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Background: The prevalence of HIV-1 resistance to antiretroviral therapies (ART) has declined in high-income countries over recent years, but drug resistance remains a substantial concern in many low and middle-income countries. The Q151M and T69 insertion (T69i) resistance mutations in the viral reverse transcriptase gene can reduce susceptibility to all nucleoside/tide analogue reverse transcriptase inhibitors, motivating the present study to investigate the risk factors and outcomes associated with these mutations. Methods: We considered all data in the UK HIV Drug Resistance Database for blood samples obtained in the period 1997-2014. Where available, treatment history and patient outcomes were obtained through linkage to the UK Collaborative HIV Cohort study. A matched case-control approach was used to assess risk factors associated with the appearance of each of the mutations in ART-experienced patients, and survival analysis was used to investigate factors associated with viral suppression. A further analysis using matched controls was performed to investigate the impact of each mutation on survival. Results: A total of 180 patients with Q151M mutation and 85 with T69i mutation were identified, almost entirely from before 2006. Occurrence of both the Q151M and T69i mutations was strongly associated with cumulative period of virological failure while on ART, and for Q151M there was a particular positive association with use of stavudine and negative association with use of boosted-protease inhibitors. Subsequent viral suppression was negatively associated with viral load at sequencing for both mutations, and for Q151M we found a negative association with didanosine use but a positive association with boosted-protease inhibitor use. The results obtained in these analyses were also consistent with potentially large associations with other drugs. Analyses were inconclusive regarding associations between the mutations and mortality, but mortality was high for patients with low CD4 at detection. Conclusions: The Q151M and T69i resistance mutations are now very rare in the UK. Our results suggest that good outcomes are possible for people with these mutations. However, in this historic sample, viral load and CD4 at detection were important factors in determining prognosis.

Objectives: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure.Design: Collaborative analysis of data from eight European and three Canadian cohorts. Methods: Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4+ cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression.Results: The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4+ cell count below, or more than, 100 cells/ml, respectively. There was no difference in mortality between subtypes A, B and C after viral failure.Conclusion: Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors.

The evanescent field intensity outside a fibre can be increased several orders of magnitude by tapering it. Several tapered optical fibre based evanescent field devices have been reported in the literature. Cambridge University, UK, reported work on miniature dye lasers using a tapered fibre in a loop arrangement; but more importantly, a tapered single mode fibre bent into a small loop. This latter tapered device was used as an imunoassay for cholera antitoxin immunoglobulins and was based on fluorescence spectroscopy. The Naval Research Laboratories, USA, have reported on a MM tapered fibre which is chemically tapered to a point and can be used as a fluorescence based biosensor.

The problem analyzed in this paper is how to allocate optimally the available surface water in a river system among those who compete for its use, while acknowledging explicitly that for coastal states the ecology of bays and estuaries must be numbered among the competitors. The objective is to maximize the benefit resulting from water use while satisfying a set of constraints on flow. Benefit is assumed to be a function of the amount of water used and the time period in which the water is used. A mathematical model of this problem is shown to fit the format of the minimum cost circulation network flow problem. The Out-of-Kilter algorithm of D. R. Fulkerson is proposed as a solution technique. Sensitivity analysis on the input data is described as a means of determining the minimum economic benefit required to justify the allocation of a given volume of water needed to sustain the ecology of an estuary.

Results obtained using a new technique for studying cell metabolism are presented. The technique, consisting in CO2 production monitoring, has been applied to Saccharomyces cerevisiae yeast cells. Also the cells were irradiated using the soft X-ray laser-plasma source at Rutherford Appleton Laboratory with the aim of producing a damage of metabolic processes at the wall level, responsible for fermentation, without great interference with respiration, taking place in mitochondria, and DNA activity. The source was calibrated with PIN diodes and X-ray spectrometers and used Teflon stripes as target, emitting X-rays at about 0.9 keV, with a very low penetration in biological material. X-ray doses delivered to the different cell compartments were calculated following a Lambert-Bouguet-Beer law. Immediately after irradiation, the damage to metabolic activity was measured again by monitoring CO2 production. Results showed a general reduction in gas production by irradiated samples, together with non-linear and non-monotone response to dose. There was also evidence of oscillations in cell metabolic activity and of X-ray induced changes in oscillation frequency.

The average annual cost of flooding in Australia is $318 million per year (BTE, 2001). Some 100 flood studies, floodplain management studies and plans are currently being undertaken in Australia to seek to reduce the potential flood risk to residents and properties in flood-affected areas. Consequently, a great body of knowledge and experience in flood modelling practices has been acquired, from one-dimensional (1D) steady-state models through to two-dimensional (2D) finite element hydrodynamic models. This paper critically appraises 1D and 2D hydraulic modelling techniques based on a quantitative comparison of MIKE-11, HEC-RAS and RMA-2 modelling results for a creek system in Australia. Based on the findings of the case study, the paper provides practical guidance for modellers on the suitability of 1D and 2D modelling for common physical channel and floodplain characteristics.