Constraints on the thermal evolution of metamorphic core complexes from the timing of high-pressure metamorphism on Naxos, Greece

Metamorphic core complexes are classically interpreted to have formed during crustal extension, although many also occur in compressional environments. New U–(Th)–Pb allanite and xenotime geochronologic data from the structurally highest Zas Unit (Cycladic Blueschist Unit) of the Naxos metamorphic core complex, Greece, integrated with pressure–temperature–time (P–T–t) histories, are incorporated into a thermal model to test the role of crustal thickening and extension in forming metamorphic core complexes. Metamorphism on Naxos is diachronous, with peak metamorphic conditions propagating down structural section over a ~30–35 m.y. period, from ca. 50 Ma to 15 Ma. At the highest structural level, the Zas Unit records blueschist-facies metamorphism (~14.5–19 kbar, 470–570 °C) at ca. 50 Ma, during northeast-directed subduction of the Adriatic continental margin. The Zas Unit was subsequently extruded toward the SW and thrust over more proximal continental margin and basement rocks (Koronos and Core units). This contractional episode resulted in crustal thickening and Barrovian metamorphism from ca. 40 Ma and reached peak kyanite-sillimanite–grade conditions of ~10–5 kbar and 600–730 °C at 20–15 Ma. Model P–T–t paths, assuming conductive relaxation of isotherms following overthrusting, are consistent with the clockwise P–T–t evolution. In contrast, extension results in exhumation and cooling of the crust, which is inconsistent with key components of the thermal evolution. Barrovian metamorphism on Naxos is therefore interpreted to have resulted from crustal thickening over a ~30–35 m.y. time period prior to extension, normal faulting, and rapid exhumation after a thermal climax at ca. 15 Ma

Developing a core outcome set for periodontal trials

Acknowledgments The authors wish to thank all patients and professionals who took part in the Delphi process and face-to-face consensus meeting. We wish to thank Jillian Sutherland, Shirley Bell, Margaret Mooney and Lorna Barnsley for helping to organise the face-to-face consensus meeting. Patient participant recruitment to this study was facilitated by SHARE–the Scottish Health Research Register. SHARE is supported by NHS Research Scotland and the Chief Scientists Office Funding: TL received research funding for the core outcome set development for the prevention and management of periodontal diseases which was provided by the Tattershall fund, Dundee Dental School. This grant provided funds for the e-Delphi software, SHARE services and the face-to-face consensus meeting travel and catering costs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

UBA1/GARS-dependent pathways drive sensory-motor connectivity defects in spinal muscular atrophy

Deafferentation of motor neurons as a result of defective sensory-motor connectivity is a critical early event in the pathogenesis of spinal muscular atrophy, but the underlying molecular pathways remain unknown. We show that restoration of ubiquitin-like modifier-activating enzyme 1 (UBA1) was sufficient to correct sensory-motor connectivity in the spinal cord of mice with spinal muscular atrophy. Aminoacyl-tRNA synthetases, including GARS, were identified as downstream targets of UBA1. Regulation of GARS by UBA1 occurred via a non-canonical pathway independent of ubiquitylation. Dysregulation of UBA1/GARS pathways in spinal muscular atrophy mice disrupted sensory neuron fate, phenocopying GARS-dependent defects associated with Charcot-Marie-Tooth disease. Sensory neuron fate was corrected following restoration of UBA1 expression and UBA1/GARS pathways in spinal muscular atrophy mice. We conclude that defective sensory motor connectivity in spinal muscular atrophy results from perturbations in a UBA1/GARS pathway that modulates sensory neuron fate, thereby highlighting significant molecular and phenotypic overlap between spinal muscular atrophy and Charcot-Marie-Tooth disease.</p

Core outcomes in periodontal trials:study protocol for core outcome set development

Abstract Background There are a large number of clinical outcome measures used to assess the effectiveness of prevention and management strategies of periodontal diseases. This heterogeneity causes difficulties when trying to synthesise data for systematic reviews or clinical guidelines, reducing their impact. Core outcome sets are an agreed, standardised list of outcomes that should be measured and reported in all trials in specific clinical areas. We aim to develop a core outcome set for effectiveness trials investigating the prevention and management of periodontal disease in primary or secondary care. Methods To identify existing outcomes we screened the Cochrane systematic reviews and their included studies on the prevention and management of periodontal diseases. The core outcome set will be defined by consensus of key stakeholders using an online e-Delphi process and face-to-face meeting. Key stakeholders involved in the development will include: patients, dentists, hygienists/therapists, specialists, clinical researchers and policy-makers. Stakeholders will be asked to prioritise outcomes and feedback will be provided in the next round(s). Stakeholders will have an opportunity to add outcomes found in the Cochrane review screening process at the end of the first round. If consensus is not reached after the second round we will provide feedback prior to a third round. Remaining outcomes will be discussed at a face-to-face meeting and agreement will be measured via defined consensus rules of outcome inclusion. Discussion The inclusive consensus process should provide a core outcome set that is relevant to all key stakeholders. We will actively disseminate our findings to help improve clinical trials, systematic reviews and clinical guidelines with the ultimate aim of improving the prevention and management of periodontal diseases. Trial registration COMET ( http://www.comet-initiative.org/studies/details/265?result=true ). Registered on August 2012

The influence of marketing on the sports betting attitudes and consumption behaviours of young men: Implications for harm reduction and prevention strategies

Background: Gambling can cause significant health and social harms for individuals, their families, and communities. While many studies have explored the individual factors that may lead to and minimise harmful gambling, there is still limited knowledge about the broader range of factors that may contribute to gambling harm. There are significant regulations to prevent the marketing of some forms of gambling but comparatively limited regulations relating to the marketing of newer forms of online gambling such as sports betting. There is a need for better information about how marketing strategies may be shaping betting attitudes and behaviours and the range of policy and regulatory responses that may help to prevent the risky or harmful consumption of these products. Methods: We conducted qualitative, semi-structured interviews with 50 Australian men (aged 20-37 years) who gambled on sports. We explored their attitudes and opinions regarding sports betting marketing, the embedding of marketing within sports and other non-gambling community environments, and the implications this had for the normalisation of betting. Results: Our findings indicate that most of the environments in which participants reported seeing or hearing betting advertisements were not in environments specifically designed for betting. Participants described that the saturation of marketing for betting products, including through sports-based commentary and sports programming, normalised betting. Participants described that the inducements offered by the industry were effective marketing strategies in getting themselves and other young men to bet on sports. Inducements were also linked with feelings of greater control over betting outcomes and stimulated some individuals to sign up with more than one betting provider. Conclusions: This research suggests that marketing plays a strong role in the normalisation of gambling in sports. This has the potential to increase the risks and subsequent harms associated with these products. Legislators must begin to consider the cultural lag between an evolving gambling landscape, which supports sophisticated marketing strategies, and effective policies and practices which aim to reduce and prevent gambling harm. © 2017 The Author(s)

The mitochondrial protein Sideroflexin 3 (SFXN3) influences neurodegeneration pathways in vivo

Synapses are a primary pathological target in neurodegenerative diseases. Identifying therapeutic targets at the synapse could delay progression of numerous conditions. The mitochondrial protein SFXN3 is a neuronally-enriched protein expressed in synaptic terminals and regulated by key synaptic proteins, including α-synuclein. We first show that SFXN3 uses the carrier import pathway to insert into the inner mitochondrial membrane. Using high-resolution proteomics on Sfxn3-KO mice synapses, we then demonstrate that SFXN3 influences proteins and pathways associated with neurodegeneration and cell death (including CSPα and Caspase-3), as well as neurological conditions (including Parkinson’s disease and Alzheimer’s disease). Over-expression of SFXN3 orthologues in Drosophila models of Parkinson’s Disease significantly reduced dopaminergic neuron loss. In contrast, the loss of SFXN3 was insufficient to trigger neurodegeneration in mice, indicating an anti- rather than pro-neurodegeneration role for SFXN3. Taken together, these results suggest a potential role for SFXN3 in the regulation of neurodegeneration pathways

The age, origin and emplacement of the Tsiknias Ophiolite, Tinos, Greece

The Tsiknias Ophiolite, exposed at the highest structural levels of Tinos, Greece, represents a thrust sheet of Tethyan oceanic crust and upper mantle emplaced onto the Attic‐Cycladic Massif. We present new field observations and a new geological map of Tinos, integrated with petrology, THERMOCALC phase diagram modelling, U–Pb geochronology and whole rock geochemistry, resulting in a tectono‐thermal model that describes the formation and emplacement of the Tsiknias Ophiolite and newly identified underlying metamorphic sole. The ophiolite comprises a succession of partially dismembered and structurally repeated ultramafic and gabbroic rocks that represent the Moho Transition Zone. A plagiogranite dated by U‐Pb zircon at 161.9 ± 2.8 Ma, reveals that the Tsiknias Ophiolite formed in a supra‐subduction zone setting, comparable to the “East‐Vardar Ophiolites”, and was intruded by gabbros at 144.4 ± 5.6 Ma. Strongly sheared metamorphic sole rocks show a condensed and inverted metamorphic gradient, from partially anatectic amphibolites at P–T conditions of ca. 8.5 kbar 850‐600 °C, down‐structural section to greenschist‐facies oceanic metasediments over ~250 m. Leucosomes generated by partial melting of the uppermost sole amphibolite, yielded a U–Pb zircon protolith age of ca. 190 Ma and a high‐grade metamorphic‐anatectic age of 74.0 ± 3.5 Ma associated with ophiolite emplacement. The Tsiknias Ophiolite was therefore obducted ~90 Myrs after it formed during initiation of a NE‐dipping intra‐oceanic subduction zone to the northeast of the Cyclades that coincides with Africa's plate motion changing from transcurrent to convergent. Continued subduction resulted in high‐pressure metamorphism of the Cycladic continental margin ~25 Myrs later

Betting is loving and bettors are predators: a conceptual metaphor approach to online sports betting advertising

The legalisation of online gambling in multiple territories has caused a growth in the exposure of consumers to online sports betting (OSB) advertising. While some efforts have been made to understand the visible structure of betting promotional messages, little is known about the latent components of OSB advertisements. The present study sought to address this issue by examining the metaphorical conceptualisation of OSB advertising. A sample of Spanish and British television OSB advertisements from 2014 to 2016 was analysed (N = 133). Following Lakoff and Johnson’s conceptual metaphor theory, four main structural metaphors that shaped how OSB advertising can be understood were identified: betting as (1) an act of love, (2) a market, (3) a sport, and (4) a natural environment. In general, these metaphors, which were found widely across 29 different betting brands, facilitated the perception of bettors as active players, with an executive role in the sport events bet upon, and greater control over bet outcomes

Compressional origin of the Naxos metamorphic core complex, Greece: structure, petrography, and thermobarometry

The island of Naxos, Greece, has been previously considered to represent a Cordilleran-style metamorphic core complex that formed during Cenozoic extension of the Aegean Sea. Although lithospheric extension has undoubtedly occurred in the region since 10 Ma, the geodynamic history of older, regional-scale, kyanite- and sillimanite-grade metamorphic rocks exposed within the core of the Naxos dome is controversial. Specifically, little is known about the pre-extensional prograde evolution and the relative timing of peak metamorphism in relation to the onset of extension. In this work, new structural mapping is presented and integrated with petrographic analyses and phase equilibrium modeling of blueschists, kyanite gneisses, and anatectic sillimanite migmatites. The kyanite-sillimanite−grade rocks within the core complex record a complex history of burial and compression and did not form under crustal extension. Deformation and metamorphism were diachronous and advanced down the structural section, resulting in the juxtaposition of several distinct tectono-stratigraphic nappes that experienced contrasting metamorphic histories. The Cycladic Blueschists attained ∼14.5 kbar and 470 °C during attempted northeast-directed subduction of the continental margin. These were subsequently thrusted onto the more proximal continental margin, resulting in crustal thickening and regional metamorphism associated with kyanite-grade conditions of ∼10 kbar and 600−670 °C. With continued shortening, the deepest structural levels underwent kyanite-grade hydrous melting at ∼8−10 kbar and 680−750 °C, followed by isothermal decompression through the muscovite dehydration melting reaction to sillimanite-grade conditions of ∼5−6 kbar and 730 °C. This decompression process was associated with top-to-the-NNE shearing along passive-roof faults that formed because of SW-directed extrusion. These shear zones predated crustal extension, because they are folded around the migmatite dome and are crosscut by leucogranites and low-angle normal faults. The migmatite dome formed at lower-pressure conditions under horizontal constriction that caused vertical boudinage and upright isoclinal folds. The switch from compression to extension occurred immediately following doming and was associated with NNE-SSW horizontal boudinage and top-to-the-NNE brittle-ductile normal faults that truncate the internal shear zones and earlier collisional features. The Naxos metamorphic core complex is interpreted to have formed via crustal thickening, regional metamorphism, and partial melting in a compressional setting, here termed the Aegean orogeny, and it was exhumed from the midcrust due to the switch from compression to extension at ca. 15 Ma