Relics of Supermassive Black Hole Seeds: The Discovery of an Accreting Black Hole in an Optically Normal, Low Metallicity Dwarf Galaxy

The detection and characterization of supermassive black holes (SMBHs) in local low mass galaxies is crucial to our understanding of the origins of SMBHs. This statement assumes that low mass galaxies have had a relatively quiet cosmic history, so that their black holes have not undergone significant growth and therefore can be treated as relics of the original SMBH seeds. While recent studies have found optical signatures of active galactic nuclei (AGNs) in a growing population of dwarf galaxies, these studies are biased against low metallicity and relatively merger-free galaxies, thus missing precisely the demographic in which to search for the relics of SMBH seeds. Here, we report the detection of the [\ion{Si}{6}]1.963~$\mu$m coronal line (CL), a robust indicator of an AGN in the galaxy SDSS~J160135.95+311353.7, a nearby ($z=0.031$) low metallicity galaxy with a stellar mass approximately an order of magnitude lower than the LMC ($M_*\approx10^{8.56}$~M$_\odot$) and no optical evidence for an AGN. The AGN bolometric luminosity implied by the CL detection is $\approx10^{42}$~erg~s$^{-1}$, precisely what is predicted from its near-infrared continuum emission based on well-studied AGNs. Our results are consistent with a black hole of mass $\approx~10^5$~M$_\odot$, in line with expectations based on its stellar mass. This is the first time a near-infrared CL has been detected in a low mass, low metallicity galaxy with no optical evidence for AGN activity, providing confirmation of the utility of infrared CLs in finding AGNs in low mass galaxies when optical diagnostics fail. These observations highlight a powerful avenue of investigation to hunt for low mass black holes in the JWST era.Comment: 11 pages, 3 figures, accepted to ApJ

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Instrument selection for the ASAS core outcome set for axial spondyloarthritis

OBJECTIVES: To define the instruments for the Assessment of SpondyloArthritis international Society-Outcomes Measures in Rheumatology (ASAS-OMERACT) core domain set for axial spondyloarthritis (axSpA). METHODS: An international working group representing key stakeholders selected the core outcome instruments following a predefined process: (1) identifying candidate instruments using a systematic literature review; (2) reducing the list of candidate instruments by the working group, (3) assessing the instruments' psychometric properties following OMERACT filter 2.2, (4) selection of the core instruments by the working group and (5) voting and endorsement by ASAS. RESULTS: The updated core set for axSpA includes seven instruments for the domains that are mandatory for all trials: Ankylosing Spondylitis Disease Activity Score and Numerical Rate Scale (NRS) patient global assessment of disease activity, NRS total back pain, average NRS of duration and severity of morning stiffness, NRS fatigue, Bath Ankylosing Spondylitis Function Index and ASAS Health Index. There are 9 additional instruments considered mandatory for disease-modifying antirheumatic drugs (DMARDs) trials: MRI activity Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joints and SPARCC spine, uveitis, inflammatory bowel disease and psoriasis assessed as recommended by ASAS, 44 swollen joint count, Maastricht Ankylosing Spondylitis Enthesitis Score, dactylitis count and modified Stoke Ankylosing Spondylitis Spinal Score. The imaging outcomes are considered mandatory to be included in at least one trial for a drug tested for properties of DMARD. Furthermore, 11 additional instruments were also endorsed by ASAS, which can be used in axSpA trials on top of the core instruments. CONCLUSIONS: The selection of the instruments for the ASAS-OMERACT core domain set completes the update of the core outcome set for axSpA, which should be used in all trials

Efeitos adversos do uso contínuo e irracional dos Inibidores de Bomba de Prótons em idosos: Adverse effects of continuous and irrational use of Proton Inhibitors in the elderly

O presente trabalho teve por objetivo avaliar os principais efeitos adversos do uso irracional dos Inibidores da Bomba de Prótons (IBPs) na população idosa a fim de compreender as principais alterações geradas no organismo pelo uso habitual dessa classe de medicamentos. Sabe-se que, os avanços tecnológicos e em saúde propiciaram o aumento na qualidade e expectativa de vida da população ao redor do mundo, culminando na elevação exponencial de idosos. Diante disso, com o avanço da idade é comum o aparecimento de patologias, entre elas as gastrointestinais, que têm a sintomatologia tratada por IBPs. Entretanto, estudos evidenciam a relação entre o uso indevido e prolongado de IBPs e prejuízos à saúde dessa população como a ocorrência de lesão renal, hipovitaminose, riscos cardiovasculares e demências. Portanto, é necessária uma avaliação do uso desses fármacos, com o viés de serem indicados apenas com finalidade terapêutica ou profilática, ressaltando a relevância do uso por período recomendado por especialistas. Dito isso, reforça-se a importância do planejamento e da execução de ações que possibilitem o uso apropriado de IBPs, além do desenvolvimento de novas pesquisas que possibilitem a oferta de outros fármacos com o mesmo objetivo terapêutico, porém com menores efeitos adversos

Enhancing cooperative responses by regional fisheries management organisations to climate-driven redistribution of tropical Pacific tuna stocks

Climate change is predicted to alter the distributions of tropical tuna stocks in the Pacific Ocean. Recent modelling projects significant future shifts in tuna biomass from west to east, and from national jurisdictions to high seas areas. As the distributions of these stocks change, the relevant regional fisheries management organisations (RFMOs)—the Western and Central Pacific Fisheries Commission (WCPFC) and the Inter-American Tropical Tuna Commission (IATTC)—will need to develop an expanded framework for cooperation and collaboration to fulfil their conservation and management responsibilities under international law. The key elements of a possible expanded framework for cooperation can be developed, and fundamental areas for collaboration identified, by applying and adapting principles established in the United Nations Convention on the Law of the Sea, the United Nations Fish Stocks Agreement, and the constituent instruments of the RFMOs themselves. Our analysis reveals a wide range of important issues requiring cooperation, and three clear priorities. First, a formal mechanism for cooperation is needed to enable effective and efficient decision-making and action by the two RFMOs on key issues. Second, further cooperation is required in scientific research and modelling to better understand the biology and distributions of Pacific tuna stocks and how they will respond to climate change, and to inform stock assessments and harvest strategies. Third, the RFMOs must cooperate to define appropriate limits on fishing for each stock in a way that ensures they are compatible across the two organisations, taking into account their different members and management regimes

Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens

This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility

Alignment of the ALICE Inner Tracking System with cosmic-ray tracks

37 pages, 15 figures, revised version, accepted by JINSTALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 micron in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10^5 charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.Peer reviewe