The world crisis: global financial governance: principles of reform

It is now increasingly acknowledged that complex global processes, from the financial to the ecological, connect the fate of communities across the world. Yet the problem-solving capacity of the existing system of global institutions is in many areas not effective, accountable, or fast enough to resolve current global dilemmas. What has recently been called the paradox of our times refers to the fact that the collective issues we must grapple with are of growing extensity and intensity, and yet the means for addressing them are weak and incomplete.1 There are a variety of reasons for the persistence of these problems, but at the most basic level the persistence of this paradox remains an issue of governance. One significant problem in this regard is that a growing number of issues span both the domestic and the international domains. The institutional fragmentation and competition between states can lead to these global issues being addressed in an ad hoc and dissonant manner. A second problem is that even when the global dimension of a problem is acknowledged, there is no clear division of labour among the myriad of international institutions that seek to address them: their functions often overlap, their mandates conflict, and their objectives often become blurred. A third problem is that the existing system of global governance suffers from severe deficits of accountability and inclusion. This problem is especially relevant in regard to how less economically powerful states and, hence, their entire populations, are marginalised or excluded from decisionmaking. This paper describes the current global economic crisis as intimately related to a problem of governance, and articulates simple principles by which the reform of governance can be guided. Increased accountability through participatory reform, we argue, helps to underwrite effectiveness

Atmospheric circulation of tidally locked exoplanets: a suite of benchmark tests for dynamical solvers

The complexity of atmospheric modelling and its inherent non-linearity, together with the limited amount of data of exoplanets available, motivate model intercomparisons and benchmark tests. In the geophysical community, the Held-Suarez test is a standard benchmark for comparing dynamical core simulations of the Earth's atmosphere with different solvers, based on statistically-averaged flow quantities. In the present study, we perform analogues of the Held-Suarez test for tidally-locked exoplanets with the GFDL-Princeton Flexible Modeling System (FMS) by subjecting both the spectral and finite difference dynamical cores to a suite of tests, including the standard benchmark for Earth, a hypothetical tidally-locked Earth, a "shallow" hot Jupiter model and a "deep" model of HD 209458b. We find qualitative and quantitative agreement between the solvers for the Earth, tidally-locked Earth and shallow hot Jupiter benchmarks, but the agreement is less than satisfactory for the deep model of HD 209458b. Further investigation reveals that closer agreement may be attained by arbitrarily adjusting the values of the horizontal dissipation parameters in the two solvers, but it remains the case that the magnitude of the horizontal dissipation is not easily specified from first principles. Irrespective of radiative transfer or chemical composition considerations, our study points to limitations in our ability to accurately model hot Jupiter atmospheres with meteorological solvers at the level of ten percent for the temperature field and several tens of percent for the velocity field. Direct wind measurements should thus be particularly constraining for the models. Our suite of benchmark tests also provides a reference point for researchers wishing to adapt their codes to study the atmospheric circulation regimes of tidally-locked Earths/Neptunes/Jupiters.Comment: Accepted by MNRAS, 23 pages, 17 figures, 2 tables. No changes from previous version, except MNRAS wants no hyphen in the title. Sample movies of simulations are available at http://www.phys.ethz.ch/~kheng/fms

Low Dose Studies with Focused X-Rays in cell and Tissue Models: Mechanisms of Bystander and Genomic Instability Responses

The management of the risks of exposure of people to ionizing radiation is important in relation to its uses in industry and medicine, also to natural and man-made radiation in the environment. The vase majority of exposures are at a very low level of radiation dose. The risks are of inducing cancer in the exposed individuals and a smaller risk of inducing genetic damage that can be indicate that they are low. As a result, the risks are impossible to detect in population studies with any accuracy above the normal levels of cancer and genetic defects unless the dose levels are high. In practice, this means that our knowledge depends very largely on the information gained from the follow-up of the survivors of the atomic bombs dropped on Japanese cities. The risks calculated from these high-dose short-duration exposures then have to be projected down to the low-dose long-term exposures that apply generally. Recent research using cells in culture has revealed that the relationship between high- and low-dose biological damage may be much more complex than had previously been thought. The aims of this and other projects in the DOE's Low-Dose Program are to gain an understanding of the biological actions of low-dose radiation, ultimately to provide information that will lead to more accurate quantification of low-dose risk. Our project is based on the concept that the processes by which radiation induces cancer start where the individual tracks of radiation impact on cells and tissues. At the dose levels of most low-dose exposures, these events are rare and any individual cells only ''sees'' radiation tracks at intervals averaging from weeks to years apart. This contrasts with the atomic bomb exposures where, on average, each cell was hit by hundreds of tracks instantaneously. We have therefore developed microbeam techniques that enable us to target cells in culture with any numbers of tracks, from one upwards. This approach enables us to study the biological ha sis of the relationship between high- and low-dose exposures. The targeting approach also allows us to study very clearly a newly recognized effect of radiation, the ''bystander effect'', which appears to dominate some low-dose responses and therefore may have a significant role in low-dose risk mechanisms. Our project also addresses the concept that the background of naturally occurring oxidative damage that takes place continually in cells due to byproducts of metabolism may play a role in low-dose radiation risk. This project therefore also examines how cells are damaged by treatments that modify the levels of oxidative damage, either alone or in combination with low-dose irradiation. In this project, we have used human and rodent cell lines and each set of experiments has been carried out on a single cell type. However, low-dose research has to extend into tissues because signaling between cells of different types is likely to influence the responses. Our studies have therefore also included microbeam experiments using a model tissue system that consists of an explant of a small piece of pig ureter grown in culture. The structure of this tissue is similar to that of epithelium and therefore it relates to the tissues in which carcinoma arises. Our studies have been able to measure bystander-induced changes in the cells growing out from the tissue fragment after it has been targeted with a few radiation tracks to mimic a low-dose exposure

STAMP: Extensions to the STADEN sequence analysis package for high throughput interactive microsatellite marker design

BackgroundMicrosatellites (MSs) are DNA markers with high analytical power, which are widely used in population genetics, genetic mapping, and forensic studies. Currently available software solutions for high-throughput MS design (i) have shortcomings in detecting and distinguishing imperfect and perfect MSs, (ii) lack often necessary interactive design steps, and (iii) do not allow for the development of primers for multiplex amplifications. We present a set of new tools implemented as extensions to the STADEN package, which provides the backbone functionality for flexible sequence analysis workflows. The possibility to assemble overlapping reads into unique contigs (provided by the base functionality of the STADEN package) is important to avoid developing redundant markers, a feature missing from most other similar tools.ResultsOur extensions to the STADEN package provide the following functionality to facilitate microsatellite (and also minisatellite) marker design: The new modules (i) integrate the state-of-the-art tandem repeat detection and analysis software PHOBOS into workflows, (ii) provide two separate repeat detection steps with different search criteria one for masking repetitive regions during assembly of sequencing reads and the other for designing repeat-flanking primers for MS candidate loci, (iii) incorporate the widely used primer design program PRIMER3 into STADEN workflows, enabling the interactive design and visualization of flanking primers for microsatellites, and (iv) provide the functionality to find optimal locus- and primer pair combinations for multiplex primer design. Furthermore, our extensions include a module for storing analysis results in an SQLite database, providing a transparent solution for data access from within as well as from outside of the STADEN Package.ConclusionThe STADEN package is enhanced by our modules into a highly flexible, high-throughput, interactive tool for conventional and multiplex microsatellite marker design. It gives the user detailed control over the workflow, enabling flexible combinations of manual and automated analysis steps. The software is available under the OpenBSD License [1,2]. The high efficiency of our automated marker design workflow has been confirmed in three microsatellite development projects

The Third wave in globalization theory

This essay examines a proposition made in the literature that there are three waves in globalization theory—the globalist, skeptical, and postskeptical or transformational waves—and argues that this division requires a new look. The essay is a critique of the third of these waves and its relationship with the second wave. Contributors to the third wave not only defend the idea of globalization from criticism by the skeptics but also try to construct a more complex and qualified theory of globalization than provided by first-wave accounts. The argument made here is that third-wave authors come to conclusions that try to defend globalization yet include qualifications that in practice reaffirm skeptical claims. This feature of the literature has been overlooked in debates and the aim of this essay is to revisit the literature and identify as well as discuss this problem. Such a presentation has political implications. Third wavers propose globalist cosmopolitan democracy when the substance of their arguments does more in practice to bolster the skeptical view of politics based on inequality and conflict, nation-states and regional blocs, and alliances of common interest or ideology rather than cosmopolitan global structures

Gliese 581g as a scaled-up version of Earth: atmospheric circulation simulations

We use three-dimensional simulations to study the atmospheric circulation on the first Earth-sized exoplanet discovered in the habitable zone of an M star. We treat Gliese 581g as a scaled-up version of Earth by considering increased values for the exoplanetary radius and surface gravity, while retaining terrestrial values for parameters which are unconstrained by current observations. We examine the long-term, global temperature and wind maps near the surface of the exoplanet --- the climate. The specific locations for habitability on Gliese 581g depend on whether the exoplanet is tidally-locked and how fast radiative cooling occurs on a global scale. Independent of whether the existence of Gliese 581g is confirmed, our study highlights the use of general circulation models to quantify the atmospheric circulation on potentially habitable, Earth-sized exoplanets, which will be the prime targets of exoplanet discovery and characterization campaigns in the next decade.Comment: Accepted by MNRAS. 15 pages, 13 figures. Sample movies of simulations are available at http://www.phys.ethz.ch/~kheng/fms

Preventing Plasmon Coupling between Gold Nanorods Improves the Sensitivity of Photoacoustic Detection of Labeled Stem Cells in Vivo

© 2016 American Chemical Society.Gold nanorods are excellent contrast agents for imaging technologies which rely on near-infrared absorption such as photoacoustic imaging. For cell tracking applications, the cells of interest are labeled with the contrast agent prior to injection. However, after uptake into cells by endocytosis, the confinement and high concentration in endosomes leads to plasmon band broadening and reduced absorbance. This would limit the potential of multispectral optoacoustic tomography in terms of spectral processing and, consequently, sensitivity. Here, we show that steric hindrance provided by silica coating of the nanorods leads to the preservation of their spectral properties and improved photoacoustic sensitivity. This strategy allowed the detection and monitoring of as few as 2 × 104 mesenchymal stem cells in mice over a period of 15 days with a high spatial resolution. Importantly, the silica-coated nanorods did not affect the viability or differentiation potential of the transplanted mesenchymal stem cells

Post-mortem magnetic resonance imaging with computed tomography-guided biopsy for foetuses and infants: a prospective, multicentre, cross-sectional study

BACKGROUND: Post-mortem imaging has been suggested as an alternative to conventional autopsy in the prenatal and postnatal periods. Noninvasive autopsies do not provide tissue for histological examination, which may limit their clinical value, especially when infection-related morbidity and mortality are suspected. METHODS: We performed a prospective, multicentre, cross-sectional study to compare the diagnostic performance of post-mortem magnetic resonance imaging with computed tomography-guided biopsy (Virtopsy®) with that of conventional autopsy in foetuses and infants. Cases referred for conventional autopsy were eligible for enrolment. After post-mortem imaging using a computed tomography scanner and a magnetic resonance imaging unit, computed tomography-guided tissue sampling was performed. Virtopsy results were compared with conventional autopsy in determining the likely final cause of death and major pathologies. The primary outcome was the proportion of cases for which the same cause of death was determined by both methods. Secondary outcomes included the proportion of false positive and false negative major pathological lesions detected by virtopsy and the proportion of computed tomography-guided biopsies that were adequate for histological examination. RESULTS: Overall, 101 cases (84 fetuses, 17 infants) were included. Virtopsy and autopsy identified the same cause of death in 91 cases (90.1%, 95% CI 82.7 to 94.5). The sensitivity and specificity of virtopsy for determining the cause of death were 96.6% (95% CI 90.6 to 98.8) and 41.7% (95% CI 19.3 to 68.0), respectively. In 32 cases (31.7%, 95% CI 23.4 to 41.3), major pathological findings remained undetected by virtopsy, and in 45 cases (44.6%, 95% CI 35.2 to 54.3), abnormalities were diagnosed by virtopsy but not confirmed by autopsy. Computed tomography-guided tissue sampling was adequate for pathological comments in 506 of 956 biopsies (52.7%) and added important diagnostic value in five of 30 cases (16.1%) with an unclear cause of death before autopsy compared with postmortem imaging alone. In 19 of 20 infective deaths (95%), biopsies revealed infection-related tissue changes. Infection was confirmed by placental examination in all fetal cases. CONCLUSIONS: Virtopsy demonstrated a high concordance with conventional autopsy for the detection of cause of death but was less accurate for the evaluation of major pathologies. Computed tomography-guided biopsy had limited additional diagnostic value. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01888380)

The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury.

INTRODUCTION Preclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI. METHODS HeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses. DISCUSSION We hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH. STUDY REGISTRATION ClinicalTrials.gov Identifier NCT04998370 . Date of registration: August 10, 2021

The HeMoVal study protocol: a prospective international multicenter cohort study to validate cerebrospinal fluid hemoglobin as a monitoring biomarker for aneurysmal subarachnoid hemorrhage related secondary brain injury

Introduction: Preclinical studies provided a strong rationale for a pathophysiological link between cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) and secondary brain injury after subarachnoid hemorrhage (SAH-SBI). In a single-center prospective observational clinical study, external ventricular drain (EVD) based CSF-Hb proved to be a promising biomarker to monitor for SAH-SBI. The primary objective of the HeMoVal study is to prospectively validate the association between EVD based CSF-Hb and SAH-SBI during the first 14 days post-SAH. Secondary objectives include the assessment of the discrimination ability of EVD based CSF-Hb for SAH-SBI and the definition of a clinically relevant range of EVD based CSF-Hb toxicity. In addition, lumbar drain (LD) based CSF-Hb will be assessed for its association with and discrimination ability for SAH-SBI. Methods: HeMoVal is a prospective international multicenter observational cohort study. Adult patients admitted with aneurysmal subarachnoid hemorrhage (aSAH) are eligible. While all patients with aSAH are included, we target a sample size of 250 patients with EVD within the first 14 day after aSAH. Epidemiologic and disease-specific baseline measures are assessed at the time of study inclusion. In patients with EVD or LD, each day during the first 14 days post-SAH, 2 ml of CSF will be sampled in the morning, followed by assessment of the patients for SAH-SBI, co-interventions, and complications in the afternoon. After 3 months, a clinical follow-up will be performed. For statistical analysis, the cohort will be stratified into an EVD, LD and full cohort. The primary analysis will quantify the strength of association between EVD based CSF-Hb and SAH-SBI in the EVD cohort based on a generalized additive model. Secondary analyses include the strength of association between LD based CSF-Hb and SAH-SBI in the LD cohort based on a generalized additive model, as well as the discrimination ability of CSF-Hb for SAH-SBI based on receiver operating characteristic (ROC) analyses. Discussion: We hypothesize that this study will validate the value of CSF-Hb as a biomarker to monitor for SAH-SBI. In addition, the results of this study will provide the potential base to define an intervention threshold for future studies targeting CSF-Hb toxicity after aSAH