Research (NIHR) [award CO-CIN-01], the Medical Research Council [grant MC_PC_19059], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant P45058), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation [OPP1209135], and Liverpool Experimental Cancer Medicine Centre (Grant Reference: C18616/A25153), NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform for European Preparedness Against (Re-) emerging Epidemics 1 [FP7 project 602525] and NIHR Clinical Research Network for providing infrastructure support for this research. LT is a Wellcome Trust clinical career development fellow, supported by grant number 205228/Z/16/Z. This research was funded in part, by the Wellcome Trust. PJMO is supported by a NIHR Senior Investigator Award [award 201385].Background : This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods : 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings : 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation : Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.Publisher PDFPeer reviewe

Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution

BACKGROUND: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. RESULTS: We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. CONCLUSIONS: Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Functional interdependence of BRD4 and DOT1L in MLL leukemia.

Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models. Mechanistically, we found a previously unrecognized functional collaboration between DOT1L and BRD4 that is especially important at highly transcribed genes in proximity to superenhancers. DOT1L, via dimethylated histone H3 K79, facilitates histone H4 acetylation, which in turn regulates the binding of BRD4 to chromatin. These data provide new insights into the regulation of transcription and specify a molecular framework for therapeutic intervention in this disease with poor prognosis

Achievement of the planetary defense investigations of the Double Asteroid Redirection Test (DART) mission

NASA's Double Asteroid Redirection Test (DART) mission was the first to demonstrate asteroid deflection, and the mission's Level 1 requirements guided its planetary defense investigations. Here, we summarize DART's achievement of those requirements. On 2022 September 26, the DART spacecraft impacted Dimorphos, the secondary member of the Didymos near-Earth asteroid binary system, demonstrating an autonomously navigated kinetic impact into an asteroid with limited prior knowledge for planetary defense. Months of subsequent Earth-based observations showed that the binary orbital period was changed by –33.24 minutes, with two independent analysis methods each reporting a 1σ uncertainty of 1.4 s. Dynamical models determined that the momentum enhancement factor, β, resulting from DART's kinetic impact test is between 2.4 and 4.9, depending on the mass of Dimorphos, which remains the largest source of uncertainty. Over five dozen telescopes across the globe and in space, along with the Light Italian CubeSat for Imaging of Asteroids, have contributed to DART's investigations. These combined investigations have addressed topics related to the ejecta, dynamics, impact event, and properties of both asteroids in the binary system. A year following DART's successful impact into Dimorphos, the mission has achieved its planetary defense requirements, although work to further understand DART's kinetic impact test and the Didymos system will continue. In particular, ESA's Hera mission is planned to perform extensive measurements in 2027 during its rendezvous with the Didymos–Dimorphos system, building on DART to advance our knowledge and continue the ongoing international collaboration for planetary defense

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Col-OSSOS: Evidence for a Compositional Gradient Inherited from the Protoplanetary Disk?

In the present-day Kuiper Belt, the number of compositional classes and the orbital distributions of these classes hold important cosmogonic implications for the solar system. The Colours of the Outer Solar System Origins Survey (Col-OSSOS) recently showed that the observed color distribution of small ( H ⪆ 6) trans-Neptunian objects (TNOs) can be accounted for by the existence of only two composition classes, named BrightIR and FaintIR, where the range of colors in each class can be modeled as mixtures of two material end-members. Here, we combine the high-precision photometric measurements of Col-OSSOS with those of previous surveys to investigate the orbital distribution of the two color classes and reinterpret the known color–inclination correlation of TNOs in the context of the BrightIR/FaintIR taxonomy. In addition to confirming the previously reported distinct orbital distributions of these classes, we identify a trend of increasing orbital inclinations toward the bluer end of the optical and near-infrared color distribution of BrightIR objects. Using the output of numerical simulations investigating the orbital evolution of TNOs during their scattering phase with Neptune, we show that this trend could reflect a composition gradient in the early protoplanetary disk, in the range of heliocentric distances over which TNOs from the BrightIR class accreted. However, tensions between this interpretation and the existence of blue contaminants among cold classical TNOs, and possible alternative origins for the detected correlation, currently bear uncertainty on our proposed interpretation

Col-OSSOS: The Distribution of Surface Classes in Neptune's Resonances

The distribution of surface classes of resonant trans-Neptunian objects (TNOs) provides constraints on the protoplanetesimal disk and giant planet migration. To better understand the surfaces of TNOs, the Colours of the Outer Solar System Origins Survey acquired multiband photometry of 102 TNOs and found that the surfaces of TNOs can be well described by two surface classifications: BrightIR and FaintIR. These classifications both include optically red members and are differentiated predominantly based on whether their near-infrared spectral slope is similar to their optical spectral slope. The vast majority of cold classical TNOs, with dynamically quiescent orbits, have the FaintIR surface classification, and we infer that TNOs in other dynamical classifications with FaintIR surfaces share a common origin with the cold classical TNOs. Comparison between the resonant populations and the possible parent populations of cold classical and dynamically excited TNOs reveal that the 3:2 has minimal contributions from the FaintIR class, which could be explained by the ν _8 secular resonance clearing the region near the 3:2 before any sweeping capture occurred. Conversely, the fraction of FaintIR objects in the 4:3 resonance, 2:1 resonance, and the resonances within the cold classical belt suggest that the FaintIR surface formed in the protoplanetary disk between ≳34.6 and ≲47 au, though the outer bound depends on the degree of resonance sweeping during migration. The presence and absence of the FaintIR surfaces in Neptune’s resonances provides critical constraints for the history of Neptune’s migration, the evolution of the ν _8 , and the surface class distribution in the initial planetesimal disk

OSSOS XX: The Meaning of Kuiper Belt Colors

International audienceObservations show that 100 km class Kuiper Belt objects (KBOs) can be divided into (at least) two color groups, red (R; g - i 1.2), reflecting a difference in their surface composition. This is thought to imply that KBOs formed over a relatively wide range of radial distance, r. The cold classicals at 42 au r*, with 30 au < r* < 40 au. The proposed transition at 30 au < r* < 40 au would explain why the VR objects in the dynamically hot population have smaller orbital inclinations than the R objects, because the orbital excitation from Neptune weakens for orbits starting beyond 30 au. Possible causes of the R-VR color bimodality are discussed