Biomolecular imaging and electronic damage using X-ray free-electron lasers

Proposals to determine biomolecular structures from diffraction experiments using femtosecond X-ray free-electron laser (XFEL) pulses involve a conflict between the incident brightness required to achieve diffraction-limited atomic resolution and the electronic and structural damage induced by the illumination. Here we show that previous estimates of the conditions under which biomolecular structures may be obtained in this manner are unduly restrictive, because they are based on a coherent diffraction model that is not appropriate to the proposed interaction conditions. A more detailed imaging model derived from optical coherence theory and quantum electrodynamics is shown to be far more tolerant of electronic damage. The nuclear density is employed as the principal descriptor of molecular structure. The foundations of the approach may also be used to characterize electrodynamical processes by performing scattering experiments on complex molecules of known structure.Comment: 16 pages, 2 figure

An Integrated Approach Providing Scientific and Policy-Relevant Insights for South-West Bangladesh

Bangladesh is identified as an impact hotspot for sea-level rise in multiple studies. However, a range of other factors must be considered including catchment management, socio-economic development and governance quality, as well as delta plain biophysical processes. Taking an integrated assessment approach highlights that to 2050 future changes are more sensitive to human choice/policy intervention than climate change, ecosystem services diminish as a proportion of the economy with time, continuing historic trends and significant poverty persists for some households. Hence under favourable policy decisions, development could transform Bangladesh by 2050 making it less vulnerable to longer-term climate change and subsidence. Beyond 2050, the threats of climate change are much larger, requiring strategic adaptation responses and policy changes that must be initiated now

Mechanical versus manual chest compressions in the treatment of in-hospital cardiac arrest patients in a non-shockable rhythm : a randomised controlled feasibility trial (COMPRESS-RCT)

Background Mechanical chest compression devices consistently deliver high-quality chest compressions. Small very low-quality studies suggest mechanical devices may be effective as an alternative to manual chest compressions in the treatment of adult in-hospital cardiac arrest patients. The aim of this feasibility trial is to assess the feasibility of conducting an effectiveness trial in this patient population. Methods COMPRESS-RCT is a multi-centre parallel group feasibility randomised controlled trial, designed to assess the feasibility of undertaking an effectiveness to compare the effect of mechanical chest compressions with manual chest compressions on 30-day survival following in-hospital cardiac arrest. Over approximately two years, 330 adult patients who sustain an in-hospital cardiac arrest and are in a non-shockable rhythm will be randomised in a 3:1 ratio to receive ongoing treatment with a mechanical chest compression device (LUCAS 2/3, Jolife AB/Stryker, Lund, Sweden) or continued manual chest compressions. It is intended that recruitment will occur on a 24/7 basis by the clinical cardiac arrest team. The primary study outcome is the proportion of eligible participants randomised in the study during site operational recruitment hours. Participants will be enrolled using a model of deferred consent, with consent for follow-up sought from patients or their consultee in those that survive the cardiac arrest event. The trial will have an embedded qualitative study, in which we will conduct semi-structured interviews with hospital staff to explore facilitators and barriers to study recruitment. Discussion The findings of COMPRESS-RCT will provide important information about the deliverability of an effectiveness trial to evaluate the effect on 30-day mortality of routine use of mechanical chest compression devices in adult in-hospital cardiac arrest patients

Calibration of Traffic Simulation Models using SPSA

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Γεωπληροφορική

Investigation of autism and GABA receptor subunit genes in multiple ethnic groups

Autism is a neurodevelopmental disorder of complex genetics, characterized by impairment in social interaction and communication, as well as repetitive behavior. Multiple lines of evidence, including alterations in levels of GABA and GABA receptors in autistic patients, indicate that the GABAergic system, which is responsible for synaptic inhibition in the adult brain, may be involved in autism. Previous studies in our lab indicated association of noncoding single nucleotide polymorphisms (SNPs) within a GABA receptor subunit gene on chromosome 4, GABRA4, and interaction between SNPs in GABRA4 and GABRB1 (also on chromosome 4), within Caucasian autism patients. Studies of genetic variation in African-American autism families are rare. Analysis of 557 Caucasian and an independent population of 54 African-American families with 35 SNPs within GABRB1 and GABRA4 strengthened the evidence for involvement of GABRA4 in autism risk in Caucasians (rs17599165, p=0.0015; rs1912960, p=0.0073; and rs17599416, p=0.0040) and gave evidence of significant association in African-Americans (rs2280073, p=0.0287 and rs16859788, p=0.0253). The GABRA4 and GABRB1 interaction was also confirmed in the Caucasian dataset (most significant pair, rs1912960 and rs2351299; p=0.004). Analysis of the subset of families with a positive history of seizure activity in at least one autism patient revealed no association to GABRA4; however, three SNPs within GABRB1 showed significant allelic association; rs2351299 (p=0.0163), rs4482737 (p=0.0339), and rs3832300 (p=0.0253). These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype

Coherent methods in the X-ray sciences

X-ray sources are developing rapidly and their coherent output is growing extremely rapidly. The increased coherent flux from modern X-ray sources is being matched with an associated rapid development in experimental methods. This article reviews the literature describing the ideas that utilise the increased brilliance from modern X-ray sources. It explores how ideas in coherent X-ray science are leading to developments in other areas, and vice versa. The article describes measurements of coherence properties and uses this discussion as a base from which to describe partially-coherent diffraction and X-ray phase contrast imaging, with its applications in materials science, engineering and medicine. Coherent diffraction imaging methods are reviewed along with associated experiments in materials science. Proposals for experiments to be performed with the new X-ray free-electron-lasers are briefly discussed. The literature on X-ray photon correlation spectroscopy is described and the features it has in common with other coherent X-ray methods are identified. Many of the ideas used in the coherent X-ray literature have their origins in the optical and electron communities and these connections are explored. A review of the areas in which ideas from coherent X-ray methods are contributing to methods for the neutron, electron and optical communities is presented.Comment: A review articel accepted by Advances in Physics. 158 pages, 29 figures, 3 table

Effects of supervised exercise on cancer-related fatigue in breast cancer survivors: a systematic review and meta-analysis

Background: Cancer-related fatigue (CRF) is the most common and distressing symptom in breast cancer survivors. Approximately 40% to 80% of cancer patients undergoing active treatment suffer from CRF. Exercise improves overall quality of life and CRF; however, the specific effects of the training modalities are not well understood.Methods: This study aimed to determine the pooled effects of supervised exercise interventions on CRF in breast cancer survivors. We searched PubMed/MEDLINE, EMBASE, Scopus, CENTRAL and CINAHL databases between December 2013 and January 2014 without language restrictions. Risk of bias and methodological quality were evaluated using the PEDro score. Pooled effects were calculated with a random-effects model according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I2 test.Results: Nine high-quality studies (n = 1156) were finally included. Supervised aerobic exercise was statistically more effective than conventional care in improving CRF among breast cancer survivors (SMD = −0.51, 95%CI −0.81 to −0.21), with high statistical heterogeneity (P = 0.001; I2 = 75%). Similar effects were found for resistance training on CRF (SMD = −0.41, 95%CI −0.76 to −0.05; P = 0.02; I2 = 64%). Meta-regression analysis revealed that exercise volume parameters are closely related with the effect estimates on CRF. Egger’s test suggested moderate evidence of publication bias (P = 0.04).Conclusions: Supervised exercise reduces CRF and must be implemented in breast cancer rehabilitation settings. High-volume exercises are safe and effective in improving CRF and overall quality of life in women with breast cancer. Further research is encouraged.The authors would like to acknowledge Universidad Santo Tomás, Bogotá for the financial support to the GICAEDS Group (Project: Práctica del autoexamen de seno y los conocimientos, factores de riesgo y estilos de vida relacionados al cáncer de mama en mujeres jóvenes de la USTA – Number: 4110060001-008)

Unexpected differential metabolic responses of Campylobacter jejuni to the abundant presence of glutamate and fucose

Introduction: Campylobacter jejuni is the leading cause of foodborne bacterial enteritis in humans, and yet little is known in regard to how genetic diversity and metabolic capabilities among isolates affect their metabolic phenotype and pathogenicity. Objectives: For instance, the C. jejuni 11168 strain can utilize both l-fucose and l-glutamate as a carbon source, which provides the strain with a competitive advantage in some environments and in this study we set out to assess the metabolic response of C. jejuni 11168 to the presence of l-fucose and l-glutamate in the growth medium. Methods: To achieve this, untargeted hydrophilic liquid chromatography coupled to mass spectrometry was used to obtain metabolite profiles of supernatant extracts obtained at three different time points up to 24 h. Results: This study identified both the depletion and the production and subsequent release of a multitude of expected and unexpected metabolites during the growth of C. jejuni 11168 under three different conditions. A large set of standards allowed identification of a number of metabolites. Further mass spectrometry fragmentation analysis allowed the additional annotation of substrate-specific metabolites. The results show that C. jejuni 11168 upon l-fucose addition indeed produces degradation products of the fucose pathway. Furthermore, methionine was faster depleted from the medium, consistent with previously-observed methionine auxotrophy. Conclusions: Moreover, a multitude of not previously annotated metabolites in C. jejuni were found to be increased specifically upon l-fucose addition. These metabolites may well play a role in the pathogenicity of this C. jejuni strain.</p

Spearfishing Regulation Benefits Artisanal Fisheries: The ReGS Indicator and Its Application to a Multiple-Use Mediterranean Marine Protected Area

The development of fishing efficiency coupled with an increase of fishing effort led to the overexploitation of numerous natural marine resources. In addition to this commercial pressure, the impact of recreational activities on fish assemblages remains barely known. Here we examined the impact of spearfishing limitation on resources in a marine protected area (MPA) and the benefit it provides for the local artisanal fishery through the use of a novel indicator. We analysed trends in the fish assemblage composition using artisanal fisheries data collected in the Bonifacio Strait Natural Reserve (BSNR), a Mediterranean MPA where the spearfishing activity has been forbidden over 15% of its area. Fish species were pooled into three response groups according to their target level by spearfishing. We developed the new flexible ReGS indicator reflecting shifts in species assemblages according to the relative abundance of each response group facing external pressure. The catch per unit effort (CPUE) increased by ca. 60% in the BSNR between 2000 and 2007, while the MPA was established in 1999. The gain of CPUE strongly depended on the considered response group: for the highly targeted group, the CPUE doubled while the CPUE of the untargeted group increased by only 15.5%. The ReGS value significantly increased from 0.31 to 0.45 (on a scale between 0 and 1) in the general perimeter of this MPA while it has reached a threshold of 0.43, considered as a reference point, in the area protected from spearfishing since 1982. Our results demonstrated that limiting recreational fishing by appropriate zoning in multiple-use MPAs represents a real benefit for artisanal fisheries. More generally we showed how our new indicator may reveal a wide range of impacts on coastal ecosystems such as global change or habitat degradation