A comparative study of blood rheology across species.

Recent advances in hemorheology are extended to study blood rheology across species, which has important clinical implications particularly in intravenous drug scaleup as drugs undergoing clinical trials are first tested in animals. Some of the first hemorheological measurements from seven different species under both steady and transient shear conditions are presented and modeled using a rheological model developed and validated on human blood rheology fit to 20 different donors. Despite similar physiological properties across the blood samples from different species, significant differences are observed, particularly at low shear rates. Blood from species that form rouleaux exhibit a yield-like behavior and enhanced viscoelasticity at low shear rates, while blood from species without rouleaux exhibit nearly Newtonian behavior at similar shear rates. Viscoelasticity due to blood cell deformation is evident for all species at high shear rates. Novel, unidirectional large amplitude oscillatory shear measurements differentiate species. Using the newly acquired data in combination with previous literature data, a new allometric scaling relation is suggested for the low-shear blood viscosity for various mammalian evolutionary orders. Using an established model for arterial branching across species, it is conjectured that the observed hemorheological scaling across species is driven by maintaining a constant wall shear stress in arterial vessels.

Recent advances in blood rheology: a review.

Due to the potential impact on the diagnosis and treatment of various cardiovascular diseases, work on the rheology of blood has significantly expanded in the last decade, both experimentally and theoretically. Experimentally, blood has been confirmed to demonstrate a variety of non-Newtonian rheological characteristics, including pseudoplasticity, viscoelasticity, and thixotropy. New rheological experiments and the development of more controlled experimental protocols on more extensive, broadly physiologically characterized, human blood samples demonstrate the sensitivity of aspects of hemorheology to several physiological factors. For example, at high shear rates the red blood cells elastically deform, imparting viscoelasticity, while at low shear rates, they form "rouleaux" structures that impart additional, thixotropic behavior. In addition to the advances in experimental methods and validated data sets, significant advances have also been made in both microscopic simulations and macroscopic, continuum, modeling, as well as novel, multiscale approaches. We outline and evaluate the most promising of these recent developments. Although we primarily focus on human blood rheology, we also discuss recent observations on variations observed across some animal species that provide some indication on evolutionary effects.

Timing of Recovery From Moderate to Severe AKI and the Risk for Future Loss of Kidney Function.

RATIONALE & OBJECTIVE: The extent of recovery of kidney function following acute kidney injury (AKI) is known to be associated with future chronic kidney disease. Less is known about how the timing of recovery affects the rate of future loss of kidney function. STUDY DESIGN: We performed a retrospective cohort study examining the independent association between the timing of recovery from moderate to severe AKI and future loss of kidney function. SETTING & PARTICIPANTS: 47,903 adult US veterans with stage 2 or 3 AKI who recovered to within 120% of baseline creatinine level within 90 days of peak injury. EXPOSURE: The timing of recovery of kidney function from peak inpatient serum creatinine level grouped into 1 to 4, 5 to 10, 11 to 30, and 31 to 90 days. OUTCOME: A sustained 40% decline in estimated glomerular filtration rate below that calculated from the last serum creatinine level available during the 90-day recovery period or kidney failure (2 outpatient estimated glomerular filtration rates<15mL/min/1.73m2, dialysis procedures > 90 days apart, kidney transplantation, or registry within the US Renal Data System). ANALYTICAL APPROACH: Time to the primary outcome was examined using multivariable Cox proportional hazards regression. RESULTS: Among 47,903 patients, 29,316 (61%), 10,360 (22%), 4,520 (9%), and 3,707 (8%) recovered within 1 to 4, 5 to 10, 11 to 30, and 31 to 90 days, respectively. With a median follow-up of 42 months, unadjusted incidence rates for the kidney outcome were 2.01, 3.55, 3.86, and 3.68 events/100 person-years, respectively. Compared with 1 to 4 days, recovery within 5 to 10, 11 to 30, and 31 to 90 days was associated with increased rates of the primary outcome: adjusted HRs were 1.33 (95% CI, 1.24-1.43), 1.41 (95% CI, 1.28-1.54), and 1.58 (95% CI, 1.43-1.75), respectively. LIMITATIONS: Predominately male population, residual confounding, and inability to make causal inferences because of the retrospective observational study design. CONCLUSIONS: The timing of recovery provides an added dimension to AKI phenotyping and prognostic information regarding the future occurrence of loss of kidney function. Studies to identify effective interventions on the timing of recovery from AKI are warranted.

Effectiveness of Respiratory Syncytial Virus Immunoprophylaxis in Reducing Bronchiolitis Hospitalizations Among High-Risk Infants.

We sought to determine the real-world effectiveness of respiratory syncytial virus (RSV) immunoprophylaxis in a population-based cohort to inform policy. The study population included infants born during 1996-2008 and enrolled in the Kaiser Permanente Northern California integrated health-care delivery system. During the RSV season (November-March), the date of RSV immunoprophylaxis administration and the following 30 days were defined as RSV immunoprophylaxis protected period(s), and all other days were defined as unprotected period(s). Numbers of bronchiolitis hospitalizations were determined using International Classification of Diseases, Ninth Revision, codes during RSV season. We used a proportional hazards model to estimate risk of bronchiolitis hospitalization when comparing infants' protected period(s) with unprotected period(s). Infants who had ever received RSV immunoprophylaxis had a 32% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.68, 95% confidence interval: 0.46, 1.00) when protected periods were compared with unprotected periods. Infants with chronic lung disease (CLD) had a 52% decreased risk of bronchiolitis hospitalization (adjusted hazard ratio = 0.48, 95% confidence interval: 0.25, 0.94) when protected periods were compared with unprotected periods. Under the new 2014 American Academy of Pediatrics (AAP) guidelines, 48% of infants eligible for RSV immunoprophylaxis on the basis of AAP guidelines in place at birth would no longer be eligible, but nearly all infants with CLD would remain eligible. RSV immunoprophylaxis is effective in decreasing hospitalization. This association is greatest for infants with CLD, a group still recommended for receipt of RSV immunoprophylaxis under the new AAP guidelines.

Understanding the Electrochemical Performance of FeS2 Conversion Cathodes.

Conversion cathodes represent a viable route to improve rechargeable Li+ battery energy densities, but their poor electrochemical stability and power density have impeded their practical implementation. Here, we explore the impact cell fabrication, electrolyte interaction, and current density have on the electrochemical performance of FeS2/Li cells by deconvoluting the contributions of the various conversion and intercalation reactions to the overall capacity. By varying the slurry composition and applied pressure, we determine that the capacity loss is primarily due to the large volume changes during (de)lithiation, leading to a degradation of the conductive matrix. Through the application of an external pressure, the loss is minimized by maintaining the conductive matrix. We further determine that polysulfide loss can be minimized by increasing the current density (>C/10), thus reducing the sulfur formation period. Analysis of the kinetics determines that the conversion reactions are rate-limiting, specifically the formation of metallic iron at rates above C/8. While focused on FeS2, our findings on the influence of pressure, electrolyte interaction, and kinetics are broadly applicable to other conversion cathode systems.

Molecular engineering of thixotropic, sprayable fluids with yield stress using associating polysaccharides.

HYPOTHESIS: Molecular engineering facilitates the development of a complex fluid with contradictory requirements of yield stress and sprayability, while minimizing the amount of structuring material (<0.05 wt%). This unique system can be achieved by a biopolymer hydrogel with tunable inter- and intra-molecular interactions for microstructural robustness and molecular extensibility by the variation of chemical conformations that microstructure breaks up under shear followed by a low molecularly extensible response. EXPERIMENTS: Blends of xanthan and konjac glucomannan containing 99.95 wt% water are demonstrated to satisfy these contradictory requirements and formulated as a function of KCl concentrations. A systematic study was performed using shear and extensional rheology and compared to a reference solution of polyethylene oxide (PEO), a well-known, Boger fluid, highlights the role of molecular elasticity in controlling critical rheological properties. Static light scattering (SLS) and simultaneous rheology and small-angle neutron scattering (RheoSANS) are also used to elucidate the equilibrium structure and flow dynamics. FINDINGS: The blends exhibit a lower yield stress and extensional resistance with added KCl, which leads to good spray characteristics in contrast to strain-hardening PEO. The results suggest that the inter-molecular attractions between the two gums leading to network formation with appropriate stiffness, that break up readily under shear, and low molecular elasticity are critical molecular design parameters necessary to achieve sprayable, yields stress fluids.

Effects of ex vivo aging and storage temperature on blood viscosity.

BACKGROUND: Research on hemorheology is driven in part by its significance in blood diseases and the possible use of hemorheology as a diagnostic tool. However, existing data on blood rheology are limited largely to measurements of steady shear behavior often with varying measurement protocols and insufficient characterization of the physiology. OBJECTIVE: The effects of ex vivo aging and environmental conditions on blood viscosity are investigated to improve standards for hemorheology measurements. METHODS: Measurements on the viscosity of blood from nine healthy donors are obtained and the physiological state of the blood determined. Steady and transient shear measurements are reported as a function of time from withdrawal. The effect of transportation temperature is also assessed. RESULTS: Blood transported at 4 °C may exhibit anomalous viscosity variations for short to intermediate times, as opposed to blood transported at room temperature. A time of approximately 3.0 hours was identified as the maximum time after the initial test that accurate rheological tests can be conducted on blood samples. CONCLUSIONS: Measurement protocol and time limit guidelines are established for conducting accurate rheological measurements on blood.

Risk of Hypoglycemia Following Hospital Discharge in Patients With Diabetes and Acute Kidney Injury.

OBJECTIVE: Hypoglycemia is common in patients with diabetes. The risk of hypoglycemia after acute kidney injury (AKI) is not well defined. The purpose of this study was to compare the risk for postdischarge hypoglycemia among hospitalized patients with diabetes who do and do not experience AKI. RESEARCH DESIGN AND METHODS: We performed a propensity-matched analysis of patients with diabetes, with and without AKI, using a retrospective national cohort of veterans hospitalized between 2004 and 2012. AKI was defined as a 0.3 mg/dL or 50% increase in serum creatinine from baseline to peak serum creatinine during hospitalization. Hypoglycemia was defined as hospital admission or an emergency department visit for hypoglycemia or as an outpatient blood glucose <60 mg/dL. Time to incident hypoglycemia within 90 days postdischarge was examined using Cox proportional hazards models. Prespecified subgroup analyses by renal recovery, baseline chronic kidney disease, preadmission drug regimen, and HbA1c were performed. RESULTS: We identified 65,151 propensity score-matched pairs with and without AKI. The incidence of hypoglycemia was 29.6 (95% CI 28.9-30.4) and 23.5 (95% CI 22.9-24.2) per 100 person-years for patients with and without AKI, respectively. After adjustment, AKI was associated with a 27% increased risk of hypoglycemia (hazard ratio [HR] 1.27 [95% CI 1.22-1.33]). For patients with full recovery, the HR was 1.18 (95% CI 1.12-1.25); for partial recovery, the HR was 1.30 (95% CI 1.23-1.37); and for no recovery, the HR was 1.48 (95% CI 1.36-1.60) compared with patients without AKI. Across all antidiabetes drug regimens, patients with AKI experienced hypoglycemia more frequently than patients without AKI, though the incidence of hypoglycemia was highest among insulin users, followed by glyburide and glipizide users, respectively. CONCLUSIONS: AKI is a risk factor for hypoglycemia in the postdischarge period. Studies to identify risk-reduction strategies in this population are warranted.