Community Emergency Management During the 2005 Ambae Eruption, Vanuatu, SW Pacific.

No abstract availabl

Biocatalytic Conversion of Cyclic Ketones Bearing α-Quaternary Stereocenters into Lactones in an Enantioselective Radical Approach to Medium-Sized Carbocycles

Cyclic ketones bearing alpha-quaternary stereocenters undergo efficient kinetic resolution using cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus. Lactones possessing tetrasubstituted stereocenters are obtained with high enantioselectivity (up to >99% ee) and complete chemoselectivity. Preparative scale biotransformations were exploited in conjunction with a SmI2-mediated cyclization process to access complex, enantiomerically enriched cycloheptan- and cycloctan-1,4-diols. In a parallel approach to structurally distinct products, enantioenriched ketones from the resolution bearing an alpha- all carbon quaternary stereocenter were used in a SmI2-mediated cyclization process to give cyclobutanol products (up to >99% ee)

Electron backscatter diffraction analysis unveils foraminiferal calcite microstructure and processes of diagenetic alteration

Electron backscatter diffraction (EBSD) analysis enables a unique perspective of the internal microstructure of foraminiferal calcite. Specifically, EBSD provides crystallographic data from within the test, highlighting the highly organised “mesocrystal” structure of crystallographically aligned domains throughout the test, formed by sequential deposits of microgranular calcite. We compared EBSD maps across the test walls of both poorly preserved and well-preserved specimens of the planktonic foraminifera species Globigerinoides ruber and Morozovella crater. The EBSD maps, paired with information about intra-test distributions of ratios, allowed us to examine the effects of different diagenetic processes on the foraminifera test. In poorly preserved specimens EBSD data show extensive reorganisation of the biogenic crystal microstructure, indicating differing phases of dissolution, re-precipitation and overgrowth. The specimens with the greatest degree of microstructural reorganisation also show an absence of higher concentration magnesium bands, which are typical features of well-preserved specimens. These findings provide important insights into the extent of post-depositional changes, in both microstructure and geochemical signals that must be considered when utilising foraminifera to generate proxy archive data

Stuart Hall and the theory and practice of articulation

In this article, I argue that the idea of articulation links three different dimensions of Stuart Hall’s work: it is central to the work of cultural politics, to the work of hegemony, and to his practice of embodied pedagogy. I claim that his approach to pedagogy entails the art of listening combined with the practice of theorising in the service of expanding who belongs to the public. This involves the work of translation, finding ways of addressing different audiences. I treat each of these aspects in turn, drawing out the salience of articulation for each and suggest that these three dimensions are themselves articulated by Hall’s commitment to the theory and practice of articulation

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Endothelial dysfunction and glycocalyx shedding in heart failure:insights from patients receiving cardiac resynchronisation therapy

To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial dysfunction and/or redox stress and is ameliorated by cardiac resynchronisation therapy. Glycocalyx shedding has been reported to be increased in heart failure and is a marker of increased mortality. Its role in dyssynchronous systolic heart failure and the effects of cardiac resynchronisation therapy (CRT) are largely unknown. Twenty-six patients with dyssynchronous HFrEF were evaluated before and 6 months after CRT insertion. Echocardiographic septal to posterior wall delay (SPWD) assessed intra-ventricular mechanical dyssynchrony, and quality of life, integrity of nitric oxide (NO) signalling, inflammatory and redox-related biomarkers were measured. Glycocalyx shedding was quantitated via plasma levels of the glycocalyx component, syndecan-1. Syndecan-1 levels pre-CRT were inversely correlated with LVEF (r = - 0.45, p = 0.02) and directly with SPWD (r = 0.44, p = 0.02), QOL (r = 0.39, p = 0.04), plasma NT-proBNP (r = 0.43, p = 0.02), and the inflammatory marker, symmetric dimethylarginine (SDMA) (r = 0.54, p = 0.003). On multivariate analysis, syndecan-1 levels were predicted by SPWD and SDMA (β = 0.42, p = 0.009 and β = 0.54, p = 0.001, respectively). No significant correlation was found between syndecan-1 levels and other markers of endothelial dysfunction/inflammatory activation. Following CRT there was no significant change in syndecan-1 levels. In patients with dyssynchronous HFrEF, markers of glycocalyx shedding are associated with the magnitude of mechanical dyssynchrony and elevation of SDMA levels and inversely with LVEF. However, CRT does not reverse this process

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention