The limits to prime ministerial autonomy: Cameron and the constraints of coalition

In heading up a coalition David Cameron has had to confront two unusual constraints that prevent him from being a dominant prime minister. The first constraint, something unfamiliar to previous prime ministers, is his having to work with and through a coalition partner firmly placed to the Conservatives’ left. The second constraint, equally problematic but more familiar, is that Cameron has faced a restive Conservative parliamentary party in which a sizable minority of Tory MPs remained unreconciled to his political agenda. These two interrelated constraints mean Cameron has lacked the freedom of manoeuvre enjoyed by most past prime ministers. Two aspects of Cameron’s premiership help cast light on his predicament: first, his relations with Nick Clegg and the Liberal Democrats and second, the nature of his dependency upon Conservative MPs. We look at these in turn and conclude by assessing Cameron’s effectiveness as prime minister

Cameron as Prime Minister: the intra-executive politics of Britain’s coalition

Forming a coalition involves compromise, so a prime minister heading up a coalition government, even one as predominant a party leader as David Cameron, should not be as powerful as a prime minister leading a single-party government. Cameron has still to work with and through ministers from his own party, but has also to work with and through Liberal Democrat ministers; not least the Liberal Democrat leader Nick Clegg. The relationship between the prime minister and his deputy is unchartered territory for recent academic study of the British prime minister. This article explores how Cameron and Clegg operate within both Whitehall and Westminster: the cabinet arrangements, the prime minister’s patronage, advisory resources and more informal mechanisms. Cameron and Clegg both possess institutional and personal resources, but Cameron remains the predominant resource-rich actor, so at this stage in the coalition government we can observe that no formal, substantial change in the role of prime minister has been enacted. Cameron’s predominance, by leading a coalition, is partially constrained by Clegg, but he too constrains Clegg. This prime minister, then, can be predominant even when he is constrained in significant ways by the imperatives of coalition government. Cameron is presently no more constrained than a prime minister who is faced with a pre-eminent intra-party rival with a significant power base

Discovery and Assessment of New Target Sites for Anti-HIV Therapies

Human immunodeficiency virus (HIV) infects cells by endocytosis and takes over parts of the cell’s reaction pathways in order to reproduce itself and spread the infection. One such pathway taken over by HIV becomes the inflammatory pathway which uses Nuclear Factor κB (NF-κB) as the principal transcription factor. Therefore, knocking out the NF-κB pathway would prevent HIV from reproducing itself. In this report, our goal is to produce a simple model for this pathway with which we can identify potential targets for anti-HIV therapies and test out various hypotheses. We present a very simple model with four coupled first-order ODEs and see what happens if we treat IκK concentration as a parameter that can be controlled (by some unspecified means). In Section 3, we augment this model to account for activation and deactivation of IκK, which is controlled (again, by some unspecified means) by TNF

Hub loads analysis of the SA349/2 helicopter

The forces and moments at the rotor hub of an Aerospatiale SA349/2 helicopter were investigated. The study included three main topics. First, measured hub forces and moments for a range of level flight conditions (mu = 0.14 to 0.37) were compared with predictions from a comprehensive rotorcraft analysis to examine the influence of the wake model on the correlations. Second, the effect of changing the blade mass distribution and blade chordwise center of gravity location on the 3/rev nonrotating frame hub loads was studied for a high-speed flight condition (mu = 0.37). Third, the use of higher harmonic control to reduce nonrotating frame 3/rev hub shear forces was investigated. The last two topics were theoretical studies only

Impact and Cost-Effectiveness of Point-Of-Care CD4 Testing on the HIV Epidemic in South Africa.

Rapid diagnostic tools have been shown to improve linkage of patients to care. In the context of infectious diseases, assessing the impact and cost-effectiveness of such tools at the population level, accounting for both direct and indirect effects, is key to informing adoption of these tools. Point-of-care (POC) CD4 testing has been shown to be highly effective in increasing the proportion of HIV positive patients who initiate ART. We assess the impact and cost-effectiveness of introducing POC CD4 testing at the population level in South Africa in a range of care contexts, using a dynamic compartmental model of HIV transmission, calibrated to the South African HIV epidemic. We performed a meta-analysis to quantify the differences between POC and laboratory CD4 testing on the proportion linking to care following CD4 testing. Cumulative infections averted and incremental cost-effectiveness ratios (ICERs) were estimated over one and three years. We estimated that POC CD4 testing introduced in the current South African care context can prevent 1.7% (95% CI: 0.4% - 4.3%) of new HIV infections over 1 year. In that context, POC CD4 testing was cost-effective 99.8% of the time after 1 year with a median estimated ICER of US$4,468/DALY averted. In healthcare contexts with expanded HIV testing and improved retention in care, POC CD4 testing only became cost-effective after 3 years. The results were similar when, in addition, ART was offered irrespective of CD4 count, and CD4 testing was used for clinical assessment. Our findings suggest that even if ART is expanded to all HIV positive individuals and HIV testing efforts are increased in the near future, POC CD4 testing is a cost-effective tool, even within a short time horizon. Our study also illustrates the importance of evaluating the potential impact of such diagnostic technologies at the population level, so that indirect benefits and costs can be incorporated into estimations of cost-effectiveness

Wing force and surface pressure data from a hover test of a 0.658-scale V-22 rotor and wing

A hover test of a 0.658-scale V-22 rotor and wing was conducted in the 40 x 80 foot wind tunnel at Ames Research Center. The principal objective of the test was to measure the surface pressures and total download on a large scale V-22 wing in hover. The test configuration consisted of a single rotor and semispan wing on independent balance systems. A large image plane was used to represent the aircraft plane of symmetry. Wing flap angles ranging from 45 to 90 degrees were examined. Data were acquired for both directions of the rotor rotation relative to the wing. Steady and unsteady wing surface pressures, total wing forces, and rotor performance data are presented for all of the configurations that were tested

Association between MAPT polymorphism but not APOE promoter and elite rugby athlete status

INTRODUCTION: Incidence and outcomes of concussions have been hypothesised to be genetically influenced. The APOE Promoter G219T (rs405509) polymorphism has been associated with differential promoter activity and unfavourable outcomes after traumatic brain injury. The TT genotype is associated with a 3-fold greater risk of multiple concussions. The TT genotype of MAPT (rs10445337) has also been associated with poorer outcomes after concussion. Rugby has one of the highest incidences of concussion in sport, so it was hypothesised that APOE Promoter TT and MAPT TT genotypes would be less prevalent in elite rugby athletes because those genotypes, previously associated with increased risk, would be less compatible with achieving elite athlete status. METHODS: Participants were from the RugbyGene project, comprising elite Caucasian male rugby athletes (n = 528; mean (standard deviation) height 1.85 (0.07) m, mass 101 (14) kg, age 29 (7) yr), including 420 rugby union (RU) athletes that for some analyses were divided into forwards and backs and 108 rugby league (RL) athletes. Non-athletes were 592 Caucasian men and women (57% male, height 1.72 (0.10) m, mass 74 (14) kg, age 31 (7) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using χ2 and odds ratio (OR) statistics. RESULTS: All genotype data were in Hardy-Weinberg equilibrium. For MAPT (rs10445337), the risk genotype (TT) was underrepresented in rugby athletes (60%) compared to non-athletes (66%), CT more common in rugby athletes (34%) than non-athletes (29%) and little difference in CC genotype frequencies (χ2 = 7.092, P = 0.029; TT genotype frequency OR = 0.80, 95% confidence intervals (CI) = 0.62-1.02). There were no differences in MAPT (rs10445337) genotype frequencies between RU forwards and backs. For APOE Promoter G219T (rs405509), there were no differences in genotype frequencies between all athletes (RU and RL) and non-athletes (27% TT genotype in players and non-athletes), nor between RU forwards and backs. CONCLUSION: The MAPT (rs10445337) TT genotype is 6% less common in elite rugby athletes than non-athletes. Therefore, carrying at least one rs10445337 C allele appears to increase the probability of sustained career success in the high-risk concussion environment of elite rugby, perhaps via a greater ability to recover from concussions.Peer reviewe

Association of MMP3 but not TIMP2 gene variants with elite rugby player status and rugby code

Introduction: Achilles tendon pathology and anterior cruciate ligament rupture are multifactorial conditions for which genetic risk factors have been identified. Single nucleotide polymorphisms (SNPs) within the MMP3 (rs591058, rs679620, rs650108) and TIMP2 (rs4789932) genes have previously been associated with tendon and ligament pathologies. Although not entirely clear, prior literature indicates the risk alleles for Achilles tendon pathology as T (rs591058), G (rs679620) and A (rs650108) for MMP3. However, prior evidence regarding TIMP2 is equivocal. MMP3 is considered an essential regulator of matrix degradation and remodelling within diseased and normal musculoskeletal soft tissues. TIMP2 maintains homeostasis in the extracellular matrix in part by inhibiting MMP function. Given the high incidence and severity of tendon and ligament injuries in elite rugby athletes, we hypothesised that the aforementioned SNPs would be associated with career success. Methods: Participants from the RugbyGene project were elite Caucasian male rugby athletes (n = 566; mean (standard deviation) height 1.85 (0.07) m, mass 101 (14) kg, age 29 (7) yr), including 420 rugby union (RU) athletes that for some analyses were divided into forwards and backs and 120 rugby league (RL) athletes. Non-athletes were 589 Caucasian men and women (n = 589, 57% male, height 1.72 (0.10) m, mass 74 (14) kg, age 31 (7) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using Χ2 and odds ratio (OR) statistics. Results: As hypothesized, the MMP3 rs591058 risk genotype (TT) was less frequent in rugby athletes (28%) compared to non-athletes (33%) (Χ2 = 7.265, P = 0.026; OR = 1.18, 95% confidence intervals (CI) = 0.86-1.63). No differences were found for MMP3 rs679620, rs650108 or TIMP2 rs4789932 between rugby athletes and non-athletes. When RL athletes were compared to non-athletes, the risk genotype (TT) of MMP3 rs591058 was underrepresented in RL athletes (19%) compared to non-athletes (33%). The MMP3 rs679620 ‘protective’ allele (C) was more frequent in RL athletes (55%) compared to non-athletes (48%) (OR = 1.3, 95% CI = 0.98-1.74). However, for MMP3 rs650108 the ‘risk’ allele (A) was overrepresented in RL athletes (32%) compared to non-athletes (26%). There were no genotype differences for any gene variant between RU athletes and non-athletes. The ‘risk’ allele (T) of the MMP3 rs679629 polymorphism and the ‘protective’ allele (G) of the MMP3 rs650108 polymorphism were less common in RL (45%, 68%, respectively) than RU athletes (54%, 76%, respectively). Conclusion: We provide evidence for elite rugby athletes possessing a protective genetic profile regarding tendon and ligament injury risk. Notably, a less frequent rs591058 TT genotype in athletes suggests a lower risk of injury could therefore enhance career success in rugby. Furthermore, RL players appear to have differing genetic characteristics compared to their RU counterparts, which might reflect some differences in physiological demands between codes.Peer reviewedFinal Published versio

Evaluation of school absenteeism data for early outbreak detection, New York City

BACKGROUND: School absenteeism data may have utility as an early indicator of disease outbreaks, however their value should be critically examined. This paper describes an evaluation of the utility of school absenteeism data for early outbreak detection in New York City (NYC). METHODS: To assess citywide temporal trends in absenteeism, we downloaded three years (2001–02, 2002–03, 2003–04) of daily school attendance data from the NYC Department of Education (DOE) website. We applied the CuSum method to identify aberrations in the adjusted daily percent absent. A spatial scan statistic was used to assess geographic clustering in absenteeism for the 2001–02 academic year. RESULTS: Moderate increases in absenteeism were observed among children during peak influenza season. Spatial analysis detected 790 significant clusters of absenteeism among elementary school children (p < 0.01), two of which occurred during a previously reported outbreak. CONCLUSION: Monitoring school absenteeism may be moderately useful for detecting large citywide epidemics, however, school-level data were noisy and we were unable to demonstrate any practical value in using cluster analysis to detect localized outbreaks. Based on these results, we will not implement prospective monitoring of school absenteeism data, but are evaluating the utility of more specific school-based data for outbreak detection