Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism.

Background: In haemodynamically stable patients with acute symptomatic pulmonary embolism (PE), studies have not evaluated the usefulness of combining the measurement of cardiac troponin, transthoracic echocardiogram (TTE), and lower extremity complete compression ultrasound (CCUS) testing for predicting the risk of PE-related death. Methods: The study assessed the ability of three diagnostic tests (cardiac troponin I (cTnI), echocardiogram, and CCUS) to prognosticate the primary outcome of PE-related mortality during 30 days of follow-up after a diagnosis of PE by objective testing. Results: Of 591 normotensive patients diagnosed with PE, the primary outcome occurred in 37 patients (6.3%; 95% CI 4.3% to 8.2%). Patients with right ventricular dysfunction (RVD) by TTE and concomitant deep vein thrombosis (DVT) by CCUS had a PE-related mortality of 19.6%, compared with 17.1% of patients with elevated cTnI and concomitant DVT and 15.2% of patients with elevated cTnI and RVD. The use of any two-test strategy had a higher specificity and positive predictive value compared with the use of any test by itself. A combined three-test strategy did not further improve prognostication. For a subgroup analysis of high-risk patients, according to the pulmonary embolism severity index (classes IV and V), positive predictive values of the two-test strategies for PE-related mortality were 25.0%, 24.4% and 20.7%, respectively. Conclusions: In haemodynamically stable patients with acute symptomatic PE, a combination of echocardiography (or troponin testing) and CCUS improved prognostication compared with the use of any test by itself for the identification of those at high risk of PE-related death.

Effects of traffic control on the soil physical quality and the cultivation of sugarcane

The cultivation of sugarcane with intensive use of machinery, especially for harvest, induces soil compaction, affecting the crop development. The control of agricultural traffic is an alternative of management in the sector, with a view to preserve the soil physical quality, resulting in increased sugarcane root growth, productivity and technological quality. The objective of this study was to evaluate the physical quality of an Oxisol with and without control traffic and the resulting effects on sugarcane root development, productivity and technological quality. The following managements were tested: no traffic control (NTC), traffic control consisting of an adjustment of the track width of the tractor and sugarcane trailer (TC1) and traffic control consisting of an adjustment of the track width of the tractor and trailer and use of an autopilot (TC2). Soil samples were collected (layers 0.00-0.10; 0.10-0.20 and 0.20-0.30 m) in the plant rows, inter-row center and seedbed region, 0.30 m away from the plant row. The productivity was measured with a specific weighing scale. The technological variables of sugarcane were measured in each plot. Soil cores were collected to analyze the root system. In TC2, the soil bulk density and compaction degree were lowest and total porosity and macroporosity highest in the plant row. Soil penetration resistance in the plant row, was less than 2 MPa in TC1 and TC2. Soil aggregation and total organic carbon did not differ between the management systems. The root surface and volume were increased in TC1 and TC2, with higher productivity and sugar yield than under NTC. The sugarcane variables did not differ between the managements. The soil physical quality in the plant row was preserved under management TC1 and TC2, with an improved root development and increases of 18.72 and 20.29 % in productivity and sugar yield, respectively.

Treating the individual hypertensive patient: considerations on dose, sequential monotherapy and drug combinations.

For the general practitioner to be able to prescribe optimal therapy to his individual hypertensive patients, he needs accurate information on the therapeutic agents he is going to administer and practical treatment strategies. The information on drugs and drug combinations has to be applicable to the treatment of individual patients and not just patient study groups. A basic requirement is knowledge of the dose-response relationship for each compound in order to choose the optimal therapeutic dose. Contrary to general assumption, this key information is difficult to obtain and often not available to the physician for many years after marketing of a drug. As a consequence, excessive doses are often used. Furthermore, the physician needs comparative data on the various antihypertensive drugs that are applicable to the treatment of individual patients. In order to minimize potential side effects due to unnecessary combinations of compounds, the strategy of sequential monotherapy is proposed, with the goal of treating as many patients as possible with monotherapy at optimal doses. More drug trials of a crossover design and more individualized analyses of the results are badly needed to provide the physician with information that he can use in his daily practice. In this time of continuous intensive development of new antihypertensive agents, much could be gained in enhanced efficacy and reduced incidence of side effects by taking a closer look at the drugs already available and using them more appropriately in individual patients.

Novel Chemotherapy Combinations in Advanced Gastric Cancer: an Updated Meta-Analysis

Combination chemotherapy is widely accepted for patients with advanced gastric cancer, but uncertainty remains regarding the choice of the regimen. Objectives: To assess the effect of: Comparison 1) irinotecan versus non-irinotecancontaining regimens, comparison 2) docetaxel versus non-docetaxel-containing regimens, comparison 3) regimens including oral 5-FU prodrugs versus intravenous fluoropyrimidines, comparison 4) oxaliplatin versus cisplatin-containing regimens on overall survival. Search Strategy: We searched: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, proceedings from ECCO, ESMO, ASCO until December 2009. Selection Criteria: Randomised controlled trials on the above mentioned chemotherapy regimens in advanced or metastatic denocarcinoma of the stomach or GE-junction. Results: The meta-analysis of overall survival for comparison 1) included 4 trials, 640 patients, and results in a HR of 0.86 (95% CI 0.73-1.02) in favour of the irinotecancontaining regimens. For comparison 2) 4 trials with a total of 924 patients have been included in the analysis of overall survival. The resulting HR is 0.93 (95% CI 0.79-1.09) in favour of the docetaxel-containing regimens, with moderate heterogeneity (I2 =7%). For comparison 3 and 4, one major relevant study (Cunningham 2008) could not be included in this meta-analysis after discussion because it included patients with squamous cell cancer of the esophagus as well. Thus, for comparison 3) one relevant study (Kang 2009; 316 patients) comparing capecitabine versus 5-FU in combination with cisplatin is eligible. The resulting HR is 0.85 (95%CI 0.65-1.11) in favour of the oral regimen. For comparison 4) two eligible trials were identified (Al Batran 2008, Popov 2008; 292 patients) with a resulting HR of 0.82 (95% CI 0.47-1.45) in favour of the oxaliplatin-based regimens. For three further trials data is incomplete at present. Conclusions: Chemotherapy combinations including irinotecan, oxaliplatin, docetaxel or oral 5-FU prodrugs are alternative treatment options to cisplatin/5-FU or cisplatin/ 5-FU/anthracycline-combinations, but do not provide significant advantages in overall survival. Supported by: KKS Halle, grant number [BMBF/FKZ 01GH01GH0105]. Disclosure: All authors have declared no conflicts of interest.

Fixed-dose combinations as initial therapy for hypertension : a review of approved agents and a guide to patient selection.

Recent guidelines recommend initiation of antihypertensive therapy with fixed-dose combinations in high-risk patients because such patients usually need two or more blood pressure (BP)-lowering agents in order to normalize their BP. Agents that block the renin-angiotensin system (ACE inhibitors or angiotensin II receptor antagonists [angiotensin receptor blockers; ARBs]) are preferred for the management of hypertension in most patients exhibiting subclinical target organ damage, or established cardiovascular or renal diseases. Unless contraindicated they should be one of the components of fixed-dose combinations, whereas the other component may be either a calcium channel antagonist or a thiazide diuretic. Fixed-dose combinations containing an ACE inhibitor or ARB plus a calcium channel antagonist appear particularly effective in preventing complications of coronary heart disease.

Identity and combinations of arbuscular mycorrhizal fungal isolates influence plant resistance and insect preference

1. Accumulating evidence indicates that plant resistance against above-ground herbivores can be affected by the presence of arbuscular mycorrhizal fungi (AMF) in association with the host plant. Little is known, however, about how AMF composition can influence herbivore choice to feed on a particular plant. 2. Unravelling the preference-performance hypothesis in a multitrophic context is needed to expand our knowledge of complex multitrophic interactions in natural systems. If given mycorrhizal fungal genotypes increase attractiveness for a herbivore (reduced plant resistance), then the benefits of increased unpalatability provided by the mycorrhizal fungi (increased plant resistance) might be outweighed by the increased herbivore recruitment. 3. This was addressed by designing three experiments to test the effects of different AMF genotypes, inoculated either alone or in combination, to measure intraspecific AMF effects on plant resistance and insect herbivore preference. Using strawberry (Fragaria vesca L.) plants that were colonised by eight different combinations of Rhizophagus irregularis isolates, we measured effects on plant growth, insect growth and survival, as well as feeding preferences of a generalist herbivore caterpillar (Spodoptera littoralis Boisduval). 4. Overall, it was found that: (i) AMF influenced plant resistance in an AMF genotype-specific manner; (ii) some AMF inoculations decreased insect performance; (iii) insects preferentially chose to feed more on leaves originating from non-mycorrhizal plants; but also that (iv) in a whole plant bioassay, insects preferentially chose the biggest plant, regardless of their mycorrhizal status. 5. Therefore, AMF-mediated trade-offs between growth and resistance against herbivores have been shown. Such trade-offs, particularly driven by plant attractiveness to herbivores, buffer the positive effects of the mycorrhizal symbiosis on enhanced plant growth.

Differential effects of pro- and anti-inflammatory cytokines alone or in combinations on the metabolic profile of astrocytes.

We have previously reported that the pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) induce profound modifications of the metabolic profile of astrocytes. The present study was undertaken to further characterize the effects of cytokines in astrocytes and to determine whether similar effects could also be observed in neurons. To do so, selected pro-inflammatory (IL-6 and interferon-γ, in addition to the above-mentioned TNFα and IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor-β1 and interferon-β) were applied to primary neuronal and astrocytic cultures, and key metabolic parameters were assessed. As a general pattern, we observed that pro-inflammatory cytokines increased glucose utilization in astrocytes while the anti-inflammatory cytokines IL-4 and IL-10 decreased astrocytic glucose utilization. In contrast, no significant change could be observed in neurons. When pairs of pro-inflammatory cytokines were co-applied in astrocytes, several additive or synergistic modifications could be observed. In contrast, IL-10 partially attenuated the effects of pro-inflammatory cytokines. Finally, the modifications of the astrocytic metabolism induced by TNFα + IL-1β and interferon-γ modulated neuronal susceptibility to an excitotoxic insult in neuron-astrocyte co-cultures. Together, these results suggest that pro- and anti-inflammatory cytokines differentially affect the metabolic profile of astrocytes, and that these changes have functional consequences for surrounding neurons.

Genomic behavior of hybrid combinations between elephant grass and pearl millet

The objective of this work was to evaluate the genomic behavior of hybrid combinations between elephant grass (Pennisetum purpureum) and pearl millet (P. glaucum). Tetraploid (AAA'B) and pentaploid (AA'A'BB) chromosome races resulting from the backcross of the hexaploid hybrid to its parents elephant grass (A'A'BB) and pearl millet (AA) were analyzed as to chromosome number and DNA content. Genotypes of elephant grass, millet, and triploid and hexaploid induced hybrids were compared. Pentaploid and tetraploid genomic combinations showed high level of mixoploidy, in discordance with the expected somatic chromosome set. The pentaploid chromosome number ranged from 20 to 34, and the tetraploid chromosome number from 16 to 28. Chromosome number variation was higher in pentaploid genomic combinations than in tetraploid, and mixoploidy was observed among hexaploids. Genomic combinations 4x and 5x are mixoploid, and the variation of chromosome number within chromosomal race 5x is greater than in 4x.

New drugs and combinations for malignant glioma.

A new chemotherapy agent and a method for local delivery of carmustine have recently been approved for the treatment of malignant glioma. However, the increase in survival remains modest at best with only a very select patients currently benefiting truly of these treatments. Combination regimen of different alkylating agents or prior O6-alkyltransferase depletion by O6-benzylguanine or continuous temozolomide administration schedules have shown some indication for increased activity. There is preclinical rational for combining temozolomide with radiotherapy and the initial results of a phase II clinical trial were promising. Several new cytotoxic agents are currently in clinical trials in patients with recurrent glioma. More importantly, targeted therapy and antiangiogenic agents have entered the clinical development phase also for patients with glioblastoma and anaplastic astrocytoma. The optimal timing of administration of non-cytotoxic substances and their integration into the currently available treatments remains a challenge. Novel study designs and identification of surrogate markers are necessary in order to make rapid and clinically meaningful progress. This review summarises the currently available evidence of activity of the recently approved drugs against malignant glioma and mentions also agents which have failed to demonstrate a significant antitumour activity. Study endpoints are critically discussed. Combination regimens with other agents and radiation therapy are reviewed. The rational for using antiangiogenic drugs in selected ongoing trials is discussed.

Chemical characteristics of grape juices from different cultivar and rootstock combinations

The objective of this work was to evaluate the influence of different combinations of grape cultivars and rootstocks on chemical characteristics of grape juices. Six treatments were evaluated, consisting of combinations between the Isabel Precoce and BRS Cora grape cultivars and the 'IAC 766', 'IAC 313', and 'IAC 572' rootstocks. Approximately 10 L of juice were obtained per treatment. Analyses of color, total soluble solids content, pH, anthocyanins, total phenolics, total sugars, and quantification and identification of biogenic amines by HPLC were performed. Biogenic amines, such as putrescine, cadaverine, spermidine, and spermine, were found in all evaluated cultivars. By principal component analysis (PCA), treatments can be divided into two groups, according to the cultivar. Juices obtained from 'Isabel Precoce' are characterized by higher levels of total sugar content and soluble solids; however, juices from 'BRS Cora' are positively correlated with phenolic content, anthocyanins, and color and acidity parameters. The differences found by PCA for juices from the Isabel Precoce and BRS Cora cultivars indicate that, regardless of the rootstock used, the most important factor in the chemical characterization of juices is the grape cultivar.

Combinations of vascular endothelial growth factor pathway inhibitors with metronomic chemotherapy: Rational and current status.

Chemotherapy given in a metronomic manner can be administered with less adverse effects which are common with conventional schedules such as myelotoxicity and gastrointestinal toxicity and thus may be appropriate for older patients and patients with decreased performance status. Efficacy has been observed in several settings. An opportunity to improve the efficacy of metronomic schedules without significantly increasing toxicity presents with the addition of anti-angiogenic targeted treatments. These combinations rational stems from the understanding of the importance of angiogenesis in the mechanism of action of metronomic chemotherapy which may be augmented by specific targeting of the vascular endothelial growth factor (VEGF) pathway by antibodies or small tyrosine kinase inhibitors. Combinations of metronomic chemotherapy schedules with VEGF pathway targeting drugs will be discussed in this paper.

Creació d’un programa informàtic per al monitoratge dels paràmetres de treball i a l’ajut al guiatge d’un tractor agrícola

L’objectiu projecte és desenvolupar un sistema d’ajut al guiatge universal adaptable a qualsevol vehicle que permeti incrementar significativament l’eficiència de les feines a realitzar per la maquinària al camp. El sistema proposat es pot configurar d’acord amb les característiques de la maquinària o de la tasca a realitzar i és capaç de guiar en línia recta i crear paral·leles a la passada recta de referència. Un altre objectiu és millorar el rendiment, la fiabilitat i la usabilitat del programari de monitoratge inicial instal·lat al tractor, com també caracteritzar el receptor GPS AgGPS 332 de Trimble® per a comprovar la precisió de l’aparell. Els resultats obtinguts en la millora del programa de monitoratge són molt satisfactoris a l’haver corregit imprecisions de funcionament que en limitaven l’usabilitat. Els resultats obtinguts en la caracterització del receptor AgGPS 332 permeten valorar millor quin tipus de correcció diferencial és més convenient per a la precisió de treball requerida segons el seu cost de posada en marxa i de funcionament.Els resultats obtinguts en la validació de l’ajut al guiatge, han validat el guiatge a 10 metres vista com un ajut al guiatge equivalent al guiatge manual quan la velocitat de treball és de 5 km/h, el tractorista té referències visuals i no està fatigat. Els resultats obtinguts pels guiatges a 3 i 50 metres no són satisfactoris a 5 km/h. Tanmateix, durant el procés de disseny, la realització dels assajos i durant l’anàlisi de resultats s’han identificat algunes mancances i limitacions i es proposen una sèrie de millores per tal de solucionar-les.