Fludarabine, Cyclophosphamide and Rituximab:an effective chemoimmunotherapy combination with high remission rates for chronic lymphocytic leukaemia

BACKGROUND: Combined Fludarabine and Cyclophosphamide is now standard first-line therapy in chronic lymphocytic leukaemia (CLL) and the addition of Rituximab improves outcome.

METHODS: We adopted a modified Fludarabine, Cyclophosphamide and Rituximab (FCR) protocol in treating 39 patients (median age 57 years) with progressive or advanced CLL. Depending on CR, treatment was given for four or six cycles.

RESULT: Twenty-six patients were treatment naïve and 13 were pre-treated. Twelve patients had progressive Binet stage A, 16 stage B and 11 stage C disease. The overall response rate (ORR) was 100%, with 75% achieving CR. Neutropenia was the major toxicity in 71/187 (38%) of the cycles. There were five deaths, two from infection and three from progressive disease. Twenty-six of 31 patients have maintained their post-treatment disease status for a median of 17 months (2-41).

CONCLUSION: We conclude that FCR is a feasible, well-tolerated and effective treatment for patients with CLL.

Modelling Future Coronary Heart Disease Mortality to 2030 in the British Isles

OBJECTIVE: Despite rapid declines over the last two decades, coronary heart disease (CHD) mortality rates in the British Isles are still amongst the highest in Europe. This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking and physical activity levels, dietary salt and saturated fat intakes on future CHD mortality in three countries: Northern Ireland (NI), Republic of Ireland (RoI) and Scotland.

METHODS: CHD mortality models previously developed and validated in each country were extended to predict potential reductions in CHD mortality from 2010 (baseline year) to 2030. Risk factor trends data from recent surveys at baseline were used to model alternative future risk factor scenarios: Absolute decreases in (i) smoking prevalence and (ii) physical inactivity rates of up to 15% by 2030; relative decreases in (iii) dietary salt intake of up to 30% by 2030 and (iv) dietary saturated fat of up to 6% by 2030. Probabilistic sensitivity analyses were then conducted.

RESULTS: Projected populations in 2030 were 1.3, 3.4 and 3.9 million in NI, RoI and Scotland respectively (adults aged 25-84). In 2030: assuming recent declining mortality trends continue: 15% absolute reductions in smoking could decrease CHD deaths by 5.8-7.2%. 15% absolute reductions in physical inactivity levels could decrease CHD deaths by 3.1-3.6%. Relative reductions in salt intake of 30% could decrease CHD deaths by 5.2-5.6% and a 6% reduction in saturated fat intake might decrease CHD deaths by some 7.8-9.0%. These projections remained stable under a wide range of sensitivity analyses.

CONCLUSIONS: Feasible reductions in four cardiovascular risk factors (already achieved elsewhere) could substantially reduce future coronary deaths. More aggressive polices are therefore needed in the British Isles to control tobacco, promote healthy food and increase physical activity.

Impacts of invasive browsers on demographic rates and forest structure in New Zealand

Background/Question/Methods

Assessing the large scale impact of deer populations on forest structure and composition is important because of their increasing abundance in many temperate forests. Deer are invasive animals and sometimes thought to be responsible for immense damage to New Zealand’s forests. We report demographic changes taking place among 40 widespread indigenous tree species over 20 years, following a period of record deer numbers in the 1950s and a period of extensive hunting and depletion of deer populations during the 1960s and 1970s.

Results/Conclusions

Across a network of 578 plots there was an overall 13% reduction in sapling density of our study species with most remaining constant and a few declining dramatically. The effect of suppressed recruitment when deer populations were high was evident in the small tree size class (30 – 80 mm dbh). Stem density decreased by 15% and species with the greatest annual decreases in small tree density were those which have the highest rates of sapling recovery in exclosures indicating that deer were responsible. Densities of large canopy trees have remained relatively stable. There were imbalances between mortality and recruitment rates for 23 of the 40 species, 7 increasing and 16 in decline. These changes were again linked with sapling recovery in exclosures; species which recovered most rapidly following deer exclusion had the greatest net recruitment deficit across the wider landscape, indicating recruitment suppression by deer as opposed to mortality induced by disturbance and other herbivores. Species are not declining uniformly across all populations and no species are in decline across their entire range. Therefore we predict that with continued deer presence some forests will undergo compositional changes but that none of the species tested will become nationally extinct.

Impacts of invasive browsers on demographic rates and forest structure in New Zealand. Available from: http://www.researchgate.net/publication/267285500_Impacts_of_invasive_browsers_on_demographic_rates_and_forest_structure_in_New_Zealand [accessed Oct 9, 2015].

Indexing and matching trajectories under inconsistent sampling rates

Quantifying the similarity between two trajectories is a fundamental operation in analysis of spatio-temporal databases. While a number of distance functions exist, the recent shift in the dynamics of the trajectory generation procedure violates one of their core assumptions; a consistent and uniform sampling rate. In this paper, we formulate a robust distance function called Edit Distance with Projections (EDwP) to match trajectories under inconsistent and variable sampling rates through dynamic interpolation. This is achieved by deploying the idea of projections that goes beyond matching only the sampled points while aligning trajectories. To enable efficient trajectory retrievals using EDwP, we design an index structure called TrajTree. TrajTree derives its pruning power by employing the unique combination of bounding boxes with Lipschitz embedding. Extensive experiments on real trajectory databases demonstrate EDwP to be up to 5 times more accurate than the state-of-the-art distance functions. Additionally, TrajTree increases the efficiency of trajectory retrievals by up to an order of magnitude over existing techniques.

Dietary Micronutrient Intake and Micronutrient Status in Patients With Chronic Stable Heart Failure: An Observational Study.

BACKGROUND: Observational studies suggest that patients with heart failure have a tendency to a reduced status of a number of micronutrients and that this may be associated with an adverse prognosis. A small number of studies also suggest that patients with heart failure may have reduced dietary intake of micronutrients, a possible mechanism for reduced status.

OBJECTIVE: The aims of this study were to assess dietary micronutrient intake and micronutrient status in a group of patients with heart failure.

METHODS: Dietary intake was assessed in 79 outpatients with chronic stable heart failure with a reduced ejection fraction using a validated food frequency questionnaire. Blood concentrations of a number of micronutrients, including vitamin D, were measured in fasting blood samples, drawn at the time of food frequency questionnaire completion.

RESULTS: More than 20% of patients reported intakes less than the reference nutrient intake or recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, and iodine. More than 5% of patients reported intakes less than the lower reference nutrient intake or minimum recommended intake for riboflavin, vitamin D, vitamin A, calcium, magnesium, potassium, zinc, selenium, and iodine. Vitamin D deficiency (plasma total 25-hydroxy-vitamin D concentration <50 nmol/L) was observed in 75.6% of patients.

CONCLUSIONS: Vitamin D deficiency was common in this group of patients with heart failure. Based on self-reported dietary intake, a substantial number of individuals may not have been consuming enough vitamin D and a modest number of individuals may not have been consuming enough riboflavin, vitamin A, calcium, magnesium, potassium, zinc, copper, selenium, or iodine to meet their dietary needs.

Rates of E1, E2, M1, and M2 transitions in Ni II

Aims. We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d⁹, 3d⁸4s, 3d⁷4s², 3d⁸4p, and 3d⁷4s4p, determined through an extensive configuration interaction calculation. 

Methods. The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. 

Results. Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. 

Conclusions. We believe that the present transition data are the best currently available.

Increasing fruit and vegetable intake has no effect on retinal vessel caliber in adults at high risk of developing cardiovascular disease

BACKGROUND AND AIM: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk.

METHODS AND RESULTS: Following a 4 week washout period, participants were randomized to consume either 2 or 4 or 7 portions of FV daily for 12 weeks. Retinal vessel caliber was measured at baseline and post-intervention. A total of 62 participants completed the study. Self-reported FV intake indicated good compliance with the intervention, with serum concentrations of zeaxanthin and lutein increasing significantly across the groups in a dose-dependent manner (P for trend < 0.05). There were no significant changes in body composition, 24-h ambulatory blood pressure or fasting blood lipid profiles in response to the FV intervention. Increasing age was a significant determinant of wider retinal venules (P = 0.004) whereas baseline systolic blood pressure was a significant determinant of narrower retinal arterioles (P = 0.03). Overall, there was no evidence of any short-term dose-response effect of FV intake on retinal vessel caliber (CRAE (P = 0.92) or CRVE (P = 0.42)).

CONCLUSIONS: This study demonstrated no effect of increasing FV intake on retinal vessel caliber in overweight adults at high risk of developing primary CVD.

Characterisation of a two-dimensional liquid-filled ion chamber detector array using flattened and unflattened beams for small fields, small MUs and high dose-rates

In this study, the PTW 1000SRS array with Octavius 4D phantom was characterised for FF and FFF beams. MU linearity, field size, dose rate, dose per pulse (DPP) response and dynamic conformal arc treatment accuracy of the 1000SRS array were assessed for 6MV, 6FFF and 10FFF beams using a Varian TrueBeam STx linac. The measurements were compared with a pinpoint IC, microdiamond IC and EBT3 Gafchromic film. Measured dose profiles and FWHMs were compared with film measurements. Verification of FFF volumetric modulated arc therapy (VMAT) clinical plans were assessed using gamma analysis with 3%/3 mm and 2%/2 mm tolerances (10% threshold). To assess the effect of cross calibration dose rate, clinical plans with different dose rates were delivered and analysed. Output factors agreed with film measurements to within 4.5% for fields between 0.5 and 1 cm and within 2.7% for field sizes between 1.5 and 10 cm and were highly correlated with the microdiamond IC detector. Field sizes measured with the 1000SRS array were within 0.5 mm of film measurements. A drop in response of up to 1.8%, 2.4% and 5.2% for 6MV, 6FFF and 10FFF beams respectively was observed with increasing nominal dose rate. With an increase in DPP, a drop of up to 1.7%, 2.4% and 4.2% was observed in 6MV, 6FFF and 10FFF respectively. The differences in dose following dynamic conformal arc deliveries were less than 1% (all energies) from calculated. Delivered VMAT plans showed an average pass percentage of 99.5(±0.8)% and 98.4(±3.4)% with 2%/2 mm criteria for 6FFF and 10FFF respectively. A drop to 97.7(±2.2)% and 88.4(±9.6)% were observed for 6FFF and 10FFF respectively when plans were delivered at the minimum dose rate and calibrated at the maximum dose rate. Calibration using a beam with the average dose rate of the plan may be an efficient method to overcome the dose rate effects observed by the 1000SRS array.