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1.  Global Multi-Level Analysis of the ‘Scientific Food Web' 
Scientific Reports  2013;3:1167.
We introduce a network-based index analyzing excess scientific production and consumption to perform a comprehensive global analysis of scholarly knowledge production and diffusion on the level of continents, countries, and cities. Compared to measures of scientific production and consumption such as number of publications or citation rates, our network-based citation analysis offers a more differentiated picture of the ‘ecosystem of science’. Quantifying knowledge flows between 2000 and 2009, we identify global sources and sinks of knowledge production. Our knowledge flow index reveals, where ideas are born and consumed, thereby defining a global ‘scientific food web’. While Asia is quickly catching up in terms of publications and citation rates, we find that its dependence on knowledge consumption has further increased.
doi:10.1038/srep01167
PMCID: PMC3558694  PMID: 23378902
2.  Design and Update of a Classification System: The UCSD Map of Science 
PLoS ONE  2012;7(7):e39464.
Global maps of science can be used as a reference system to chart career trajectories, the location of emerging research frontiers, or the expertise profiles of institutes or nations. This paper details data preparation, analysis, and layout performed when designing and subsequently updating the UCSD map of science and classification system. The original classification and map use 7.2 million papers and their references from Elsevier’s Scopus (about 15,000 source titles, 2001–2005) and Thomson Reuters’ Web of Science (WoS) Science, Social Science, Arts & Humanities Citation Indexes (about 9,000 source titles, 2001–2004)–about 16,000 unique source titles. The updated map and classification adds six years (2005–2010) of WoS data and three years (2006–2008) from Scopus to the existing category structure–increasing the number of source titles to about 25,000. To our knowledge, this is the first time that a widely used map of science was updated. A comparison of the original 5-year and the new 10-year maps and classification system show (i) an increase in the total number of journals that can be mapped by 9,409 journals (social sciences had a 80% increase, humanities a 119% increase, medical (32%) and natural science (74%)), (ii) a simplification of the map by assigning all but five highly interdisciplinary journals to exactly one discipline, (iii) a more even distribution of journals over the 554 subdisciplines and 13 disciplines when calculating the coefficient of variation, and (iv) a better reflection of journal clusters when compared with paper-level citation data. When evaluating the map with a listing of desirable features for maps of science, the updated map is shown to have higher mapping accuracy, easier understandability as fewer journals are multiply classified, and higher usability for the generation of data overlays, among others.
doi:10.1371/journal.pone.0039464
PMCID: PMC3395643  PMID: 22808037
3.  Probing Dry-Weight Improves Left Ventricular Mass Index 
American Journal of Nephrology  2011;33(4):373-380.
Background
Although probing dry-weight improves blood pressure control, its effect on echocardiographic left ventricular mass index (LVMI) is unknown.
Methods
Shortly following dialysis, 292 echocardiograms in 150 patients participating in the DRIP trial were obtained at baseline and longitudinally every 4 weeks on 2 occasions.
Results
At baseline, LVMI was 136.3 g/m2 in the control group and 138.7 g/m2 in the ultrafiltration group (p > 0.2 for difference). The change from baseline in LVMI in the control group was +3.5 g/m2 at 4 weeks and +0.3 g/m2 at 8 weeks (p > 0.2 for both changes). The change from baseline in LVMI in the ultrafiltration group was −7.4 g/m2 at 4 weeks (p = 0.005) and −6.3 g/m2 at 8 weeks (p = 0.045). With ultrafiltration, the change in LVMI diameter was −10.9 g/m2 more compared to the control group at 4 weeks (p = 0.012) and −6.6 g/m2 more compared to the control group at 8 weeks (p = 0.21). The reduction in interdialytic ambulatory blood pressure was also greater in response to probing dry-weight in those in the top half of LVMI at baseline (p = 0.02 for interaction effect at week 8).
Conclusion
LVMI, an important determinant of prognosis among long-term dialysis patients, is responsive to probing dry-weight.
doi:10.1159/000326235
PMCID: PMC3078237  PMID: 21447945
Hemodialysis; Hypertension; Ultrafiltration; Ambulatory blood pressure; Volume overload; Echocardiogram; Left ventricular hypertrophy; Left ventricular systolic function
4.  Intradialytic hypertension is a marker of volume excess 
Nephrology Dialysis Transplantation  2010;25(10):3355-3361.
Background. Intradialytic blood pressure (BP) profiles have been associated with all-cause mortality, but its pathophysiology remains unknown. We tested the hypothesis that intradialytic changes in BP reflect excess volume.
Methods. The dry weight reduction in hypertensive haemodialysis patients (DRIP) trial probed dry weight in 100 prevalent haemodialysis patients; 50 patients who did not have their dry weight probed served as time controls. In this post hoc analysis, intradialytic BP was recorded at each of the 30 dialysis treatments during the trial. The slope of intradialytic BP over dialysis was calculated by the log of BP regressed over time. Using a linear mixed model, we compared these slopes between control and ultrafiltration groups at baseline and over time, tested the effect of dry weight reduction on these slopes and finally tested the ability of change in intradialytic slopes to predict change in interdialytic systolic BP.
Results. At baseline, intradialytic systolic and diastolic BP dropped at a rate of ~3%/h (P < 0.0001). Over the course of the trial, compared to the control group, the slopes steepened in the ultrafiltration group for systolic but not diastolic BP. Those who lost the most post-dialysis weight from baseline to 4 weeks and baseline to 8 weeks also experienced the greatest steepening of slopes. Each percent per hour steepening of the intradialytic systolic BP slope was associated with 0.71 mmHg [95% confidence interval (CI) 0.01–1.42, P = 0. 048] reduction in interdialytic ambulatory systolic pressure.
Conclusions. Intradialytic BP changes appear to be associated with change in dry weight among haemodialysis patients. Among long-term haemodialysis patients, intradialytic hypertension may, thus, be a sign of volume overload.
doi:10.1093/ndt/gfq210
PMCID: PMC2948838  PMID: 20400448
ambulatory BP; dry weight; haemodialysis; hypertension; sodium
5.  Relative plasma volume monitoring during hemodialysis aids the assessment of dry-weight 
Hypertension  2009;55(2):305.
Among hemodialysis patients the assessment of dry-weight remains a matter of clinical judgment because tests to assess dry-weight have not been validated. The objective of this study was to evaluate and validate relative plasma volume monitoring as a marker of dry-weight. We performed relative plasma volume monitoring using the Critline monitor at baseline and 8 weeks in 150 patients participating in the dry-weight reduction in hypertensive hemodialysis patients (DRIP) trial. The intervention group of 100 patients had dry-weight probed whereas 50 patients served as time controls. Relative plasma volume slopes were defined as flat when they were less than the median (1.33%/hour) at the baseline visit. Among predominantly (87%) African-American hemodialysis patients, we found that flat relative plasma volume slopes suggest a volume overloaded state because of the following reasons: 1) probing dry-weight in these patients leads to steeper slopes; 2) those with flatter slopes at baseline had greater weight loss; 3) both baseline relative plasma volume slopes and the intensity of weight loss were found to be important for subsequent change in relative plasma volume slopes; and most importantly 4) relative plasma volume slopes predicted the subsequent reduction in interdialytic ambulatory systolic BP. Those with the flattest slopes had the greatest decline in BP upon probing dry-weight. Both baseline relative plasma volume slopes and the change in relative plasma volume slopes were important for subsequent changes in ambulatory systolic BP. We conclude that relative plasma volume slope monitoring is a valid method to assess dry-weight among hypertensive hemodialysis patients.
doi:10.1161/HYPERTENSIONAHA.109.143974
PMCID: PMC2819307  PMID: 20038754
hypertension; hemodialysis; dry-weight; plasma volume; diagnostic test
6.  Chronobiology of Arterial Hypertension in Hemodialysis Patients: Implications for Home Blood Pressure Monitoring 
Background
Hemodialysis patients have a steady increase in blood pressure (BP) over the 44-hour interdialytic interval when ambulatory BP monitoring is used. Home BP recording allows for longer period of monitoring between dialysis and may better define the chronobiology of arterial hypertension. This study sought to determine the optimal time to perform home BP monitoring in hemodialysis patients to improve the strength of prediction of 44-hour interdialytic ambulatory BP.
Study Design
Diagnostic test study
Setting and Participants
This is an ancillary analysis of patients participating in the dry-weight reduction in hypertensive hemodialysis patients (DRIP) trial.
Index test
Home BP measured three times a day for one week using a validated oscillometric monitor on 3 occasions at 4 week intervals after randomization. Home BP measured during the first third, second third and last third of time elapsed after dialysis as well as each third of dialysis was compared to the overall ambulatory BP.
Reference Tests
Interdialytic ambulatory BP measured on 3 occasions at 4 week intervals after randomization.
Results
Over the interdialytic interval, we found an increase in systolic ambulatory BP of 0.30 ± 0.36 mmHg/hr and an increase in systolic home BP of 0.40 ± 0.25 mmHg/hr. This relationship in home BP reached a plateau after approximately 48 hrs. A similar pattern was seen for diastolic home BP. Probing dry-weight steepened the slope of ambulatory BP but did not alter the time-dependent relationship of home BP. Home BP was on average higher (bias) by 14.1 (95% CI 12.0 to 16.2)/5.7 (95% CI 4.6 to 6.9) mmHg. The standard deviation of differences between methods (precision) was 4.6/2.8 mmHg. Measurement of BP during each third of the interdialytic interval gave the best precision as measured by model fit compared to ambulatory BP measurements.
Limitations
Our cohort was overrepresented by African American hemodialysis patients. Whether African American participants have a different pattern of BP response than non-African American participants in the interdialytic period is not known.
Conclusions
Our findings suggest that time elapsed after dialysis must to be considered in interpreting the home BP recordings in hemodialysis patients. Home BP measured in each third of the interdialytic interval is likely to yield the most reliable BP estimate.
doi:10.1053/j.ajkd.2009.03.018
PMCID: PMC2753716  PMID: 19515473
Home BP; ambulatory BP monitoring; hemodialysis; hypertension; chronobiology
7.  Dry-weight reduction in hypertensive hemodialysis patients (DRIP): A randomized controlled trial 
Hypertension  2009;53(3):500-507.
Volume excess is thought to be important in the pathogenesis of hypertension among hemodialysis patients. To determine whether additional volume reduction will result in improvement in blood pressure (BP) among hypertensive patients on hemodialysis and to evaluate the time-course of this response we randomized long-term hypertensive hemodialysis patients to ultrafiltration or control groups. In the additional ultrafiltration group (n=100) we probed the dry-weight without increasing time or duration of dialysis while the control group (n=50) only had physician visits. The primary outcome was change in systolic interdialytic ambulatory BP. Post-dialysis weight was reduced by 0.9 kg at 4 weeks and resulted in -6.9 mm Hg (95% CI -12.4, -1.3 mm Hg, p=0.016) change in systolic BP and -3.1 mm Hg (95% CI -6.2, -0.02 mm Hg, p=0.048) change in diastolic BP. At 8 weeks, dry-weight was reduced 1 kg, systolic BP changed -6.6 mm Hg (95% CI -12.2, -1.0 mm Hg, p=0.021) and diastolic BP -3.3 mm Hg (95% CI -6.4, -0.2 mm Hg, p=0.037) from baseline. The Mantel-Hanzel combined odds-ratio for systolic BP reduction of at least 10 mm Hg was 2.24 (95% CI 1.32, 3.81, p=0.003). There was no deterioration seen in any domain of the kidney disease quality of life health survey despite an increase in intradialytic signs and symptoms of hypotension. The reduction of dry-weight is a simple, efficacious and well tolerated maneuver to improve BP control in hypertensive hemodialysis patients. Long-term control of BP will depend on continued assessment and maintenance of dry-weight.
doi:10.1161/HYPERTENSIONAHA.108.125674
PMCID: PMC2679163  PMID: 19153263
hemodialysis; hypertension; ultrafiltration; ambulatory blood pressure; volume overload
8.  Home Blood Pressure Measurements for Managing Hypertension in Hemodialysis Patients 
American Journal of Nephrology  2009;30(2):126-134.
Home blood pressure (BP) monitoring serves as a practical method to detect changes in BP instead of ambulatory BP monitoring in hemodialysis patients. To evaluate the relationship of reduction in home BP compared to interdialytic ambulatory BP measurements we analyzed the data from the dry-weight reduction in hypertensive hemodialysis patients (DRIP) trial in which 100 patients had their dry weight probed based on clinical sign and symptoms and 50 patients served as controls. We measured home BP 3 times a day for 1 week using a validated oscillometric monitor on 3 occasions at 4-week intervals after randomization. Changes from baseline in home, predialysis BP and postdialysis BP were compared to interdialytic 44-hour ambulatory BP. Home and ambulatory BP monitoring was available in 141 of 150 (94%) patients. Predialysis systolic BP was not as sensitive as ambulatory BP in detecting change in BP with dry-weight reduction. Whereas postdialysis BP was capable of detecting an improvement in systolic BP in response to probing dry weight, by itself it does not provide evidence that change in postdialysis BP persists over the interdialytic period. Home BP reliably detected changes in ambulatory BP, albeit with less sensitivity at 4 weeks. However, at 4 and at 8 weeks, changes in home systolic BP were most strongly related to changes in interdialytic ambulatory systolic BP compared to predialysis and postdialysis BP. The reproducibility of BP measurements followed the order home > ambulatory >> predialysis > postdialysis. These data provide support for the use of home BP monitoring for the management of hypertension in hemodialysis patients.
doi:10.1159/000206698
PMCID: PMC2786027  PMID: 19246891
Home blood pressure monitoring; Ambulatory blood pressure monitoring; Hemodialysis; Hypertension
9.  Relationships of N-terminal pro-B-natriuretic peptide and cardiac troponin T to left ventricular mass and function and mortality in asymptomatic hemodialysis patients 
Background:
Although the cardiac biomarker troponin T (cTnT) is strongly related to mortality in end-stage renal disease, the independent association of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cTnT in predicting outcomes is unknown.
Objective:
To determine factors associated with NT-proBNP and cTnT, and to determine whether these levels are associated with mortality.
Study Design:
Cohort Study
Settings and Participants:
Asymptomatic hemodialysis patients (n=150) in 4 university-affiliated hemodialysis units.
Exposure and Outcomes:
For cross-sectional analysis, echocardiographic variables as exposures and N-terminal proBNP and cardiac troponin T as outcomes; for longitudinal analysis, association of N-terminal proBNP and cardiac troponin T as exposures to all-cause and cardiovascular disease mortality as outcomes.
Results:
In a multivariate regression analysis, low midwall fractional shortening a measure of poor systolic function was an independent correlate of log NT-proBNP (p<0.01), while left ventricular mass index was an independent correlate of cTnT (p<0.01). Over a median follow-up of 24 months, 46 patients died of which, 26 died due to cardiovascular causes. NT-ProBNP had a strong graded relationship with all-cause (Hazard Ratio (HR) 1.54, 4.78 and 4.03 for increasing quartiles, Chi2 32.2, p<0.001) and cardiovascular mortality (HR 2.99, 10.95, 8.54 Chi2 23.66, p<0.01), while cTnT had a weaker relationship with all-cause (HR 1.57, 2.32, 3.39, Chi2 23.09, p<0.01) and cardiovascular mortality (HR 1, 0.81, 2.12, 2.14, Chi2 15.05, p=0.1). The combination of the two biomarkers did not improve the association with all-cause or cardiovascular mortality compared to NT-proBNP alone. NT-proBNP was a marker of mortality even after adjusting for left ventricular mass index and midwall fractional shortening.
Limitations:
Our cohort was predominantly black and of limited sample size.
Conclusion:
NT-proBNP strongly correlates with left ventricular systolic dysfunction and is more strongly associated with mortality than cTnT in asymptomatic hemodialysis patients.
doi:10.1053/j.ajkd.2007.08.017
PMCID: PMC2408379  PMID: 18037101
NT-proBNP; Troponin T; left ventricular mass; left ventricular function; mortality; hemodialysis
10.  Location Not Quantity of Blood Pressure Measurements Predicts Mortality in Hemodialysis Patients 
American Journal of Nephrology  2007;28(2):210-217.
Background
Blood pressure (BP) measurements obtained outside the dialysis unit are prognostically superior. Whether it is the greater number of measurements made outside the dialysis unit that correlates with prognosis or whether BPs outside dialysis units are ecologically more valid is unknown.
Methods and Results
A prospective cohort study was conducted in 133 patients on chronic hemodialysis. BP was measured by the patients at home for 1 week, over an interdialytic interval by ambulatory recording, and by ‘routine’ and standardized methods in the dialysis unit for 2 weeks. Up to 6 BPs were randomly selected from a 44-hour recording of ambulatory or 1-week recording of home BPs, such that the dialysis unit BPs were exactly matched to the number of ambulatory or home BPs. The relationship with left ventricular hypertrophy and all-cause mortality was analyzed using receiver-operating characteristic curves and Cox proportional hazards analysis, respectively. Over a median follow-up of 24 months, 46 patients (31%) died. A BP change of 10/5 mm Hg increased the risk of all-cause mortality by 1.22 (95% CI 1.07–1.38)/1.18 (95% CI 1.05–1.31) with the average of the 44-hour recording and 1.20 (95% CI 1.07–1.34)/1.15 (95% CI 1.03–1.27) when up to 6 random BPs from the same ambulatory recording were drawn and averaged. With home BPs the hazard ratios were 1.17/1.15 per 10/5 mm Hg increase in BP with the average of 1-week recording and 1.18/1.13 when up to 6 random BPs were drawn and averaged. Limited duration ambulatory BP monitoring of any 6-hour interval during the first 24 h or 4-day home BP recorded after the midweek dialysis was similarly predictive of all-cause mortality.
Conclusions
In patients on hemodialysis, the location, not the quantity, of the BP recordings obtained outside the dialysis unit is associated with target organ damage and mortality.
doi:10.1159/000110090
PMCID: PMC2785904  PMID: 17960059
Blood pressure, self-measured; Ambulatory blood pressure; End-stage renal disease

Results 1-10 (10)