Research and innovation as a catalyst for food system transformation.

BACKGROUND: Food systems are associated with severe and persistent problems worldwide. Governance approaches aiming to foster sustainable transformation of food systems face several challenges due to the complex nature of food systems. SCOPE AND APPROACH: In this commentary we argue that addressing these governance challenges requires the development and adoption of novel research and innovation (R&I) approaches that will provide evidence to inform food system transformation and will serve as catalysts for change. We first elaborate on the complexity of food systems (transformation) and stress the need to move beyond traditional linear R&I approaches to be able to respond to persistent problems that affect food systems. Though integrated transdisciplinary approaches are promising, current R&I systems do not sufficiently support such endeavors. As such, we argue, we need strategies that trigger a double transformation - of food systems and of their R&I systems. KEY FINDINGS AND CONCLUSIONS: Seizing the opportunities to transform R&I systems has implications for how research is done - pointing to the need for competence development among researchers, policy makers and society in general - and requires specific governance interventions that stimulate a systemic approach. Such interventions should foster transdisciplinary and transformative research agendas that stimulate portfolios of projects that will reinforce one another, and stimulate innovative experiments to shape conditions for systemic change. In short, a thorough rethinking of the role of R&I as well as how it is funded is a crucial step towards the development of the integrative policies that are necessary to engender systemic change - in the food system and beyond.

Contribution of tenosynovitis of small joints to the symptom morning stiffness in patients presenting with undifferentiated and rheumatoid arthritis.

Objective: Morning stiffness (MS) is characteristic of rheumatoid arthritis (RA). Despite its association with functional disability, the extent to which local inflammatory processes contribute to this symptom is unknown. Magnetic resonance imaging (MRI)-detected tenosynovitis of small joints is recognized as an early feature of RA, which is also associated with functional impairments. It has been proposed that tenosynovitis contributes to MS. Therefore, we assessed the relationship between MS and MRI-detected inflammation, in particular tenosynovitis.Method: In total, 286 consecutive patients newly presenting with undifferentiated arthritis and RA underwent contrast-enhanced 1.5 T MRI of (2-5) metacarpophalangeal, wrist, and (1-5) metatarsophalangeal joints. Scans were scored for tenosynovitis according to Haavardsholm, and for synovitis by Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). MS was dichotomized as ≥ 60 min or not. Associations between MS and tenosynovitis/synovitis were tested with logistic regression, data were categorized (solitary or simultaneous presence of synovitis/tenosynovitis), and the presence of an additive interaction was assessed.Results: MS was present in 40% of patients. Tenosynovitis was more often present in patients with MS than without MS [80% vs 65%, odds ratio (OR) 2.11, 95% confidence interval (1.21;3.69)]. Synovitis was more often present in patients with MS [58% vs 44%, OR 1.79 (1.11;2.91)]. In categorized analyses, concurrent synovitis and tenosynovitis had the largest association [OR 2.43 (1.30;4.54)], in contrast to solitary synovitis [OR 0.85 (0.21;3.47)]. The additive interaction was non-significant. The variance explained in all analyses was small (range 4-5%).Conclusion: Tenosynovitis, combined with synovitis, at small joints is associated with MS and contributes to the pathophysiology of MS.

What is the additional value of MRI of the foot to the hand in undifferentiated arthritis to predict rheumatoid arthritis development?

BACKGROUND: MRI-detected subclinical joint inflammation in the hand joints of patients with undifferentiated arthritis (UA) predicts progression to rheumatoid arthritis (RA). It is unknown if adding MRI of the foot increases predictive accuracy compared to the hand alone. METHODS: 1.5-T contrast-enhanced MRI of the unilateral foot (MTP-1-5) and hand (MCP-2-5 and wrist) was performed in 123 patients presenting with UA (not fulfilling the 2010 RA criteria) and scored for bone marrow edema (BME), synovitis and tenosynovitis. Symptom-free controls (n = 193) served as a reference for defining an abnormal MRI. Patients were followed for RA development ≤ 1 year, defined as fulfilling the classification criteria or initiation of disease-modifying antirheumatic drugs because of the expert opinion of RA. The added predictive value of foot MRI to hand MRI was evaluated. RESULTS: Fifty-two percent developed RA. Foot tenosynovitis was predictive (OR 2.55, 95% CI 1.01-6.43), independent of BME and synovitis (OR 3.29, 95% CI 1.03-10.53), but not independent of CRP and number of swollen joints (OR 2.14, 95% CI 0.77-5.95). Hand tenosynovitis was also predictive independent of BME and synovitis (OR 3.99, 95% CI 1.64-9.69) and independent of CRP and swollen joints (OR 2.36, 95% CI 1.04-5.38). Adding foot tenosynovitis to hand tenosynovitis changed the sensitivity from 72 to 73%, specificity from 59 to 54% and AUC from 0.66 to 0.64; the net reclassification index was - 3.5. CONCLUSION: MRI-detected tenosynovitis of the foot predicts progression to RA. However, adding MRI of the foot does not improve the predictive accuracy compared to MRI of the hand alone. In view of cost reduction, the performance of foot MRI for prognostic purposes in UA can be omitted.

Human recombinant insulin and amyloidosis: an unexpected association.

A 48-year-old patient with diabetes mellitus was treated with human (recombinant) insulin. He developed cutaneous amyloidosis twice at different locations where subcutaneous insulin had been injected. There were no signs of systemic amyloidosis. Additional pathological-anatomical investigations demonstrated insulin in one (the most recent) amyloid tumour. A limited number of similar cases have been reported in the literature, although mostly associated with porcine insulin. Cutaneous amyloidosis may be associated with local injections of human (recombinant) insulin. One should therefore also consider this diagnosis when finding tumours at sites where insulin has been injected.

Transanal endoscopic microsurgery versus total mesorectal excision of T1 rectal adenocarcinomas with curative intention.

PURPOSE: After total mesorectal excision (TME) for rectal cancer, pathology is standardized with margin status as a predictor for recurrence. This has yet to be implemented after transanal endoscopic microsurgery (TEM) and was investigated prospectively for T1 rectal adenocarcinomas. PATIENTS AND METHODS: Eighty patients after TEM were compared to 75 patients after TME. The study protocol included standardized pathology. TEM patients were eligible when excision margins were negative. RESULTS: TEM was safer than TME as reflected by operating time, blood loss, hospital stay, morbidity, re-operation rate and stoma formation (all P<0.001). Mortality after TEM was 0% and after TME 4%. At 5 years after TEM and TME, both overall survival (TEM 75% versus TME 77%, P=0.9) and cancer-specific survival (TEM 90% versus TME 87%, P=0.5) were comparable. Local recurrence rate after TEM was 24% and after TME 0% (HR 79.266, 95% CI, 1.208 to 5202, P<0.0001). CONCLUSION: For T1 rectal adenocarcinomas TEM is much saver than TME and survival is comparable. After TEM local recurrence rate is substantial, despite negative excision margins.

Fast sample preparation involving MASE and coupled column normal phase liquid chromatography for the rapid trace analysis of dioxins in air-dust samples from fire catastrophe emissions.

A new approach has been developed and tested for the urgent analysis of dioxins in samples of air-dust filters originating from catastrophe emissions. The procedure consists of a fast extraction of the sample with microwave solvent extraction (MASE) and acetone as solvent followed by a fast cleanup of the extract with normal phase coupled column liquid chromatography (LC/LC). The multi-dimensional LC/LC system employs a 50 mm x4.6 mm i.d. column packed with 3mum silica and a 150 mm x4.6 mm i.d. column packed with 5mum PYE as the first and second analytical column, respectively. Iso-hexane is used on both columns to perform cleanup and dichloromethane to perform efficient back-flush elution of the compounds from the second column. The obtained polarity-based separation in the first dimension and molecular-structure based separation in the second dimension provides a fast and powerful cleanup. Validation was done by analysing samples of homemade RIVM air-dust with aged residues (n=8, spiking level about 15pgmg(-1) per compound) of dioxins/furans and samples of reference Urban Dust SRM 1649a (n=4) with both the new approach and the existing conventional procedure and were instrumentally analyzed with capillary gas chromatography and high resolution mass spectrometric detection (GC/HRMS). In comparison to the existing conventional procedure, the new approach reduces sample processing from several days to several hours per sample. As regards the aged-residue air-dust samples, the new method shows a good accuracy, precision and high selectivity providing a performance in good agreement with the existing procedure. In SRM air-dust, the concentration of a few compounds obtained by the new method was below (10-50%) the certified value.

Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy.

In view of the similarity in chemical structure of the available 5HT(3)-receptor antagonists it is assumed, whilst these agents all act at the same receptor, that failure to one agent would predict subsequent failure to all 5HT(3)-receptor antagonists. We conducted a randomized double blind trial of granisetron 3 mg plus dexamethasone 10 mg versus continued treatment with ondansetron 8 mg plus dexamethasone 10 mg in patients with protection failure on ondansetron 8 mg plus dexamethasone 10 mg during the first 24 hours following highly emetogenic chemotherapy. Of 40 eligible patients, 21 received ondansetron + dexamethasone and 19 received granisetron + dexamethasone. We found a significant benefit from crossing-over to granisetron after failure on ondansetron. Of the 19 patients who crossed over to granisetron, 9 patients obtained complete protection, whereas this was observed in 1 of the 21 patients continuing ondansetron, P = 0.005. These results indicate that there is no complete cross-resistance between 5HT(3)-receptor antagonists, and that patients who have acute protection failure on one 5HT(3)-receptor antagonist should be offered cross-over to another 5HT(3)-receptor antagonist.

Semi-permeable surface analytical reversed-phase column for the improved trace analysis of acidic pesticides in water with coupled-column reversed-phase liquid chromatography with UV detection. Determination of bromoxynil and bentazone in surface water.

The coupled-column (LC-LC) configuration consisting of a 3 microm C18 column (50 x 4.6 mm I.D.) as the first column and a 5 microm C18 semi-permeable-surface (SPS) column (150 x 4.6 mm I.D.) as the second column appeared to be successful for the screening of acidic pesticides in surface water samples. In comparison to LC-LC employing two C18 columns, the combination of C18/SPS-C18 significantly decreased the baseline deviation caused by the hump of the co-extracted humic substances when using UV detection (217 nm). The developed LC-LC procedure allowed the simultaneous determination of the target analytes bentazone and bromoxynil in uncleaned extracts of surface water samples to a level of 0.05 microg/l in less than 15 min. In combination with a simple solid-phase extraction step (200 ml of water on a 500 mg C18-bonded silica) the analytical procedure provides a high sample throughput. During a period of about five months more than 200 ditch-water samples originating from agricultural locations were analyzed with the developed procedure. Validation of the method was performed by randomly analyzing recoveries of water samples spiked at levels of 0.1 microg/l (n=10), 0.5 microg/l (n=7) and 2.5 microg/l (n=4). Weighted regression of the recovery data showed that the method provides overall recoveries of 95 and 100% for bentazone and bromoxynil, respectively, with corresponding intra-laboratory reproducibilities of 10 and 11%, respectively. Confirmation of the analytes in part of the samples extracts was carried out with GC-negative ion chemical ionization MS involving a derivatization step with bis(trifluoromethyl)benzyl bromide. No false negatives or positives were observed.

The significance of venography in the management of patients with clinically suspected pulmonary embolism.

The accurate diagnosis of pulmonary embolism causes many problems. Clinical signs are non-specific, and ventilation-perfusion lung scanning has high sensitivity but variable specificity. In more than 90% of cases a pulmonary embolus is derived from deep venous thrombosis in the lower extremities. We have performed a prospective study to evaluate venography in the management of patients with suspected pulmonary embolism. A total of 169 patients were included in the study, and a ventilation-perfusion scan was performed in all cases. Forty-four (26%) patients had a normal scan and treatment was not given (group A). The other 125 (74%) patients, who had an abnormal scan, underwent bilateral venography. Venous thrombosis was demonstrated in 63 patients, and they were treated with oral anticoagulants for 3 months (group B). The remaining 62 patients, who showed no venous thrombosis, did not receive anticoagulant therapy (group C). During follow-up, 1 patient in group A, 3 patients in group B and 1 patient in group C developed a new deep venous thrombosis. One patient in group B suffered a pulmonary embolus. It is concluded that venography of the lower extremities can be of additional value in the management of patients with pulmonary embolism when the lung scan does not provide sufficient information.

Is quantitative determination of fibrin(ogen) degradation products and thrombin-antithrombin III complexes useful to diagnose deep venous thrombosis in outpatients?

We studied the diagnostic value of recently introduced ELISA's for the determination of thrombin-antithrombin III (TAT) complexes, fibrin degradation products (FbDP), fibrinogen degradation products (FgDP) and total degradation products (TDP) for deep venous thrombosis (DVT) in plasma of 239 consecutive outpatients, suspected for DVT by their family doctor. DVT was confirmed by impedance plethysmography in 60 patients. Using the 95th percentile range of 42 healthy volunteers the sensitivity for the detection of DVT was: 37% for TAT, 95% for TDP, 92% for FbDP and 90% for FgDP. Specificity was: 88% for TAT, 16% for TDP, 20% for FbDP and 25% for FgDP. We conclude that these assays are of little value in the diagnosis of DVT in outpatients.

The value of adding thermographic leg scanning to impedance plethysmography in the detection of deep vein thrombosis.

The clinical value of adding thermographic leg scanning to impedance plethysmography was evaluated and compared in 52 patients with clinically suspected deep venous thrombosis. Both tests were performed on the day of referral and phlebography within 72 hours. The sensitivity of thermography was 83%, the specificity 41% and the accuracy 61%. In comparison IPG had a sensitivity of 83%, a specificity of 96% and an accuracy of 90% The combination of thermography and IPG showed a sensitivity of 92%, a specificity of 41% and an accuracy of 65%. It is concluded that the addition of thermography to IPG is of no clinical value.

An evaluation of suloctidil in the prevention of deep vein thrombosis in neurosurgical patients.

Suloctidil (200 mg t.i.d.) was compared with placebo in a randomized, double-blind trial to assess its value in preventing deep venous thrombosis (DVT) in high-risk neurosurgical patients, comprising 136 patients with brain or spinal tumour, head or spinal injury, or subarachnoid or intracranial hemorrhage. 125I fibrinogen leg scanning and impedance plethysmography were performed for up to 14 days to detect DVT. The two groups were also evenly balanced for DVT risk factors. Seventeen of 68 patients (25%) (95% confidence interval, 15-35%) treated with suloctidil and 12 of 68 patients (21%) (95% confidence interval, 11-32%) treated with placebo developed deep venous thrombosis. This observed difference in outcomes is not statistically significant (X2 = 1.096; p = 0.30). The estimated 95% confidence interval for the true difference in the incidence of DVT between suloctidil-treated and placebo-treated patients ranges from an 11% benefit in favour of suloctidil to an 18% benefit in favour of placebo. Major deep vein thrombosis occurred in two patients on suloctidil and three patients in the placebo group; there were no fatal pulmonary emboli during the 14-day study period, during which time four patients in each group died of non-thromboembolic complications. There was no observed difference in hemorrhagic complications. Long-term outcomes at three-months follow-up were similar between the two treatment groups. It is concluded that there is no real evidence that suloctidil (200 mg t.i.d.) is an effective regimen for the prevention of DVT in high-risk neurosurgical patients.

The effect of diabetes regulation on platelet release, fibrinolysis and coagulation tests, before and after stimulation with DDAVP.

In this longitudinal study we measured beta-TG, PF4, fibrinolytic activity (extrinsic and euglobulin fraction), fibrinogen, FVIII RAg and FVIII Rcof before and after i.v. DDAVP (FPA was only measured before DDAVP) in 20 patients with diabetes mellitus. These parameters were measured on three occasions: phase I: during disregulation, phase II: after three weeks of strict control, phase III: after nine weeks of good control. Twenty-two healthy volunteers served as normal controls. No significant differences related to metabolic control were found for beta-TG, PF4, FPA and fibrinogen. There was no change after i.v. DDAVP administration. Fibrinolytic activity showed a significant increase after i.v. DDAVP. Baseline values and post-DDAVP increase were not significantly different from our normal controls. FVIII RAg and FVIII Rcof were both significantly elevated in diabetes mellitus. Both increased significantly after DDAVP. The FVIII RAg release (delta FVIII RAg) was significantly less in the diabetics. Fibrinolytic activity, FVIII RAg and FVIII Rcof are independent of the degree of metabolic control in patients with diabetes.

Exercise capacity with transdermal nitroglycerin in patients with stable angina pectoris.

Transdermally delivered nitroglycerin (TTS-NTG) through a rate-controlling membrane yields stable blood levels for 24 h. We studied the effect of TTS-NTG (25 mg per 10 cm2) on exercise induced angina in 10 patients with stable angina pectoris, all in NYHA class III, who were not under treatment with other cardiac drugs. In a pre-study exercise test, all patients had angina pectoris and more than one mm ST depression. The study was placebo controlled and double blind with a randomized cross-over. Exercise tests were carried out on a treadmill according to the Bruce-protocol, 12 to 16 h after administration of TTS-NTG or of an identical placebo. After a 48 h wash-out period, the procedure was repeated after application of a plaster with the alternative content. A significant improvement was seen on TTS nitroglycerin compared with placebo in the total duration of exercise (7.2 +/- 3.6 min (mean +/- SD) vs 6.2 +/- 3.8 min; P less than 0.002). In 7 patients, the time to onset of angina was extended by TTS nitroglycerin. Maximal ST depression (lead V4 and V6) was significantly lower on TTS nitroglycerin (1.85 +/- 1 mm) compared with placebo (2.2 +/- 1 mm; P less than 0.05). It is concluded that 12 to 16 h after administration, transdermally delivered nitroglycerin improves exercise capacity and reduces maximal ST depression in patients with stable angina.

Platelet tests and antiplatelet drugs in coronary artery disease.

This study was designed to clarify discrepancies in the literature concerning platelet survival time and beta-thromboglobulin (beta TG) levels in patients with coronary artery disease (CAD) and the effect of platelet-suppressant drugs on these tests. Platelet survival time and plasma beta TG levels were determined in 48 patients with angiographically documented CAD. The effect of sulfinpyrazone or aspirin/dipyridamole on these measurements was investigated in a double-blind, crossover trial that included a placebo phase. In patients with CAD, the mean plasma beta TG concentration was significantly elevated, but the mean platelet survival time was not significantly different from that in controls. Treatment with sulfinpyrazone or aspirin/dipyridamole did not produce changes in platelet survival time or plasma beta TG concentration that were significantly different from the values during the placebo phase. This study demonstrates that compared with the spontaneous variation in platelet survival time or beta TG concentration, there was no measureable effect of sulfinpyrazone or aspirin/dipyridamole on the results of the tests.

Home-diagnosis of deep venous thrombosis with impedance plethysmography.

In order to assess the value of I.P.G. for the diagnosis of D.V.T. in general practice, an I.P.G. was carried out by a skilled technician in 255 consecutive patients with suspected D.V.T. at home. Ascending venography was carried out in 185 of these patients. In addition, blood for assay of AT III, platelet count, fibrinogen, a2-antiplasmin, ethanol gelation test and spontaneous platelet aggregation was collected at the time the I.P.G. was performed. In 61 patients (33%) venography showed the presence of D.V.T., and was negative in the remaining 124 patients. I.P.G. was positive in 51 of the 61 patients with D.V.T., a sensitivity of 84%. I.P.G. was normal in 115 of the 124 patients with a negative venogram, a specificity of 93%. The sensitivity of the I.P.G. for proximal vein thrombosis was 92% and for calf vein thrombosis 68%. Mean a2-antiplasmin concentration was significant (p less than 0.05) lower (101 +/- 15%, mean +/- SD) in patients with D.V.T. compared with patients with a normal venogram (107 +/- 11%, mean +/- SD). No differences between the two groups were observed in the other coagulation parameters assayed, and none was of diagnostic value, either alone or in combination with I.P.G. This study shows that I.P.G. is of potential value for the home diagnosis of D.V.T., in particular proximal vein thrombosis. This is potentially clinically useful, because these thrombi are thought to carry a high risk for pulmonary embolism.