Glacial cycles drive variations in the production of oceanic crust

Glacial cycles redistribute water between oceans and continents causing pressure changes in the upper mantle, with consequences for melting of Earth's interior. Using Plio-Pleistocene sea-level variations as a forcing function, theoretical models of mid-ocean ridge dynamics that include melt transport predict temporal variations in crustal thickness of hundreds of meters. New bathymetry from the Australian-Antarctic ridge shows significant spectral energy near the Milankovitch periods of 23, 41, and 100 ky, consistent with model predictions. These results suggest that abyssal hills, one of the most common bathymetric features on Earth, record the magmatic response to changes in sea level. The models and data support a link between glacial cycles at the surface and mantle melting at depth, recorded in the bathymetric fabric of the sea floor.Comment: 30 pages, 6 figures (including supplementary information). Resubmitted to Science on 12 December 201

Glacial cycles drive variations in the production of oceanic crust

Glacial cycles redistribute water between oceans and continents, causing pressure changes in the upper mantle, with consequences for the melting of Earth’s interior. Using Plio-Pleistocene sea-level variations as a forcing function, theoretical models of mid-ocean ridge dynamics that include melt transport predict temporal variations in crustal thickness of hundreds of meters. New bathymetry from the Australian-Antarctic ridge shows statistically significant spectral energy near the Milankovitch periods of 23, 41, and 100 thousand years, which is consistent with model predictions. These results suggest that abyssal hills, one of the most common bathymetric features on Earth, record the magmatic response to changes in sea level. The models and data support a link between glacial cycles at the surface and mantle melting at depth, recorded in the bathymetric fabric of the sea floor.Earth and Planetary Science

Hepatic and adipose phenotype in Alström syndrome

BACKGROUND AND AIMS: Alström syndrome (AS) is a recessive monogenic syndrome characterized by obesity, extreme insulin resistance and multi-organ fibrosis. Despite phenotypically being high risk of non-alcoholic fatty liver disease (NAFLD), there is a lack of data on the extent of fibrosis in the liver and its close links to adipose in patients with AS. Our aim was to characterize the hepatic and adipose phenotype in patients with AS. METHODS: Observational cohort study with comprehensive assessment of metabolic liver phenotype including liver elastography (Fibroscan® ), serum Enhanced Liver Fibrosis (ELF) Panel and liver histology. In addition, abdominal adipose histology and gene expression was assessed. We recruited 30 patients from the UK national AS clinic. A subset of six patients underwent adipose biopsies which was compared with control tissue from nine healthy participants. RESULTS: Patients were overweight/obese (BMI 29.3 (25.95-34.05) kg/m2 ). A total of 80% (24/30) were diabetic; 74% (20/27) had liver ultrasound scanning suggestive of NAFLD. As judged by the ELF panel, 96% (24/25) were categorized as having fibrosis and 10/21 (48%) had liver elastography consistent with advanced liver fibrosis/cirrhosis. In 7/8 selected cases, there was evidence of advanced NAFLD on liver histology. Adipose tissue histology showed marked fibrosis as well as disordered pro-inflammatory and fibrotic gene expression profiles. CONCLUSIONS: NAFLD and adipose dysfunction are common in patients with AS. The severity of liver disease in our cohort supports the need for screening of liver fibrosis in AS.Alström UKThis is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/liv.1316

A phase II study of glembatumumab vedotin for metastatic uveal melanoma

Glembatumumab vedotin (CDX-011, GV) is a fully human Immunoglobulin G2 monoclonal antibody directed against glycoprotein NMB coupled via a peptide linker to monomethyl auristatin E (MMAE), a potent cytotoxic microtubule inhibitor. This phase II study evaluated the overall response rate and safety of GV, glycoprotein NMB (GPNMB) expression, and survival in patients with metastatic uveal melanoma. Eligible patients with metastatic uveal melanoma who had not previously been treated with chemotherapy received GV 1.9 mg/kg every three weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included GPNMB expression, progression-free survival (PFS), overall survival (OS), and toxicity analysis. GPNMB expression was assessed pre- and post-treatment via immunohistochemistry for patients with available tumor tissue. Out of 35 patients who received treatment, two patients had confirmed partial responses (PRs; 6%), and 18 patients had a stable disease (SD; 51%) as the best objective response. 38% of the patients had stable disease \u3e100 days. The grade 3 or 4 toxicities that occurred in two or more patients were neutropenia, rash, hyponatremia, and vomiting. The median progression-free survival was 3.1 months (95% CI: 1.5-5.6), and the median overall survival was 11.9 months (95% CI 9.0-16.9) in the evaluable study population. GV is well-tolerated in metastatic uveal melanoma. The disease control rate was 57% despite a low objective response rate. Exploratory immune correlation studies are underway to provide insight into target saturation, combination strategies, and antigen release

Radiation dose tracking in computed tomography: Red alerts and feedback. Implementing a radiation dose alert system in CT

Introduction: This study investigates instances of elevated radiation dose on a radiation tracking system to determine their aetiologies. It aimed to investigate the impact of radiographer feedback on these alerts. Methods: Over two six-month periods 11,298 CT examinations were assessed using DoseWatch. Red alerts (dose length products twice the median) were identified and two independent reviewers established whether alerts were true (unjustifiable) or false (justifiable). During the second time period radiographers used a feedback tool to state the cause of the alert. A Chi–Square test was used to assess whether red alert incidence decreased following the implementation of radiographer feedback. Results: There were 206 and 357 alerts during the first and second time periods, respectively. These occurred commonly with CT pulmonary angiography, brain, and body examinations. Procedural documentation errors and patient size accounted for 57% and 43% of false alerts, respectively. Radiographer feedback was provided for 17% of studies; this was not associated with a significant change in the number of alerts, but the number of true alerts declined (from 7 to 3) (χ2 = 4.14; p = 0.04). Conclusion: Procedural documentation errors as well as patient-related factors are associated with false alerts in DoseWatch. Implementation of a radiographer feedback tool reduced true alerts. Implications for practice: The implementation of a radiographer feedback tool reduced the rate of true dose alerts. Low uptake with dose alert systems is an issue; the workflow needs to be considered to address this

To what extent does a regional dialect and accent impact on the development of reading and writing skills?

The issue of whether a regional accent and/or dialect impact(s) on the development of literacy skills remains current in the UK. For decades the issue has dogged debate about education outcomes, portable skills and employability. The article summarizes research on the topic using systematic review methodology. A scoping review was undertaken with the research question ‘To what extent does a regional dialect and accent impact on the development of reading and writing skills?’. The review covers research relevant to the teaching of 5-16 year olds in England, but also draws on research within Europe, the USA, Australia and the Caribbean. The results suggest that curricula have marginalized language variation; that the impact of regional accent and dialect on writing is relatively minor; that young people are adept at style-shifting between standard and non-standard forms; and that inappropriate pedagogical responses to regional variation can have detrimental effects on children’s educational achievement

Genome-wide mapping of cystitis due to Streptococcus agalactiae and Escherichia coli in mice identifies a unique bladder transcriptome that signifies pathogen-specific antimicrobial defense against urinary tract infection

The most common causes of urinary tract infections (UTIs) are Gram-negative pathogens such as Escherichia coli; however, Gram-positive organisms, including Streptococcus agalactiae, or group B streptococcus (GBS), also cause UTI. In GBS infection, UTI progresses to cystitis once the bacteria colonize the bladder, but the host responses triggered in the bladder immediately following infection are largely unknown. Here, we used genome-wide expression profiling to map the bladder transcriptome of GBS UTI in mice infected transurethrally with uropathogenic GBS that was cultured from a 35-year-old women with cystitis. RNA from bladders was applied to Affymetrix Gene-1.0ST microarrays; quantitative reverse transcriptase PCR (qRT-PCR) was used to analyze selected gene responses identified in array data sets. A surprisingly small significant-gene list of 172 genes was identified at 24 h; this compared to 2,507 genes identified in a side-by-side comparison with uropathogenic E. coli (UPEC). No genes exhibited significantly altered expression at 2 h in GBS-infected mice according to arrays despite high bladder bacterial loads at this early time point. The absence of a marked early host response to GBS juxtaposed with broad-based bladder responses activated by UPEC at 2 h. Bioinformatics analyses, including integrative system-level network mapping, revealed multiple activated biological pathways in the GBS bladder transcriptome that regulate leukocyte activation, inflammation, apoptosis, and cytokine-chemokine biosynthesis. These findings define a novel, minimalistic type of bladder host response triggered by GBS UTI, which comprises collective antimicrobial pathways that differ dramatically from those activated by UPEC. Overall, this study emphasizes the unique nature of bladder immune activation mechanisms triggered by distinct uropathogens

Digital girl:Cyberfeminism and the emancipation potential of digital entrepreneurship in emerging economies

Digital entrepreneurship has been described as a “great leveler” in terms of equalizing the entrepreneurial playing field for women. However, little is known of the emancipatory possibilities offered by digital entrepreneurship for women constrained by social and cultural practices such as male guardianship of female relatives and legally enforced gender segregation. In order to address this research gap, this paper examines women’s engagement in digital entrepreneurship in emerging economies with restrictive social and cultural practices. In so doing, we draw upon the analytical frameworks provided by entrepreneurship as emancipation and cyberfeminism. Using empirical data from an exploratory investigation of entrepreneurship in Saudi Arabia, we examine how women use digital technologies in the pursuit of entrepreneurial opportunities. Our findings reveal that women in Saudi Arabia use digital entrepreneurship to transform their embodied selves and lived realities rather than to escape gender embodiment as offered by the online environment