Plausible responses to the threat of rapid sea-level rise for the Thames Estuary

This paper considers the perceptions and responses of selected stakeholders to a scenarion of rapid rise in sea-level due to the collapse of the West Antarctic ice sheet, which could produce a global rise in sea-level of 5 to 6 metres. Through a process of dialogue involving one-to one interviews and a one-day policy exercise, we addressed influences on decision-making when information is uncertain and our ability to plan, prepare for and implement effective ways of coping with this extreme scenario. Through these interactions we hoped to uncover plausible responses to the scenario and identify potential weaknesses in our current flood management approaches to dealing with such an occurrence. By undertaking this exploratory exercise we hoped to find out whether this was a feasible way to deal with such a low probability but high consequence scenario. It was the process of finding a solution that interested us rather than the technical merits of one solution over another. We were not intending to produce definitive set of recommendations on how to respond but to gain insights into the process of making a decision, specifically what influences it and what assumptions are made.Sea level rise, London

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Effectiveness of mindfulness-based stress reduction in mood, breast- and endocrine-related quality of life, and well-being in stage 0 to III breast cancer : a randomized, controlled trial

Purpose To assess the effectiveness of mindfulness-based stress reduction (MBSR) for mood, breast- and endocrine-specific quality of life, and well-being after hospital treatment in women with stage 0 to III breast cancer. Patients and Methods A randomized, wait-listed, controlled trial was carried out in 229 women after surgery, chemotherapy, and radiotherapy for breast cancer. Patients were randomly assigned to the 8-week MBSR program or standard care. Profile of Mood States (POMS; primary outcome), Functional Assessment of Cancer Therapy–Breast (FACT-B), Functional Assessment of Cancer Therapy–Endocrine Symptoms (FACT-ES) scales and the WHO five-item well-being questionnaire (WHO-5) evaluated mood, quality of life, and well-being at weeks 0, 8, and 12. For each outcome measure, a repeated-measures analysis of variance model, which incorporated week 0 measurements as a covariate, was used to compare treatment groups at 8 and 12 weeks. Results There were statistically significant improvements in outcome in the experimental group compared with control group at both 8 and 12 weeks (except as indicated) for POMS total mood disturbance (and its subscales of anxiety, depression [8 weeks only], anger [12 weeks only], vigor, fatigue, and confusion [8 weeks only]), FACT-B, FACT-ES, (and Functional Assessment of Cancer Therapy subscales of physical, social [8 weeks only], emotional, and functional well-being), and WHO-5. Conclusion MSBR improved mood, breast- and endocrine-related quality of life, and well-being more effectively than standard care in women with stage 0 to III breast cancer, and these results persisted at three months. To our knowledge, this study provided novel evidence that MBSR can help alleviate long-term emotional and physical adverse effects of medical treatments, including endocrine treatments. MBSR is recommended to support survivors of breast cancer

In situ oligonucleotide synthesis on poly(dimethylsiloxane): a flexible substrate for microarray fabrication

In this paper, we demonstrate in situ synthesis of oligonucleotide probes on poly(dimethylsiloxane) (PDMS) microchannels through use of conventional phosphoramidite chemistry. PDMS polymer was moulded into a series of microchannels using standard soft lithography (micro-moulding), with dimensions <100 μm. The surface of the PDMS was derivatized by exposure to ultraviolet/ozone followed by vapour phase deposition of glycidoxypropyltrimethoxysilane and reaction with poly(ethylene glycol) spacer, resulting in a reactive surface for oligonucleotide coupling. High, reproducible yields were achieved for both 6mer and 21mer probes as assessed by hybridization to fluorescent oligonucleotides. Oligonucleotide surface density was comparable with that obtained on glass substrates. These results suggest PDMS as a stable and flexible alternative to glass as a suitable substrate in the fabrication and synthesis of DNA microarrays

Interaction Effects in a One-Dimensional Constriction

We have investigated the transport properties of one-dimensional (1D) constrictions defined by split-gates in high quality GaAs/AlGaAs heterostructures. In addition to the usual quantized conductance plateaus, the equilibrium conductance shows a structure close to $0.7(2e^2/h)$, and in consolidating our previous work [K.~J. Thomas et al., Phys. Rev. Lett. 77, 135 (1996)] this 0.7 structure has been investigated in a wide range of samples as a function of temperature, carrier density, in-plane magnetic field $B_{\parallel}$ and source-drain voltage $V_{sd}$. We show that the 0.7 structure is not due to transmission or resonance effects, nor does it arise from the asymmetry of the heterojunction in the growth direction. All the 1D subbands show Zeeman splitting at high $B_{\parallel}$, and in the wide channel limit the $g$-factor is $\mid g \mid \approx 0.4$, close to that of bulk GaAs. As the channel is progressively narrowed we measure an exchange-enhanced $g$-factor. The measurements establish that the 0.7 structure is related to spin, and that electron-electron interactions become important for the last few conducting 1D subbands.Comment: 8 pages, 7 figures (accepted in Phys. Rev. B

Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.

UnlabelledMigalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.Trial registrationClinicalTrials.gov NCT01196871

Visuospatial asymmetries do not modulate the cheerleader effect

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The cheerleader effect occurs when the same individual appears to be more attractive when seen in a group, compared to alone. As observers over-attend to visual information presented in the left visual field, we investigated whether the spatial arrangement of the faces in a group would influence the magnitude of the cheerleader effect. In Experiment 1, target faces were presented twice in the centre of the display: once alone, and once in a group. Group images featured two distractor faces, which were presented in either the left or the right visual field, or on either side of the target. The location of the distractor faces did not modulate the size of the cheerleader effect, which was observed in each group configuration. In Experiment 2, we manipulated the location of the target faces, which were presented at the far left, far right, or centre of the group. Faces were again significantly more attractive in each group configuration, and the spatial location of the target face did not influence the size of the cheerleader effect. Together, our results show that the cheerleader effect is a robust phenomenon, which is not influenced by the spatial arrangement of the faces in the group

An improved database of coastal flooding in the United Kingdom from 1915 to 2016

Coastal flooding caused by extreme sea levels can produce devastating and wide-ranging consequences. The ‘SurgeWatch’ v1.0 database systematically documents and assesses the consequences of historical coastal flood events around the UK. The original database was inevitably biased due to the inconsistent spatial and temporal coverage of sea-level observations utilised. Therefore, we present an improved version integrating a variety of ‘soft’ data such as journal papers, newspapers, weather reports, and social media. SurgeWatch2.0 identifies 329 coastal flooding events from 1915 to 2016, a more than fivefold increase compared to the 59 events in v1.0. Moreover, each flood event is now ranked using a multi-level categorisation based on inundation, transport disruption, costs, and fatalities: from 1 (Nuisance) to 6 (Disaster). For the 53 most severe events ranked Category 3 and above, an accompanying event description based upon the Source-Pathway-Receptor-Consequence framework was produced. Thus, SurgeWatch v2.0 provides the most comprehensive and coherent historical record of UK coastal flooding. It is designed to be a resource for research, planning, management and education