Narrowing the agronomic yield gap with improved nitrogen use efficiency: a modeling approach.

Improving nitrogen use efficiency (NUE) in the major cereals is critical for more sustainable nitrogen use in high-input agriculture, but our understanding of the potential for NUE improvement is limited by a paucity of reliable on-farm measurements. Limited on-farm data suggest that agronomic NUE (AE(N)) is lower and more variable than data from trials conducted at research stations, on which much of our understanding of AE(N) has been built. The purpose of this study was to determine the magnitude and causes of variability in AE(N) across an agricultural region, which we refer to as the achievement distribution of AE(N). The distribution of simulated AE(N) in 80 farmers' fields in an irrigated wheat system in the Yaqui Valley, Mexico, was compared with trials at a local research center (International Wheat and Maize Improvement Center; CIMMYT). An agroecosystem simulation model WNMM was used to understand factors controlling yield, AE(N), gaseous N emissions, and nitrate leaching in the region. Simulated AE(N) in the Yaqui Valley was highly variable, and mean on-farm AE(N) was 44% lower than trials with similar fertilization rates at CIMMYT. Variability in residual N supply was the most important factor determining simulated AE(N). Better split applications of N fertilizer led to almost a doubling of AE(N), increased profit, and reduced N pollution, and even larger improvements were possible with technologies that allow for direct measurement of soil N supply and plant N demand, such as site-specific nitrogen management.

[Deterioration of vision in conjunction with retinal changes]. / Sehverschlecherung bei seltener Netzhautveränderung. Diagnose: Kombiniertes Hamartom der Netzhaut und des retinalen Pigmentepithels.

A combined hamartoma of the retinal pigment epithelium and the retina is a rare alteration of the ocular fundus. Knowledge of this mostly benign clinical picture is important to be able to differentiate it from malignant tumors such as choroidal melanoma. Occurrence in parallel with phacomatoses is known although it is not present in every case.

Soil warming and carbon-cycle feedbacks to the climate system.

In a decade-long soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon and nitrogen cycling in order to investigate the consequences of these changes for the climate system. Here we show that whereas soil warming accelerates soil organic matter decay and carbon dioxide fluxes to the atmosphere, this response is small and short-lived for a mid-latitude forest, because of the limited size of the labile soil carbon pool. We also show that warming increases the availability of mineral nitrogen to plants. Because plant growth in many mid-latitude forests is nitrogen-limited, warming has the potential to indirectly stimulate enough carbon storage in plants to at least compensate for the carbon losses from soils. Our results challenge assumptions made in some climate models that lead to projections of large long-term releases of soil carbon in response to warming of forest ecosystems.

The role of CD44 during CD40 ligand-induced dendritic cell clustering and maturation.

The interaction between CD40 on dendritic cells (DC) and its ligand CD154 has been recognized to be an important feature in the maturation of DC. Here, we were interested in the role of CD44 a surface receptor shown to mediate cell-cell adhesion and binding to Hyaluronic acid (HA). Western blot analysis of human DC stimulated for 3-12 h with CD154 revealed the rapid induction of the 85 kDa standard form of CD44 and an increased HA-binding affinity. Time-lapse video-imaging microscopy of human DC co-cultured on CD154-transfected murine fibroblasts showed that the CD44 up-regulation coincided with the rapid induction of homotypic DC clustering, which did not occur on empty vector-transfected fibroblasts. In this system, addition of anti-CD44s mAbs abrogated DC-cluster formation, thereby inhibiting further maturation, as shown by a reduced TNF-alpha production and inhibition of CD154-induced MHC class II up-regulation. However, co-incubation with HA-degrading enzymes induced no changes in the CD154-mediated DC clustering and maturation.

Osteopontin is involved in the initiation of cutaneous contact hypersensitivity by inducing Langerhans and dendritic cell migration to lymph nodes.

Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and alphav integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

End-tidal carbon dioxide measurements as a prognostic indicator of outcome in cardiac arrest.

PURPOSE: To evaluate the use of end-tidal carbon dioxide values in predicting survival in cardiopulmonary arrest. BACKGROUND: The decision about when to terminate resuscitative efforts for patients with cardiopulmonary arrest is often subjective. End-tidal carbon dioxide values have been suggested as potential objective criteriafor making this decision. METHODS: This study was a cooperative effort of the St Louis chapter of the American Association of Critical-Care Nurses and its members and involved 6 hospitals and an air evacuation service. All adult patients who had a cardiopulmonary arrest were eligiblefor the study. Once a patient with cardiac arrest was intubated, end-tidal carbon dioxide and cardiac rhythms were measured and recorded every 5 minutes for 20 minutes or until resuscitation efforts were terminated. Patients' survival at the time of the arrest, survival 24 hours after the arrest, and discharge status were followed up. RESULTS: A total of 127 patients were enrolled in the study. All but 1 patient with end-tidal carbon dioxide values less than 10 mm Hg died before discharge. End-tidal carbon dioxide values greater than 10 mm Hg were associated with various degrees of survival. Overall survival to discharge was less than 14%, regardless of the end-tidal carbon dioxide value. CONCLUSION: Measurements of end-tidal carbon dioxide can be used to accurately predict nonsurvival of patients with cardiopulmonary arrest. End-tidal carbon dioxide levels should be monitored during cardiopulmonary arrest and should be considered a useful prognostic value for determining the outcome of resuscitative efforts.

Recognition of E-cadherin by integrin alpha(E)beta(7): requirement for cadherin dimerization and implications for cadherin and integrin function.

We have investigated the importance of dimerization of E-cadherin in the heterophilic adhesive interaction between E-cadherin and integrin alpha(E)beta(7). Dimerization of cadherin molecules in parallel alignment is known to be essential for homophilic adhesion and has been attributed to Ca(2+)-dependent interactions in the domain 1-2 junction or to cross-intercalation of Trp2 from one molecule to the other. We have disrupted either or both of these proposed mechanisms by point mutations in E-cadherin-Fc and have tested the modified proteins for alpha(E)beta(7)-mediated cell adhesion. Prevention of Trp2 intercalation had no adverse effect on integrin-mediated adhesion, whereas disruption of Ca(2+) binding permitted adhesion but with reduced efficiency. Both modifications in combination abolished recognition by alpha(E)beta(7). In EGTA, alpha(E)beta(7) adhered to wild type E-cadherin but not to the Trp2 deletion mutant. Independent evidence that the mutations prevented either or both mechanisms for dimerization is presented. The data show that dimerization is required for recognition by alpha(E)beta(7) and that it can take place by either of two mechanisms. Implications for the roles of the alpha(E) and beta(7) integrin subunits in ligand binding and for Trp2 and Ca(2+) in the assembly of cadherin complexes are discussed.

Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid.

Proteolytic cleavage of the extracellular domain of CD44 from the surface of cells has been observed recently in different cell types. In cell culture supernatants of human melanoma cell lines a 70 kDa soluble CD44 protein (solCD44) was detected at concentrations of 250-300 ng/ml. Protease inhibitor studies revealed that serine proteases and metalloproteases are involved in the cleavage of CD44 from the surface of melanoma cells. To analyse a possible function of soluble CD44 a human malignant melanoma cell line was stably transfected with cDNAs encoding either wild type soluble CD44s or mutated forms with defective HA binding properties (CD44sR41A and CD44sR150A/R154A). Soluble CD44s almost completely inhibited hyaluronic acid binding by melanoma cells, whereas soluble CD44 mutated in the HA binding domain had no effect. When cultivated on hyaluronic acid, melanoma cell proliferation was induced by 30% for both the parental and the control transfected cells. This increase in proliferation was blocked completely in solCD44s-secreting transfectants, whereas solCD44sR41A and solCD44sR150A/R154A-secreting cells again showed hyaluronic acid-induced cell proliferation. These cell lines were subcutaneously injected into MF1 nu/nu mice to compare their growth as tumors in vivo. Compared to tumors derived from parental and control transfected cells, we observed a dramatic reduction of primary tumor growth with solCD44s expressing MM cells. Transfectants expressing solCD44s mutated in the HA binding domain in contrast developed fast-growing primary tumors. These results provide strong evidence that direct solCD44 interactions with hyaluronic acid interfere competitively with processes induced by hyaluronic acid binding to surface CD44. Autocrine, or drug-induced secretion of solCD44 by human melanoma cells may thus exert potent antitumoral effects in vivo.

Comparison of pulmonary artery and central venous pressure waveform measurements via digital and graphic measurement methods.

BACKGROUND: Techniques to measure pulmonary artery (PA) pressure waveforms include digital measurement, graphic measurement, and freeze-cursor measurement. Previous studies reported the inaccuracy of digital and freeze-cursor measurements. However, many of the previous studies were small and did not thoroughly examine the circumstances of when digital measurements might be inaccurate. OBJECTIVES: To compare digital measurements and graphic measurements of PA and central venous pressure (CVP) waveforms in patients with a variety of respiratory patterns, and to compare digital measurements and graphic measurements of CVPs in patients with abnormal or right ventricular waveforms. METHODS: A total of 928 patients were enrolled in this study. Waveforms from the PA and CVP were collected from each patient. The monitor pressure value (digital measurement) printed on the recorded waveform was compared with the pressure value obtained by a graphic strip recording and measured by one of the primary investigators (graphic measurement). RESULTS: Digital measurements were found to be inaccurate in measuring waveforms in all respiratory categories and in measuring right ventricular waveforms. PA diastolic values and CVP values were the most inaccurately measured waveforms. Digital errors of more than 4 mm Hg were common. CONCLUSION: There were instances in which the monitor's digital measurement was substantially different from the graphically measured value. This difference has the potential to mislead interpretation of clinical situations. The monitor's ability to occasionally give digital measurement values similar to the graphic measurements may lead to a false sense of security in clinicians. Because the accuracy of the monitor is inconsistent, the bedside clinician should interpret waveforms through use of a graphic recording rather than rely on the digital measurement on the monitor.

CD44 is the principal mediator of hyaluronic-acid-induced melanoma cell proliferation.

Interactions of the extracellular matrix component hyaluronic acid and its cellular receptors CD44 and RHAMM/IHABP have been linked to tumor progression and metastasis formation. We investigated the expression and hyaluronic-acid-dependent functions of CD44 and RHAMM/IHABP in human melanoma. Immunohistochemistry of tumor specimens at different stages of melanoma progression revealed an increased expression of CD44 and RHAMM/IHABP. High mRNA expression of CD44 was found in three highly tumorigenic melanoma cell lines compared with less tumorigenic melanoma cells or nontransformed melanocytes. RHAMM/IHABP expression was upregulated in all cell lines analyzed but not in melanocytes. In contrast to the cell surface localization of CD44, RHAMM/IHABP was detected exclusively within the cytoplasm of melanoma cells. Binding and adhesion of melanoma cells to hyaluronic acid is mainly CD44 dependent as it was inhibited to 60%--80% by an anti-CD44 monoclonal antibody whereas anti-RHAMM/IHABP sera had no effect. Culture of melanoma cells in the presence of hyaluronic acid resulted in a dose-dependent, CD44-mediated increase of melanoma cell proliferation and enhanced release of basic fibroblast growth factor and transforming growth factor beta 1. We conclude that (i) the expression of CD44 and RHAMM/IHABP is increased during melanoma progression, (ii) CD44 is the principal hyaluronic acid surface receptor on melanoma cells, and (iii) the hyaluronic-acid-induced increase of the proliferative capacity of melanoma cells is mainly dependent on CD44--hyaluronic acid interactions.

Controversies in the use of the pulmonary artery catheter.

The pulmonary artery catheter (PAC) has been in use for more than 30 years. The amount and detail of hemodynamic information provided by the PAC cannot be matched by any other single technology. Whether or not this information makes a difference in the clinical outcomes of critically ill patients is uncertain, however. The Pulmonary Artery Catheter Consensus Conference scrutinized the available research data on the catheter and provided guidelines for clinicians on its use. This article summarizes the controversy and the guidelines available for use of the PAC. It notes the need for further research on patient outcomes.

New technologies in the assessment of hemodynamic parameters.

Pulmonary artery catheter (PAC) use has led to major advances in the assessment of hemodynamics. Since its introduction three decades ago, features have been added to the PAC to enhance its hemodynamic monitoring capabilities. In addition, newer technologies have been proposed to replace the PAC. This article discusses three features that enhance the PAC--measures of mixed venous oxyhemoglobin, right ventricular ejection fraction, and continuous cardiac output--and two newer technologies--esophageal Doppler and exhaled carbon dioxide measurements. The article describes current and future applications of hemodynamic monitoring.

Hemodynamic applications of capnography.

The measurement of the pressure of exhaled carbon dioxide (PetCO2) via capnography has several useful hemodynamic applications. This article discusses integrating PetCO2 values with hemodynamic assessment. Capnography can be applied to hemodynamic assessment in three key ways: (1) identification of end-expiration during pulmonary artery and central venous pressure measurements, (2) assessment of pulmonary perfusion and alveolar deadspace, (3) assessment of cardiopulmonary resuscitative efforts. The article presents research, sample waveforms for end-expiration identification, and case examples.

Oligosaccharides of hyaluronan are potent activators of dendritic cells.

The extracellular matrix component hyaluronan (HA) exists physiologically as a high m.w. polymer but is cleaved at sites of inflammation, where it will be contacted by dendritic cells (DC). To determine the effects of HA on DC, HA fragments of different size were established. Only small HA fragments of tetra- and hexasaccharide size (sHA), but not of intermediate size (m.w. 80, 000-200,000) or high m.w. HA (m.w. 1,000,000-600,000) induced immunophenotypic maturation of human monocyte-derived DC (up-regulation of HLA-DR, B7-1/2, CD83, down-regulation of CD115). Likewise, only sHA increased DC production of the cytokines IL-1beta, TNF-alpha, and IL-12 as well as their allostimulatory capacity. These effects were highly specific for sHA, because they were not induced by other glycosaminoglycans such as chondroitin sulfate or heparan sulfate or their fragmentation products. Interestingly, sHA-induced DC maturation does not involve the HA receptors CD44 or the receptor for hyaluronan-mediated motility, because DC from CD44-deficient mice and wild-type mice both responded similarly to sHA stimulation, whereas the receptor for hyaluronan-mediated motility is not detectable in DC. However, TNF-alpha is an essential mediator of sHA-induced DC maturation as shown by blocking studies with a soluble TNFR1. These findings suggest that during inflammation, interaction of DC with small HA fragments induce DC maturation.

Clinical predictors and outcomes for patients requiring tracheostomy in the intensive care unit.

OBJECTIVE: To identify clinical predictors for tracheostomy among patients requiring mechanical ventilation in the intensive care unit (ICU) setting and to describe the outcomes of patients receiving a tracheostomy. DESIGN: Prospective cohort study. SETTING: Intensive care units of Barnes-Jewish Hospital, an urban teaching hospital. PATIENTS: 521 patients requiring mechanical ventilation in an ICU for >12 hours. INTERVENTIONS: Prospective patient surveillance and data collection. MEASUREMENTS AND MAIN RESULTS: The main variables studied were hospital mortality, duration of mechanical ventilation, length of stay in the ICU and the hospital, and acquired organ-system derangements. Fifty-one (9.8%) patients received a tracheostomy. The hospital mortality of patients with a tracheostomy was statistically less than the hospital mortality of patients not receiving a tracheostomy (13.7% vs. 26.4%; p = .048), despite having a similar severity of illness at the time of admission to the ICU (Acute Physiology and Chronic Health Evaluation [APACHE] II scores, 19.2 +/- 6.1 vs. 17.8 +/- 7.2; p = .173). Patients receiving a tracheostomy had significantly longer durations of mechanical ventilation (19.5 +/- 15.7 days vs. 4.1 +/- 5.3 days; p < .001) and hospitalization (30.9 +/- 18.1 days vs. 12.8 +/- 10.1 days; p < .001) compared with patients not receiving a tracheostomy. Similarly, the average duration of intensive care was significantly longer among the hospital nonsurvivors receiving a tracheostomy (n = 7) compared with the hospital nonsurvivors without a tracheostomy (n = 124; 30.9 +/- 16.3 days vs. 7.9 +/- 7.3 days; p < .001). Multiple logistic regression analysis demonstrated that the development of nosocomial pneumonia (adjusted odds ratio [AOR], 4.72; 95% confidence interval [CI], 3.24-6.87; p < .001), the administration of aerosol treatments (AOR, 3.00; 95% CI, 2.184.13; p < .001), having a witnessed aspiration event (AOR, 3.79; 95% CI, 2.30-6.24; p = .008), and requiring reintubation (AOR, 2.21; 95% CI, 1.54-3.18; p = .028) were variables independently associated with patients undergoing tracheostomy and receiving prolonged ventilatory support. Among the 44 survivors receiving a tracheostomy in the ICU, 38 (86.4%) were alive 30 days after hospital discharge and 31 (70.5%) were living at home. CONCLUSIONS: Despite having longer lengths of stay in the ICU and hospital, patients with respiratory failure who received a tracheostomy had favorable outcomes compared with patients who did not receive a tracheostomy. These data suggest that physicians are capable of selecting critically ill patients who most likely will benefit from placement of a tracheostomy. Additionally, specific clinical variables were identified as risk factors for prolonged ventilatory assistance and the need for tracheostomy.

Continuous mixed venous (SvO2) monitoring. Too expensive or indispensible?

Based on theoretic principles and clear literature support, SvO2 (mixed venous oxyhemoglobin) monitoring offers an important advantage over traditional hemodynamic parameters. SvO2 allows more precise understanding of the adequacy of cardiac and pulmonary function than traditional parameters. SvO2 values do not replace the need to measure individual parameters of oxygen delivery or consumption but serves as the standard for assessing the impact of each parameter on tissue oxygenation. SvO2 has the ability to reflect a threat to tissue oxygenation that is unmatched by other parameters. Its ability to give a real time indication of tissue oxygenation makes it a preferred parameter for monitoring the adequacy of hemodynamics. Its use as an end point for determining the adequacy of hemodynamics (BP, CO/CI), measurement of Qs/Qt, and prediction of potential hemodynamic instability make this parameter invaluable for the knowledgeable clinician. SvO2 catheters cost more than traditional PA catheters, a factor that has limited their acceptance as the standard PA catheter. The added cost of the SvO2 catheter has not been adequately addressed in the research literature. However, research does support SvO2 allows more rapid termination of drug therapies, may improve movement out of the ICU, and reduces the incidence of mechanical ventilator manipulation. These features increase the cost-effectiveness of SvO2 catheters. The cost-effectiveness of the catheter, like any technology, is predicated on the clinician. Clinicians++ must be educated to use SvO2 as a primary end point for treatment decisions regarding hemodynamic therapy and patient stability. If used properly, every PAC should use fiberoptic SvO2 capabilities.

Hemodynamic monitoring.

Hemodynamic monitoring is one of the most exciting and potentially useful technologies in critical care. Hemodynamic monitoring, particularly the PAC, is the technology most often associated with the critical care unit. However, it is a difficult technology to master and is associated with clear (although infrequent) serious complications. It can also be associated with increased costs. With appropriate implementation, this technology can improve patient outcome and moderately reduce costs. Appropriate implementation is not easy with this technology. This type of technology should only be employed in hospitals willing to invest the education and quality monitoring to ensure its appropriate application. As a part of this infrastructure, physicians and nurses need frequent communication in terms of what is expected from this technology for each patient.

Capnography. A key underutilized technology.

Based on the multiple applications and the potential cost savings, every ICU should have enough capnography for all intubations and probably for all mechanically ventilated patients. Of the multiple clinical applications of capnography, most attention should be focused on its use with intubation and resuscitation. Other applications, such as blood gas and ventilation-perfusion scan reduction, should be instituted after the primary areas have been implemented. While capnography modules may appear to be expensive at first glance, an analysis of their clinical application reveals they can save the hospital hundreds of thousands of dollars beyond the purchase price.

Pulse oximetry.

Pulse oximetry is one of the most commonly applied technologies in acute and critical care. It has the potential to continuously monitor pulmonary function, avoid unnecessary blood gases, and alert clinicians to hypoxemic events that are not readily apparent by physical assessment. Due to these advantages, pulse oximetry has a firm place in health care. Unfortunately, pulse oximetry will not usually have a major impact on reducing hospital resources. In addition, oximetry has the potential to be misused owing to its widespread application. In order to obtain the maximum benefits from this technology, clinicians must be educated about the strengths and limitations of oximetry. If this education effectively changes clinicians' behavior, pulse oximetry will provide an excellent clinical advantage in patient assessment as well as moderate cost benefits.