54 resultados para HIGH-ORDER HARMONICS


Relevância:

30.00% 30.00%

Publicador:

Resumo:

INTRODUCTION: The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. METHODS: Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. RESULTS: The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. CONCLUSION: A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

BACKGROUND: The Mannheimia subclades belong to the same bacterial genus, but have taken divergent paths toward their distinct lifestyles. For example, M. haemolytica + M. glucosida are potential pathogens of the respiratory tract in the mammalian suborder Ruminantia, whereas M. ruminalis, the supposed sister group, lives as a commensal in the ovine rumen. We have tested the hypothesis that vertical inheritance of the leukotoxin (lktCABD) operon has occurred from the last common ancestor of genus Mannheimia to any ancestor of the diverging subclades by exploring gene order data. RESULTS: We examined the gene order in the 5' flanking region of the leukotoxin operon and found that the 5' flanking gene strings, hslVU-lapB-artJ-lktC and xylAB-lktC, are peculiar to M. haemolytica + M. glucosida and M. granulomatis, respectively, whereas the gene string hslVU-lapB-lktC is present in M. ruminalis, the supposed sister group of M. haemolytica + M. glucosida, and in the most ancient subclade M. varigena. In M. granulomatis, we found remnants of the gene string hslVU-lapB-lktC in the xylB-lktC intergenic region. CONCLUSION: These observations indicate that the gene string hslVU-lapB-lktC is more ancient than the hslVU-lapB-artJ-lktC and xylAB-lktC gene strings. The presence of (remnants of) the ancient gene string hslVU-lapB-lktC among any subclades within genus Mannheimia supports that it has been vertically inherited from the last common ancestor of genus Mannheimia to any ancestor of the diverging subclades, thus reaffirming the hypothesis of vertical inheritance of the leukotoxin operon. The presence of individual 5' flanking regions in M. haemolytica + M. glucosida and M. granulomatis reflects later genome rearrangements within each subclade. The evolution of the novel 5' flanking region in M. haemolytica + M. glucosida resulted in transcriptional coupling between the divergently arranged artJ and lkt promoters. We propose that the chimeric promoter have led to high level expression of the leukotoxin operon which could explain the increased potential of certain M. haemolytica + M. glucosida strains to cause a particular type of infection.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

We developed a geospatial model that calculates ambient high-frequency electromagnetic field (HF-EMF) strengths of stationary transmission installations such as mobile phone base stations and broadcast transmitters with high spatial resolution in the order of 1 m. The model considers the location and transmission patterns of the transmitters, the three-dimensional topography, and shielding effects by buildings. The aim of the present study was to assess the suitability of the model for exposure monitoring and for epidemiological research. We modeled time-averaged HF-EMF strengths for an urban area in the city of Basel as well as for a rural area (Bubendorf). To compare modeling with measurements, we selected 20 outdoor measurement sites in Basel and 18 sites in Bubendorf. We calculated Pearson's correlation coefficients between modeling and measurements. Chance-corrected agreement was evaluated by weighted Cohen's kappa statistics for three exposure categories. Correlation between measurements and modeling of the total HF-EMF strength was 0.67 (95% confidence interval (CI): 0.33-0.86) in the city of Basel and 0.77 (95% CI: 0.46-0.91) in the rural area. In both regions, kappa coefficients between measurements and modeling were 0.63 and 0.77 for the total HF-EMF strengths and for all mobile phone frequency bands. First evaluation of our geospatial model yielded substantial agreement between modeling and measurements. However, before the model can be applied for future epidemiologic research, additional validation studies focusing on indoor values are needed to improve model validity.Journal of Exposure Science and Environmental Epidemiology (2008) 18, 183-191; doi:10.1038/sj.jes.7500575; published online 4 April 2007.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

BACKGROUND AND OBJECTIVE: Insufficient blood flow and oxygenation in the intestinal tract is associated with increased incidence of postoperative complications after bowel surgery. High fluid volume administration may prevent occult regional hypoperfusion and intestinal tissue hypoxia. We tested the hypothesis that high intraoperative fluid volume administration increases intestinal wall tissue oxygen pressure during laparotomy. METHODS: In all, 27 pigs were anaesthetized, ventilated and randomly assigned to one of the three treatment groups (n = 9 in each) receiving low (3 mL kg-1 h-1), medium (7 mL kg-1 h-1) or high (20 mL kg-1 h-1) fluid volume treatment with lactated Ringer's solution. All animals received 30% and 100% inspired oxygen in random order. Cardiac index was measured with thermodilution and tissue oxygen pressure with a micro-oximetry system in the jejunum and colon wall and subcutaneous tissue. RESULTS: Groups receiving low and medium fluid volume treatment had similar systemic haemodynamics. The high fluid volume group had significantly higher mean arterial pressure, cardiac index and subcutaneous tissue oxygenation. Tissue oxygen pressures in the jejunum and colon were comparable in all three groups. CONCLUSIONS: The three different fluid volume regimens tested did not affect tissue oxygen pressure in the jejunum and colon, suggesting efficient autoregulation of intestinal blood flow in healthy subjects undergoing uncomplicated abdominal surgery.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Bronchus stump insufficiency (BSI) is one of the major complications after pneumonectomy; we analyzed all patients who underwent extra pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM) in order to detect the role of muscle flap (MF) on preventing early and late stump insufficiency. From January 2000 until December 2005, there were 42 patients admitted with MPM for further intervention at our institution. Thirty patients were suitable for surgery and thus received a multimodal treatment with neo-adjuvant chemotherapy using Cisplatin and Gemcitabin (Gemzar), EPP followed by 54 Gray (Gy) adjuvant radiotherapy. Data were collected from the surgical and oncological records. There were 37 male patients (88%), the median age was 65 years (range 40-83 years). Seven (17%) patients had concomitant diseases. Forty patients (95%) had asbestos exposition. The operative procedures were EPP with muscle flap through an anterolateral thoracotomy. Univariate and multivariate analyses were done. One patient (3%) died on the 2nd postoperative day due to lung embolism. Mild complications were noticed in the early postoperative phase in 8 (25%) patients. There was no early or late stump insufficiency during the 15-month follow-up. Surgical techniques using muscle flap seems to play a major role in the prevention of bronchus stump insufficiency especially after neo-adjuvant chemotherapy.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

OBJECTIVE: The aim of this study was to use morphological as well as biochemical (T2 and T2* relaxation times and diffusion-weighted imaging (DWI)) magnetic resonance imaging (MRI) for the evaluation of healthy cartilage and cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) of the ankle joint. MATERIALS AND METHODS: Ten healthy volunteers (mean age, 32.4 years) and 12 patients who underwent MACT of the ankle joint (mean age, 32.8 years) were included. In order to evaluate possible maturation effects, patients were separated into short-term (6-13 months) and long-term (20-54 months) follow-up cohorts. MRI was performed on a 3.0-T magnetic resonance (MR) scanner using a new dedicated eight-channel foot-and-ankle coil. Using high-resolution morphological MRI, the magnetic resonance observation of cartilage repair tissue (MOCART) score was assessed. For biochemical MRI, T2 mapping, T2* mapping, and DWI were obtained. Region-of-interest analysis was performed within native cartilage of the volunteers and control cartilage as well as cartilage repair tissue in the patients subsequent to MACT. RESULTS: The overall MOCART score in patients after MACT was 73.8. T2 relaxation times (approximately 50 ms), T2* relaxation times (approximately 16 ms), and the diffusion constant for DWI (approximately 1.3) were comparable for the healthy volunteers and the control cartilage in the patients after MACT. The cartilage repair tissue showed no significant difference in T2 and T2* relaxation times (p > or = 0.05) compared to the control cartilage; however, a significantly higher diffusivity (approximately 1.5; p < 0.05) was noted in the cartilage repair tissue. CONCLUSION: The obtained results suggest that besides morphological MRI and biochemical MR techniques, such as T2 and T2* mapping, DWI may also deliver additional information about the ultrastructure of cartilage and cartilage repair tissue in the ankle joint using high-field MRI, a dedicated multichannel coil, and sophisticated sequences.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

BACKGROUND AND PURPOSE: In order to use a single implant with one treatment plan in fractionated high-dose-rate brachytherapy (HDR-B), applicator position shifts must be corrected prior to each fraction. The authors investigated the use of gold markers for X-ray-based setup and position control between the single fractions. PATIENTS AND METHODS: Caudad-cephalad movement of the applicators prior to each HDR-B fraction was determined on radiographs using two to three gold markers, which had been inserted into the prostate as intraprostatic reference, and one to two radiopaque-labeled reference applicators. 35 prostate cancer patients, treated by HDR-B as a monotherapy between 10/2003 and 06/2006 with four fractions of 9.5 Gy each, were analyzed. Toxicity was scored according to the CTCAE Score, version 3.0. Median follow-up was 3 years. RESULTS: The mean change of applicators positions compared to baseline varied substantially between HDR-B fractions, being 1.4 mm before fraction 1 (range, -4 to 2 mm), -13.1 mm before fraction 2 (range, -36 to 0 mm), -4.1 mm before fraction 3 (range, -21 to 9 mm), and -2.6 mm at fraction 4 (range, -16 to 9 mm). The original position of the applicators could be readjusted easily prior to each fraction in every patient. In 18 patients (51%), the applicators were at least once readjusted > 10 mm, however, acute or late grade > or = 2 genitourinary toxicity was not increased (p = 1.0) in these patients. CONCLUSION: Caudad position shifts up to 36 mm were observed. Gold markers represent a valuable tool to ensure setup accuracy and precise dose delivery in fractionated HDR-B monotherapy of prostate cancer.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Orphan- or understudied-crops are mostly staple food crops in developing world. They are broadly classified under cereals, legumes, root crops, fruits and vegetables. These under-researched crops contribute to the diet of a large portion of resource-poor consumers and at the same time generate income for small-holder farmers in developing countries, particularly in Africa. In addition, they perform better than major crops of the world under extreme soil and climatic conditions. However, orphan crops are not without problems. Due to lack of scientific investigation, most of them produce low yields while others have a variety of toxins that affect the health of consumers. Here, we present some highlights on the status and future perspectives of the Tef Biotechnology Project that employs modern improvement technique in order to genetically improve tef (Eragrostis tef), one of the most important orphan crop in Africa. A reverse genetics approach known as TILLING (Targeting Induced Local Lesions IN Genome) is implemented in order to tackle lodging, the major yield limiting factor in tef.Key words: Orphan crops, underresearched crops, Eragrostis tef, TILLING, semi-dwarf.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

OBJECTIVES: In order to create a suitable model for high-throughput drug screening, a Giardia lamblia WB C6 strain expressing Escherichia coli glucuronidase A (GusA) was created and tested with respect to susceptibility to the anti-giardial drugs nitazoxanide and metronidazole. METHODS: GusA, a well-established reporter gene in other systems, was cloned into the vector pPacVInteg allowing stable expression in G. lamblia under control of the promoter from the glutamate dehydrogenase (gdh) gene. The resulting transgenic strain was compared with the wild-type strain in a vitality assay, characterized with respect to susceptibility to nitazoxanide, metronidazole and -- as assessed in a 96-well plate format -- to a panel of 15 other compounds to be tested for anti-giardial activity. RESULTS: GusA was stably expressed in G. lamblia. Using a simple glucuronidase assay protocol, drug efficacy tests yielded results similar to those from cell counting. CONCLUSIONS: G. lamblia WB C6 GusA is a suitable tool for high-throughput anti-giardial drug screening.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

The accurate reconstruction of sea surface temperature (SST) history in climate-sensitive regions (e.g. tropical and polar oceans) became a challenging task in palaeoceanographic research. Biogenic shell carbonate SST proxies successfully developed for tropical regions often fail in cool water environments. Their major regional shortcomings and the cryptic diversity now found within the major high latitude proxy carrier Neogloboquadrina pachyderma (sin.) highlight an urgent need to explore complementary SST proxies for these cool-water regions. Here we incorporate the genetic component into a calibration study of a new SST proxy for the high latitudes. We found that the calcium isotopic composition (δ44/40Ca) of calcite from genotyped net catches and core-top samples of the planktonic foraminifera Neogloboquadrina pachyderma (sin.) is related to temperature and unaffected by genetic variations. The temperature sensitivity has been found to be 0.17 (±0.02)‰ per 1°C, highlighting its potential for downcore applications in open marine cool-water environments. Our results further indicate that in extreme polar environments, below a critical threshold temperature of 2.0 (±0.5)°C associated with salinities below 33.0 (±0.5)‰, a prominent shift in biomineralization affects the δ44/40Ca of genotyped and core-top N. pachyderma (sin.), becoming insensitive to temperature. These findings highlight the need of more systematic calibration studies on single planktonic foraminiferal species in order to unravel species-specific factors influencing the temperature sensitivity of Ca isotope fractionation and to validate the proxies' applicability.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

High-resolution, well-calibrated records of lake sediments are critically important for quantitative climate reconstructions, but they remain a methodological and analytical challenge. While several comprehensive paleotemperature reconstructions have been developed across Europe, only a few quantitative high-resolution studies exist for precipitation. Here we present a calibration and verification study of lithoclastic sediment proxies from proglacial Lake Oeschinen (46°30′N, 7°44′E, 1,580 m a.s.l., north–west Swiss Alps) that are sensitive to rainfall for the period AD 1901–2008. We collected two sediment cores, one in 2007 and another in 2011. The sediments are characterized by two facies: (A) mm-laminated clastic varves and (B) turbidites. The annual character of the laminae couplets was confirmed by radiometric dating (210Pb, 137Cs) and independent flood-layer chronomarkers. Individual varves consist of a dark sand-size spring-summer layer enriched in siliciclastic minerals and a lighter clay-size calcite-rich winter layer. Three subtypes of varves are distinguished: Type I with a 1–1.5 mm fining upward sequence; Type II with a distinct fine-sand base up to 3 mm thick; and Type III containing multiple internal microlaminae caused by individual summer rainstorm deposits. Delta-fan surface samples and sediment trap data fingerprint different sediment source areas and transport processes from the watershed and confirm the instant response of sediment flux to rainfall and erosion. Based on a highly accurate, precise and reproducible chronology, we demonstrate that sediment accumulation (varve thickness) is a quantitative predictor for cumulative boreal alpine spring (May–June) and spring/summer (May–August) rainfall (rMJ = 0.71, rMJJA = 0.60, p < 0.01). Bootstrap-based verification of the calibration model reveals a root mean squared error of prediction (RMSEPMJ = 32.7 mm, RMSEPMJJA = 57.8 mm) which is on the order of 10–13 % of mean MJ and MJJA cumulative precipitation, respectively. These results highlight the potential of the Lake Oeschinen sediments for high-resolution reconstructions of past rainfall conditions in the northern Swiss Alps, central and eastern France and south-west Germany.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Phase stability, elastic behavior, and pressure-induced structural evolution of synthetic boron-mullite Al5BO9 (a = 5.6780(7), b = 15.035(6), and c =7.698(3) Å, space group Cmc21, Z = 4) were investigated up to 25.6(1) GPa by in situ single-crystal synchrotron X-ray diffraction with a diamond anvil cell (DAC) under hydrostatic conditions. No evidence of phase transition was observed up to 21.7(1) GPa. At 25.6(1) GPa, the refined unit-cell parameters deviated significantly from the compressional trend, and the diffraction peaks appeared broader than at lower pressure. At 26.7(1) GPa, the diffraction pattern was not indexable, suggesting amorphization of the material or a phase transition to a high-pressure polymorph. Fitting the P–V data up to 21.7(1) GPa with a second-order Birch–Murnaghan Equation-of-State, we obtained a bulk modulus KT0 = 164(1) GPa. The axial compressibilities, here described as linearized bulk moduli, are as follows: KT0(a) = 244(9), KT0(b) = 120(4), and KT0(c) = 166(11) GPa (KT0(a):KT0(b):KT0(c) = 2.03:1:1.38). The structure refinements allowed a description of the main deformation mechanisms in response to the applied pressure. The stiffer crystallographic direction appears to be controlled by the infinite chains of edge-sharing octahedra running along [100], making the structure less compressible along the a-axis than along the b- and c-axis.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Recent improvements in the precision of mass spectrometric measurements have reduced the uncertainty of K-Ar and 39Ar-40Ar ages measured on geological materials. Now the major sources of uncertainty are the uncertainties on the 40K decay constant and the absolute abundance of 40K. In order to improve on this situation we determined the abundance of the 40K isotope in terrestrial standards. A ThermoFischer Triton+ thermal ionization mass spectrometer was used for K isotope ratio measurements of the NIST K standard reference materials SRM 918b and SRM 985. Ion beams were measured in Faraday cups with amplifiers equipped with 1E10, 1E11 and 1E12 Ω resistors. Three measurement protocols were used: (A) dynamic measurement with in-run fractionation correction by normalization to the IUPAC recommended isotope ratio 41K/39K = 0.0721677; (B) total evaporation; (C) a modified total evaporation with interblock baseline measurements. Different measurement protocols were combined with different loading procedures. The best results were obtained by loading samples on single tantalum filaments with 0.1M H3PO4. The total ion yields (ionization + transmission) were tested for the evaporation procedures (B) and (C) and ranged up to 48 %. The resulting best estimate for the 40K/39K ratio is 0.000 125 116 ± 57 (2σ), corresponding to 40K/K = (1.1668 ± 8; 2σ) x 10-4.

Relevância:

30.00% 30.00%

Publicador:

Resumo:

Upper Jurassic (Kimmeridgian)±Upper Cretaceous (Cenomanian) inner platform carbonates in the Western Taurides are composed of metre-scale upward-shallowing cyclic deposits (parasequences) and important karstic surfaces capping some of the cycles. Peritidal cycles (shallow subtidal facies capped by tidal-¯at laminites or fenestrate limestones) are regressive- and transgressive-prone (upward-deepening followed by upward-shallowing facies trends). Subtidal cycles are of two types and indicate incomplete shallowing. Submerged subtidal cycles are composed of deeper subtidal facies overlain by shallow subtidal facies. Exposed subtidal cycles consist of deeper subtidal facies overlain by shallow subtidal facies that are capped by features indicative of prolonged subaerial exposure. Subtidal facies occur characteristically in the Jurassic, while peritidal cycles are typical for the Lower Cretaceous of the region. Within the foraminiferal and dasyclad algal biostratigraphic framework, four karst breccia levels are recognized as the boundaries of major second-order cycles, introduced for the ®rst time in this study. These levels correspond to the Kimmeridgian±Portlandian boundary, mid-Early Valanginian, mid-Early Aptian and mid-Cenomanian and represent important sea level falls which affected the distribution of foraminiferal fauna and dasyclad ¯ora of the Taurus carbonate platform. Within the Kimmeridgian±Cenomanian interval 26 third-order sequences (types 1 and 2) are recognized. These sequences are the records of eustatic sea level ¯uctuations rather than the records of local tectonic events because the boundaries of the sequences representing 1±4 Ma intervals are correlative with global sea level falls. Third-order sequences and metre-scale cyclic deposits are the major units used for long-distance, high-resolution sequence stratigraphic correlation in the Western Taurides. Metre-scale cyclic deposits (parasequences) in the Cretaceous show genetical stacking patterns within third-order sequences and correspond to fourth-order sequences representing 100±200 ka. These cycles are possibly the E2 signal (126 ka) of the orbital eccentricity cycles of the Milankovitch band. The slight deviation of values, calculated for parasequences, from the mean value of eccentricity cycles can be explained by the currently imprecise geochronology established in the Cretaceous and missed sea level oscillations when the platform lay above fluctuating sea level.