Critical realism and causal analysis in international relations

Kurki, M. (2007). Critical realism and causal analysis in international relations. Millennium: Journal of International Studies, 35 (2), 361-378. RAE2008

Letter to Rev. Epaphras Kibby. 01/11/1801

Handwritten letter from Timothy Merritt to Rev. Epaphras Kibby regarding lodging and preaching schedule. Sent in care of Mr. Lambert. Dated Jan. 11, 1801, Bath, ME.

Letter to nephew, 01/13/1868

January 13 1868 letter from Daniel A. Whedon to nephew.

CAA paper 2006/01: a database to record human experience of evacuation in aviation accidents: the aircraft accident statistics and knowledge database (AASK)

This report concerns the development of the AASK V4.0 database (CAA Project 560/SRG/R+AD). AASK is the Aircraft Accident Statistics and Knowledge database, which is a repository of survivor accounts from aviation accidents. Its main purpose is to store observational and anecdotal data from interviews of the occupants involved in aircraft accidents. The AASK database has wide application to aviation safety analysis, being a source of factual data regarding the evacuation process. It is also key to the development of aircraft evacuation models such as airEXODUS, where insight into how people actually behave during evacuation from survivable aircraft crashes is required. With support from the UK CAA (Project 277/SRG/R&AD), AASK V3.0 was developed. This was an on-line prototype system available over the internet to selected users and included a significantly increased number of passenger accounts compared with earlier versions, the introduction of cabin crew accounts, the introduction of fatality information and improved functionality through the seat plan viewer utility. The most recently completed AASK project (Project 560/SRG/R+AD) involved four main components: a) analysis of the data collected in V3.0; b) continued collection and entry of data into AASK; c) maintenance and functional development of the AASK database; and d) user feedback survey. All four components have been pursued and completed in this two-year project. The current version developed in the last year of the project is referred to as AASK V4.0. This report provides summaries of the work done and the results obtained in relation to the project deliverables.

The reform of Welfare Regimes in Costa Rica, Chile, Argentina, Brazil and Uruguay

The aim of this article is to analyze the social policy in Latin America in a context of emerging welfare states. To understand the changes one takes into consideration the theories about institutional reform and the transformations produced in the XX century and the beginning of the XXI to substitute a social security regime mainly based on segmentation of benefi ts and on programs to fi ght poverty by another with an institutional and redistributive nature. The paper pays attention in particular to the path of the most developed welfare states of Latin America: Costa Rica, Chile, Argentina, Brasil y Uruguay.

Imaging quantum vibrations on an ultrashort timescale: the deuterium molecular ion

The vibrational wavepacket revival of a basic quantum system is demonstrated experimentally. Using few-cycle laser pulse technology, pump and probe imaging of the vibrational motion of D+2 molecules is conducted, and together with a quantum-mechanical simulation of the excited wavepacket motion, the vibrational revival phenomenon has been characterised. The simulation shows good correlation with the temporal motion and structural features obtained from the data, relaying fundamental information on this diatomic system.

Observations towards early-type stars in the ESO-POP Survey - II. Searches for intermediate- and high-velocity clouds

We present Ca it K and Ti it optical spectra of early-type stars taken mainly from the ultraviolet and visual echelle spectrograph (LIVES) Paranal Observatory Project, plus H 1 21-cm spectra, from the Vila-Elisa and Leiden-Dwingeloo Surveys, which are employed to obtain distances to intermediate- and high-velocity clouds (IHVCs). H I emission at a velocity of -117 km s(-1) towards the sightline HD 30677 (l, b = 190 degrees.2, -22 degrees.2) with column density -1.7 x 10(19) cm(-2) has no corresponding Ca Pi K absorption in the LIVES spectrum, which has a signal-to-noise ratio (S/N) of 610 per resolution element. The star has a spectroscopically determined distance of 2.7 kpc, and hence sets this as a firm lower distance limit towards Anti-Centre cloud ACII. Towards another sightline (HD 46185 with 1, b = 222 0, -10 degrees.1), H1 at a velocity of +122 km s(-1) and column density of 1.2 x 10(19) cm(-2) is seen. The corresponding Ca Pi K spectrum has a S/N of 780, although no absorption is observed at the cloud velocity. This similarly places a firm lower distance limit of 2.9 kpc towards this parcel of gas that may be an intermediate-velocity (IV) cloud. The lack of IV Ca it absorption towards HD 196426 (1, b = 45 degrees.8, -23 degrees.3) at a S/N of 500 reinforces a lower distance limit of -700 pc towards this part of complex gp, where the H I column density is 1.1 x 1019 cm(-2) and velocity is +78 km s(-1). Additionally, no IV Cart is seen in absorption in the spectrum of HD 19445, which is strong in H I with a column density of 8 x 10(19) cm(-2) at a velocity of - -42 km s(-1), placing a firm although uninteresting lower distance limit of 39 pc to this part of IV South. Finally, no high-velocity Call K absorption is seen towards HD 115363 (l, b = 306.0,-1.0) at a S/N of 410, placing a lower distance of -3.2 kpc towards the HVC gas at velocity of - +224 km s(-1) and WE column density of 5.2 x 10(19) cm(-2). This gas is in the same region of the sky as complex WE (Wakker 2001), but at higher velocities. The non-detection of Ca it K absorption sets a lower distance of -3.2 kpc towards the HVC, which is unsurprising if this feature is indeed related to the Magellanic System.

Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Background: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk.
Methods: We undertook a meta-analysis of individual patient data for 10?801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease.
Findings: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35·0% to 19·3% (absolute reduction 15·7%, 95% CI 13·7–17·7, 2p<0·00001) and reduced the 15-year risk of breast cancer death from 25·2% to 21·4% (absolute reduction 3·8%, 1·6–6·0, 2p=0·00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31·0% to 15·6% (absolute recurrence reduction 15·4%, 13·2–17·6, 2p<0·00001) and from 20·5% to 17·2% (absolute mortality reduction 3·3%, 0·8–5·8, 2p=0·005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (=20%), intermediate (10–19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7·8% (95% CI 3·1–12·5), 1·1% (–2·0 to 4·2), and 0·1% (–7·5 to 7·7) respectively (trend in absolute mortality reduction 2p=0·03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63·7% to 42·5% (absolute reduction 21·2%, 95% CI 14·5–27·9, 2p<0·00001) and the 15-year risk of breast cancer death from 51·3% to 42·8% (absolute reduction 8·5%, 1·8–15·2, 2p=0·01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease.
Interpretation: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made.
Funding: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.

Genome-wide Association Study Implicates HLA-C*01:02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

BACKGROUND: We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia. METHODS: The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis. RESULTS: One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10(-9) and in combined samples (rs2523722 p combined = 2.88 × 10(-16)) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study. CONCLUSIONS: This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.

The Anti-Migratory Effects of FKBPL and Its Peptide Derivative, AD-01: Regulation of CD44 and the Cytoskeletal Pathway

FK506 binding protein-like (FKBPL) and its peptide derivatives exert potent anti-angiogenic activity and and control tumour growth in xenograft models, when administered exogenously. However, the role of endogenous FKBPL in angiogenesis is not well characterised. Here we investigated the molecular effects of the endogenous protein and its peptide derivative, AD-01, leading to their anti-migratory activity. Inhibition of secreted FKBPL using a blocking antibody or siRNA-mediated knockdown of FKBPL accelerated the migration of human microvascular endothelial cells (HMEC-1). Furthermore, MDA-MB-231 tumour cells stably overexpressing FKBPL inhibited tumour vascular development suggesting that FKBPL secreted from tumour cells could inhibit angiogenesis. Whilst FKBPL and AD-01 target CD44, the nature of this interaction is not known and here we have further interrogated this aspect. We have demonstrated that FKBPL and AD-01 bind to the CD44 receptor and inhibit tumour cell migration in a CD44 dependant manner; CD44 knockdown abrogated AD-01 binding as well as its anti-migratory activity. Interestingly, FKBPL overexpression and knockdown or treatment with AD-01, regulated CD44 expression, suggesting a co-regulatory pathway for these two proteins. Downstream of CD44, alterations in the actin cytoskeleton, indicated by intense cortical actin staining and a lack of cell spreading and communication were observed following treatment with AD-01, explaining the anti-migratory phenotype. Concomitantly, AD-01 inhibited Rac-1 activity, up-regulated RhoA and the actin binding proteins, profilin and vinculin. Thus the anti-angiogenic protein, FKBPL, and AD-01, offer a promising and alternative approach for targeting both CD44 positive tumours and vasculature networks.