Healthcare workers' experiences protecting themselves and their families during the COVID-19 pandemic in 2020-2021.

We characterized experiences and strategies used by frontline healthcare workers to prevent severe-acute-respiratory-syndrome-related coronavirus transmission at work and to household members during the coronavirus disease pandemic. Alongside an online questionnaire (n = 234), remote semi-structured interviews (n = 23: 15 clinicians, 8 non-clinicians) were conducted in 2021. Mitigation challenges and facilitators were identified from data to represent experiences as a process considering the before, during, and after work shifts. Journey mapping was utilized to visually describe how healthcare workers experienced the stages of the work environment, leaving work, commuting home, and the home environment, and strategies implemented to stay safe. Major facilitators included the uptake of coronavirus disease vaccines and testing, information regarding virus transmission, and adequate personal protective equipment. The most critical challenges identified included a lack of designated areas for end-of-day disinfection, changing rooms, showers, and lockers in the leaving work stage. Psychosocial and environmental factors must be considered in future hospital pandemic preparations.

Tangled webs and spider-flowers: Phylogenomics, biogeography, and seed morphology inform the evolutionary history of Cleomaceae.

PREMISE: Cleomaceae is an important model clade for studies of evolutionary processes including genome evolution, floral form diversification, and photosynthetic pathway evolution. Diversification and divergence patterns in Cleomaceae remain tangled as research has been restricted by its worldwide distribution, limited genetic sampling and species coverage, and a lack of definitive fossil calibration points. METHODS: We used target sequence capture and the Angiosperms353 probe set to perform a phylogenetic study of Cleomaceae. We estimated divergence times and biogeographic analyses to explore the origin and diversification of the family. Seed morphology across extant taxa was documented with multifocal image-stacking techniques and morphological characters were extracted, analyzed, and compared to fossil records. RESULTS: We recovered a well-supported and resolved phylogenetic tree of Cleomaceae generic relationships that includes 236 (~86%) species. We identified 11 principal clades and confidently placed Cleomella as sister to the rest of the family. Our analyses suggested that Cleomaceae and Brassicaceae diverged ~56 mya, and Cleomaceae began to diversify ~53 mya in the Palearctic and Africa. Multiple transatlantic disjunct distributions were identified. Seeds were imaged from 218 (~80%) species in the family and compared to all known fossil species. CONCLUSIONS: Our results represent the most comprehensive phylogenetic study of Cleomaceae to date. We identified transatlantic disjunctions and proposed explanations for these patterns, most likely either long-distance dispersals or contractions in latitudinal distributions caused by climate change over geological timescales. We found that seed morphology varied considerably but mostly mirrored generic relationships.

Tensionable lesser tuberosity osteotomy repair for anatomic total shoulder arthroplasty.

A lesser tuberosity osteotomy (LTO) is commonly performed during total shoulder arthroplasty to access the glenohumeral joint. Healing of the LTO is critical to optimizing the outcome of the procedure and is enhanced by a repair that provides stability and compression across the osteotomy site. The purpose of this article is to describe a technique that uses a tensionable suture construct to repair the LTO during anatomic total shoulder arthroplasty using a stemless humeral component. The technique involves passing a row of high-tensile sutures through bone tunnels lateral to the osteotomy site (transosseous sutures) and another row of sutures through the humeral implant (implant sutures). One limb of each bone tunnel suture is then tied to its corresponding limb of implant suture and the remaining free strands of the tied sutures are manually tensioned and tied to each other. This technique is an efficient and reproducible method for creating compression and stability across the osteotomy site that facilitates bony healing.

Phylogenomics of the pantropical Connaraceae: revised infrafamilial classification and the evolution of heterostyly.

Connaraceae is a pantropical family of about 200 species containing lianas and small trees with remarkably diverse floral polymorphisms, including distyly, tristyly, homostyly, and dioecy. To date, relationships within the family have not been investigated using a targeted molecular phylogenetic treatment, severely limiting systematic understanding and reconstruction of trait evolution. Accordingly, their last infrafamilial classification was based only on morphological data. Here, we used phylogenomic data obtained using the Angiosperms353 nuclear target sequence capture probes, sampling all tribes and almost all genera, entirely from herbarium specimens, to revise infrafamilial classification and investigate the evolution of heterostyly. The backbone of the resulting molecular phylogenetic tree is almost entirely resolved. Connaraceae consists of two clades, one containing only the African genus Manotes (4 or 5 species), which we newly recognize at the subfamily level. Vegetative and reproductive synapomorphies are proposed for Manotoideae. Within Connaroideae, Connareae is expanded to include the former Jollydoreae. The backbone of Cnestideae, which contains more than half of the Connaraceae species, remains incompletely resolved. Reconstructions of reproductive system evolution are presented that tentatively support tristyly as the ancestral state for the family, with multiple parallel losses, in agreement with previous hypotheses, plus possible re-gains. However, the great diversity of stylar polymorphisms and their phylogenetic lability preclude a definitive answer. Overall, this study reinforces the usefulness of herbarium phylogenomics, and unlocks the reproductive diversity of Connaraceae as a model system for the evolution of complex biological phenomena. Supplementary Information: The online version contains supplementary material available at 10.1007/s00606-024-01909-y.

Laparoscopy With Percutaneous Transgastric Endoscopy for the Assessment of Gastric Cancer in the Excluded Stomach of a Roux-en-Y Gastric Bypass Patient.

Primary adenocarcinoma in the excluded stomach of Roux-en-Y gastric bypass (RYGB) patients is extremely rare. As such, the most effective diagnostic approach has not yet been determined. In typical patients, endoscopic ultrasound (EUS) is the first-line technique for evaluating suspected gastric cancer. However, RYGB patients require a more personalized approach. Endoscopic evaluation of the excluded stomach in RYGB patients, whether by EUS-directed, enteroscopy-assisted, or percutaneous means, is undoubtedly more complex than in patients with normal anatomy. In addition, gastric cancer is often diagnosed at an advanced stage due to its asymptomatic early course. With the added complexity of endoscopy in RYGB patients, a laparoscopic-assisted endoscopic approach may have a more favorable diagnostic and therapeutic utility in the case of gastric remnant malignancy in RYGB patients. The following case describes this comprehensive laparoscopic and endoscopic approach for the diagnosis of gastric cancer of the excluded stomach in an RYGB patient.

Genomic incongruence accompanies the evolution of flower symmetry in Eudicots: a case study in the poppy family (Papaveraceae, Ranunculales).

Reconstructing evolutionary trajectories and transitions that have shaped floral diversity relies heavily on the phylogenetic framework on which traits are modelled. In this study, we focus on the angiosperm order Ranunculales, sister to all other eudicots, to unravel higher-level relationships, especially those tied to evolutionary transitions in flower symmetry within the family Papaveraceae. This family presents an astonishing array of floral diversity, with actinomorphic, disymmetric (two perpendicular symmetry axes), and zygomorphic flowers. We generated nuclear and plastid datasets using the Angiosperms353 universal probe set for target capture sequencing (of 353 single-copy nuclear ortholog genes), together with publicly available transcriptome and plastome data mined from open-access online repositories. We relied on the fossil record of the order Ranunculales to date our phylogenies and to establish a timeline of events. Our phylogenomic workflow shows that nuclear-plastid incongruence accompanies topological uncertainties in Ranunculales. A cocktail of incomplete lineage sorting, post-hybridization introgression, and extinction following rapid speciation most likely explain the observed knots in the topology. These knots coincide with major floral symmetry transitions and thus obscure the order of evolutionary events.

Spectroscopic confirmation of two luminous galaxies at a redshift of 14.

The first observations of the James Webb Space Telescope (JWST) have revolutionized our understanding of the Universe by identifying galaxies at redshift z ≈ 13 (refs. 1-3). In addition, the discovery of many luminous galaxies at Cosmic Dawn (z > 10) has suggested that galaxies developed rapidly, in apparent tension with many standard models4-8. However, most of these galaxies lack spectroscopic confirmation, so their distances and properties are uncertain. Here we present JWST Advanced Deep Extragalactic Survey-Near-Infrared Spectrograph spectroscopic confirmation of two luminous galaxies at z = 14.32 - 0.20 + 0.08 and z = 13.90 ± 0.17. The spectra reveal ultraviolet continua with prominent Lyman-α breaks but no detected emission lines. This discovery proves that luminous galaxies were already in place 300 million years after the Big Bang and are more common than what was expected before JWST. The most distant of the two galaxies is unexpectedly luminous and is spatially resolved with a radius of 260 parsecs. Considering also the very steep ultraviolet slope of the second galaxy, we conclude that both are dominated by stellar continuum emission, showing that the excess of luminous galaxies in the early Universe cannot be entirely explained by accretion onto black holes. Galaxy formation models will need to address the existence of such large and luminous galaxies so early in cosmic history.

Using 30-day modified rankin scale score to predict 90-day score in patients with intracranial hemorrhage: Derivation and validation of prediction model.

Whether 30-day modified Rankin Scale (mRS) scores can predict 90-day scores is unclear. This study derived and validated a model to predict ordinal 90-day mRS score in an intracerebral hemorrhage (ICH) population using 30-day mRS values and routinely available baseline variables. Adults enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) trial between May 2011 and September 2015 with acute ICH, who were alive at 30 days and had mRS scores reported at both 30 and 90 days were included in this post-hoc analysis. A proportional odds regression model for predicting ordinal 90-day mRS scores was developed and internally validated using bootstrapping. Variables in the model included: mRS score at 30 days, age (years), hematoma volume (cm3), hematoma location (deep [basal ganglia, thalamus], lobar, or infratentorial), presence of intraventricular hemorrhage (IVH), baseline Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale (NIHSS) score at randomization. We assessed model fit, calibration, discrimination, and agreement (ordinal, dichotomized functional independence), and EuroQol-5D ([EQ-5D] utility weighted) between predicted and observed 90-day mRS. A total of 898/1000 participants were included. Following bootstrap internal validation, our model (calibration slope = 0.967) had an optimism-corrected c-index of 0.884 (95% CI = 0.873-0.896) and R2 = 0.712 for 90-day mRS score. The weighted ĸ for agreement between observed and predicted ordinal 90-day mRS score was 0.811 (95% CI = 0.787-0.834). Agreement between observed and predicted functional independence (mRS score of 0-2) at 90 days was 74.3% (95% CI = 69.9-78.7%). The mean ± SD absolute difference between predicted and observed EQ-5D-weighted mRS score was negligible (0.005 ± 0.145). This tool allows practitioners and researchers to utilize clinically available information along with the mRS score 30 days after ICH to reliably predict the mRS score at 90 days.

The Silent Threat of Hypokalemia after High Voltage Electrical Injuries: A Case Study and Review of the Literature.

High-voltage electrical injuries, especially from lightning strikes, can cause life-threatening complications due to extreme temperature and voltage exposure. While burns and cardiac complications have been widely described, the documentation of metabolic imbalances, particularly hypokalemia, has not been as prevalent. This report focuses on a patient with profound transient hypokalemia following a lightning strike, alongside a review of three similar cases of transient hypokalemia from the literature. Our patient, a previously healthy young man, was struck by lightning and subsequently suffered transient hypokalemia with lower extremity sensory changes, which resolved after the normalization of serum potassium levels. While the exact underlying mechanisms of transient hypokalemia following high-voltage electrical injuries are unknown, we propose a multifactorial mechanism, which includes massive intracellular shifts of potassium due to elevated epinephrine levels and the prevention of potassium efflux through the electrical disruption of voltage-gated potassium channels. Our report underscores the importance of recognizing hypokalemia in patients with high-voltage electrical injuries and contributes to the understanding of the complex mechanisms involved. Further research is necessary to understand the connection between cellular changes induced by high-voltage exposure and their effects on metabolism, particularly in relation to hypokalemia.

Andexanet alfa versus PCC products for factor Xa inhibitor bleeding: A systematic review with meta-analysis.

Previous meta-analyses assessed andexanet alfa (AA) or prothrombin complex concentrate (PCC) products for the treatment of Factor Xa inhibitor (FXaI)-associated major bleeding. However, they did not include recent studies or assess the impact of the risk of bias. We conducted a systematic review with meta-analysis on the effectiveness of AA versus PCC products for FXaI-associated major bleeding, inclusive of the studies' risk of bias. PubMed and Embase were searched for comparative studies assessing major bleeding in patients using FXaI who received AA or PCC. We used the Methodological Index for NOn-Randomized Studies (MINORS) checklist and one question from the Joanna Briggs Institute (JBI) Critical Appraisal of Case Series tool to assess the risk of bias. Random-effects meta-analyses were performed to provide a pooled estimate for the effect of AA versus PCC products on hemostatic efficacy, in-hospital mortality, 30-day mortality, and thrombotic events. Low-moderate risk of bias studies were meta-analyzed separately, as well as combined with high risk of bias studies. Eighteen comparative evaluations of AA versus PCC were identified. Twenty-eight percent of the studies (n = 5) had low-moderate risk and 72% (n = 13) had a high risk of bias. Studies with low-moderate risk of bias suggested improvements in hemostatic efficacy [Odds Ratio (OR) 2.72 (95% Confidence Interval (CI): 1.15-6.44); one study], lower in-hospital mortality [OR 0.48 (95% CI: 0.38-0.61); three studies], and reduced 30-day mortality [OR 0.49 (95% CI: 0.30-0.80); two studies] when AA was used versus PCC products. When studies were included regardless of the risk of bias, pooled effects showed improvements in hemostatic efficacy [OR 1.36 (95% CI: 1.01-1.84); 12 studies] and reductions in 30-day mortality [OR 0.53 (95% CI: 0.37-0.76); six studies] for AA versus PCC. The difference in thrombotic events with AA versus PCC was not statistically significant in the low-moderate, high, or combined risk of bias groups. The evidence from low-moderate quality real-world studies suggests that AA is superior to PCC in enhancing hemostatic efficacy and reducing in-hospital and 30-day mortality. When studies are assessed regardless of the risk of bias, the pooled hemostatic efficacy and 30-day mortality risk remain significantly better with AA versus PCC.

Hydrophobic residues in S1 modulate enzymatic function and voltage sensing in voltage-sensing phosphatase.

The voltage-sensing domain (VSD) is a four-helix modular protein domain that converts electrical signals into conformational changes, leading to open pores and active enzymes. In most voltage-sensing proteins, the VSDs do not interact with one another, and the S1-S3 helices are considered mainly scaffolding, except in the voltage-sensing phosphatase (VSP) and the proton channel (Hv). To investigate its contribution to VSP function, we mutated four hydrophobic amino acids in S1 to alanine (F127, I131, I134, and L137), individually or in combination. Most of these mutations shifted the voltage dependence of activity to higher voltages; however, not all substrate reactions were the same. The kinetics of enzymatic activity were also altered, with some mutations significantly slowing down dephosphorylation. The voltage dependence of VSD motions was consistently shifted to lower voltages and indicated a second voltage-dependent motion. Additionally, none of the mutations broke the VSP dimer, indicating that the S1 impact could stem from intra- and/or intersubunit interactions. Lastly, when the same mutations were introduced into a genetically encoded voltage indicator, they dramatically altered the optical readings, making some of the kinetics faster and shifting the voltage dependence. These results indicate that the S1 helix in VSP plays a critical role in tuning the enzyme's conformational response to membrane potential transients and influencing the function of the VSD.

Phylogeny, biogeography and ecological diversification of New Caledonian palms (Arecaceae).

BACKGROUND AND AIMS: The geographical origin and evolutionary mechanisms underpinning the rich and distinctive New Caledonian flora remain poorly understood. This is attributable to the complex geological past of the island and to the scarcity of well-resolved species-level phylogenies. Here, we infer phylogenetic relationships and divergence times of New Caledonian palms, which comprise 40 species. We use this framework to elucidate the biogeography of New Caledonian palm lineages and to explore how extant species might have formed. METHODS: A phylogenetic tree including 37 New Caledonian palm species and 77 relatives from tribe Areceae was inferred from 151 nuclear genes obtained by targeted sequencing. Fossil-calibrated divergence times were estimated and ancestral ranges inferred. Ancestral and extant ecological preferences in terms of elevation, precipitation and substrate were compared between New Caledonian sister species to explore their possible roles as drivers of speciation. KEY RESULTS: New Caledonian palms form four well-supported clades, inside which relationships are well resolved. Our results support the current classification but suggest that Veillonia and Campecarpus should be resurrected and fail to clarify whether Rhopalostylidinae is sister to or nested in Basseliniinae. New Caledonian palm lineages are derived from New Guinean and Australian ancestors, which reached the island through at least three independent dispersal events between the Eocene and Miocene. Palms then dispersed out of New Caledonia at least five times, mainly towards Pacific islands. Geographical and ecological transitions associated with speciation events differed across time and genera. Substrate transitions were more frequently associated with older events than with younger ones. CONCLUSIONS: Neighbouring areas and a mosaic of local habitats shaped the palm flora of New Caledonia, and the island played a significant role in generating palm diversity across the Pacific region. This new spatio-temporal framework will enable population-level ecological and genetic studies to unpick the mechanisms underpinning New Caledonian palm endemism.

A recently quenched galaxy 700 million years after the Big Bang.

Local and low-redshift (z < 3) galaxies are known to broadly follow a bimodal distribution: actively star-forming galaxies with relatively stable star-formation rates and passive systems. These two populations are connected by galaxies in relatively slow transition. By contrast, theory predicts that star formation was stochastic at early cosmic times and in low-mass systems1-4. These galaxies transitioned rapidly between starburst episodes and phases of suppressed star formation, potentially even causing temporary quiescence-so-called mini-quenching events5,6. However, the regime of star-formation burstiness is observationally highly unconstrained. Directly observing mini-quenched galaxies in the primordial Universe is therefore of utmost importance to constrain models of galaxy formation and transformation7,8. Early quenched galaxies have been identified out to redshift z < 5 (refs. 9-12) and these are all found to be massive (M⋆ > 1010 M⊙) and relatively old. Here we report a (mini-)quenched galaxy at z = 7.3, when the Universe was only 700 Myr old. The JWST/NIRSpec spectrum is very blue (U-V = 0.16 ± 0.03 mag) but exhibits a Balmer break and no nebular emission lines. The galaxy experienced a short starburst followed by rapid quenching; its stellar mass (4-6 × 108 M⊙) falls in a range that is sensitive to various feedback mechanisms, which can result in perhaps only temporary quenching.

High failure rate of 2-stage revision for the infected total elbow arthroplasty: a single institution's experience.

BACKGROUND: Despite 2-stage revision being a common treatment for elbow prosthetic joint infection (PJI), failure rates are high. The purpose of this study was to report on a single institution's experience with 2-stage revisions for elbow PJI and determine risk factors for failed eradication of infection. The secondary purpose was to determine risk factors for needing allograft bone at the second stage of revision in the setting of compromised bone stock. METHODS: We retrospectively analyzed all 2-stage revision total elbow arthroplasties (TEAs) performed for infection at a single institution between 2006 and 2020. Data collected included demographics and treatment course prior to, during, and after 2-stage revision. Radiographs obtained after explantation and operative reports were reviewed to evaluate for partial component retention and incomplete cement removal. The primary outcome was failed eradication of infection, defined as the need for repeat surgery to treat infection after the second-stage revision. The secondary outcome was the use of allograft for compromised bone stock during the second-stage revision. Risk factors for both outcomes were determined. RESULTS: Nineteen patients were included. Seven patients (37%) had either the humeral or ulnar component retained during the first stage, and 10 (53%) had incomplete removal of cement in either the humerus or ulna. Nine patients (47%) had allograft strut used during reimplantation and reconstruction. Nine patients (47%) failed to eradicate the infection after 2-stage revision. Demographic data were similar between the repeat-infection and nonrepeat-infection groups. Six patients (60%) with retained cement failed compared with 3 patients (33%) with full cement removal (P = .370). Two patients (29%) with a retained component failed compared to 7 patients (58%) with full component removal (P = .350). Allograft was used less frequently when a well-fixed component or cement was retained, with no patients with a retained component needing allograft compared to 9 with complete component removal (P = .003). Three patients (30%) with retained cement needed allograft, compared with 6 patients (67%) who had complete cement removal (P = .179). CONCLUSION: Nearly half of the patients failed to eradicate infection after 2-stage revision. The data did not demonstrate a clear association between retained cement or implants and risk of recurrent infection. Allograft was used less frequently when a component and cement were retained, possibly serving as a proxy for decreased bone loss during the first stage of revision. Therefore, the unclear benefit of removing well-fixed components and cement need to be carefully considered as it likely leads to compromised bone stock that complicates the second stage of revision.

Repeated upslope biome shifts in Saxifraga during late-Cenozoic climate cooling.

Mountains are among the most biodiverse places on Earth, and plant lineages that inhabit them have some of the highest speciation rates ever recorded. Plant diversity within the alpine zone - the elevation above which trees cannot grow-contributes significantly to overall diversity within mountain systems, but the origins of alpine plant diversity are poorly understood. Here, we quantify the processes that generate alpine plant diversity and their changing dynamics through time in Saxifraga (Saxifragaceae), an angiosperm genus that occurs predominantly in mountain systems. We present a time-calibrated molecular phylogenetic tree for the genus that is inferred from 329 low-copy nuclear loci and incorporates 73% (407) of known species. We show that upslope biome shifts into the alpine zone are considerably more prevalent than dispersal of alpine specialists between regions, and that the rate of upslope biome shifts increased markedly in the last 5 Myr, a timeframe concordant with a cooling and fluctuating climate that is likely to have increased the extent of the alpine zone. Furthermore, alpine zone specialists have lower speciation rates than generalists that occur inside and outside the alpine zone, and major speciation rate increases within Saxifraga significantly pre-date increased rates of upslope biome shifts. Specialisation to the alpine zone is not therefore associated with speciation rate increases. Taken together, this study presents a quantified and broad scale perspective of processes underpinning alpine plant diversity.

Agreement between 30-day and 90-day modified Rankin Scale score and utility-weighted modified Rankin Scale score in acute intracerebral hemorrhage: An analysis of ATACH-2 trial data.

The relationship between 30- and 90-day modified Rankin Scale (mRS) scores in intracerebral hemorrhage (ICH) patients was evaluated. This post hoc cohort analysis of the ATACH-2 trial included patients with acute ICH who were alive at 30 days and who had mRS scores reported at 30 and 90 days. The mRS score was then converted to a utility (EuroQol-5 Dimension-3 Level [EQ-5D-3L])-weighted mRS score. After adjustment of 30-day mRS score for key covariates using multivariable ordinal regression, the relationship between 30-day and observed 90-day functional outcome was assessed via absolute difference in the utility-weighted version. Of the 1000 trial subjects, 898 met inclusion criteria. This low-moderate severity ICH cohort had a median baseline GCS score of 15 and median hematoma volume of 9.7 mL. Observed 30-day mRS had the largest association with observed 90-day values (χ2 = 302.9, p < 0.0001). Patients generally either maintained the same mRS scores between 30 and 90 days (48 %) or experienced a 1-point (32 %) or 2-point (10 %) improvement by 90 days. The mean ± standard deviation (SD) EQ-5D-3L at 90 days was 0.67 ± 0.26. Following adjustment, the mean absolute difference between predicted and observed utility-weighted 90-day mRS scores was 0.006 ± 0.13 points and less than the estimated minimal clinically important difference of 0.13 points. The difference in average utility-weighted mRS scores at 30 and 90 days was not clinically relevant, suggesting 30-day score may be a reasonable proxy for 90-day values in patients with ICH when 90-day values are not available.

The origin and speciation of orchids.

Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation.

A small and vigorous black hole in the early Universe.

Several theories have been proposed to describe the formation of black hole seeds in the early Universe and to explain the emergence of very massive black holes observed in the first thousand million years after the Big Bang1-3. Models consider different seeding and accretion scenarios4-7, which require the detection and characterization of black holes in the first few hundred million years after the Big Bang to be validated. Here we present an extensive analysis of the JWST-NIRSpec spectrum of GN-z11, an exceptionally luminous galaxy at z = 10.6, revealing the detection of the [NeIV]λ2423 and CII*λ1335 transitions (typical of active galactic nuclei), as well as semi-forbidden nebular lines tracing gas densities higher than 109 cm-3, typical of the broad line region of active galactic nuclei. These spectral features indicate that GN-z11 hosts an accreting black hole. The spectrum also reveals a deep and blueshifted CIVλ1549 absorption trough, tracing an outflow with velocity 800-1,000 km s-1, probably driven by the active galactic nucleus. Assuming local virial relations, we derive a black hole mass of log ( M BH / M ⊙ ) = 6.2 ± 0.3 , accreting at about five times the Eddington rate. These properties are consistent with both heavy seeds scenarios and scenarios considering intermediate and light seeds experiencing episodic super-Eddington phases. Our finding explains the high luminosity of GN-z11 and can also provide an explanation for its exceptionally high nitrogen abundance.