The Growing Block’s past problems

The Growing-Block view of time has some problems with the past. It is committed to the existence of the past, but needs to say something about the difference between the past and present. I argue that we should resist Correia and Rosenkranz’ (Oxford studies in metaphysics, vol 8, pp 333–350, 2013) response to Braddon-Mitchell’s (Analysis 64:199–203, 2004) argument that the Growing-Block leads to scepticism about whether we are present. I consider an approach, similar to Peter Forrest (Analysis 64:358–362, 2004), and show it is not so counter-intuitive as Braddon-Mitchell suggests and further show that it requires no ‘semantic and metaphysical gymnastics’, as Chris Heathwood (Analysis 65:249–251, 2005) has suggested. In doing these things I make the problem of the past on the Growing-Block view a problem in its history, not its present

Systematic analysis of the literature in search of defining systemic sclerosis subsets

OBJECTIVE: Systemic sclerosis (SSc) is a multisystem disease with heterogeneity in presentation and prognosis. An international collaboration to develop new SSc subset criteria is underway. Our objectives were to identify systems of SSc subset classification and synthesize novel concepts to inform development of new criteria. METHODS: Medline, Cochrane MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Web of Science were searched from their inceptions to December 2019 for studies related to SSc subclassification, limited to humans and without language or sample size restrictions. RESULTS: Of 5686 citations, 102 studies reported original data on SSc subsets. Subset classification systems relied on extent of skin involvement and/or SSc-specific autoantibodies (n = 61), nailfold capillary patterns (n = 29), and molecular, genomic, and cellular patterns (n = 12). While some systems of subset classification confer prognostic value for clinical phenotype, severity, and mortality, only subsetting by gene expression signatures in tissue samples has been associated with response to therapy. CONCLUSION: Subsetting on extent of skin involvement remains important. Novel disease attributes including SSc-specific autoantibodies, nailfold capillary patterns, and tissue gene expression signatures have been proposed as innovative means of SSc subsetting

Familial Linkage between Neuropsychiatric Disorders and Intellectual Interests

From personality to neuropsychiatric disorders, individual differences in brain function are known to have a strong heritable component. Here we report that between close relatives, a variety of neuropsychiatric disorders covary strongly with intellectual interests. We surveyed an entire class of high-functioning young adults at an elite university for prospective major, familial incidence of neuropsychiatric disorders, and demographic and attitudinal questions. Students aspiring to technical majors (science/mathematics/engineering) were more likely than other students to report a sibling with an autism spectrum disorder (p = 0.037). Conversely, students interested in the humanities were more likely to report a family member with major depressive disorder (p = 8.8×10−4), bipolar disorder (p = 0.027), or substance abuse problems (p = 1.9×10−6). A combined PREdisposition for Subject MattEr (PRESUME) score based on these disorders was strongly predictive of subject matter interests (p = 9.6×10−8). Our results suggest that shared genetic (and perhaps environmental) factors may both predispose for heritable neuropsychiatric disorders and influence the development of intellectual interests

A randomised, double-blind, placebo-controlled phase 3 study of lenabasum in diffuse cutaneous systemic sclerosis: RESOLVE-1 design and rationale

OBJECTIVES: The multi-systemic, heterogenous nature of diffuse cutaneous systemic sclerosis (dcSSc) presents challenges in designing clinical studies that can demonstrate a treatment effect on overall disease burden. We describe the design of the first Phase 3 study in dcSSc patients where the American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score was chosen prospectively as the primary outcome. The CRISS measures key clinical disease parameters and patient-reported outcomes (PROs). METHODS: RESOLVE-1 is a Phase 3, randomised, double-blind, placebo-controlled trial of dcSSc patients evaluating the efficacy and safety of lenabasum. Patients ≥18 years of age with dc-SSc and disease duration ≤6 years were eligible. Patients could continue stable background therapy for dcSSc, including stable immunosuppressive therapies. They were randomised to lenabasum 5 or 20 mg twice daily or placebo. The primary efficacy outcome was the mean change from baseline to 52 weeks in the ACR CRISS score. RESULTS: The study enrolled 365 patients over 1.5 years at 77 sites in 13 countries in North America, Europe, Israel, and Asia-Pacific, with the last patient first visit on May 1, 2019. CONCLUSIONS: RESOLVE-1 is the first Phase 3 interventional study to date in dcSSc to prospectively use the ACR CRISS as the primary efficacy outcome. Eligibility criteria allowed background therapy as might occur in clinical practice. This approach also facilitated timely patient enrolment. RESOLVE-1 provides a novel study design that may be used for future Phase 3 dcSSc studies to assess the holistic efficacy of therapy

Attachment styles and personal growth following romantic breakups: The mediating roles of distress, rumination, and tendency to rebound

© 2013 Marshall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.The purpose of this research was to examine the associations of attachment anxiety and avoidance with personal growth following relationship dissolution, and to test breakup distress, rumination, and tendency to rebound with new partners as mediators of these associations. Study 1 (N = 411) and Study 2 (N = 465) measured attachment style, breakup distress, and personal growth; Study 2 additionally measured ruminative reflection, brooding, and proclivity to rebound with new partners. Structural equation modelling revealed in both studies that anxiety was indirectly associated with greater personal growth through heightened breakup distress, whereas avoidance was indirectly associated with lower personal growth through inhibited breakup distress. Study 2 further showed that the positive association of breakup distress with personal growth was accounted for by enhanced reflection and brooding, and that anxious individuals’ greater personal growth was also explained by their proclivity to rebound. These findings suggest that anxious individuals’ hyperactivated breakup distress may act as a catalyst for personal growth by promoting the cognitive processing of breakup-related thoughts and emotions, whereas avoidant individuals’ deactivated distress may inhibit personal growth by suppressing this cognitive work

30 days wild: development and evaluation of a large-scale nature engagement campaign to improve well-being

There is a need to increase people’s engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro-nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature

Dyspraxia and autistic traits in adults with and without autism spectrum conditions

BACKGROUND: Autism spectrum conditions (ASC) are frequently associated with motor coordination difficulties. However, no studies have explored the prevalence of dyspraxia in a large sample of individuals with and without ASC or associations between dyspraxia and autistic traits in these individuals. METHODS: Two thousand eight hundred seventy-one adults (with ASC) and 10,706 controls (without ASC) self-reported whether they have been diagnosed with dyspraxia. A subsample of participants then completed the Autism Spectrum Quotient (AQ; 1237 ASC and 6765 controls) and the Empathy Quotient (EQ; 1147 ASC and 6129 controls) online through the Autism Research Centre website. The prevalence of dyspraxia was compared between those with and without ASC. AQ and EQ scores were compared across the four groups: (1) adults with ASC with dyspraxia, (2) adults with ASC without dyspraxia, (3) controls with dyspraxia, and (4) controls without dyspraxia. RESULTS: Adults with ASC were significantly more likely to report a diagnosis of dyspraxia (6.9%) than those without ASC (0.8%). In the ASC group, those with co-morbid diagnosis of dyspraxia did not have significantly different AQ or EQ scores than those without co-morbid dyspraxia. However, in the control group (without ASC), those with dyspraxia had significantly higher AQ and lower EQ scores than those without dyspraxia. CONCLUSIONS: Dyspraxia is significantly more prevalent in adults with ASC compared to controls, confirming reports that motor coordination difficulties are significantly more common in this group. Interestingly, in the general population, dyspraxia was associated with significantly higher autistic traits and lower empathy. These results suggest that motor coordination skills are important for effective social skills and empathy

Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections

Copyright: © 2013 Baron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by ANR (ANR-07-BLAN-0214 and ANR-12-EMMA-00O7-01), CNRS and INRA. PvW was financially supported by the BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

Tribological performance of Graphene/Carbon nanotube hybrid reinforced Al2O3 composites

Tribological performance of the hot-pressed pure Al2O3 and its composites containing various hybrid contents of graphene nanoplatelets (GNPs) and carbon nanotubes (CNTs) were investigated under different loading conditions using the ball-on-disc method. Benchmarked against the pure Al2O3, the composite reinforced with a 0.5 wt% GNP exhibited a 23% reduction in the friction coefficient along with a promising 70% wear rate reduction, and a hybrid reinforcement consisting of 0.3 wt.% GNPs + 1 wt.% CNTs resulted in even better performance, with a 86% reduction in the wear rate. The extent of damage to the reinforcement phases caused during wear was studied using Raman spectroscopy. The wear mechanisms for the composites were analysed based on the mechanical properties, brittleness index and microstructural characterizations. The excellent coordination between GNPs and CNTs contributed to the excellent wear resistance property in the hybrid GNT-reinforced composites. GNPs played the important role in the formation of a tribofilm on the worn surface by exfoliation; whereas CNTs contributed to the improvement in fracture toughness and prevented the grains from being pulled out during the tribological test