Low arthroplasty survival after treatment for proximal humerus fracture sequelae: 3,245 shoulder replacements from the Nordic Arthroplasty Register Association

Background and purpose - Proximal humerus fractures (PHF) may result in sequelae indicating arthroplasty. We report cumulative survival rates and reasons for revision after arthroplasty for proximal humerus fracture sequelae (PHFS). Patients and methods - Data were derived from the Nordic Arthroplasty Register Association. The Kaplan-Meier method was used to illustrate survival rates. A scaled Schoenfeld residual plot was used to report the risk of revision for men relative to women in patients who were treated with reverse shoulder arthroplasty (RSA). Revision was defined as removal or exchange of any component or the addition of a glenoid component. Results - 30,190 primary arthroplasties were reported from 2004 to 2016, of which 3,245 were for PHFS. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 96% (95-97), 90% (89-92), and 86% (83-88) for stemmed hemiarthroplasty and 94% (92-95), 89% (87-91), and 86% (82-90) for RSA with a median time to revision of 18 months (IQR 9-44) and 3 months (IQR 0-17). The risk of revision for men relative to women in patients who were treated with RSA was 3.2 (1.9-5.1) 0-1 year after surgery and 1.9 (0.9-4.1) 1-8 years after surgery. The estimated 1-, 5-, and 10-year cumulative survival rates (95% CI) were 94% (92-96), 88% (85-90), and 80% (75-86) for men and 95% (94-96), 86% (84-89), and 81% (77-84) for young patients. Interpretation - Shoulder arthroplasty for PHFS was associated with lower survival rates, compared with previously published results of shoulder arthroplasty for acute PHF. The low arthroplasty survival rates for men and young patients especially are worrying

Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3

The eukaryotic initiation factor 3 (eIF3) plays an important role in translation initiation, acting as a docking site for several eIFs that assemble on the 40S ribosomal subunit. Here, we use mass spectrometry to probe the subunit interactions within the human eIF3 complex. Our results show that the 13-subunit complex can be maintained intact in the gas phase, enabling us to establish unambiguously its stoichiometry and its overall subunit architecture via tandem mass spectrometry and solution disruption experiments. Dissociation takes place as a function of ionic strength to form three stable modules eIF3(c:d:e:l:k), eIF3(f:h:m), and eIF3(a:b:i:g). These modules are linked by interactions between subunits eIF3b:c and eIF3c:h. We confirmed our interaction map with the homologous yeast eIF3 complex that contains the five core subunits found in the human eIF3 and supplemented our data with results from immunoprecipitation. These results, together with the 27 subcomplexes identified with increasing ionic strength, enable us to define a comprehensive interaction map for this 800-kDa species. Our interaction map allows comparison of free eIF3 with that bound to the hepatitis C virus internal ribosome entry site (HCV-IRES) RNA. We also compare our eIF3 interaction map with related complexes, containing evolutionarily conserved protein domains, and reveal the location of subunits containing RNA recognition motifs proximal to the decoding center of the 40S subunit of the ribosome

Clinical value of CT-derived simulations of transcatheter-aortic-valve-implantation in challenging anatomies the PRECISE-TAVI trial.

BACKGROUND: Preprocedural computed tomography planning improves procedural safety and efficacy of transcatheter aortic valve implantation (TAVI). However, contemporary imaging modalities do not account for device-host interactions. AIMS: This study evaluates the value of preprocedural computer simulation with FEops HEARTguideTM on overall device success in patients with challenging anatomies undergoing TAVI with a contemporary self-expanding supra-annular transcatheter heart valve. METHODS: This prospective multicenter observational study included patients with a challenging anatomy defined as bicuspid aortic valve, small annulus or severely calcified aortic valve. We compared the heart team's transcatheter heart valve (THV) planning decision based on (1) conventional multislice computed tomography (MSCT) and (2) MSCT imaging with FEops HEARTguideTM simulations. Clinical outcomes and THV performance were followed up to 30 days. RESULTS: A total of 77 patients were included (median age 79.9 years (IQR 74.2-83.8), 42% male). In 35% of the patients, preprocedural planning changed after FEops HEARTguideTM simulations (change in valve size selection [12%] or target implantation height [23%]). A new permanent pacemaker implantation (PPI) was implanted in 13% and >trace paravalvular leakage (PVL) occurred in 28.5%. The contact pressure index (i.e., simulation output indicating the risk of conduction abnormalities) was significantly higher in patients with a new PPI, compared to those without (16.0% [25th-75th percentile 12.0-21.0] vs. 3.5% [25th-75th percentile 0-11.3], p < 0.01) The predicted PVL was 5.7 mL/s (25th-75th percentile 1.3-11.1) in patients with none-trace PVL, 12.7 (25th-75th percentile 5.5-19.1) in mild PVL and 17.7 (25th-75th percentile 3.6-19.4) in moderate PVL (p = 0.04). CONCLUSION: FEops HEARTguideTM simulations may provide enhanced insights in the risk for PVL or PPI after TAVI with a self-expanding supra-annular THV in complex anatomies

Final Pre-40S Maturation Depends on the Functional Integrity of the 60S Subunit Ribosomal Protein L3

Ribosomal protein L3 is an evolutionarily conserved protein that participates in the assembly of early pre-60S particles. We report that the rpl3[W255C] allele, which affects the affinity and function of translation elongation factors, impairs cytoplasmic maturation of 20S pre-rRNA. This was not seen for other mutations in or depletion of L3 or other 60S ribosomal proteins. Surprisingly, pre-40S particles containing 20S pre-rRNA form translation-competent 80S ribosomes, and translation inhibition partially suppresses 20S pre-rRNA accumulation. The GTP-dependent translation initiation factor Fun12 (yeast eIF5B) shows similar in vivo binding to ribosomal particles from wild-type and rpl3[W255C] cells. However, the GTPase activity of eIF5B failed to stimulate processing of 20S pre-rRNA when assayed with ribosomal particles purified from rpl3[W255C] cells. We conclude that L3 plays an important role in the function of eIF5B in stimulating 3′ end processing of 18S rRNA in the context of 80S ribosomes that have not yet engaged in translation. These findings indicate that the correct conformation of the GTPase activation region is assessed in a quality control step during maturation of cytoplasmic pre-ribosomal particles

A deep spectromorphological study of the γ\gamma-ray emission surrounding the young massive stellar cluster Westerlund 1

Young massive stellar clusters are extreme environments and potentially provide the means for efficient particle acceleration. Indeed, they are increasingly considered as being responsible for a significant fraction of cosmic rays (CRs) accelerated within the Milky Way. Westerlund 1, the most massive known young stellar cluster in our Galaxy is a prime candidate for studying this hypothesis. While the very-high-energy $\gamma$-ray source HESS J1646-458 has been detected in the vicinity of Westerlund 1 in the past, its association could not be firmly identified. We aim to identify the physical processes responsible for the $\gamma$-ray emission around Westerlund 1 and thus to better understand the role of massive stellar clusters in the acceleration of Galactic CRs. Using 164 hours of data recorded with the High Energy Stereoscopic System (H.E.S.S.), we carried out a deep spectromorphological study of the $\gamma$-ray emission of HESS J1646-458. We furthermore employed H I and CO observations of the region to infer the presence of gas that could serve as target material for interactions of accelerated CRs. We detected large-scale ($\sim 2^\circ$ diameter) $\gamma$-ray emission with a complex morphology, exhibiting a shell-like structure and showing no significant variation with $\gamma$-ray energy. The combined energy spectrum of the emission extends to several tens of TeV, and is uniform across the entire source region. We did not find a clear correlation of the $\gamma$-ray emission with gas clouds as identified through H I and CO observations. We conclude that, of the known objects within the region, only Westerlund 1 can explain the bulk of the $\gamma$-ray emission. Several CR acceleration sites and mechanisms are conceivable, and discussed in detail. (abridged)Comment: 15 pages, 9 figures. Corresponding authors: L. Mohrmann, S. Ohm, R. Rauth, A. Specoviu

H.E.S.S. observations of the 2021 periastron passage of PSR B1259-63/LS 2883

PSR B1259-63 is a gamma-ray binary system that hosts a pulsar in an eccentric orbit, with a 3.4 year period, around an O9.5Ve star. At orbital phases close to periastron passages, the system radiates bright and variable non-thermal emission. We report on an extensive VHE observation campaign conducted with the High Energy Stereoscopic System, comprised of ~100 hours of data taken from $t_p-24$ days to $t_p+127$ days around the system's 2021 periastron passage. We also present the timing and spectral analyses of the source. The VHE light curve in 2021 is consistent with the stacked light curve of all previous observations. Within the light curve, we report a VHE maximum at times coincident with the third X-ray peak first detected in the 2021 X-ray light curve. In the light curve -- although sparsely sampled in this time period -- we see no VHE enhancement during the second disc crossing. In addition, we see no correspondence to the 2021 GeV flare in the VHE light curve. The VHE spectrum obtained from the analysis of the 2021 dataset is best described by a power law of spectral index $\Gamma = 2.65 \pm 0.04_{\text{stat}}$ $\pm 0.04_{\text{sys}}$, a value consistent with the previous H.E.S.S. observations of the source. We report spectral variability with a difference of $\Delta \Gamma = 0.56 ~\pm~ 0.18_{\text{stat}}$ $~\pm~0.10_{\text{sys}}$ at 95% c.l., between sub-periods of the 2021 dataset. We also find a linear correlation between contemporaneous flux values of X-ray and TeV datasets, detected mainly after $t_p+25$ days, suggesting a change in the available energy for non-thermal radiation processes. We detect no significant correlation between GeV and TeV flux points, within the uncertainties of the measurements, from $\sim t_p-23$ days to $\sim t_p+126$ days. This suggests that the GeV and TeV emission originate from different electron populations.Comment: accepted to A&

Prospects for combined analyses of hadronic emission from γ\gamma-ray sources in the Milky Way with CTA and KM3NeT

The Cherenkov Telescope Array and the KM3NeT neutrino telescopes are major upcoming facilities in the fields of $\gamma$-ray and neutrino astronomy, respectively. Possible simultaneous production of $\gamma$ rays and neutrinos in astrophysical accelerators of cosmic-ray nuclei motivates a combination of their data. We assess the potential of a combined analysis of CTA and KM3NeT data to determine the contribution of hadronic emission processes in known Galactic $\gamma$-ray emitters, comparing this result to the cases of two separate analyses. In doing so, we demonstrate the capability of Gammapy, an open-source software package for the analysis of $\gamma$-ray data, to also process data from neutrino telescopes. For a selection of prototypical $\gamma$-ray sources within our Galaxy, we obtain models for primary proton and electron spectra in the hadronic and leptonic emission scenario, respectively, by fitting published $\gamma$-ray spectra. Using these models and instrument response functions for both detectors, we employ the Gammapy package to generate pseudo data sets, where we assume 200 hours of CTA observations and 10 years of KM3NeT detector operation. We then apply a three-dimensional binned likelihood analysis to these data sets, separately for each instrument and jointly for both. We find that the largest benefit of the combined analysis lies in the possibility of a consistent modelling of the $\gamma$-ray and neutrino emission. Assuming a purely leptonic scenario as input, we obtain, for the most favourable source, an average expected 68% credible interval that constrains the contribution of hadronic processes to the observed $\gamma$-ray emission to below 15%.Comment: 18 pages, 15 figures. Submitted to journa

The KM3NeT potential for the next core-collapse supernova observation with neutrinos

The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris Ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia (ref. SOMM17/6104/UGR), Generalitat Valenciana: Grisolia (ref. GRISO-LIA/2018/119) and GenT (ref. CIDEGENT/2018/034 and CIDE-GENT/2019/043) programs, La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 713673), Spain. This work has also received funding from the European Union'sHorizon 2020 research and innovation program under Grant agreement no 739560.The KM3NeT research infrastructure is under construction in the Mediterranean Sea. It consists of two water Cherenkov neutrino detectors, ARCA and ORCA, aimed at neutrino astrophysics and oscillation research, respectively. Instrumenting a large volume of sea water with similar to 6200 optical modules comprising a total of similar to 200,000 photomultiplier tubes, KM3NeT will achieve sensitivity to similar to 10 MeV neutrinos from Galactic and near-Galactic core-collapse supernovae through the observation of coincident hits in photomultipliers above the background. In this paper, the sensitivity of KM3NeT to a supernova explosion is estimated from detailed analyses of background data from the first KM3NeT detection units and simulations of the neutrino signal. The KM3NeT observational horizon (for a 5 sigma discovery) covers essentially the Milky-Way and for the most optimistic model, extends to the Small Magellanic Cloud (similar to 60 kpc). Detailed studies of the time profile of the neutrino signal allow assessment of the KM3NeT capability to determine the arrival time of the neutrino burst with a few milliseconds precision for sources up to 5-8 kpc away, and detecting the peculiar signature of the standing accretion shock instability if the core-collapse supernova explosion happens closer than 3-5 kpc, depending on the progenitor mass. KM3NeT's capability to measure the neutrino flux spectral parameters is also presented.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)Commission Europeenne, FranceInstitut Universitaire de France (IUF), FranceLabEx UnivEarthS, France ANR-10-LABX-0023 ANR-18-IDEX-0001Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTGreek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program, Italy NAT-NET 2017W4HA7SMinistry of Higher Education Scientific Research and Professional Training, ICTP, Morocco AF-13Netherlands Organization for Scientific Research (NWO)Netherlands GovernmentNational Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento, Spain PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-B-C43 PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), SpainJunta de Andalucia European Commission SOMM17/6104/UGRGeneralitat Valenciana: Grisolia, Spain GRISO-LIA/2018/119 GenT program, Spain CIDEGENT/2018/034 CIDE-GENT/2019/043La Caixa Foundation LCF/BQ/IN17/11620019 EU: MSC program, Spain 713673European Commission 73956

Joint searches by FACT, H.E.S.S., MAGIC and VERITAS for VHE gamma-ray emission associated with neutrinos detected by IceCube

The sources of the astrophysical flux of high-energy neutrinos detected by IceCube are still largely unknown, but searches for temporal and spatial correlation between neutrinos and electromagnetic radiation are a promising approach in this endeavor. All major imaging atmospheric Cherenkov telescopes (IACTs) - FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program of target-of-opportunity observations of neutrino alerts issued by IceCube. These programs use several complementary neutrino alert streams. A publicly distributed alert stream is formed by individual high-energy neutrino candidate events of potentially astrophysical origin, such as IceCube-170922A (which could be linked to the flaring blazar TXS 0506+056). A privately distributed alert stream is formed by clusters of neutrino events in time and space around either pre-selected gamma-ray sources or anywhere in the sky. Here, we present joint searches for multi-wavelength emission associated with a set of IceCube alerts, both private and public, received through mid-January 2021. We will give an overview of the programs of the participating IACTs. We will showcase the various follow-up and data analysis strategies employed in response to the different alert types and various possible counterpart scenarios. Finally, we will present results from a combined analysis of the VHE gamma-ray observations obtained across all involved instruments, as well as relevant multi-wavelength data