Robert M. Richardson

Monodisperse cylindrical micelles by crystallization-driven living self-assembly

Non-spherical nanostructures derived from soft matter and with uniform size-that is, monodisperse materials-are of particular utility and interest, but are very rare outside the biological domain. We report the controlled formation of highly monodisperse cylindrical block copolymer micelles (length dispersity < or = 1.03; length range, approximately 200 nm to 2 microm) by the use of very small (approximately 20 nm) uniform crystallite seeds that serve as initiators for the crystallization-driven living self-assembly of added block-copolymer unimers with a crystallizable, core-forming metalloblock. This process is analogous to the use of small initiator molecules in classical living polymerization reactions. The length of the nanocylinders could be precisely controlled by variation of the unimer-to-crystallite seed ratio. Samples of the highly monodisperse nanocylinders of different lengths that are accessible using this approach have been shown to exhibit distinct liquid-crystalline alignment behaviour.

Neutron reflectivity of adsorbed β-casein and β-lactoglobulin at the air/water interface

Adsorption of the pure milk proteins, β-casein and β-lactoglobulin, at the air/water interface has been studied using the technique of specular neutron reflectance. By fitting appropriate models of the protein films to the reflectivity data the detailed structures of the interfaces have been determined. The effects of protein concentration, substrate pH, film ageing and the presence of calcium ions on the film structures have been investigated.At neutral pH both β-casein and β-lactoglobulin form a monolayer at the air/water boundary that can be divided into a protein-rich, hydrophobic, inner layer closest to the interface, and a more diffuse, hydrophilic, outer layer extending into the bulk aqueous phase. The adsorbed amount of protein follows the adsorption isotherms determined by other methods. Ageing has little effect on β-casein layers, but with β-lactoglobulin there is an increases in the adsorbed amount of protein with time and the two-layer model of the film configuration tends to become less distinct such that a one-layer model form is equally appropriate. The rate and extent of the changes occurring as a function of the age of the surface depend on the pH of the substrate solution. The adsorbed amount of both proteins increases as the pH is lowered towards their respective isoelectric points. Models are proposed to account for the changes in layer structure occurring during these processes. The presence of calcium ions modifies the structure of β-casein layers, reducing the hydrophilic layer thickness and the adsorbed amount of protein.

Prediction of early death in end-stage renal disease patients starting dialysis

Demand for dialysis for patients with end-stage renal disease is growing, as is the comorbidity of dialysis patients. Accurate prediction of those destined to die quickly despite dialysis could be useful to patients, providers, and society in making decisions about starting dialysis. To determine whether age and comorbidity accurately predict death within 6 months of first dialysis for end-stage renal disease, a prospective cohort study of 822 patients starting dialysis at one of 11 Canadian centers was performed. Patient characteristics were recorded at first dialysis. Follow-up continued until death or study end (at least 6 months after enrollment). One hundred thirteen of 822 (13.7%) patients died within 6 months. Although an existing scoring system predicted prognosis, adverse scores greater than 9 were found in only 9.7% of those who died; only 52% of those who scored higher than 9 died within 6 months. No score cutoff point combined high true-positive and low false-positive rates for predicting early death. Age, severity of heart failure or peripheral vascular disease, arrhythmias, malnutrition, malignancy, or myeloma were independent prognostic factors identified in multivariate models. However, the best fit discriminant and logistic models were also unable to accurately predict death within 6 months. Clinicians were very accurate in assigning patients to prognostic groups up to a 50% risk of death by 6 months, above which they tended to overestimate risk. However, clinicians were only marginally better than the predictive models in determining whether a given high-risk patient would die. The inability of a scoring system or clinical intuition to accurately predict death soon after starting dialysis for end-stage renal disease suggests that limiting access to dialysis on the basis of likely short survival may be inappropriate in Canada.

A practical approach to vascular access for hemodialysis and predictors of success

PURPOSE The long-term results and predictors of success for vascular access at The Toronto Hospital were studied. This report describes the access program and emphasizes the role of the vascular access coordinator. METHODS A total of 384 consecutive patients underwent 466 vascular access procedures. The access program is centered around a dedicated, full-time vascular access coordinator, who is a registered nurse and is responsible for all aspects of access care, including follow-up. Outcome variables were collected prospectively. Primary, primary-assisted, and secondary success was determined by means of Kaplan-Meier analysis, and the stepwise Cox proportional hazards model was used for multivariate analysis of the factors that were independently predictive of primary success. RESULTS There were 235 autogenous arteriovenous fistulae (AVFs) and 231 arteriovenous grafts (AVGs). The cumulative primary, assisted-primary, and secondary success (patent and functional for effective dialysis) at 24 months for all 466 cases combined was 36% +/- 3%, 54% +/- 3%, and 66% +/- 3%, respectively. The primary success for AVFs and AVGs at 2 years was 54% +/- 4% and 18% +/- 4%, respectively (P <.001; log-rank test); the primary-assisted success for AVFs and AVGs at 2 years was 62% +/- 4% and 44% +/- 6%, respectively (P <.001; log-rank test); and the secondary success for AVFs and AVGs at 2 years was 70% +/- 4% and 60% +/- 5%, respectively (P =.331; log-rank test). Stratification of variables revealed significant benefit for AVFs (P =.001), the female sex (P =.014), and the absence of diabetes mellitus (P =.001). Multivariate analysis with Cox regression determined that access type (AVF vs AVG; P =.001) and diabetes mellitus (P =.024) were independently predictive of primary success. The improved clinical coordination of access patients with the initiation of the vascular access program resulted in a significant reduction in length of hospital stay before and after the program was organized (2.5 +/- 0.06 vs 1.1 +/- 0.03 days; P =.001). CONCLUSION The organization of a vascular access program in a practical and cost-effective way for reduced length of hospital stay is streamlined through a dedicated access coordinator, who ensures an integrated, multidisciplinary approach. The results for the Cox model is useful when discussing the anticipated results of access procedures with individual patients.

Anionic Surfactant Ionic Liquids with 1-Butyl-3-methyl-imidazolium Cations: Characterization and Application

For the first time a series of anionic surfactant ionic liquids (SAILs) has been synthesized based on organic surfactant anions and 1-butyl-3-methyl-imidazolium cations. These compounds are more environmentally friendly and chemically tunable as compared to other common ionic liquids. A detailed investigation of physicochemical properties highlights potential applications from battery design to reaction control, and studies into aqueous aggregation behavior, as well as structuring in pure ILs, point to possible uses in electrochemistry.

Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.

In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.

A liquid-crystalline silsesquioxane dendrimer exhibiting chiral nematic and columnar mesophases

A hexadecamer, first-generation, octasilsesquioxane liquid-crystalline dendrimer was synthesized by a platinum-catalyzed hydrosilylation reaction of the parent first-generation vinyl octasilsesquioxane dendrimer with a modified, laterally substituted mesogen. The structure and purity of the octasilsesquioxane substrate was confirmed by 1H, 13C, and 29 Si NMR spectroscopy, microanalysis, and size exclusion chromatography (SEC). The mesogenic substrate was found to exhibit only a chiral nematic phase, whereas the resulting hexadecamer dendrimer displays enantiotropic chiral nematic, disordered hexagonal columnar, and disordered rectangular columnar phases, with a glass transition below room temperature. The lateral or side-on attachment of the mesogen to the dendritic core was found to be a key design feature in the formation of the mesophases.

Mesogenic Behaviour of some 1,4,8,11,15,18,22,25-Octa-alkylphthalocyanines

Abstract Discotic columnar mesophase behaviour exhibited by ten metal-free and copper 1,4,8,11,15,18,22,25- octa-alkylphthalocyanines has been characterised by optical microscopy, differential scanning calorimetry, x-ray diffraction and electronic absorption spectroscopy. Compounds with side-chains as short as hexyl exhibit one or more mesophases, and a total of three different mesophases are apparent for the series as a whole. The highest temperature mesophase is assigned as Dhd. At lower temperatures, some compounds develop a second mesophase of hexagonal symmetry, whereas others form a mesophase of rectangular symmetry. One example shows all three mesophases.

New asymmetric substitution of phthalocyanines: Derivatives designed for deposition as Langmuir-Blodgett films☆

Abstract The monolayer and deposition behaviours of 1,4,8,11,15,18-hexa-alkyl-22,25-bis (carboxyethyl)phthalocyanines and 1,4,8,11,15,18,22,25-octa-alkylphthalocyanines have been compared. Compounds in the former series show better monolayer behaviour at the air-water interface than those in the latter series, which form rigid films that cannot be deposited onto substrates. Examples of the first series are excellent for fabrication as Langmuir-Blodgett (LB) films, giving evenly deposited well-ordered bilayer assemblies by Y-type deposition. The effect of temperature on an LB film of one of the compounds has been monitored using polarized absorption spectroscopy and low-angle X-ray diffraction. Up to 50°C the film undergoes some initial reorganization of what is presumed to be a metastable state formed during initial deposition. The molecular structure undergoes a more substantial transition at 127.5°C over a 0.5°C temperature range to a modified film in which adjacent molecules lose translational non-equivalence. Furthermore, there is a reduction in the bilayer thickness from 41 to 36 A. This process is irreversible as judged by UV-visible spectroscopy.

Fabrication of ordered Langmuir-Blodgett multilayers of octa-n-alkoxy phthalocyanines

Abstract The monolayer and deposition behaviour was investigated for a series of eight 1, 4, 8, 11, 15, 18, 22, 25-octa-alkoxy phthalocyanines. Relative to their metal-free analogues, the copper octapropoxy, copper octabutoxy and copper octapentyloxy phthalocyanines gave larger values for the average area per molecule at a standard surface pressure, showed much reduced hysteresis in the π-A isotherm and exhibited greater monolayer stability. The best deposition onto hydrophilic glass was observed for compounds bearing octabutoxy and octapentyloxy chains. These gave even, green multilayer films by either Y- or Z-type deposition. Films of copper and zinc octapentyloxy phthalocyanines gave X-ray diffraction patterns consistent with domains of layer structuring. The layer thickness was 24 A for the former and 26 A for the latter. These values correspond well to the maximum molecular dimension obtained from space-filling models and suggest that, where layer structuring occurs, the molecules are arranged with their planes approximately orthogonal to the substrate surface. The photostability of two examples was investigated.