Basal topographic controls on rapid retreat of Humboldt Glacier, northern Greenland

This is the final version of the article. Available from CUP via the DOI in this record.Discharge from marine-terminating outlet glaciers accounts for up to half the recent mass loss from the Greenland ice sheet, yet the causal factors are not fully understood. Here we assess the factors controlling the behaviour of Humboldt Glacier (HG), allowing us to evaluate the influence of basal topography on outlet glacier response to external forcing since part of HG’s terminus occupies a large overdeepening. HG’s retreat accelerated dramatically after 1999, coinciding with summer atmospheric warming of up to 0.19°C a–1 and sea-ice decline. Retreat was an order of magnitude greater in the northern section of the terminus, underlain by a major basal trough, than in the southern section, where the bedrock is comparatively shallow. Velocity change following retreat was spatially non-uniform, potentially due to a pinning point near HG’s northern lateral margin. Consistent with observations, numerical modelling demonstrates an order-of-magnitude greater sensitivity to sea-ice buttressing and crevasse depth (used as a proxy for atmospheric warming) in the northern section. The trough extends up to 72 km inland, so it is likely to facilitate sustained retreat and ice loss from HG during the 21st century.Funding for this work was provided by a Durham Doctoral Studentship to J.R.C. Radio-echo sounding data were acquired and processed through UK Natural Environment Research Council (NERC) grant NE/H020667 to J.A.D. and P.C. and a G. Unger Vetlesen grant to the University of Texas Institute for Geophysics (UTIG). GrOGG laser altimetry was supported by NNXAD33G to D.D.B. This paper is UTIG contribution No. 2733. S.S.R.J. was supported by UK NERC fellowship NE/J018333/1

Heat shock protein amplification improves cerebellar myelination in the Npc1nih mouse model.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1nih (Npc1-/-) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1-/- mice. Taken together, these findings prompted the investigation of the effects of HSP amplification on CNS myelination. METHODS: We administered bimoclomol daily or rhHSP70 6 times per week to Npc1-/- (BALB/cNctr-Npc1m1N/J, also named Npc1nih) mice by intraperitoneal injection from P7 through P34 to investigate the impact on CNS myelination. The Src-kinase inhibitor saracatinib was administered with/without bimoclomol twice daily to explore the contribution of Fyn kinase to bimoclomol's effects. FINDINGS: Treatment with either bimoclomol or rhHSP70 improved myelination and increased the numbers of mature oligodendrocytes (OLs) as well as the ratio of active-to-inactive forms of phosphorylated Fyn kinase in the cerebellum of Npc1-/- mice. Additionally, treatment with bimoclomol preserved cerebellar weight, an effect that was abrogated when co-administered with saracatinib, an inhibitor of Fyn kinase. Bimoclomol-treated mice also exhibited increased numbers of immature OLs within the cortex. INTERPRETATION: These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC. FUNDING: Funding for this study was provided by Orphazyme A/S (Copenhagen, Denmark) and a Pathfinder Award from The Wellcome Trust

Antiplatelet agents for chronic kidney disease

To evaluate the benefits and harms of antiplatelet therapy in patients with any form of kidney disease, including patients with CKD not receiving renal replacement therapy (RRT), patients receiving any form of dialysis, and kidney transplant recipients

Even Between-Lap Pacing Despite High Within-Lap Variation During Mountain Biking

Purpose: Given the paucity of research on pacing strategies during competitive events, this study examined changes in dynamic high-resolution performance parameters to analyze pacing profiles during a multiple-lap mountain-bike race over variable terrain. Methods: A global-positioning-system (GPS) unit (Garmin, Edge 305, USA) recorded velocity (m/s), distance (m), elevation (m), and heart rate at 1 Hz from 6 mountain-bike riders (mean ± SD age = 27.2 ± 5.0 y, stature = 176.8 ± 8.1 cm, mass = 76.3 ± 11.7 kg, VO2max = 55.1 ± 6.0 mL · kg–1 . min–1) competing in a multilap race. Lap-by-lap (interlap) pacing was analyzed using a 1-way ANOVA for mean time and mean velocity. Velocity data were averaged every 100 m and plotted against race distance and elevation to observe the presence of intralap variation. Results: There was no significant difference in lap times (P = .99) or lap velocity (P = .65) across the 5 laps. Within each lap, a high degree of oscillation in velocity was observed, which broadly reflected changes in terrain, but high-resolution data demonstrated additional nonmonotonic variation not related to terrain. Conclusion: Participants adopted an even pace strategy across the 5 laps despite rapid adjustments in velocity during each lap. While topographical and technical variations of the course accounted for some of the variability in velocity, the additional rapid adjustments in velocity may be associated with dynamic regulation of self-paced exercise

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

A contemporaneous infrared flash from a long gamma-ray burst: an echo from the central engine

The explosion that results in a cosmic gamma-ray burst (GRB) is thought to produce emission from two physical processes -- the activity of the central engine gives rise to the high-energy emission of the burst through internal shocking and the subsequent interaction of the flow with the external environment produces long-wavelength afterglow. While afterglow observations continue to refine our understanding of GRB progenitors and relativistic shocks, gamma-ray observations alone have not yielded a clear picture of the origin of the prompt emission nor details of the central engine. Only one concurrent visible-light transient has been found and was associated with emission from an external shock. Here we report the discovery of infrared (IR) emission contemporaneous with a GRB, beginning 7.2 minutes after the onset of GRB 041219a. Our robotic telescope acquired 21 images during the active phase of the burst, yielding the earliest multi-colour observations of any long-wavelength emission associated with a GRB. Analysis of an initial IR pulse suggests an origin consistent with internal shocks. This opens a new possibility to study the central engine of GRBs with ground-based observations at long wavelengths.Comment: Accepted to Nature on March 1, 2005. 9 pages, 4 figures, nature12.cls and nature1.cls files included. This paper is under press embargo until print publicatio

Induction of the GABA Cell Phenotype: An In Vitro Model for Studying Neurodevelopmental Disorders

Recent studies of the hippocampus have suggested that a network of genes is associated with the regulation of the GAD67 (GAD1) expression and may play a role in γ-amino butyric acid (GABA) dysfunction in schizophrenia (SZ) and bipolar disorder (BD). To obtain a more detailed understanding of how GAD67 regulation may result in GABAergic dysfunction, we have developed an in vitro model in which GABA cells are differentiated from the hippocampal precursor cell line, HiB5. Growth factors, such as PDGF, and BDNF, regulate the GABA phenotype by inducing the expression of GAD67 and stimulating the growth of cellular processes, many with growth cones that form appositions with the cell bodies and processes of other GAD67-positive cells. These changes are associated with increased expression of acetylated tubulin, microtubule-associated protein 2 (MAP2) and the post-synaptic density protein 95 (PSD95). The addition of BDNF, together with PDGF, increases the levels of mRNA and protein for GAD67, as well as the high affinity GABA uptake protein, GAT1. These changes are associated with increased concentrations of GABA in the cytoplasm of “differentiated” HiB5 neurons. In the presence of Ca2+ and K+, newly synthesized GABA is released extracellularly. When the HiB5 cells appear to be fully differentiated, they also express GAD65, parvalbumin and calbindin, and GluR subtypes as well as HDAC1, DAXX, PAX5, Runx2, associated with GAD67 regulation. Overall, these results suggest that the HiB5 cells can differentiate into functionally mature GABA neurons in the presence of gene products that are associated with GAD67 regulation in the adult hippocampus

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).

Self-compassion and bedtime procrastination: an emotion regulation perspective

The current study extended previous research on self-compassion and health behaviours by examining the associations of self-compassion to bedtime procrastination, an important sleep-related behaviour. We hypothesized that lower negative affect and adaptive emotion regulation would explain the proposed links between self-compassion and less bedtime procrastination. Two cross-sectional online studies were conducted. Study 1 included 134 healthy individuals from the community (mean age 30.22, 77.4% female). Study 2 included 646 individuals from the community (mean age 30.74, 68.9% female) who were screened for the absence of clinical insomnia. Participants in both studies completed measures of self-compassion, positive and negative affect and bedtime procrastination. Participants in study 2 also completed a measure of cognitive reappraisal. Multiple mediation analysis in study 1 revealed the expected indirect effects of self-compassion on less bedtime procrastination through lower negative affect [b = − .09, 95% CI = (− .20, − .02), but not higher positive affect. Path analysis in study 2 replicated these findings and further demonstrated that cognitive reappraisal explained the lower negative affect linked to self-compassion [b = − .011; 95% CI = (− .025; − .003)]. The direct effect of self-compassion on less bedtime procrastination remained significant. Our novel findings provide preliminary evidence that self-compassionate people are less likely to engage in bedtime procrastination, due in part to their use of healthy emotion regulation strategies that downregulate negative mood