Getting to the bottom of research funding: Acknowledging the complexity of funding dynamics.

Research funding is an important factor for public science. Funding may affect which research topics get addressed, and what research outputs are produced. However, funding has often been studied simplistically, using top-down or system-led perspectives. Such approaches often restrict analysis to confined national funding landscapes or single funding organizations and instruments in isolation. This overlooks interlinkages, broader funding researchers might access, and trends of growing funding complexity. This paper instead frames a 'bottom-up' approach that analytically distinguishes between increasing levels of aggregation of funding instrument co-use. Funding of research outputs is selected as one way to test this approach, with levels traced via funding acknowledgements (FAs) in papers published 2009-18 by researchers affiliated to Denmark, the Netherlands or Norway, in two test research fields (Food Science, Renewable Energy Research). Three funding aggregation levels are delineated: at the bottom, 'funding configurations' of funding instruments co-used by individual researchers (from single-authored papers with two or more FAs); a middle, 'funding amalgamations' level, of instruments co-used by collaborating researchers (from multi-authored papers with two or more FAs); and a 'co-funding network' of instruments co-used across all researchers active in a research field (all papers with two or more FAs). All three levels are found to include heterogenous funding co-use from inside and outside the test countries. There is also co-funding variety in terms of instrument 'type' (public, private, university or non-profit) and 'origin' (domestic, foreign or supranational). Limitations of the approach are noted, as well as its applicability for future analyses not using paper FAs to address finer details of research funding dynamics.

Assessment of plasma and red cell trace element concentrations, disease severity, and outcome in patients with critical illness.

PURPOSE: The purpose of the study is to examine the value of both plasma and red cell trace element measurements when assessing nutritional status in patients with critical illness. MATERIALS AND METHODS: A total of 125 patients who were admitted to intensive care unit with evidence of systemic inflammatory response as per Bone's criteria were recruited. Venous blood samples were obtained from all on admission and, in 31 of the 125 patients, on approximately days 4 and 7. Copper, zinc, and selenium concentrations were measured in plasma and erythrocytes and results related to mortality and patient outcome measures. RESULTS: A total of 125 critically ill patients were recruited; 81 (66%) were male, the median age was 60 (range, 18-100), and the medical/surgical proportion was 55/70 (44%/56%). The median (lower and upper 2.5th percentile) Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and length of stay and mortality were 21 (16-26), 7 (4-9) 3.7 days (1.5-11.1) and 19%, respectively. Plasma zinc and selenium concentrations were significantly lower on admission compared with reference intervals, whereas copper was increased. Normal plasma glutathione peroxidase activity suggested selenium status was adequate on admission; erythrocyte concentrations of glutathione peroxidase and trace elements were normal, suggesting adequate nutritional status 1 to 2 months before admission. Only plasma zinc and selenium were inversely associated with C-reactive protein (rs = -0.266, P = .004, rs = -0.322, P < .001, respectively). Compared with survivors, albumin (P < .001) concentrations were significantly lower in the nonsurvivor group. No significant difference of plasma selenium and zinc between survivors and nonsurvivors was found, although plasma selenium concentrations tended to be lower (P = .04). On multivariate logistic regression analysis of the significant variables, none was independently associated with mortality. CONCLUSION: The altered plasma concentrations of zinc, selenium, and copper in patients with critical illness were primarily due to the effects of the systemic inflammatory response and do not reliably indicate their status.

Assessment of vitamin E status in patients with systemic inflammatory response syndrome: plasma, plasma corrected for lipids or red blood cell measurements?

BACKGROUND: There is some evidence that the plasma vitamin E status is perturbed as part of systemic inflammatory response and correcting this with other plasma markers may not lead to reliable results. The aim of the present study was to examine the longitudinal inter-relationships between plasma and red blood cell vitamin alpha-tocopherol in patients with systemic inflammatory response syndrome. METHODS: alpha-tocopherol concentrations were measured, by HPLC, in plasma and red blood cells in normal subjects (n=67) and in critically ill patients with systemic inflammatory response syndrome (n=82) on admission and on follow-up. RESULTS: Plasma alpha-tocopherol was significantly lower in the critically ill patients compared with the controls (all p<0.001) with 41% of patients having concentrations below the 95% confidence interval. In contrast, when corrected for cholesterol, alpha-tocopherol concentrations were significantly higher in the critically ill patients compared with the control group (p<0.001, 27% above the 95% confidence interval) and when corrected for triglycerides, alpha-tocopherol concentrations were significantly lower in the critically ill patients compared with the control group (p<0.001). Red blood cell alpha-tocopherol corrected for haemoglobin was similar (p=0.852) in the critically ill patients compared with control subjects. The longitudinal measurements (n=53) gave similar results. CONCLUSIONS: These results indicate that there is a discrepancy between vitamin E measurements in plasma, in plasma corrected for lipids and in red blood cells. Although the value of correcting vitamin E concentrations by lipids is well established in population studies, the present study indicates that such correction is unreliable in the presence of systemic inflammatory response syndrome and that vitamin E status should be assessed using red blood cell alpha-tocopherol measurement.

Assessment of dietary intake and trace element status in patients with ileal pouch-anal anastomosis.

PURPOSE: Panproctocolectomy and ileal pouch-anal anastomosis is the operation of choice for patients with ulcerative colitis and familial polyposis. The long-term nutritional consequences after pouch surgery are unknown. We have assessed the nutritional status of the essential trace elements-zinc, copper, manganese, and selenium-in patients several years (median, 10 (range, 2-15) years) after surgery. METHODS: Fifty-five patients with uncomplicated ileal pouch-anal anastomosis and 46 healthy control subjects were studied. A dietary assessment of trace element intake was undertaken by using a semiquantitative food frequency questionnaire. The patients' trace elements status for zinc, copper, manganese, and selenium was assessed by measuring their concentrations in blood. RESULTS: The dietary intake of individual trace elements was similar in both groups (all P values > 0.4). There was no significant difference in the concentrations of plasma copper, zinc, and selenium between patients and healthy control subjects (all P values > 0.07). The concentration of whole blood manganese was significantly higher (P = 0.004) in patients (median, 178.5 nmol/l; range, 59-478 nmol/l) compared with healthy control subjects (median, 140 nmol/l; range, 53-267 nmol/l). Four (7 percent) patients had manganese concentrations more than three standard deviations of the mean of control group (>255 nmol/l). CONCLUSIONS: This study shows that patients who have had uncomplicated pouch surgery have a normal dietary intake of trace elements and do not develop deficiencies in copper, zinc, manganese, and selenium. However, these patients may be at increased risk of manganese toxicity.