IMF conditionality and development policy space, 1985–2014

In recent years, the International Monetary Fund (IMF) has re-emerged as a central actor in global economic governance. Its rhetoric and policies suggest that the organization has radically changed the ways in which it offers financial assistance to countries in economic trouble. We revisit two long-standing controversies: Has the policy content of IMF programmes evolved to allow for more policy space? Do these programmes now allow for the protection of labour and social policies? We collected relevant archival material on the IMF's lending operations and identified all policy conditionality in IMF loan agreements between 1985 and 2014, extracting 55,465 individual conditions across 131 countries in total. We find little evidence of a fundamental transformation of IMF conditionality. The organization's post-2008 programmes reincorporated many of the mandated reforms that the organization claims to no longer advocate and the number of conditions has been increasing. We also find that policies introduced to ameliorate the social consequences of IMF macroeconomic advice have been inadequately incorporated into programme design. Drawing on this evidence, we argue that multiple layers of rhetoric and ceremonial reforms have been designed to obscure the actual practice of adjustment programmes, revealing an escalating commitment to hypocrisy.The authors gratefully acknowledge funding by the Institute for New Economic Thinking (INET Grant INO13-00020: ‘The Political Economy of Structural Adjustment’), the Cambridge Political Economy Society Trust, and the Centre for Business Research at the University of Cambridge

KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.

Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that specifically inhibit the KRAS isoform by binding to an allosteric site encompassing the region around KRAS-specific residue histidine 95 at the helix α3/loop 7/helix α4 interface. We show that these DARPins specifically inhibit KRAS/effector interactions and the dependent downstream signalling pathways in cancer cells. Binding by the DARPins at that region influences KRAS/effector interactions in different ways, including KRAS nucleotide exchange and inhibiting KRAS dimerization at the plasma membrane. These results highlight the importance of targeting the α3/loop 7/α4 interface, a previously untargeted site in RAS, for specifically inhibiting KRAS function

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

The Human Retinoblastoma Gene Is Imprinted

Genomic imprinting is an epigenetic process leading to parent-of-origin–specific DNA methylation and gene expression. To date, ∼60 imprinted human genes are known. Based on genome-wide methylation analysis of a patient with multiple imprinting defects, we have identified a differentially methylated CpG island in intron 2 of the retinoblastoma (RB1) gene on chromosome 13. The CpG island is part of a 5′-truncated, processed pseudogene derived from the KIAA0649 gene on chromosome 9 and corresponds to two small CpG islands in the open reading frame of the ancestral gene. It is methylated on the maternal chromosome 13 and acts as a weak promoter for an alternative RB1 transcript on the paternal chromosome 13. In four other KIAA0649 pseudogene copies, which are located on chromosome 22, the two CpG islands have deteriorated and the CpG dinucleotides are fully methylated. By analysing allelic RB1 transcript levels in blood cells, as well as in hypermethylated and 5-aza-2′-deoxycytidine–treated lymphoblastoid cells, we have found that differential methylation of the CpG island skews RB1 gene expression in favor of the maternal allele. Thus, RB1 is imprinted in the same direction as CDKN1C, which operates upstream of RB1. The imprinting of two components of the same pathway indicates that there has been strong evolutionary selection for maternal inhibition of cell proliferation

Challenges and opportunities in the care of chronic subdural haematoma: perspectives from a multi-disciplinary working group on the need for change.

INTRODUCTION: A chronic subdural haematoma (cSDH) is a collection of altered blood products between the dura and brain resulting in a slowly evolving neurological deficit. It is increasingly common and, in high income countries, affects an older, multimorbid population. With changing demographics improving the care of this cohort is of increasing importance. METHODS: We convened a cross-disciplinary working group (the 'Improving Care in Elderly Neurosurgery Initiative') in October 2020. This comprised experts in neurosurgical care and a range of perioperative stakeholders. An Implementation Science framework was used to structure discussions around the challenges of cSDH care within the United Kingdom. The outcomes of these discussions were recorded and summarised, before being circulated to all attendees for comment and refinement. RESULTS: The working group identified four key requirements for improving cSDH care: (1) data, audit, and natural history; (2) evidence-based guidelines and pathways; (3) shared decision-making; and (4) an overarching quality improvement strategy. Frequent transfers between care providers were identified as impacting on both perioperative care and presenting a barrier to effective data collection and teamworking. Improvement initiatives must be cognizant of the complex, system-wide nature of the problem, and may require a combination of targeted trials at points of clinical equipoise (such as anesthetic technique or anticoagulant management), evidence-based guideline development, and a cycle of knowledge acquisition and implementation. CONCLUSION: The care of cSDH is a growing clinical problem. Lessons may be learned from the standardised pathways of care such as those as used in hip fracture and stroke. A defined care pathway for cSDH, encompassing perioperative care and rehabilitation, could plausibly improve patient outcomes but work remains to tailor such a pathway to cSDH care. The development of such a pathway at a national level should be a priority, and the focus of future work

Swift follow-up observations of candidate gravitational-wave transient events

We present the first multi-wavelength follow-up observations of two candidate gravitational-wave (GW) transient events recorded by LIGO and Virgo in their 2009-2010 science run. The events were selected with low latency by the network of GW detectors and their candidate sky locations were observed by the Swift observatory. Image transient detection was used to analyze the collected electromagnetic data, which were found to be consistent with background. Off-line analysis of the GW data alone has also established that the selected GW events show no evidence of an astrophysical origin; one of them is consistent with background and the other one was a test, part of a "blind injection challenge". With this work we demonstrate the feasibility of rapid follow-ups of GW transients and establish the sensitivity improvement joint electromagnetic and GW observations could bring. This is a first step toward an electromagnetic follow-up program in the regime of routine detections with the advanced GW instruments expected within this decade. In that regime multi-wavelength observations will play a significant role in completing the astrophysical identification of GW sources. We present the methods and results from this first combined analysis and discuss its implications in terms of sensitivity for the present and future instruments.Comment: Submitted for publication 2012 May 25, accepted 2012 October 25, published 2012 November 21, in ApJS, 203, 28 ( http://stacks.iop.org/0067-0049/203/28 ); 14 pages, 3 figures, 6 tables; LIGO-P1100038; Science summary at http://www.ligo.org/science/Publication-S6LVSwift/index.php ; Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p110003

Implementation and testing of the first prompt search for gravitational wave transients with electromagnetic counterparts

Aims. A transient astrophysical event observed in both gravitational wave (GW) and electromagnetic (EM) channels would yield rich scientific rewards. A first program initiating EM follow-ups to possible transient GW events has been developed and exercised by the LIGO and Virgo community in association with several partners. In this paper, we describe and evaluate the methods used to promptly identify and localize GW event candidates and to request images of targeted sky locations. Methods. During two observing periods (Dec 17 2009 to Jan 8 2010 and Sep 2 to Oct 20 2010), a low-latency analysis pipeline was used to identify GW event candidates and to reconstruct maps of possible sky locations. A catalog of nearby galaxies and Milky Way globular clusters was used to select the most promising sky positions to be imaged, and this directional information was delivered to EM observatories with time lags of about thirty minutes. A Monte Carlo simulation has been used to evaluate the low-latency GW pipeline's ability to reconstruct source positions correctly. Results. For signals near the detection threshold, our low-latency algorithms often localized simulated GW burst signals to tens of square degrees, while neutron star/neutron star inspirals and neutron star/black hole inspirals were localized to a few hundred square degrees. Localization precision improves for moderately stronger signals. The correct sky location of signals well above threshold and originating from nearby galaxies may be observed with ~50% or better probability with a few pointings of wide-field telescopes.Comment: 17 pages. This version (v2) includes two tables and 1 section not included in v1. Accepted for publication in Astronomy & Astrophysic

Insect Pollinated Crops, Insect Pollinators and US Agriculture: Trend Analysis of Aggregate Data for the Period 1992–2009

In the US, the cultivated area (hectares) and production (tonnes) of crops that require or benefit from insect pollination (directly dependent crops: apples, almonds, blueberries, cucurbits, etc.) increased from 1992, the first year in this study, through 1999 and continued near those levels through 2009; aggregate yield (tonnes/hectare) remained unchanged. The value of directly dependent crops attributed to all insect pollination (2009 USD) decreased from $14.29 billion in 1996, the first year for value data in this study, to$10.69 billion in 2001, but increased thereafter, reaching $15.12 billion by 2009. The values attributed to honey bees and non-Apis pollinators followed similar patterns, reaching$11.68 billion and $3.44 billion, respectively, by 2009. The cultivated area of crops grown from seeds resulting from insect pollination (indirectly dependent crops: legume hays, carrots, onions, etc.) was stable from 1992 through 1999, but has since declined. Production of those crops also declined, albeit not as rapidly as the decline in cultivated area; this asymmetry was due to increases in aggregate yield. The value of indirectly dependent crops attributed to insect pollination declined from$15.45 billion in 1996 to $12.00 billion in 2004, but has since trended upward. The value of indirectly dependent crops attributed to honey bees and non-Apis pollinators, exclusive of alfalfa leafcutter bees, has declined since 1996 to$5.39 billion and $1.15 billion, respectively in 2009. The value of alfalfa hay attributed to alfalfa leafcutter bees ranged between$4.99 and $7.04 billion. Trend analysis demonstrates that US producers have a continued and significant need for insect pollinators and that a diminution in managed or wild pollinator populations could seriously threaten the continued production of insect pollinated crops and crops grown from seeds resulting from insect pollination

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni

Parasitic infection caused by blood flukes of the genus Schistosoma is a major global health problem. More than 200 million people are infected. Identifying and characterizing the constituent enzymes of the parasite's biochemical pathways should reveal opportunities for developing new therapies (i.e., vaccines, drugs). Schistosomes feed on host blood, and a number of proteolytic enzymes (proteases) contribute to this process. We have identified and characterized a new protease, SmCL3 (for Schistosoma mansoni cathepsin L3), that is found within the gut tissue of the parasite. We have employed various biochemical and molecular biological methods and sequence similarity analyses to characterize SmCL3 and obtain insights into its possible functions in the parasite, as well as its evolutionary position among cathepsin L proteases in general. SmCL3 hydrolyzes major host blood proteins (serum albumin and hemoglobin) and is expressed in parasite life stages infecting the mammalian host. Enzyme substrate specificity detected by positional scanning-synthetic combinatorial library was confirmed by molecular modeling. A sequence analysis placed SmCL3 to the cluster of other cathepsins L in accordance with previous phylogenetic analyses