Quantitative imaging of concentrated suspensions under flow

We review recent advances in imaging the flow of concentrated suspensions, focussing on the use of confocal microscopy to obtain time-resolved information on the single-particle level in these systems. After motivating the need for quantitative (confocal) imaging in suspension rheology, we briefly describe the particles, sample environments, microscopy tools and analysis algorithms needed to perform this kind of experiments. The second part of the review focusses on microscopic aspects of the flow of concentrated model hard-sphere-like suspensions, and the relation to non-linear rheological phenomena such as yielding, shear localization, wall slip and shear-induced ordering. Both Brownian and non-Brownian systems will be described. We show how quantitative imaging can improve our understanding of the connection between microscopic dynamics and bulk flow.Comment: Review on imaging hard-sphere suspensions, incl summary of methodology. Submitted for special volume 'High Solid Dispersions' ed. M. Cloitre, Vol. xx of 'Advances and Polymer Science' (Springer, Berlin, 2009); 22 pages, 16 fig

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The association between neuroticism and heart rate variability is not fully explained by cardiovascular disease and depression

Neuroticism is associated with cardiovascular disease, autonomic reactivity, and depression. Here we address the extent to which neuroticism accounts for the excess heart disease risk associated with depression and test whether cardiac autonomic tone plays a role as mediator. Subjects were derived from a nationally representative sample (n = 1,255: mean age 54.5, SD = 11.5). Higher neuroticism was associated with reduced heart rate variability equally under rest and stress. The baseline structural equation model revealed significant paths from neuroticism to heart rate variability, cardiovascular disease and depression, and between depression and cardiovascular disease, controlling for age, sex, height, weight, and BMI. Dropping both the neuroticism to heart rate variability, and neuroticism to heart disease paths significantly reduced the model fit (p < .001 in each case). We conclude that neuroticism has independent associations with both autonomic reactivity and cardiovascular disease, over and above its associations with depression and other related variables

Sphingomonas paucimobilis BPSI-3 mutant AN2 produces a red catabolite during biphenyl degradation

The biphenyl degradation pathway of Sphingomonas paucimobilis BPSI-3 was investigated using a degradation-deficient mutant generated by 1-methyl-3-nitro-1-nitrosoguanidine (NTG) mutagenesis. The mutant, designated AN2, was confirmed as originating from BPSI-3 through the use of ERIC (Enterobacterial Repetitive Intergenic Consensus) PCR and by detection of the diagnostic pigment, nostoxanthin, in cellular methanol extracts. Mutant AN2 produced a yellow followed by red extracellular substance when grown in the presence of biphenyl. In the presence of 2,3-dihydroxybiphenyl, yellow followed by red then yellow compounds were formed over time. This colour change was consistent with the characteristics of a quinone, 1-phenyl-2,3-benzoquinone, which could arise from the oxidation of 2,3-dihydroxybiphenyl. A quinone was synthesised from 2,3-dihydroxybiphenyl and compared to the red compound produced by mutant AN2. Gas chromatography-mass spectrophotometry (GC-MS) confirmed that a similar quinone (4,5-dimethoxy-3-phenyl-1,2-benzoquinone) compared to the structure of the proposed biogenic compound, had been formed. This compound was also found after GC-MS analysis of mutant AN2 culture extracts. Spectrophotometric analysis of the quinone synthesised and the red product produced revealed almost identical spectral profiles. A likely inference from this evidence is that the mutant AN2 is blocked, or its activity altered, in the first gene cluster, bphA to C, of the biphenyl degradation pathway