Liberal intervention in the foreign policy thinking of Tony Blair and David Cameron

David Cameron was a critic of Tony Blair’s doctrine of the international community, which was used to justify war in Kosovo and more controversially in Iraq, suggesting caution in projecting military force abroad while in opposition. However, and in spite of making severe cuts to the defence budget, the Cameron-led Coalition government signed Britain up to a military intervention in Libya within a year of coming into office. What does this say about the place liberal interventionism occupies in contemporary British foreign policy? To answer this question, this article studies the nature of what we describe as the ‘bounded liberal’ tradition that has informed British foreign policy thinking since 1945, suggesting that it puts a distinctly UK national twist on conventional conservative thought about international affairs. Its components are: scepticism of grand schemes to remake the world; instinctive Atlanticism; security through collective endeavour; and anti-appeasement. We then compare and contrast the conditions for intervention set out by Tony Blair and David Cameron. We explain the similarities but crucially also the vital differences between the two leaders’ thinking on intervention, with particular reference to Cameron’s perception that Downing Street needed to loosen its control over foreign policy-making after Iraq. Our argument is that policy substance, policy style and party political dilemmas prompted Blair and Cameron to reconnect British foreign policy with its ethical roots, ingraining a bounded liberal posture to British foreign policy after the moral bankruptcy of the John Major years. This return to a patient, pragmatic and ethically informed foreign policy meant that military operations in Kosovo and Libya were undertaken in quite different circumstances, yet came to be justified by similar arguments from the two leaders

Chaos game representation for comparison of whole genomes

BACKGROUND: Chaos game representation of genome sequences has been used for visual representation of genome sequence patterns as well as alignment-free comparisons of sequences based on oligonucleotide frequencies. However the potential of this representation for making alignment-based comparisons of whole genome sequences has not been exploited. RESULTS: We present here a fast algorithm for identifying all local alignments between two long DNA sequences using the sequence information contained in CGR points. The local alignments can be depicted graphically in a dot-matrix plot or in text form, and the significant similarities and differences between the two sequences can be identified. We demonstrate the method through comparison of whole genomes of several microbial species. Given two closely related genomes we generate information on mismatches, insertions, deletions and shuffles that differentiate the two genomes. CONCLUSION: Addition of the possibility of large scale sequence alignment to the repertoire of alignment-free sequence analysis applications of chaos game representation, positions CGR as a powerful sequence analysis tool

Camparison of the Hanbury Brown-Twiss effect for bosons and fermions

Fifty years ago, Hanbury Brown and Twiss (HBT) discovered photon bunching in light emitted by a chaotic source, highlighting the importance of two-photon correlations and stimulating the development of modern quantum optics . The quantum interpretation of bunching relies upon the constructive interference between amplitudes involving two indistinguishable photons, and its additive character is intimately linked to the Bose nature of photons. Advances in atom cooling and detection have led to the observation and full characterisation of the atomic analogue of the HBT effect with bosonic atoms. By contrast, fermions should reveal an antibunching effect, i.e., a tendency to avoid each other. Antibunching of fermions is associated with destructive two-particle interference and is related to the Pauli principle forbidding more than one identical fermion to occupy the same quantum state. Here we report an experimental comparison of the fermion and the boson HBT effects realised in the same apparatus with two different isotopes of helium, 3He (a fermion) and 4He (a boson). Ordinary attractive or repulsive interactions between atoms are negligible, and the contrasting bunching and antibunching behaviours can be fully attributed to the different quantum statistics. Our result shows how atom-atom correlation measurements can be used not only for revealing details in the spatial density, or momentum correlations in an atomic ensemble, but also to directly observe phase effects linked to the quantum statistics in a many body system. It may thus find applications to study more exotic situations >.Comment: Nature 445, 402 (2007). V2 includes the supplementary informatio

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Improving the use of research evidence in guideline development: 10. Integrating values and consumer involvement

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 10(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on integrating values and consumers in guideline development. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We did not conduct a full systematic review ourselves. Our conclusions based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not find a systematic review of methods for integrating values in guidelines, but we found several systematic reviews that dealt with related topics. Whose values should WHO use when making recommendations? • Values, the relative importance or worth of a state or consequences of a decision (outcomes relating to benefits, harms, burden and costs), play a role in every recommendation. Ethical considerations, concepts that determine what is right, also play a role. • The values used in making recommendations should reflect those of the people affected. Judgements should be explicit and should be informed by input from those affected (including citizens, patients, clinicians and policy makers). • When differences in values may lead to different decisions or there is uncertainty about values, this should also be explicit. If differences in values are likely to affect a decision, such that people in different setting would likely make different choices about interventions or actions based on differences in their values, global recommendations should be explicit in terms of which values were applied and allow for adaptation after incorporating local values. How should WHO ensure that appropriate values are integrated in recommendations? • All WHO guideline groups should uniformly apply explicit, transparent and clearly described methods for integrating values. • WHO should consider involving relevant stakeholders if this is feasible and efficient. • WHO should develop a checklist for guidelines panels to help them to ensure that ethical considerations relevant to recommendations are addressed explicitly and transparently. How should users and consumers be involved in generating recommendations? • Including consumers in groups that are making global recommendations presents major challenges with respect to the impossibility of including a representative spectrum of consumers from a variety of cultures and settings. Nonetheless, consideration should be given to including consumers in groups who are able to challenge assumptions that are made about the values used for making recommendations, rather than represent the values of consumers around the world. • WHO should establish a network to facilitate involvement of users. • Draft recommendations should be reviewed by consumers, who should be asked explicitly to consider the values that were used. How should values be presented in recommendations? • Recommendations should include a description of how decisions were made about the relative importance of the consequences (benefits, harms and costs) of a decision. • Values that influence recommendations should be reported along with the research evidence underlying recommendations. • When differences in values would lead to different decisions or there is important uncertainty about values that are critical to a decision, this should be flagged and reflected in the strength of the recommendation. • Adaptable guideline templates that allow for integration of different values should be developed and used when differences in values are likely to be critical to a decision

Does targeting children with hygiene promotion messages work? The effect of handwashing promotion targeted at children, on diarrhoea, soil-transmitted helminth infections and behaviour change, in low- and middle-income countries.

OBJECTIVES: To synthesise evidence on the effect of handwashing promotion interventions targeting children, on diarrhoea, soil-transmitted helminth infection and handwashing behaviour, in low- and middle-income country settings. METHODS: A systematic review of the literature was performed by searching eight databases, and reference lists were hand-searched for additional articles. Studies were reviewed for inclusion according to pre-defined inclusion criteria and the quality of all studies was assessed. RESULTS: Eight studies were included in this review: seven cluster-randomised controlled trials and one cluster non-randomised controlled trial. All eight studies targeted children aged 5-12 attending primary school but were heterogeneous for both the type of intervention and the reported outcomes so results were synthesised qualitatively. None of the studies were of high quality and the large majority were at high risk of bias. The reported effect of child-targeted handwashing interventions on our outcomes of interest varied between studies. Of the different interventions reported, no one approach to promoting handwashing among children appeared most effective. CONCLUSION: Our review found very few studies that evaluated handwashing interventions targeting children and all had various methodological limitations. It is plausible that interventions which succeed in changing children's handwashing practices will lead to significant health impacts given that much of the attributable disease burden is concentrated in that age group. The current paucity of evidence in this area, however, does not permit any recommendations to be made as to the most effective route to increasing handwashing with soap practice among children in LMIC

Biological sequences as pictures – a generic two dimensional solution for iterated maps

<p>Abstract</p> <p>Background</p> <p>Representing symbolic sequences graphically using iterated maps has enjoyed an enduring popularity since it was first proposed in Jeffrey 1990 as chaos game representation (CGR). The usefulness of this representation goes beyond the convenience of a scale independent representation. It provides a variable memory length representation of transition. This includes the representation of succession with non-integer order, which comes with the promise of generalizing Markovian formalisms. The original proposal targeted genomic sequences only but since then several generalizations have been proposed, many specifically designed to handle protein data.</p> <p>Results</p> <p>The challenge of a general solution is that of deriving a bijective transformation of symbolic sequences into bi-dimensional planes. More specifically, it requires the regular fractal nesting of polygons. A first attempt at a general solution was proposed by Fiser 1994 by using non-overlapping circles that contain the polygons. This was used as a starting point to identify a more efficient solution where the encapsulating circles can overlap without the same happening for the sequence maps which are circumscribed to fractal polygon domains.</p> <p>Conclusion</p> <p>We identified the optimal inscribed packing solution for iterated maps of any Biological sequence, indeed of any symbolic sequence. The new solution maintains the prized bijective mapping property and includes the Sierpinski triangle and the CGR square as particular solutions of the more encompassing formulation.</p

Negotiating the transition from adolescence to motherhood: Coping with prenatal and parenting stress in teenage mothers in Mulago hospital, Uganda

<p>Abstract</p> <p>Background</p> <p>Adolescence is a transitional stage from childhood to adulthood that is characterized by physical, physiological, psychosocial and behavioral changes that are influenced to a large extent by the age, culture and socialization of the individual. To explore what adolescent mothers perceive as their struggles during the period of transition from childhood to parenthood (through motherhood) and to describe strategies employed in coping with stress of pregnancy, motherhood and parenthood.</p> <p>Methods</p> <p>Longitudinal qualitative study involving twenty two in-depth interviews and six focus group discussions among pregnant adolescents who were followed from pregnant to delivery, from January 2004 to August 2005. Participant were selected by theoretical sampling and data was analyzed using grounded theory.</p> <p>Results</p> <p>Overall, young adolescents reported more anxiety, loss of self esteem (when they conceived), difficulty in accessing financial, moral and material support from parents or partners and stigmatization by health workers when they sought care from health facilities. Three strategies by which adolescent mothers cope with parenting and pregnancy stress that were described as utilizing opportunities (thriving), accommodating the challenges (bargaining and surviving), or failure (despairing), and varied in the extent to which they enabled adolescents to cope with the stress.</p> <p>Conclusion</p> <p>Adolescents on the transition to motherhood have variable needs and aspirations and utilize different strategies to cope with the stress of pregnancy and parenthood.</p

Treatable Traits in Elderly Asthmatics from the Australasian Severe Asthma Network: A Prospective Cohort Study.

BACKGROUND: Data on treatable traits (TTs) in different populations are limited. OBJECTIVE: To assess TTs in elderly patients with asthma and compare them to younger patients, to evaluate the association of TTs with future exacerbations, and to develop an exacerbation prediction model. METHODS: We consecutively recruited 521 participants at West China Hospital, Sichuan University based on the Australasian Severe Asthma Network, classified as elderly (n = 62) and nonelderly (n = 459). Participants underwent a multidimensional assessment to characterize the TTs and were then followed up for 12 months. TTs and their relationship with future exacerbations were described. Based on the TTs and asthma control levels, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort. RESULTS: A total of 38 TTs were assessed. Elderly patients with asthma had more chronic metabolic diseases, fixed airflow limitation, emphysema, and neutrophilic inflammation, whereas nonelderly patients with asthma exhibited more allergic characteristics and psychiatric diseases. Nine traits were associated with increased future exacerbations, of which exacerbation prone, upper respiratory infection-induced asthma attack, cardiovascular disease, diabetes, and depression were the strongest. A model including exacerbation prone, psychiatric disease, cardiovascular disease, upper respiratory infection-induced asthma attack, noneosinophilic inflammation, cachexia, food allergy, and asthma control was developed to predict exacerbation risk and showed good performance. CONCLUSIONS: TTs can be systematically assessed in elderly patients with asthma, some of which are associated with future exacerbations, proving their clinical utility of evaluating them. A model based on TTs can be used to predict exacerbation risk in people with asthma

Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice

Microtubule associated protein tau (MAPT) is involved in the pathogenesis of Alzheimer’s disease and many forms of frontotemporal dementia (FTD). We recently reported that Aβ-mediated inhibition of hippocampal long-term potentiation (LTP) in mice requires tau. Here, we asked whether expression of human $MAPT$ can restore Aβ-mediated inhibition on a mouse $Tau−/−$ background and whether human tau with an FTD-causing mutation (N296H) can interfere with Aβ-mediated inhibition of LTP. We used transgenic mouse lines each expressing the full human $MAPT$ locus using bacterial artificial chromosome technology. These lines expressed all six human tau protein isoforms on a $Tau−/−$ background. We found that the human wild-type $MAPT$ H1 locus was able to restore Aβ$_{42}$-mediated impairment of LTP. In contrast, Aβ$_{42}$ did not reduce LTP in slices in two independently generated transgenic lines expressing tau protein with the mutation N296H associated with frontotemporal dementia (FTD). Basal phosphorylation of tau measured as the ratio of AT8/Tau5 immunoreactivity was significantly reduced in N296H mutant hippocampal slices. Our data show that human $MAPT$ is able to restore Aβ$_{42}$-mediated inhibition of LTP in $Tau−/−$ mice. These results provide further evidence that tau protein is central to Aβ-induced LTP impairment and provide a valuable tool for further analysis of the links between Aβ, human tau and impairment of synaptic function.MVC was supported by a Wellcome Trust OXION Training Fellowship and an equipment grant from Alzheimer’s Research UK. MVC is funded by the Institute for Life Sciences University of Southampton. RW-M was supported by a Wellcome Trust Research Career Development Fellowship (073141/Z/03/Z), CurePSP and the Alzheimer’s Society; FD held a Wellcome Trust DPhil in Neuroscience (075406/Z/04/A), and CMP is funded by the Gerald Kerkut Trust and IfLS. We thank Hana N. Dawson and Michael P. Vitek for Tau−/− mice. We thank Jenny Dworzak for her participation at an early phase of this project