Rb-sr ages of chondrules and carbonaceous chondrites

Rubidium-strontium and potassium-strontium isotope composition of carbonaceous chondrites and chondrules - age of carbonaceous meteorite

Climate policy strength compared: China, the US, the EU, India, Russia, and Japan

The few systematic international comparisons of climate policy strength made so far have serious weaknesses, particularly those that assign arbitrary weightings to different policy instrument types in order to calculate an aggregate score for policy strength. This article avoids these problems by ranking the six biggest emitters by far – China, the US, the EU, India, Russia, and Japan – on a set of six key policy instruments that are individually potent and together representative of climate policy as a whole: carbon taxes, emissions trading, feed-in tariffs, renewable energy quotas, fossil fuel power plant bans, and vehicle emissions standards. The results cast strong doubt on any idea that there is a clear hierarchy on climate policy with Europe at the top: the EU does lead on a number of policies but so does Japan. China, the US, and India each lead on one area. Russia is inactive on all fronts. At the same time climate policy everywhere remains weak compared to what it could be. Policy relevance This study enables climate policy strength, defined as the extent to which the statutory provisions of climate policies are likely to restrict GHG emissions if implemented as intended, to be assessed and compared more realistically across space and time. As such its availability for the six biggest emitters, which together account for over 70% of global CO2 emissions, should facilitate international negotiations (1) by giving participants a better idea of where major emitters stand relative to each other as far as climate policy stringency is concerned, and (2) by identifying areas of weakness that need action

No evidence of a significant role for CTLA-4 in multiple sclerosis

Variation in the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene plays a significant role in determining susceptibility to autoimmune thyroid disease and type 1 diabetes. Its role in multiple sclerosis is more controversial. In order to explore this logical candidate more thoroughly, we genotyped 771 multiple sclerosis trio families from the United Kingdom for the 3? untranslated region variable number tandem repeat, the CT60 single nucleotide polymorphism (SNP) and five haplotype-tagging SNPs. No individual marker or common haplotype showed evidence of association with disease. These data suggest that any effect of CTLA-4 on multiple sclerosis susceptibility is likely to be very small

Access to fracture risk assessment by FRAX and linked National Osteoporosis Guideline Group (NOGG) guidance in the UK—an analysis of anonymous website activity

Purpose/Introduction In the UK, guidance on assessment of osteoporosis and fracture risk is provided by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG). We wished to determine access to this guidance by exploring website activity. Methods We undertook an analysis of FRAX and NOGG website usage for the year between 1st July 2013 and 30th June 2014 using GoogleAnalytics software. Results During this period, there was a total of 1,774,812 sessions (a user interaction with the website) on the FRAX website with 348,964 of these from UK-based users; 253,530 sessions were recorded on the NOGG website. Of the latter, two-thirds were returning visitors, with the vast majority (208,766, 82%) arising from sites within the UK. The remainder of sessions were from other countries demonstrating that some users of FRAX in other countries make use of the NOGG guidance. Of the UK-sourced sessions, the majority were from England, but the session rate (adjusted for population) was highest for Scotland. Almost all (95.7%) of the UK sessions arose from calculations being passed through from the FRAX tool (www.shef.ac.uk/FRAX) to the NOGG website, comprising FRAX calculations in patients without a BMD measurement (74.5%) or FRAX calculations with a BMD result (21.2%). National Health Service (NHS) sites were identified as the major source of visits to the NOGG website, comprising 79.9% of the identifiable visiting locations, but this is an underestimate as many sites from within the NHS are not classified as such. Conclusion The study shows that the facilitated interaction between web based fracture risk assessment and clinical guidelines is widely used in the UK. The approach could usefully be adopted in other countries for which a FRAX model is available

Effects of water and fluorine on the viscosity of albite melt at high pressure: a preliminary investigation

The viscosities of fluorine- and water-bearing melts based on albite composition have been determined at 7.5, 15 and 22.5 kbar by the falling-sphere method. All melt viscosities decrease isothermally with increasing pressure. At 1200°C the viscosity of the fluorine-bearing melt (albite + 5.8 wt.% fluorine substituted for oxygen, denoted AbF2O−1) decreases from5000 ± 750P at7.5kbar to1600 ± 240P at22.5kbar. At 1400°C the viscosity of this melt decreases from1300 ± 200P at7.5kbar to430 ± 65P at22.5kbar. At 1400°C the viscosity of albite + 2.79 wt.% water (denoted AbH2O) decreases from650 ± 100P at7.5kbar to400 ± 60P at22.5kbar. Fluorine (as F2O−1) and water strongly decrease the viscosity of albite melt over the entire range of investigated pressures. The ratio of the effects of 5.8 wt.% fluorine [F/(F + O)molar = 0.10] and 2.79 wt.% water [OH/(OH + O)molar = 0.10] on the log of melt viscosity [Δ log η(AbF2O−1)/Δ log η(AbH2O)] equals0.90 ± 0.05, 0.84 ± 0.05and0.97 ± 0.05at7.5, 15and22.5kbar, respectively. Comparison with available data on the high-pressure viscosity of albite melt indicates that both F2O−1 and H2O maintain their viscosity-reducing roles to lower crustal pressures. The difference between the viscosities of melts of albite, AbF2O−1 and AbH2O, may be explained in terms of the relatively depolymerized structures of AbF2O−1 and AbH2O melts. The depolymerization of albite melt by the addition of water results from the formation of SiOH bonds. The depolymerization of albite melt by F2O−1 substitution results from the formation of non-bridging oxygens associated with network-modifying aluminum cations that are formed upon fluorine solution. The strong viscosity-reducing effects of water and fluorine in albite melt at pressures corresponding to the mid- to lower continental crust indicate that these two components will strongly influence the dynamic behavior of anatectic melts during initial magma coalescence and restite-melt segregation

Targeting synaptic pathology in multiple sclerosis: fingolimod to the rescue?

Multiple sclerosis (MS) is an inflammatory disorder affecting the brain and spinal cord. Major hallmarks of MS typically include inflammation, demyelination and axon degeneration, although recent studies have also implicated synaptic dysfunction and degeneration in disease pathogenesis. The discovery that treatment with the orally active immunomodulatory drug fingolimod (FTY720) confers benefits in animal models and human patients has opened up new avenues for the treatment of MS. In the present issue of the BJP, Rossi and colleagues used a mouse model of MS [experimental autoimmune encephalomyelitis (EAE)] to provide new evidence suggesting that fingolimod may target MS symptoms, at least in part, by ameliorating synaptic dysfunction. They demonstrated that fingolimod reversed modifications in glutamatergic transmission found in the striatum of EAE mice, accompanied by a reduction in the severity of dendritic spine loss. This report suggests that fingolimod treatment can have beneficial effects on synaptic pathology in MS, raising the intriguing possibility that fingolimod treatment may also be advantageous in other diseases of the nervous system where inflammation and synaptic pathology contribute to disease pathogenesis. LINKED ARTICLE: This article is a commentary on Rossi et al., pp. 861–869 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01579.

Dynamic walking features and improved walking performance in multiple sclerosis patients treated with fampridine (4-aminopyridine)

Background: Impaired walking capacity is a frequent confinement in Multiple Sclerosis (MS). Patients are affected by limitations in coordination, walking speed and the distance they may cover. Also abnormal dynamic walking patterns have been reported, involving continuous deceleration over time. Fampridine (4-aminopyridine), a potassium channel blocker, may improve walking in MS. The objective of the current study was to comprehensively examine dynamic walking characteristics and improved walking capacity in MS patients treated with fampridine. Methods: A sample of N = 35 MS patients (EDSS median: 4) underwent an electronic walking examination prior to (Time 1), and during treatment with fampridine (Time 2). Patients walked back and forth a distance of 25 ft for a maximum period of 6 min (6-minute 25-foot-walk). Besides the total distance covered, average speed on the 25-foot distance and on turns was determined separately for each test minute, at Time 1 and Time 2. Results: Prior to fampridine administration, 27/35 patients (77 %) were able to complete the entire 6 min of walking, while following the administration, 34/35 patients (97 %) managed to walk for 6 min. In this context, walking distance considerably increased and treatment was associated with faster walking and turning across all six test minutes (range of effect sizes: partial eta squared = .34-.72). Importantly, previously reported deceleration across test minutes was consistently observable at Time 1 and Time 2. Discussion: Fampridine administration is associated with improved walking speed and endurance. Regardless of a treatment effect of fampridine, the previously identified, abnormal dynamic walking feature, i.e. the linear decline in walking speed, may represent a robust feature. Conclusions: The dynamic walking feature might hence be considered as a candidate for a new outcome measure in clinical studies involving interventions other than symptomatic treatment, such as immune-modulating medication. Trial registration: DRKS00009228 (German Clinical Trials Register). Date obtained: 25.08.2015

Damaged axons promote OPC differentiation

Oligodendrocyte progenitor cell (OPC) differentiation is an important therapeutic target to promote remyelination in multiple sclerosis (MS). We previously reported hyperphosphorylated and aggregated microtubule-associated protein tau in MS lesions, suggesting its involvement in axonal degeneration. However, the influence of pathological tau-induced axonal damage on the potential for remyelination is unknown. Therefore, we investigated OPC differentiation in human P301S tau (P301S-htau) transgenic mice, both in vitro and in vivo following focal demyelination. In 2-month-old P301S-htau mice, which show hyperphosphorylated tau in neurons, we found atrophic axons in the spinal cord in the absence of prominent axonal degeneration. These signs of early axonal damage were associated with microgliosis and an upregulation of IL-1β and TNFα. Following in vivo focal white matter demyelination we found that OPCs differentiated more efficiently in P301S-htau mice than wild type (Wt) mice. We also found an increased level of myelin basic protein within the lesions, which however did not translate into increased remyelination due to higher susceptibility of P301S-htau axons to demyelination-induced degeneration compared to Wt axons. In vitro experiments confirmed higher differentiation capacity of OPCs from P301S-htau mice compared with Wt mice-derived OPCs. Because the OPCs from P301S-htau mice do not ectopically express the transgene, and when isolated from newborn mice behave like Wt mice-derived OPCs, we infer that their enhanced differentiation capacity must have been acquired through microenvironmental priming. Our data suggest the intriguing concept that damaged axons may signal to OPCs and promote their differentiation in the attempt at rescue by remyelination. GLIA 2016;64:457-471.This project was funded by the Multiple Sclerosis Society UK via the Cambridge Centre for Myelin Repair consortium, and core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute

Endocortical bone loss in osteoporosis: The role of bone surface availability

Age-related bone loss and postmenopausal osteoporosis are disorders of bone remodelling, in which less bone is reformed than resorbed. Yet, this dysregulation of bone remodelling does not occur equally in all bone regions. Loss of bone is more pronounced near and at the endocortex, leading to cortical wall thinning and medullary cavity expansion, a process sometimes referred to as "trabecularisation" or "cancellisation". Cortical wall thinning is of primary concern in osteoporosis due to the strong deterioration of bone mechanical properties that it is associated with. In this paper, we examine the possibility that the non-uniformity of microscopic bone surface availability could explain the non-uniformity of bone loss in osteoporosis. We use a computational model of bone remodelling in which microscopic bone surface availability influences bone turnover rate and simulate the evolution of the bone volume fraction profile across the midshaft of a long bone. We find that bone loss is accelerated near the endocortical wall where the specific surface is highest. Over time, this leads to a substantial reduction of cortical wall thickness from the endosteum. The associated expansion of the medullary cavity can be made to match experimentally observed cross-sectional data from the Melbourne Femur Collection. Finally, we calculate the redistribution of the mechanical stresses in this evolving bone structure and show that mechanical load becomes critically transferred to the periosteal cortical bone.Comment: 13 pages, 3 figures. V2: minor stylistic improvements in text/figures; more accurately referenced subsection "Internal mechanical stress distribution"; some improved remarks in the Discussion sectio