383 research outputs found

    Personhood, consciousness, and god : how to be a proper pantheist

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    © Springer Nature B.V. 2018In this paper I develop a theory of personhood which leaves open the possibility of construing the universe as a person. If successful, it removes one bar to endorsing pantheism. I do this by examining a rising school of thought on personhood, on which persons, or selves, are understood as identical to episodes of consciousness. Through a critique of this experiential approach to personhood, I develop a theory of self as constituted of qualitative mental contents, but where these contents are also capable of unconscious existence. On this theory, though we can be conscious of our selves, consciousness turns out to be inessential to personhood. This move, I then argue, provides resources for responding to the pantheist’s problem of God’s person.Peer reviewedFinal Accepted Versio

    Barriers and progress in the treatment of low back pain

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    Low back pain is a common and costly condition and for most people is likely to be a recurrent problem throughout their lifetime. The management of patients with low back pain has been positively influenced by the rise in high quality clinical trials and systematic reviews in recent decades, and this body of evidence, synthesized in many clinical practice guidelines, has improved our knowledge about which treatments for low back pain are useful and which are not. For the largest group of patients, those with non-specific low back pain for whom a clear diagnosis cannot be given, the reality is that the treatments we have to offer tend to produce small effects, often only in the short term and none appear to effectively change long-term prognosis. This commentary summarizes the array of treatments currently available, notes the results of recent trials and guidelines and considers alternative approaches that may prove more valuable in achieving better patient outcomes in the future

    Staphylococcus aureus Protein A Binds to Osteoblasts and Triggers Signals That Weaken Bone in Osteomyelitis

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    Osteomyelitis is a debilitating infectious disease of the bone. It is predominantly caused by S. aureus and is associated with significant morbidity and mortality. It is characterised by weakened bones associated with progressive bone loss. Currently the mechanism through which either bone loss or bone destruction occurs in osteomyelitis patients is poorly understood. We describe here for the first time that the major virulence factor of S. aureus, protein A (SpA) binds directly to osteoblasts. This interaction prevents proliferation, induces apoptosis and inhibits mineralisation of cultured osteoblasts. Infected osteoblasts also increase the expression of RANKL, a key protein involved in initiating bone resorption. None of these effects was seen in a mutant of S. aureus lacking SpA. Complementing the SpA-defective mutant with a plasmid expressing spa or using purified protein A resulted in attachment to osteoblasts, inhibited proliferation and induced apoptosis to a similar extent as wildtype S. aureus. These events demonstrate mechanisms through which loss of bone formation and bone weakening may occur in osteomyelitis patients. This new information may pave the way for the development of new and improved therapeutic agents to treat this disease

    The SAR11 Group of Alpha-Proteobacteria Is Not Related to the Origin of Mitochondria

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    Although free living, members of the successful SAR11 group of marine alpha-proteobacteria contain a very small and A+T rich genome, two features that are typical of mitochondria and related obligate intracellular parasites such as the Rickettsiales. Previous phylogenetic analyses have suggested that Candidatus Pelagibacter ubique, the first cultured member of this group, is related to the Rickettsiales+mitochondria clade whereas others disagree with this conclusion. In order to determine the evolutionary position of the SAR11 group and its relationship to the origin of mitochondria, we have performed phylogenetic analyses on the concatenation of 24 proteins from 5 mitochondria and 71 proteobacteria. Our results support that SAR11 group is not the sistergroup of the Rickettsiales+mitochondria clade and confirm that the position of this group in the alpha-proteobacterial tree is strongly affected by tree reconstruction artefacts due to compositional bias. As a consequence, genome reduction and bias toward a high A+T content may have evolved independently in the SAR11 species, which points to a different direction in the quest for the closest relatives to mitochondria and Rickettsiales. In addition, our analyses raise doubts about the monophyly of the newly proposed Pelagibacteraceae family

    Binary and Millisecond Pulsars at the New Millennium

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    We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

    Future therapeutic targets in rheumatoid arthritis?

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    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

    Ecological Implications of Extreme Events: Footprints of the 2010 Earthquake along the Chilean Coast

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    Deciphering ecological effects of major catastrophic events such as earthquakes, tsunamis, volcanic eruptions, storms and fires, requires rapid interdisciplinary efforts often hampered by a lack of pre-event data. Using results of intertidal surveys conducted shortly before and immediately after Chile's 2010 Mw 8.8 earthquake along the entire rupture zone (ca. 34–38°S), we provide the first quantification of earthquake and tsunami effects on sandy beach ecosystems. Our study incorporated anthropogenic coastal development as a key design factor. Ecological responses of beach ecosystems were strongly affected by the magnitude of land-level change. Subsidence along the northern rupture segment combined with tsunami-associated disturbance and drowned beaches. In contrast, along the co-seismically uplifted southern rupture, beaches widened and flattened increasing habitat availability. Post-event changes in abundance and distribution of mobile intertidal invertebrates were not uniform, varying with land-level change, tsunami height and coastal development. On beaches where subsidence occurred, intertidal zones and their associated species disappeared. On some beaches, uplift of rocky sub-tidal substrate eliminated low intertidal sand beach habitat for ecologically important species. On others, unexpected interactions of uplift with man-made coastal armouring included restoration of upper and mid-intertidal habitat seaward of armouring followed by rapid colonization of mobile crustaceans typical of these zones formerly excluded by constraints imposed by the armouring structures. Responses of coastal ecosystems to major earthquakes appear to vary strongly with land-level change, the mobility of the biota and shore type. Our results show that interactions of extreme events with human-altered shorelines can produce surprising ecological outcomes, and suggest these complex responses to landscape alteration can leave lasting footprints in coastal ecosystems

    A Phylometagenomic Exploration of Oceanic Alphaproteobacteria Reveals Mitochondrial Relatives Unrelated to the SAR11 Clade

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    BACKGROUND: According to the endosymbiont hypothesis, the mitochondrial system for aerobic respiration was derived from an ancestral Alphaproteobacterium. Phylogenetic studies indicate that the mitochondrial ancestor is most closely related to the Rickettsiales. Recently, it was suggested that Candidatus Pelagibacter ubique, a member of the SAR11 clade that is highly abundant in the oceans, is a sister taxon to the mitochondrial-Rickettsiales clade. The availability of ocean metagenome data substantially increases the sampling of Alphaproteobacteria inhabiting the oxygen-containing waters of the oceans that likely resemble the originating environment of mitochondria. METHODOLOGY/PRINCIPAL FINDINGS: We present a phylogenetic study of the origin of mitochondria that incorporates metagenome data from the Global Ocean Sampling (GOS) expedition. We identify mitochondrially related sequences in the GOS dataset that represent a rare group of Alphaproteobacteria, designated OMAC (Oceanic Mitochondria Affiliated Clade) as the closest free-living relatives to mitochondria in the oceans. In addition, our analyses reject the hypothesis that the mitochondrial system for aerobic respiration is affiliated with that of the SAR11 clade. CONCLUSIONS/SIGNIFICANCE: Our results allude to the existence of an alphaproteobacterial clade in the oxygen-rich surface waters of the oceans that represents the closest free-living relative to mitochondria identified thus far. In addition, our findings underscore the importance of expanding the taxonomic diversity in phylogenetic analyses beyond that represented by cultivated bacteria to study the origin of mitochondria

    Evaluation of a Theory-Informed Implementation Intervention for the Management of Acute Low Back Pain in General Medical Practice: The IMPLEMENT Cluster Randomised Trial

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    Introduction: This cluster randomised trial evaluated an intervention to decrease x-ray referrals and increase giving advice to stay active for people with acute low back pain (LBP) in general practice. Methods: General practices were randomised to either access to a guideline for acute LBP (control) or facilitated interactive workshops (intervention). We measured behavioural predictors (e.g. knowledge, attitudes and intentions) and fear avoidance beliefs. We were unable to recruit sufficient patients to measure our original primary outcomes so we introduced other outcomes measured at the general practitioner (GP) level: behavioural simulation (clinical decision about vignettes) and rates of x-ray and CT-scan (medical administrative data). All those not involved in the delivery of the intervention were blinded to allocation. Results: 47 practices (53 GPs) were randomised to the control and 45 practices (59 GPs) to the intervention. The number of GPs available for analysis at 12 months varied by outcome due to missing confounder information; a minimum of 38 GPs were available from the intervention group, and a minimum of 40 GPs from the control group. For the behavioural constructs, although effect estimates were small, the intervention group GPs had greater intention of practising consistent with the guideline for the clinical behaviour of x-ray referral. For behavioural simulation, intervention group GPs were more likely to adhere to guideline recommendations about x-ray (OR 1.76, 95%CI 1.01, 3.05) and more likely to give advice to stay active (OR 4.49, 95%CI 1.90 to 10.60). Imaging referral was not statistically significantly different between groups and the potential importance of effects was unclear; rate ratio 0.87 (95%CI 0.68, 1.10) for x-ray or CT-scan. Conclusions: The intervention led to small changes in GP intention to practice in a manner that is consistent with an evidence-based guideline, but it did not result in statistically significant changes in actual behaviour. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN01260600009853
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