Electroneutrality and Phase Behavior of Colloidal Suspensions

Several statistical mechanical theories predict that colloidal suspensions of highly charged macroions and monovalent microions can exhibit unusual thermodynamic phase behavior when strongly deionized. Density-functional, extended Debye-H\"uckel, and response theories, within mean-field and linearization approximations, predict a spinodal phase instability of charged colloids below a critical salt concentration. Poisson-Boltzmann cell model studies of suspensions in Donnan equilibrium with a salt reservoir demonstrate that effective interactions and osmotic pressures predicted by such theories can be sensitive to the choice of reference system, e.g., whether the microion density profiles are expanded about the average potential of the suspension or about the reservoir potential. By unifying Poisson-Boltzmann and response theories within a common perturbative framework, it is shown here that the choice of reference system is dictated by the constraint of global electroneutrality. On this basis, bulk suspensions are best modeled by density-dependent effective interactions derived from a closed reference system in which the counterions are confined to the same volume as the macroions. Linearized theories then predict bulk phase separation of deionized suspensions only when expanded about a physically consistent (closed) reference system. Lower-dimensional systems (e.g., monolayers, small clusters), depending on the strength of macroion-counterion correlations, may be governed instead by density-independent effective interactions tied to an open reference system with counterions dispersed throughout the reservoir, possibly explaining observed structural crossover in colloidal monolayers and anomalous metastability of colloidal crystallites.Comment: 12 pages, 5 figures. Discussion clarified, references adde

Binding effects in multivalent Gibbs-Donnan equilibrium

The classical Gibbs-Donnan equilibrium describes excess osmotic pressure associated with confined colloidal charges embedded in an electrolyte solution. In this work, we extend this approach to describe the influence of multivalent ion binding on the equilibrium force acting on a charged rod translocating between two compartments, thereby mimicking ionic effects on force balance during in vitro DNA ejection from bacteriophage. The subtle interplay between Gibbs-Donnan equilibrium and adsorption equilibrium leads to a non-monotonic variation of the ejection force as multivalent salt concentration is increased, in qualitative agreement with experimental observations

Smoking as a Crucial Independent Determinant of Stroke

<p>Abstract</p> <p>Background</p> <p>Although smoking is known to be powerful risk factor for other vascular diseases, such as cardiac and peripheral vascular disease, only relatively recently has evidence for the role of smoking in the development of stroke been established. The reasons for this advance lie in the acknowledgement that stroke is a heterogeneous disease, in which its subtypes are associated with different risk factors. Furthermore, improvements in the stringency of epidemiological studies and the greater use of CT scanning have enabled the role of smoking in the development of stroke to be elucidated.</p> <p>Summary of review</p> <p>This is a qualitative examination of high quality epidemiological studies in which the role of smoking and passive smoking, as a risk factor for cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage, is examined. In addition, the pathological mechanisms by which smoking or passive smoking may contribute to the development of stroke are reviewed.</p> <p>Conclusion</p> <p>Smoking is a crucial independent determinant of cerebral infarction and subarachnoid haemorrhage, however its role in intracerebral haemorrhage is unclear. Although studies are limited, there is evidence that exposure to passive smoking may also increase the risk of stroke. Smoking appears to be involved in the pathogenesis of stroke via direct injury to the vasculature and also by altering haemodynamic factors within the circulation. Importantly, smoking is modifiable risk factor for stroke. Therefore, the encouragement of smoking cessation may result in a substantial reduction in the incidence of this devastating disease.</p

Phase behaviour of charged colloidal sphere dispersions with added polymer chains

We study the stability of mixtures of highly screened repulsive charged spheres and non-adsorbing ideal polymer chains in a common solvent using free volume theory. The effective interaction between charged colloids in an aqueous salt solution is described by a screened-Coulomb pair potential, which supplements the pure hard-sphere interaction. The ideal polymer chains are treated as spheres that are excluded from the colloids by a hard-core interaction, whereas the interaction between two ideal chains is set to zero. In addition, we investigate the phase behaviour of charged colloid-polymer mixtures in computer simulations, using the two-body (Asakura-Oosawa pair potential) approximation to the effective one-component Hamiltonian of the charged colloids. Both our results obtained from simulations and from free volume theory show similar trends. We find that the screened-Coulomb repulsion counteracts the effect of the effective polymer-mediated attraction. For mixtures of small polymers and relatively large charged colloidal spheres, the fluid-crystal transition shifts to significantly larger polymer concentrations with increasing range of the screened-Coulomb repulsion. For relatively large polymers, the effect of the screened-Coulomb repulsion is weaker. The resulting fluid-fluid binodal is only slightly shifted towards larger polymer concentrations upon increasing the range of the screened-Coulomb repulsion. In conclusion, our results show that the miscibility of dispersions containing charged colloids and neutral non-adsorbing polymers increases, upon increasing the range of the screened-Coulomb repulsion, or upon lowering the salt concentration, especially when the polymers are small compared to the colloids.Comment: 25 pages,13 figures, accepted for publication on J.Phys.:Condens. Matte

Aging and ultra-slow equilibration in concentrated colloidal hard spheres

We study the dynamic behaviour of concentrated colloidal hard spheres using Time Resolved Correlation, a light scattering technique that can detect the slow evolution of the dynamics in out-of-equilibrium systems. Surprisingly, equilibrium is reached a very long time after sample initialization, the non-stationary regime lasting up to three orders of magnitude more than the relaxation time of the system. Before reaching equilibrium, the system displays unusual aging behaviour. The intermediate scattering function decays faster than exponentially and its relaxation time evolves non-monotonically with sample age.Comment: Submitted to the proceedings of the 6th EPS Liquid Matter Conference, Utrecht 2-6 July 200

Development and application of model of resource utilization, costs, and outcomes for stroke (MORUCOS): an Australian economic model for stroke

Objectives: To outline the development, structure, data assumptions, and application of an Australian economic model for stroke (Model of Resource Utilization, Costs, and Outcomes for Stroke [MORUCOS]).Methods: The model has a linked spreadsheet format with four modules to describe the disease burden and treatment pathways, estimate prevalence-based and incidence-based costs, and derive life expectancy and quality of life consequences. The model uses patient-level, community-based, stroke cohort data and macro-level simulations. An interventions module allows options for change to be consistently evaluated by modifying aspects of the other modules. To date, model validation has included sensitivity testing, face validity, and peer review. Further validation of technical and predictive accuracy is needed. The generic pathway model was assessed by comparison with a stroke subtypes (ischemic, hemorrhagic, or undetermined) approach and used to determine the relative cost-effectiveness of four interventions.Results: The generic pathway model produced lower costs compared with a subtypes version (total average first-year costs/case AUD$15,117 versus AUD$17,786, respectively). Optimal evidence-based uptake of anticoagulation therapy for primary and secondary stroke prevention and intravenous thrombolytic therapy within 3 hours of stroke were more cost-effective than current practice (base year, 1997).Conclusions: MORUCOS is transparent and flexible in describing Australian stroke care and can effectively be used to systematically evaluate a range of different interventions. Adjusting results to account for stroke subtypes, as they influence cost estimates, could enhance the generic model

Development and application of model of resource utilization, costs, and outcomes for stroke (MORUCOS): an Australian economic model for stroke

Objectives: To outline the development, structure, data assumptions, and application of an Australian economic model for stroke (Model of Resource Utilization, Costs, and Outcomes for Stroke [MORUCOS]).Methods: The model has a linked spreadsheet format with four modules to describe the disease burden and treatment pathways, estimate prevalence-based and incidence-based costs, and derive life expectancy and quality of life consequences. The model uses patient-level, community-based, stroke cohort data and macro-level simulations. An interventions module allows options for change to be consistently evaluated by modifying aspects of the other modules. To date, model validation has included sensitivity testing, face validity, and peer review. Further validation of technical and predictive accuracy is needed. The generic pathway model was assessed by comparison with a stroke subtypes (ischemic, hemorrhagic, or undetermined) approach and used to determine the relative cost-effectiveness of four interventions.Results: The generic pathway model produced lower costs compared with a subtypes version (total average first-year costs/case AUD$15,117 versus AUD$17,786, respectively). Optimal evidence-based uptake of anticoagulation therapy for primary and secondary stroke prevention and intravenous thrombolytic therapy within 3 hours of stroke were more cost-effective than current practice (base year, 1997).Conclusions: MORUCOS is transparent and flexible in describing Australian stroke care and can effectively be used to systematically evaluate a range of different interventions. Adjusting results to account for stroke subtypes, as they influence cost estimates, could enhance the generic model

AVERT2(a very early rehabilitation trial, a very effective reproductive trigger): retrospective observational analysis of the number of babies born to trial staff

Objective: To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Design: Retrospective observational analysis. Setting: 56 acute stroke hospitals in eight countries. Participants: 1074 trial physiotherapists, nurses, and other clinicians. Outcome measures: Number of babies born during trial recruitment per trial participant recruited. Results: With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. Conclusion: The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators’ meetings and helped maintain a cohesive collaborative group

Association of opioid prescribing practices with chronic pain and benzodiazepine co-prescription:a primary care data linkage study

Background: Opioid prescribing is increasing worldwide with associated increases in misuse and other harms. We studied variations in national opioid prescription rates, indicators of prescribing quality, co-prescribing of benzodiazepines and relationship with pain severity in Scotland. Methods: Electronic linkages of opioid prescribing in Scotland were determined from: (i) national data from Information Services Division, NHS Scotland (2003–2012); and (ii) individual data from Generation Scotland: Scottish Family Health Study. Descriptive analyses were conducted on national data, multilevel modelling to examine factors associated with variations in prescribing rates. χ2 tests examined associations between individual pain severity and opioid prescriptions. Results: The number of strong opioid prescriptions more than doubled from 474 385 in 2003 to 1 036 446 in 2012, and weak opioid prescribing increased from 3 261 547 to 4 852 583. In Scotland, 938 674 individuals were prescribed an opioid in 2012 (18% of the population). Patients in the most deprived areas were 3.5 times more likely to receive a strong opioid than patients in the least deprived. There was significant variation in prescribing rates between geographical areas, with much of this explained by deprivation. Of women aged 25–40 yr prescribed a strong opioid, 40% were also prescribed a benzodiazepine. There was significant association between pain severity and receipt of opioid prescription. Over 50% of people reporting severe pain were not prescribed an opioid analgesic. Conclusions: We found opioid prescribing in primary care to be common and increasing in Scotland, particularly for severe pain. Co-prescribing of opioids and benzodiazepines was common

One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke

BACKGROUND Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists. METHODS We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD2 score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year. RESULTS From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan–Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan–Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD2 score of 6 or 7 were each associated with more than a doubling of the risk of stroke. CONCLUSIONS We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD2 score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.)Supported by an unrestricted grant from Sanofi and Bristol-Myers Squibb