LINTUL-Cassava-NPK: A simulation model for nutrient-limited cassava growth.

A solid understanding of the dynamics of plant nutrient requirements and uptake from the soil is needed to provide robust fertilizer recommendations, timing of applications and nutrient use efficiency. Our objective was to develop and test the ability of the crop model LINTUL-Cassava-NPK to simulate biomass growth and yield of cassava under nutrient-limited conditions. We used experimental data from six fields located in three different agro-ecologies in Nigeria: Rainforest Zone- Ogoja and Ikom (Cross River), Rainforest Transition Zone - Ekpoma (Edo) and Guinea Savanna Zone - Otukpo (Benue) over two consecutive growing seasons from 2016 to 2018. Nutrient stress in the model was implemented by combining N, P and K nutrition indices (NI) to account for the interaction of multiple nutrient limitations for crop growth. Nutrient uptake was determined by balancing demand and supply of nutrient equivalents. We parameterized and calibrated the model using observations from an experiment conducted under optimal growing conditions in Edo during the 2016 planting season. The model was then tested with data from experiments conducted in the 2017 season in Edo, Cross River and Benue. The model captured the uptake patterns of N, P and K well. Uptakes of N, P and K, and storage root yield were predicted with a small root mean squared error of 5.1 g N m-2, 0.8 g P m-2, 3.3 g K m-2 and 308 g DM roots m-2, with an R 2 of 0.7 - 0.8 for linear relationships between simulated and observed values. The time course of development of nutrient-limited yield of green leaves, stems and storage roots were simulated reasonably well. In general, the model responded aptly to both nutrient omissions and varying amounts of NPK. These findings increase our understanding of nutrient limitations and N, P and K interactions on cassava growth and yield. The model provided insight into surplus amounts of nutrients in the soil at the end of the season and, specifically, the need to balance the supply of N and K for cassava. To our knowledge, this is the first tested cassava process-based model that includes the three macro-nutrients.

A competitive cell growth assay for the detection of subtle effects of gene transduction on cell proliferation.

RNA interference (RNAi) is a sequence-specific gene silencing mechanism with therapeutic potential against many human pathogens. To obtain a durable therapeutic effect, stable transduction of target cells with for instance a lentiviral vector that expresses a short hairpin (shRNA) inducer of the RNAi pathway is necessary. Apart from the intended therapeutic effect, this treatment can induce negative effects on cell proliferation via off-target effects. A careful evaluation of the transduced cells is required to develop a safe gene therapy approach. Stably transduced cells are usually selected by expression of the enhanced green fluorescent protein (GFP) marker. In this study we show that the mixed transduction culture, containing both transduced GFP(+) and untransduced GFP(-) cells, can simply be passaged to score the GFP(+)/GFP(-) ratio by longitudinal flow cytometric analysis as a measure of the negative impact of the RNAi treatment on the cellular proliferation rate. We show that this assay is sensitive, easy to use and internally controlled for assessing subtle effects on cell proliferation of lentiviral transduction and transgene expression.

Angiotensin converting enzyme gene polymorphism and cardiovascular morbidity and mortality: the Rotterdam Study.

BACKGROUND: Findings on the association between the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene and cardiovascular morbidity and mortality have been inconsistent. Considering the possible interaction between this polymorphism and smoking, we evaluated the association between ACE I/D polymorphism and myocardial infarction (MI), mortality due to coronary heart disease (CHD), and cardiovascular disease (CVD). METHODS: The study was performed within the Rotterdam Study, a population based cohort study. The ACE I/D polymorphism was determined for 6714 participants and smoking status recorded at baseline. Fatal and non-fatal MIs and mortality events were regularly recorded. Cox proportional hazard analysis was performed separately for current smokers and non-smokers. We used age as the follow up time, presenting age specific survivals. RESULTS: During follow up, 248 MIs and 301 and 482 deaths, respectively, due to CHD and CVD occurred. There were no significant differences between the genotypes as regards MI incidence. Among smokers, there was an increased risk of CHD and CVD mortality in carriers of the DD genotype compared to the II genotype, which diminished at later ages (p<0.01 for gene-age interaction). Subgroup analysis in a younger and older group (based on the median age of 68.2 years) showed a significantly increased risk of CVD mortality in the younger group (hazard ratio = 5.19; 95% confidence interval: 1.15 to 23.42). CONCLUSIONS: This study showed that the ACE I/D polymorphism is not a strong risk factor for MI but its interaction with smoking might play a role in cardiovascular mortality especially at younger ages.

Heritability of the function and structure of the arterial wall: findings of the Erasmus Rucphen Family (ERF) study.

BACKGROUND AND PURPOSE: Using 930 individuals connected in a single pedigree from an isolated population, participants of the Erasmus Rucphen Family (ERF) study, we investigated the heritability of carotid-femoral pulse wave velocity (PWV), carotid intima media thickness (IMT), and carotid plaque score. METHODS: PWV was measured between the carotid and femoral arteries as an indicator of aortic stiffness. Common carotid IMT and plaque score, quantifying alterations in arterial wall structure, were measured by ultrasonography. RESULTS: All 3 traits were significantly associated with classic cardiovascular risk factors. Age- and gender-adjusted heritability estimates were 0.36 for PWV, 0.41 for carotid IMT, and 0.28 for plaque score. After adjustment for appropriate risk factors, the heritabilities were 0.26, 0.35, and 0.21 for PWV, IMT, and plaque score, respectively. All heritability estimates were statistically significant (P<0.001). Taking into account different proportions of variance associated with covariates for each trait, genetic factors explained &12% of the total variability for each of the phenotypes. CONCLUSIONS: To our knowledge, this is the first report on the heritability of PWV. The heritability estimates of IMT and plaque score were similar to those in previous reports. We conclude that genetic factors significantly contribute to arterial structure and function in this isolated population, presenting the opportunity to locate susceptibility genes related to cardiovascular disorders.

A study of gene--environment interaction on the gene for angiotensin converting enzyme: a combined functional and population based approach.

INTRODUCTION: Studies on the role of the insertion/deletion (I/D) polymorphism of the gene coding for angiotensin converting enzyme (ACE) in atherosclerosis have been inconsistent. In a meta-analysis, we recently showed that this relationship is stronger in high risk populations. In this paper, we used a combined functional and population based approach to investigate the gene-environment interaction of the ACE I/D polymorphism in relation to carotid artery wall thickness. METHODS: The study was part of the Rotterdam Study, a prospective population based cohort study. In 5321 subjects, IMT was measured in the carotid arteries by ultrasonography and ACE genotype was determined by size analysis of polymerase chain reaction products. RESULTS: In multiple regression analysis, I/D polymorphism and smoking were the main determinants for plasma ACE activity (r(2) = 0.28). There was a positive association between the D allele of the I/D polymorphism and carotid artery thickness among current smokers (p = 0.03). Subjects carrying only one of the risk factors (smoking or the D allele) did not show significant differences in IMT compared with the non-/former smokers group carrying two II alleles, while carriers of both risk factors had significant higher IMT. The association was not present in non-/former smokers. DISCUSSION: The results provide further evidence that genetic and environmental factors interact in the formation of the arterial lesions. This study shows that large population based studies can be extremely helpful in unravelling the genetic origin of complex diseases such as atherosclerosis.

Is biolectrical impedance analysis a tool at bedside, during heat waves to assist geriatricians with discriminative diagnosis of hypertonic dehydration?

OBJECTIVES: To assess BIA data given by Analycor 3 and some bio-impedance equations to assist geriatricians with discriminative diagnosis of hypertonic dehydration, during heat waves. DESIGN: Prospective study: a dehydrated patients group has been compared with a randomised control group. SETTING: The study was carried out in a French geriatric department, in the Emile Roux geriatric hospital. PARTICIPANTS: 36: six men and twelve women in each group. MEASUREMENTS: The most valuable clinical indicators of dehydration severity were recorded and scored. BIA measurements were performed with an Analycor 3 analyzer; TBW was calculated from impedances at 50 and 100 kHz, ECW from impedance at 5 kHz; Calculations were made also with formula described in the literature, validated in healthy or in institutionalised elderly subjects. RESULTS: TBW and ECW values were always lower in dehydrated group than in control group, but without significance, whatever the applied formula; however ICW values calculated with "manufacturers equations" significantly decreased in dehydrated group. Data given by the analyzer used in this study, as well as BIA age specific equations discriminated the severely hypertonic dehydrated patients sub-group, but not the mildly hypertonic dehydrated patients sub-group. CONCLUSION: The BIA data given by the analyzer used in this study assist geriatricians at bedside with discriminative diagnosis of hypertonic dehydration, especially in severe hypertonic dehydration, but data given by the analyzer used in this study, as well as age specific equations are sometimes in poor agreement with clinical and biological parameters usually selected to assess dehydration, in mildly dehydrated patients.

Decreased plasma levels of activated factor VII in patients with deep vein thrombosis.

BACKGROUND: The initiating trigger in the development of deep vein thrombosis (DVT) remains unidentified. It has been suggested that tissue factor (TF)-bearing microparticles play a key role, which indicates a role for the TF pathway in the initiation of DVT. OBJECTIVE: To assess the role of the TF pathway in the initiation of venous thrombosis, we measured plasma levels of factor VII and VIIa in patients with acute DVT and in controls. METHODS: We included 148 patients diagnosed with acute DVT and 179 controls in this study. Antigen levels of FVII and FVIIa were measured by using assays recently developed in our laboratory. RESULTS: Median FVII levels in patients were 109.8% (interquartile range [IQR] 86.0-153.2) compared with 102.2% (IQR 76.1-141.7) in controls. Individuals with FVII levels in the upper quartile had a 1.6-fold increased risk for the presence of a DVT (odds ratio 1.6, 95% confidence interval 0.8-3.1). Median FVIIa levels in patients were 50.2 ng mL(-1) (IQR 25.2-86.1) compared with 96.6 ng mL(-1) (69.9-168.9) in controls. Individuals with FVIIa levels in the lowest quartile had a > 5-fold increased risk for the presence of a DVT (odds ratio 5.5, 95% confidence interval 2.8-10.6). Both risks did not change substantially after adjustment for potential confounders. CONCLUSION: Decreased plasma levels of FVIIa in patients with deep vein thrombosis may indicate ongoing consumption of FVIIa and suggest a contributory role for TF in venous thrombus formation.

Polymorphism in the promoter region of the insulin-like growth factor I gene is related to carotid intima-media thickness and aortic pulse wave velocity in subjects with hypertension.

BACKGROUND AND PURPOSE: Low circulating levels of insulin-like growth factor I (IGF-I) have been associated with an increased risk for atherosclerosis. Absence of the 192-bp (wild-type) allele in the promoter region of the IGF-I gene has been associated with low circulating IGF-I levels. We examined the role of this polymorphism in relation to blood pressure and 2 early markers of atherosclerosis: carotid intima-media thickness (IMT) and aortic pulse wave velocity (PWV). METHODS: A total of 5132 subjects of the Rotterdam Study, aged 55 to 75 years, were included in this study. In 3769 subjects who did not use blood pressure-lowering medication, the association between the IGF-I polymorphism and blood pressure was examined. In the total population, and in 3484 normotensive subjects, 1648 hypertensive and 462 untreated hypertensive subjects, the association between this polymorphism and IMT and PWV was examined. RESULTS: Mean systolic and diastolic blood pressure did not differ between genotypes. In hypertensive subjects IMT was significantly increased in noncarriers of the 192-bp allele (0.83 mm) compared with heterozygous or homozygous carriers (0.80 mm) (P=0.04). PWV was also significantly higher in hypertensive subjects who were noncarriers of the 192-bp allele (14.3 m/s) compared with heterozygous (14.1 m/s) or homozygous carriers (13.7 m/s) (P=0.02). Findings were more pronounced in hypertensive subjects without medication use. In normotensive subjects, no association between this polymorphism, IMT, and PWV was observed. CONCLUSIONS: Our study suggests that hypertensive subjects who have low IGF-I levels because of a genetic polymorphism in the IGF-I gene are at increased risk of developing atherosclerosis.

Management of trigonocephaly.

Trigonocephaly, resulting from premature fusion of the metopic suture, is one of the least common forms of craniosynostosis referred to our institution. We describe a method of treating this condition that has been satisfactory in our hands. A bicoronal scalp flap is reflected down to the glabella and supraorbital ridges and a "gull-wing" bone flap is then formed in the frontal region, hinged forward on the metopic ridge. The midline strut in the area of the fused metopic suture is then burred down using a high-speed drill, but is not removed. We feel that this method results in an excellent immediate cosmetic result and is technically easier then the morselization procedures which have previously been described. We have found this to give a satisfactory result in 13 patients who underwent this procedure.

Iowa Case Management for rural drug abuse. Preliminary results.

The Iowa Case Management Project (ICMP) was developed to evaluate the effectiveness of a comprehensive, solution-focused model of case management with rural clients in drug abuse treatment. For this preliminary report, 483 clients who were admitted to residential or outpatient treatment at a local facility volunteered to participate and were randomly assigned to one of four research conditions. Clients in three of the conditions received Iowa Case Management (ICM), while clients in the fourth condition received standard treatment services and served as the control group. Clients were assessed regarding psychosocial characteristics at intake and three additional times during the subsequent 12 months.

Time from symptom onset to treatment and outcome in prehospital thrombolysis for acute ST-elevation myocardial infarction.

BACKGROUND: Prehospital thrombolysis for acute ST-elevation myocardial infarction shortened treatment by 60 minutes, and created a large patient group who were treated within two hours. OBJECTIVES: We analysed our database of patients undergoing prehospital treatment for acute ST-elevation myocardial infarction in search of characteristics for a better outcome in the early treatment group. METHODS: From 1994 to 2000 a total of 475 patients were treated using prehospital administration of anistreplase (in 407 patients) or reteplase (in 68 patients) after diagnosis was confirmed with transtelephonic transmission of the ECG. There was no age limit. The patient data were divided into two groups: one treated within two hours after onset of pain (291 patients, 62%), and one treated later (171 patients, 37%). Thirty-day mortality, symptoms and clinical signs of heart failure were used as parameters of outcome. Both univariate and stepwise logistic regression analyses were used to test 30-day mortality against age, actual time to treatment, prior myocardial infarction, hypertension, diabetes, anterior myocardial infarction, Killip class, systolic blood pressure and heart rate at presentation. RESULTS: Overall 30-day mortality was 9.1%. Overall heart failure was in 16.6% of patients. Both mortality (5.5% vs. 15.5%, p<0.02) and heart failure (12.7% vs. 23.2%, p<0.02) were significantly lower in the early treatment group compared with the group treated late. Independent parameters showing a relation with 30-day mortality were age, time to treatment, hypertension and prior myocardial infarction. Age, time to treatment, hypertension and hyperlipidaemia were identified as predicting heart failure within the first 30 days. CONCLUSION: With prehospital thrombolysis, both 30-day mortality and heart failure were lower in an early treatment group with acute ST-elevation myocardial infarction. Independent variables for 30-day mortality were age, hypertension, prior myocardial infarction and time to treatment, and age, hypertension, hyperlipidaemia and time to treatment were independent predictors for heart failure.

Sustained pro-haemostatic activity of rFVIIa in plasma and platelets in non-bleeding pigs may explain the efficacy of a once-daily prophylaxis in humans.

Recombinant factor VIIa (rFVIIa) is registered for treatment of inhibitor-complicated haemophilia, and a once-daily prophylactic administration of rFVIIa is successful in reducing the number of bleeding events. This suggests that a single rFVIIa dose has a pro-haemostatic effect up to 24 hours (h), which is difficult to explain given its half-life of 2 h. In this study, six pigs received a 90 µg/kg rFVIIa bolus. Plasma was collected and platelets were isolated at various time points up to 48 h, and analysed for FVIIa levels and associated haemostatic activity. Elevated plasma FVIIa levels were detected up to 24 h post-administration (36 (32-56) mU/ml [median (interquartile range [IQR]), 24 h] vs 2 (2-14) mU/ml [baseline]). Corresponding prothrombin time (PT) values remained shortened compared to baseline until 24 h post-administration (9.4 (9.3-9.9) seconds (s) [24 h] vs 10.5 (10.2-11.0) s [baseline], p ≤0.01). The lag time in thrombin generation testing as well as clotting times in plasma-based assays were shortened up to 12 or 24 h post-administration, respectively (lag times 1.8 (1.7-2.1) minutes (min) [12 h] vs 2.3 (2.3-2.6) min [baseline], p ≤0.01 and clotting times 3.8 (3.2-3.9) min [24 h] vs 5.2 (4.6-5.5) min [baseline], p ≤0.001). Platelet FVIIa levels were elevated up to 48 h (7.7 (3.4-9.0) ng VIIa/mg actin [48 h] vs 2.5 (0.7-4.8) ng VIIa/mg actin [baseline]). In conclusion, elevated and haemostatically active plasma and platelet FVIIa levels are detectable up to 24-48 h following rFVIIa administration in pigs. This prolonged pro-haemostatic effect of FVIIa may explain the prophylactic efficacy of a once-daily rFVIIa treatment.

Familial aggregation, the PDE4D gene, and ischemic stroke in a genetically isolated population.

OBJECTIVE: The purpose of this investigation was to study the familial aggregation of ischemic stroke and the association between the PDE4D gene and ischemic stroke. METHODS: The study was performed in an isolated population in The Netherlands, where the authors identified 91 patients with ischemic stroke. Ischemic stroke was subclassified in large- and small-vessel infarction. The authors calculated kinship and inbreeding coefficients and genotyped all patients for three single-nucleotide polymorphisms (SNPs) in the PDE4D gene. RESULTS: The proportion of related pairs was higher in patients with ischemic stroke (68.8%) compared with controls (30.7%; p < 0.001). For large-vessel infarction, the proportion of related pairs was higher (71%) compared with small-vessel infarction (62.8%; p < 0.001). Familial aggregation was strongest for patients with early onset (age at onset < 45 years). All stroke groups were significantly more inbred compared with controls. In inbred individuals, the C allele of SNP45 increased the risk of small-vessel infarction 4.8 times (95% CI 1.1 to 22.3) compared with controls (p = 0.04). The T allele of SNP39 increased the risk of small-vessel infarction 6.3 times (95% CI 1.4 to 28.7) compared with controls (p = 0.02). No associations were found for large-vessel stroke. CONCLUSIONS: There was familial aggregation of ischemic stroke and a difference in degree of familial clustering between stroke subtypes. The authors also found that the PDE4D gene is significantly associated with small-vessel infarction in inbred individuals.

Angiotensin converting enzyme gene, smoking and mortality in a population-based study.

BACKGROUND: The genetic and environmental risk factors, which may influence longevity and mortality, have received much attention during more than one decade. One of the major risks for mortality is cardiovascular disease and the renin angiotensin system (RAS) plays a major role in maintaining blood pressure homeostasis. In this system, the Angiotensin Converting Enzyme (ACE) is one of the key regulators and has been studied in relation to cardiovascular disease and mortality. We aimed to evaluate if the ACE I/D polymorphism is related to total mortality in the elderly. MATERIALS AND METHODS: Some 6968 elderly individuals from the Rotterdam study were genotyped for this polymorphism. Smoking was studied as a possible covariable or effect modifier. To examine the effect of the ACE genotype on mortality, a Cox proportional hazards model was fitted. RESULTS: Our results show an increased risk of total mortality in subjects with age at death below 65 years carriers of the DD genotype (HR 1.8, 95% CI 1.1-2.9, P = 0.016). This association was significant in total and cause specific mortality only in those who smoke (P-value < 0.001 for gene-age interaction). Our findings suggest that the ACE gene is rather associated with early mortality than with late. CONCLUSIONS: Individuals who carry the DD genotype appear to be susceptible to early mortality if they smoke, suggesting a possible interaction between smoking and the ACE gene.

Compulsive checking behaviors in generalized anxiety disorder.

Recent evidence suggests that a relationship exists between worry, the central feature of generalized anxiety disorder (GAD), and compulsive behaviors, particularly compulsive checking. In this article we report the results from two studies. The first study assessed the frequency of obsessions and compulsions in 107 principally diagnosed GAD clients. The second study examined levels of alexithymia in analogue samples of GAD checkers (n = 31), GAD noncheckers (n = 30), and non-GAD nonchecking controls (n = 27) using the Toronto Alexithymia Scale-20 (Bagby, Parker, & Taylor, 1994). The results from these studies suggest that compulsive behaviors in the form of compulsive checking is more common in GAD than previously expected and that such behaviors in GAD may act as an additional mechanism by which affective experiences are avoided.

[A case of artero-ureteral fistula. Review of the literature]. / Un cas de fistule artério-urétérale. Revue de la littérature.

We report a case of a 78-year old male patient with a history of hematuria. Diagnosis of a shunt between a left common iliac artery aneurysm and the ipsilateral ureter was arrived at on the basis of arteriographic findings. Surgery consisted in ligating the left ureter proximal and distal to its communication with the aneurysm (left kidney silent on intravenous urogram), in closing the arterial orifices proximal and distal to the aneurysm, and in constructing an extraanatomical interfemoral bypass. At sixteen months' hindsight, the patient is doing well. Literature is reviewed (24 entries).

Abortion of acute ST segment elevation myocardial infarction after reperfusion: incidence, patients' characteristics, and prognosis.

OBJECTIVES: To study the incidence and patient characteristics of aborted myocardial infarction in both prehospital and in-hospital thrombolysis. DESIGN: Retrospective, controlled, observational study. SETTING: Two cities in the Netherlands, one with prehospital thrombolysis, one with in-hospital treatment. PATIENTS: 475 patients with suspected acute ST elevation myocardial infarction treated before admission to hospital, 269 patients treated in hospital. MAIN OUTCOME MEASURES: Aborted myocardial infarction, defined as the combination of subsiding of cumulative ST segment elevation and depression to < 50% of the level at presentation, together with a rise of creatine kinase of less than twice the upper normal concentration. A stepwise regression analysis was used to test independent predictors for aborted myocardial infarction. RESULTS: After correction for "unjustified" thrombolysis, 17.1% of the 468 prehospital treated patients and 4.5% of the 264 in-hospital treated patients fulfilled the criteria for aborted myocardial infarction. There was no difference in age, sex, risk factors, haemodynamic status, and infarct location of aborted myocardial infarction compared with established myocardial infarction. Time to treatment was shorter in the patients with aborted myocardial infarction (86 versus 123 minutes, p = 0.05). A shorter time to treatment, lower ST elevation at presentation, and higher incidence of preinfarction angina were independent predictors for aborted myocardial infarction. Aborted myocardial infarction had a 12 month mortality of 2.2%, significantly less than the 11.6% of established myocardial infarction. CONCLUSION: Prehospital thrombolysis is associated with a fourfold increase of aborted myocardial infarction compared with in-hospital treatment. A shorter time to treatment, a lower ST elevation, and a higher incidence of preinfarction angina were predictors of aborted myocardial infarction.