المؤلفون: Singh, Rishabh, Watchorn, James C, Zarbock, Alexander, Forni, Lui G

المصدر: Research & Reports in Urology; Mar2024, Vol. 16, p65-78, 14p

مصطلحات موضوعية: PROGNOSIS, KIDNEY physiology, ACUTE kidney failure, CHRONIC kidney failure, KIDNEY function tests, KIDNEY transplantation, NEPHRECTOMY

مستخلص: Acute kidney injury (AKI) is a common complication after surgery and the more complex the surgery, the greater the risk. During surgery, patients are exposed to a combination of factors all of which are associated with the development of AKI. These include hypotension and hypovolaemia, sepsis, systemic inflammation, the use of nephrotoxic agents, tissue injury, the infusion of blood or blood products, ischaemia, oxidative stress and reperfusion injury. Given the risks of AKI, it would seem logical to conclude that early identification of patients at risk of AKI would translate into benefit. The conventional markers of AKI, namely serum creatinine and urine output are the mainstay of defining chronic kidney disease but are less suited to the acute phase. Such concerns are compounded in surgical patients given they often have significantly reduced mobility, suboptimal levels of nutrition and reduced muscle bulk. Many patients may also have misleadingly low serum creatinine and high urine output due to aggressive fluid resuscitation, particularly in intensive care units. Over the last two decades, considerable information has accrued with regard to the performance of what was termed "novel" biomarkers of AKI, and here, we discuss the most examined molecules and performance in surgical settings. We also discuss the application of biomarkers to guide patients' postoperative care. Plain Language Summary: Kidney damage is common after major surgery with a recent study showing almost 1 in 5 patients suffer kidney damage. The usual tests for measuring kidney function are excellent in the outpatient but not so good in acute scenario's. Therefore, there has been a lot of interest in new markers of kidney damage (so-called novel biomarkers) which perform well acutely and allow earlier detection of damage allowing treatment to be started earlier. This article summarises the currently available biomarkers for use post-operatively and points out the different information that can be achieved by using them routinely. [ABSTRACT FROM AUTHOR]

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المؤلفون: Zarbock, Alexander^1,2 (AUTHOR) zarbock@uni-muenster.de, Forni, Lui G.^3,4 (AUTHOR), Ostermann, Marlies⁵ (AUTHOR), Ronco, Claudio^6,7,8 (AUTHOR), Bagshaw, Sean M.⁹ (AUTHOR), Mehta, Ravindra L.¹⁰ (AUTHOR), Bellomo, Rinaldo^11,12,13,14 (AUTHOR), Kellum, John A.¹⁵ (AUTHOR)

المصدر: Nature Reviews Nephrology. Feb2024, Vol. 20 Issue 2, p137-146. 10p.

مصطلحات موضوعية: *ACUTE kidney failure, *BIOMARKERS, *CLINICAL trials, *CHRONIC kidney failure, *DISEASE risk factors, *KIDNEY failure

مستخلص: Acute kidney injury (AKI) is a common clinical condition with various causes and is associated with increased mortality. Despite advances in supportive care, AKI increases not only the risk of premature death compared with the general population but also the risk of developing chronic kidney disease and progressing towards kidney failure. Currently, no specific therapy exists for preventing or treating AKI other than mitigating further injury and supportive care. To address this unmet need, novel therapeutic interventions targeting the underlying pathophysiology must be developed. New and well-designed clinical trials with appropriate end points must be subsequently designed and implemented to test the efficacy of such new interventions. Herein, we discuss predictive and prognostic enrichment strategies for patient selection, as well as primary and secondary end points that can be used in different clinical trial designs (specifically, prevention and treatment trials) to evaluate novel interventions and improve the outcomes of patients at a high risk of AKI or with established AKI. Several factors complicate the identification of effective interventions that can improve the outcomes of patients with acute kidney injury (AKI). Here, the authors discuss key design considerations for clinical trials in hospitalized patients with AKI, including the selection of adequate patient cohorts and study end points. Key points: Acute kidney injury (AKI) is a very heterogeneous syndrome; therefore, enrichment strategies are required to reduce heterogeneity within the study patient cohort and to reduce sample size. Several factors, including risk scores, biomarkers and clinical features, can be used for prognostic and predictive enrichment. Careful selection of end points is crucial for any trial. Different end points are required for phase II and phase III trials, and for prevention, attenuation and treatment trials. The occurrence of AKI is a key end point in prevention or attenuation trials and is mainly assessed based on current AKI definitions (based on serum creatinine and urine output) but biomarkers can be used as surrogate end points in phase II trials. Major adverse kidney events cannot be used in prevention trials, but different components in this composite end point should always be reported when used in treatment trials. The trajectory of AKI is an important outcome in intervention trials, because clinical measures or drugs might influence the course of AKI and subsequently influence the mortality rate. [ABSTRACT FROM AUTHOR]

المؤلفون: Zarbock, Alexander¹ (AUTHOR) zarbock@uni-muenster.de, Koyner, Jay L² (AUTHOR), Gomez, Hernando³ (AUTHOR), Pickkers, Peter⁴ (AUTHOR), Forni, Lui^5,6 (AUTHOR), group, the Acute Disease Quality Initiative (AUTHOR)

المصدر: Nephrology Dialysis Transplantation. Jan2024, Vol. 39 Issue 1, p26-35. 10p.

مصطلحات موضوعية: *ACUTE kidney failure, *RENAL replacement therapy, *CRITICALLY ill, *SEPSIS

مستخلص: Sepsis is a host's deleterious response to infection, which could lead to life-threatening organ dysfunction. Sepsis-associated acute kidney injury (SA-AKI) is the most frequent organ dysfunction and is associated with increased morbidity and mortality. Sepsis contributes to ≈50% of all AKI in critically ill adult patients. A growing body of evidence has unveiled key aspects of the clinical risk factors, pathobiology, response to treatment and elements of renal recovery that have advanced our ability to detect, prevent and treat SA-AKI. Despite these advancements, SA-AKI remains a critical clinical condition and a major health burden, and further studies are needed to diminish the short and long-term consequences of SA-AKI. We review the current treatment standards and discuss novel developments in the pathophysiology, diagnosis, outcome prediction and management of SA-AKI. [ABSTRACT FROM AUTHOR]

المؤلفون: Zarbock, Alexander^1,2 (AUTHOR) zarbock@uni-muenster.de, Weiss, Raphael¹ (AUTHOR), Albert, Felix³ (AUTHOR), Rutledge, Kristen⁴ (AUTHOR), Kellum, John A.⁵ (AUTHOR), Bellomo, Rinaldo^6,7,8,9 (AUTHOR), Grigoryev, Evgeny¹⁰ (AUTHOR), Candela-Toha, Angel M.¹¹ (AUTHOR), Demir, Z. Aslı¹² (AUTHOR), Legros, Vincent¹³ (AUTHOR), Rosenberger, Peter¹⁴ (AUTHOR), Galán Menéndez, Patricia¹⁵ (AUTHOR), Garcia Alvarez, Mercedes¹⁶ (AUTHOR), Peng, Ke¹⁷ (AUTHOR), Léger, Maxime¹⁸ (AUTHOR), Khalel, Wegdan¹⁹ (AUTHOR), Orhan-Sungur, Mukadder²⁰ (AUTHOR), Meersch, Melanie¹ (AUTHOR), Makhloufi, Hichem (AUTHOR), Sakhraoui, Rachida (AUTHOR)

المصدر: Intensive Care Medicine. Dec2023, Vol. 49 Issue 12, p1441-1455. 15p.

مصطلحات موضوعية: *ACUTE kidney failure, *LENGTH of stay in hospitals, *CHRONIC kidney failure, *RENAL replacement therapy, *INTENSIVE care units

مستخلص: Purpose: The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. Methods: We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. Results: We studied 10,568 patients and 1945 (18.4%) developed PO-AKI (1236 (63.5%) KDIGO stage 1500 (25.7%) KDIGO stage 2209 (10.7%) KDIGO stage 3). In 33.8% PO-AKI was persistent, and 170/1945 (8.7%) of patients with PO-AKI received RRT in the ICU. Patients with PO-AKI had greater ICU (6.3% vs. 0.7%) and hospital (8.6% vs. 1.4%) mortality, and longer ICU (median 2 (Q1-Q3, 1–3) days vs. 3 (Q1-Q3, 1–6) days) and hospital length of stay (median 14 (Q1-Q3, 9–24) days vs. 10 (Q1-Q3, 7–17) days). Risk factors for PO-AKI included older age, comorbidities (hypertension, diabetes, chronic kidney disease), type, duration and urgency of surgery as well as intraoperative vasopressors, and aminoglycosides administration. Conclusion: In a comprehensive multinational study, approximately one in five patients develop PO-AKI after major surgery. Increasing severity of PO-AKI is associated with a progressive increase in adverse outcomes. Our findings indicate that PO-AKI represents a significant burden for health care worldwide. [ABSTRACT FROM AUTHOR]

المؤلفون: La, Ashley M., Gunning, Samantha, Trevino, Sharon A., Kunczt, Alissa, Forni, Lui G., Swamy, Varsha, Zarbock, Alexander, Groboske, Sarah, Leung, Edward K.Y., Yeo, Kiang-Teck J., Koyner, Jay L.

المصدر: American Journal of Nephrology; 2023, Vol. 54 Issue 7/8, p281-290, 10p

مصطلحات موضوعية: INSULIN-like growth factor-binding proteins, ACUTE kidney failure, BIOMARKERS, INTENSIVE care units

مستخلص: Introduction: Novel urinary biomarkers, including tissue inhibitor metalloprotease-2 and insulin-like growth factor binding protein 7 ([TIMP-2]*[IGFBP7]), have been developed to identify patients at risk for acute kidney injury (AKI). We investigated the "real-world" clinical utility of [TIMP-2]*[IGFBP7] in preventing AKI. Methods: We performed a before and after single-center quality improvement study of intensive care unit (ICU) patients at risk for severe (KDIGO stage 2 or 3) AKI. In the prospective cohort, ICU providers were allowed to order [TIMP-2]*[IGFBP7] for patients at their discretion, then offered AKI practice recommendations based on the results. Outcomes were compared to a historical cohort in which biomarker values were not reported to clinical teams. Results: There was no difference in 7-day progression to severe AKI between the prospective (n = 116) and historical cohorts (n = 63) when [TIMP-2]*[IGFBP7] ≥0.3 (24 [28%] versus 8 [21%], p = 0.38) despite more stage 1 AKI at time of biomarker measurement in the prospective cohort (58 [67%] versus 9 [23%], p < 0.001). In the prospective cohort, patients with higher [TIMP-2]*[IGFBP7] values were more likely to receive a nephrology consult. Early consultation (within 24 h of biomarker measurement, n = 20) had a nonsignificant trend toward net negative volume balance (−1,787 mL [6,716 mL] versus + 4,974 mL [15,540 mL]) and more diuretic use (19 [95%] versus 8 [80%]) and was associated with less severe AKI (9 [45%] versus 10 [100%], p = 0.004) and inpatient dialysis (2 [10%] versus 7 [70%], p = 0.002) compared to delayed consultation (n = 10). Conclusions: Despite the prospective cohort having more preexisting stage 1 AKI, there were equal rates of progression to severe AKI in the prospective and historical cohorts. In the setting of [TIMP-2]*[IGFBP7] reporting, there were more nephrology consults in response to elevated biomarker levels. Early nephrology consultation resulted in improved volume balance and favorable outcomes compared to delayed consultation. [ABSTRACT FROM AUTHOR]

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المؤلفون: Zarbock, Alexander^1,2 (AUTHOR), Nadim, Mitra K.³ (AUTHOR), Pickkers, Peter⁴ (AUTHOR), Gomez, Hernando⁵ (AUTHOR), Bell, Samira⁶ (AUTHOR), Joannidis, Michael⁷ (AUTHOR), Kashani, Kianoush⁸ (AUTHOR), Koyner, Jay L.⁹ (AUTHOR), Pannu, Neesh¹⁰ (AUTHOR), Meersch, Melanie¹ (AUTHOR), Reis, Thiago^11,12 (AUTHOR), Rimmelé, Thomas¹³ (AUTHOR), Bagshaw, Sean M.¹⁴ (AUTHOR), Bellomo, Rinaldo^15,16,17,18 (AUTHOR), Cantaluppi, Vicenzo¹⁹ (AUTHOR), Deep, Akash²⁰ (AUTHOR), De Rosa, Silvia^21,22 (AUTHOR), Perez-Fernandez, Xose²³ (AUTHOR), Husain-Syed, Faeq²⁴ (AUTHOR), Kane-Gill, Sandra L.²⁵ (AUTHOR)

المصدر: Nature Reviews Nephrology. Jun2023, Vol. 19 Issue 6, p401-417. 17p.

مصطلحات موضوعية: *ACUTE kidney failure, *ACUTE diseases, *DISEASE risk factors, *CHRONIC kidney failure, *NEONATAL diseases, *KIDNEY diseases

مستخلص: Sepsis-associated acute kidney injury (SA-AKI) is common in critically ill patients and is strongly associated with adverse outcomes, including an increased risk of chronic kidney disease, cardiovascular events and death. The pathophysiology of SA-AKI remains elusive, although microcirculatory dysfunction, cellular metabolic reprogramming and dysregulated inflammatory responses have been implicated in preclinical studies. SA-AKI is best defined as the occurrence of AKI within 7 days of sepsis onset (diagnosed according to Kidney Disease Improving Global Outcome criteria and Sepsis 3 criteria, respectively). Improving outcomes in SA-AKI is challenging, as patients can present with either clinical or subclinical AKI. Early identification of patients at risk of AKI, or at risk of progressing to severe and/or persistent AKI, is crucial to the timely initiation of adequate supportive measures, including limiting further insults to the kidney. Accordingly, the discovery of biomarkers associated with AKI that can aid in early diagnosis is an area of intensive investigation. Additionally, high-quality evidence on best-practice care of patients with AKI, sepsis and SA-AKI has continued to accrue. Although specific therapeutic options are limited, several clinical trials have evaluated the use of care bundles and extracorporeal techniques as potential therapeutic approaches. Here we provide graded recommendations for managing SA-AKI and highlight priorities for future research. Sepsis-associated acute kidney injury (SA-AKI) is linked with poor outcomes in critically ill patients. This Consensus Statement from the Acute Disease Quality Initiative discusses the definition, epidemiology and pathophysiology of SA-AKI, fluid, resuscitation and extracorporeal therapies, and the role of biomarkers in risk stratification and diagnosis. [ABSTRACT FROM AUTHOR]

المؤلفون: Bergholz, Alina, Meidert, Agnes S., Flick, Moritz, Krause, Linda, Vettorazzi, Eik, Zapf, Antonia, Brunkhorst, Frank M., Meybohm, Patrick, Zacharowski, Kai, Zarbock, Alexander, Sessler, Daniel I., Kouz, Karim, Saugel, Bernd

المصدر: Trials; 11/17/2022, Vol. 23 Issue 1, p1-9, 9p, 1 Diagram, 1 Chart

مصطلحات موضوعية: BLOOD pressure, INTRA-abdominal infections, ABDOMINAL surgery, SURGICAL complications, POSTOPERATIVE care, ACUTE kidney failure, DEEP brain stimulation, PREVENTION of surgical complications, RESEARCH, CLINICAL trials, CARDIAC arrest, DISEASE complications

مستخلص: Background: Intraoperative hypotension is common in patients having non-cardiac surgery and is associated with serious complications and death. However, optimal intraoperative blood pressures for individual patients remain unknown. We therefore aim to test the hypothesis that personalized perioperative blood pressure management-based on preoperative automated blood pressure monitoring-reduces the incidence of a composite outcome of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery.Methods: IMPROVE-multi is a multicenter randomized trial in 1272 high-risk patients having elective major abdominal surgery that we plan to conduct at 16 German university medical centers. Preoperative automated blood pressure monitoring using upper arm cuff oscillometry will be performed in all patients for one night to obtain the mean of the nighttime mean arterial pressures. Patients will then be randomized either to personalized blood pressure management or to routine blood pressure management. In patients assigned to personalized management, intraoperative mean arterial pressure will be maintained at least at the mean of the nighttime mean arterial pressures. In patients assigned to routine management, intraoperative blood pressure will be managed per routine. The primary outcome will be a composite of acute kidney injury, acute myocardial injury, non-fatal cardiac arrest, and death within 7 days after surgery.Discussion: Our trial will determine whether personalized perioperative blood pressure management reduces the incidence of major postoperative complications and death within 7 days after surgery compared to routine blood pressure management in high-risk patients having major abdominal surgery.Trial Registration: ClinicalTrials.gov NCT05416944. Registered on June 14, 2022. [ABSTRACT FROM AUTHOR]

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المؤلفون: von Groote, Thilo, Albert, Felix, Meersch, Melanie, Koch, Raphael, Porschen, Christian, Hartmann, Oliver, Bergmann, Deborah, Pickkers, Peter, Zarbock, Alexander

المصدر: Critical Care; 10/31/2022, Vol. 26 Issue 1, p1-12, 12p

مصطلحات موضوعية: EVALUATION research, THERAPEUTICS, RENAL replacement therapy, RESEARCH funding, CATASTROPHIC illness, ACUTE kidney failure, RESEARCH, COMPARATIVE studies, TIME

مستخلص: Background: Renal replacement therapy (RRT) remains the key rescue therapy for critically ill patients with severe acute kidney injury (AKI). However, there are currently no tools available to predict successful liberation from RRT. Biomarkers may allow for risk stratification and individualization of treatment strategies. Proenkephalin A 119-159 (penKid) has been suggested as a promising marker of kidney function in the context of AKI, but has not yet been evaluated for RRT liberation in critically ill patients with AKI.Methods: This post hoc analysis included 210 patients from the randomized clinical ELAIN trial and penKid levels were measured in the blood of these patients. Competing risk time-to-event analyses were performed for pre-RRT penKid at initiation of RRT and in a landmark analysis at day 3 after initiation of RRT. Competing risk endpoints were successful liberation from RRT or death without prior liberation from RRT.Results: Low pre-RRT penKid levels (penKid ≤ 89 pmol/l) at RRT initiation were associated with early and successful liberation from RRT compared to patients with high pre-RRT penKid levels (subdistribution hazard ratio (sHR) 1.83, 95%CI 1.26-2.67, p = 0.002, estimated 28d-cumulative incidence function (28d-CIF) of successful liberation from RRT 61% vs. 45%, p = 0.022). This association persisted in the landmark analysis on day 3 of RRT (sHR 1.78, 95%CI 1.17-2.71, p = 0.007, 28d-CIF of successful liberation from RRT 67% vs. 47%, p = 0.018). For both time points, no difference in the competing event of death was detected.Conclusions: In critically ill patients with RRT-dependent AKI, plasma penKid appears to be a useful biomarker for the prediction of shorter duration and successful liberation from RRT and may allow an individualized approach to guide strategies of RRT liberation in critically ill patients with RRT-dependent AKI.Trial Registration: The ELAIN trial was prospectively registered at the German Clinical Trial Registry (Identifier: DRKS00004367) on 28th of May 2013. [ABSTRACT FROM AUTHOR]

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المؤلفون: Wald, Ron, Beaubien-Souligny, William, Chanchlani, Rahul, Clark, Edward G., Neyra, Javier A., Ostermann, Marlies, Silver, Samuel A., Vaara, Suvi, Zarbock, Alexander, Bagshaw, Sean M.

المصدر: Intensive Care Medicine; Oct2022, Vol. 48 Issue 10, p1368-1381, 14p, 1 Color Photograph, 3 Diagrams, 3 Charts

مصطلحات موضوعية: INTENSIVE care units, THERAPEUTICS, RENAL replacement therapy, CATASTROPHIC illness, ACUTE kidney failure

مستخلص: Critical illness is often complicated by acute kidney injury (AKI). In patients with severe AKI, renal replacement therapy (RRT) is deployed to address metabolic dysfunction and volume excess until kidney function recovers. This review is intended to provide a comprehensive update on key aspects of RRT prescription and delivery to critically ill patients. Recently completed trials have enhanced the evidence base regarding several RRT practices, most notably the timing of RRT initiation and anticoagulation for continuous therapies. Better evidence is still needed to clarify several aspects of care including optimal targets for ultrafiltration and effective strategies for RRT weaning and discontinuation. [ABSTRACT FROM AUTHOR]

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المؤلفون: Margraf, Andreas, Liu, Chang, Küllmar, Mira, Meersch, Melanie, Rossaint, Jan, Zarbock, Alexander

المصدر: Cells (2073-4409); Jun2022, Vol. 11 Issue 11, p1815-1815, 12p

مصطلحات موضوعية: HEPARIN, LEUCOCYTES, ACUTE kidney failure, CITRATES, ANTICOAGULANTS

مستخلص: Acute kidney injury (AKI) is a frequent complication in critically ill patients. Supportive treatment of AKI patients is based on renal-replacement therapy, including continuous veno-venous hemofiltration (CVVH). To limit clotting events on extracorporeal surfaces, anticoagulants are administered, including systemic heparin and local citrate. The differential and comparative effects of these anticoagulants on leukocyte function in acute kidney injury patients are, so far, insufficiently understood. In this bio-add-on-study, AKI patients were randomized as part of a parallel-group trial to either systemic heparin or regional citrate anticoagulation. Patient samples were collected upon inclusion, prior to CVVH initiation at day 0, day 1, day 3 and day 5, following CVVH initiation, and one day after cessation of CVVH, then immediately analyzed. Flow cytometric assessment of surface-receptor molecules was conducted. Whole-blood-perfused human microfluidic chambers were used for the analysis of neutrophil rolling and adhesion. Acute kidney injury was associated with significant changes in the surface expression of CD182 and CD16 throughout CVVH treatment, independent of the anticoagulation regime. AKI furthermore abrogated selectin-induced slow leukocyte rolling and diminished chemokine-induced leukocyte arrest. Subgroup analyses of citrate vs. heparin treatment showed no significant differences between groups, independent of the duration of CVVH treatment. CD182 and CD16 expression remained low in both groups throughout CVVH therapy. These data confirm that AKI impairs selectin-mediated leukocyte slow rolling and chemokine-induced leukocyte arrest in vitro. Systemic heparin or local citrate anticoagulation have no differential effect on the leukocyte recruitment steps examined in this study. [ABSTRACT FROM AUTHOR]

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