At this stage the lagoon still had to form and the rivers were flowing directly into the sea. The abundance of fresh water due to the presence of numerous rivers would probably have convinced the first communities to move to the margins of the future lagoon. Numerous sites belonging to the recent Mesolithic Period (from 6000–5500 to 5500–4500 BC) were found in close proximity to the palaeorivers PR-171 manufacturer of this area (Bianchin Citton, 1994).

During the Neolithic Period (5500–3300 BC) communities settled in a forming lagoonal environment, while the first lithic instruments in the city of Venice date back to the late Neolithic–Eneolithic Period (3500–2300 BC) (Bianchin Citton, 1994). During the third millennium BC (Eneolithic or Copper Age: 3300–2300 BC) there was a demographic boom, as evidenced by the many findings in the mountains and in the plain. This population increase would also have affected the Venice Lagoon (Fozzati, 2013). In the first centuries of the second millennium BC, corresponding to the ancient Bronze Age in Northern Italy, there was a major demographic fall extending

from Veneto to the Friuli area. It is just in the advanced phase of the Middle Bronze Age (14th century BC) that a new almost systematic occupation of the area took place, with the maximal demographical expansion occurring in the recent Bronze Age (13th buy Baf-A1 century BC) (Bianchin Citton, 1994 and Fozzati, 2013). Between the years 1000 and 800 BC, with the spreading of the so Tau-protein kinase called

Venetian civilization, the cities of Padua and Altino were founded in the mainland and at the northern margins of the lagoon (Fig. 1a), respectively. Between 600 and 200 years BC, the area underwent the Celtic invasions. Starting from the 3rd century BC, the Venetian people intensified their relationship with Rome and at the end of the 1st century BC the Venetian region became part of the roman state. The archeological record suggests a stable human presence in the islands starting from the 2nd century BC onwards. There is a lot of evidence of human settlements in the Northern lagoon from Roman Times to the Early Medieval Age (Canal, 1998, Canal, 2013 and Fozzati, 2013). In this time, the mean sea level increased so that the settlements depended upon the labor-intensive work of land reclamation and consolidation (Ammerman et al., 1999). Archeological investigation has revealed two phases of human settlements in the lagoon: the first phase began in the 5th–6th century AD, while a second more permanent phase began in the 6th–7th century. This phase was “undoubtedly linked to the massive and permanent influx of the Longobards, which led to the abandonment of many of the cities of the mainland” (De Min, 2013). Although some remains of the 6th–7th century were found in the area of S. Pietro di Castello and S.

The fertile soils become extremely vulnerable as soon as rural land abandonment see more takes place (see Fig. 8 and Fig. 9). Other factors contributing to the degradation of the terraces are the lack of effective rules against land degradation, the reduced competitiveness of terrace cultivation, and the dating of the traditional techniques only seldom replaced by new technologies ( Violante et al., 2009). The degradation of the terraces is now dramatically

under way in some mountain zones of the Amalfi Coast, historically cultivated with chestnut and olive trees and also with the presence of small dairy farms. In the lower zones of the hill sides, the terraces cultivated with lemons and grapes remain, but with difficulty. In most mountainous parts of the Amalfi Coast, the landscape is shaped as Veliparib datasheet continuous bench terraces planted with chestnut or olive trees and with the risers protected by grass. Whereas terraces along steep hillsides mainly serve to provide

levelled areas for crop planting, to limit the downward movement of the soil particles dragged by overland flow, and to enhance land stabilization, carelessness in their maintenance and land abandonment enhance the onset of soil erosion by water with different levels of intensity. This situation is clearly illustrated in Fig. 9, taken in a chestnut grove located at a summit of a hillside near the village of Scala. The circular Org 27569 lunette surrounding the chestnut tree disappeared completely because of an increase in runoff as a result of more soil crusting and the loss of control on water moving as

overland flow between the trees. The erosion process here is exacerbated by the fact that the soil profile is made up of an uppermost layer of volcanic materials (Andisols) deposited on a layer of pumices, both lying over fractured limestone rocks. This type of fertile volcanic soil developed on steep slopes is extremely vulnerable and prone to erosion. Fig. 9 shows that soil erosion was so intense that the pumices are now exposed and transported by unchannelled overland flow. A form of economic degradation is added to this physical degradation because it is not cost-effective to restore terraces that were exploited with nearly unprofitable crops, such as chestnut or olive plantations. Fig. 10 shows two examples of terrace failure documented during surveys carried out recently in some lowlands of the Amalfi Coast. The picture in Fig. 10a was taken near the head of Positano and depicts a slump in a dry-stone wall.

In both valleys there exists a clear lithostratigraphic boundary between basal gravels with organic channel fills and a thick capping sandy silt unit (up to 5 m thick). In both valleys this sedimentary MG-132 research buy discontinuity or bounding surface can be traced throughout the valley fill. In terms of sedimentary architecture it is therefore clear that it is higher than a 5th order bounding surface (sensu Miall, 1996) and so must be a 6th order surface comparable to the discontinuity which exists between the bedrock and valley fill or between Pleistocene glacial sediments and the Holocene fill ( Table 3; Murton and Belshaw, 2011). Such surfaces often form boundaries for geological

Stages and also Epochs. However, in the Frome this bounding surface is dated at 3600–4400 cal BP but in the Culm it is dated to 1300–220 cal BP. From palaeoecological and archaeological data we can see that this abrupt change in sedimentation is primarily a function of intensive arable agriculture. Even over as short a distance as 100 km this

boundary is time-transgressive by at least 2300 years and could not be associated with any one climatic episode in the Holocene. This presents significant problems for the recognition of this sedimentary boundary as the start of the Anthropocene. This agriculturally created sedimentary boundary is also common across North West Europe. AC220 research buy Excellent examples have been documented in Northern France (Lespez et al., 2008), Saxony in northern Germany (Bork, 1989 and Bork and Lang, 2003), mid-Germany (Houben, 2012), south Germany (Dotterweich, 2008) and further east in Poland (Starkel et al., 2006 and Dotterweich et al., 2012) and Slovakia (Dotterweich et al., 2013). Indeed wherever lowland Holocene sedimentary sequences are investigated such a discontinuity is discovered. Moving south the picture is complicated by the greater sensitivity of Mediterranean catchments to climatic influences (cf. Maas and Macklin, 2002, Butzer, 2005 and Fuchs, 2007). However, it has been identified in northern and central Italy ( Brown and Ellis, 1996) and Greece oxyclozanide ( van Andel et al., 1990,

Lespez, 2003 and Fuchs, 2007) and Spain ( Schulte, 2002 and Thorndycraft and Benito, 2006). It is clear that in Europe there is significant diachrony in the late Holocene increase in valley sedimentation but it most frequently occurs over the last 1000 to 2000 years ( Notebaert and Verstraeten, 2010). Recent studies have also shown similar alluvial chronologies in northern Africa, which appear primarily driven by rapid climate change events but with sedimentation response being intensified by anthropogenic impact ( Faust et al., 2004 and Schuldenrein, 2007). Studies to the east from the Levant to India have largely been part of archaeological investigations and have focussed on climatic influences on early agricultural societies.

5 in PGA and 1.5 in PAA, indicating that nitrogen of cationic lipoplex was completely covered with a sulfate group or a carboxyl group of the anionic polymers. In a previous

study, we reported that ζ-potentials of the lipoplexes of pDNA after the addition of anionic polymers were almost consistently negative around charge ratios (−/+) of 5.8 in CS and 7 in PGA [5]. The amount Capmatinib mouse of anionic polymer needed for covering cationic lipoplex of siRNA was sufficient at a lower level than for the lipoplex of pDNA. Therefore, in subsequent experiments, we decided to use 1 in CS, 1.5 in PGA and 1.5 in PAA as optimal charge ratios (−/+) for the preparation of anionic polymer-coated lipoplex. The association of siRNA with cationic liposome was monitored by gel retardation electrophoresis. Naked siRNA was detected as bands on acrylamide gel. Beyond a charge ratio (−/+) of 1/3, no migration of siRNA was observed

for cationic lipoplex (Fig. 2A). However, migration of siRNA was observed for CS-, PGA- and PAA-coated lipoplexes at all charge ratios (−/+) of anionic polymer/DOTAP when anionic polymers were added into cationic lipoplex (Fig. 2B), indicating that anionic polymers caused dissociation of siRNA from lipoplex by competition for binding Navitoclax chemical structure to cationic liposome. Previously, we reported that CS and PGA could coat cationic lipoplex of pDNA without PDK4 releasing pDNA from the cationic lipoplex, and formed stable anionic lipoplexes [5]. In lipoplex of siRNA, the association of cationic liposome with siRNA might be weaker than that with pDNA. Furthermore, we examined the association of siRNA with cationic liposome using SYBR® Green I. SYBR® Green I is a DNA/RNA-intercalating agent whose fluorescence is dramatically enhanced upon binding to siRNA and quenched when displaced by condensation of the siRNA structure. Unlike gel retardation electrophoresis, fluorescence of SYBR® Green I was markedly decreased by the formation of anionic polymer-coated

lipoplex, compared with that in siRNA solution (Supplemental Fig. S1). These findings suggested that the CS-, PGA- and PAA-coated lipoplexes were completely formed even at charge ratios (−/+) of 1, 1.5 and 1.5, respectively. Although a discrepancy between the results from the accessibility of SYBR® Green I and gel retardation electrophoresis was observed, siRNA might be released from the anionic polymer-coated lipoplex under electrophoresis by weak association between siRNA and cationic liposomes. To increase the association between siRNA and cationic liposome, we decided to use siRNA-Chol for the preparation of anionic polymer-coated lipoplex. In siRNA-Chol, beyond a charge ratio (−/+) of 1/1, no migration of siRNA was observed for cationic lipoplex (Fig. 2A).

For a sedation policy to address competencies for nonanesthesiologist administration of moderate sedation, a joint collaborative effort among the national gastroenterology societies, including the Society of Gastroenterology Nurses and Associates, created the “”Multisociety sedation curriculum for gastrointestinal endoscopy.”"2 DAPT This curriculum is robust (eg, didactic, Web-based learning, simulation) and should be considered as a resource in developing training and competencies for moderate sedation during gastrointestinal procedures. In an ASC or office-based setting, a moderate

sedation policy must have checks and balances in place, such as a plan of action in the event of emergencies or inadvertent progression to deep sedation and the necessary equipment to perform these actions. An additional RN circulator is strongly suggested for situations during which procedure complexity may change over time or whenever a child or patient who has selleck kinase inhibitor cognitive challenges is receiving care. As new technology for monitoring the patient and administering medication evolves, policy stakeholders must stay informed and be aware of how policy may be affected. For example, a colonoscopy is one of the most frequently performed procedures in ASCs. New monitoring tools allow for nonanesthesiologist administration of propofol for gastrointestinal endoscopy. There are many considerations, and AORN encourages

nurses to take part in these discussions. Clear guidelines, specific training and competencies, contingency plans, and compliance with all applicable local, state, and federal regulations should be part of an ASC’s policy and procedure on moderate sedation. Terri Link, MPH, RN, CNOR, CIC, is an ambulatory education specialist at AORN, Inc, Denver, CO. Ms Link has no declared affiliation that could be

perceived as posing a potential conflict of interest in the publication of this article. “
“Continuing Education: Understanding Medication Compounding Issues indicates that continuing education (CE) contact hours are SB-3CT available for this activity. Earn the CE contact hours by reading this article, reviewing the purpose/goal and objectives, and completing the online Examination and Learner Evaluation at http://www.aorn.org/CE. A score of 70% correct on the examination is required for credit. Participants receive feedback on incorrect answers. Each applicant who successfully completes this program can immediately print a certificate of completion. Event: #14510 Session: #0001 Fee: Members $17.60, Nonmembers $35.20 The CE contact hours for this article expire April 30, 2017. Prices are subject to change. To provide learners with knowledge specific to the use of compounded medications in the OR. 1. Describe the threats to patient safety that compounded medications pose. AORN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

It has been proposed that the non-stoichiometric OCP structure has excess hydrogen, resulting in a non-stoichiometric chemical formula, Ca16H4+x(PO4)12(OH)x·(10 − x)H2O, which resembles the structure of HA even more closely than previously anticipated [50]. The preparation conditions may be critical for producing diversity in the chemical INCB024360 price and physical properties of OCP, because OCP crystals exhibit plate-like morphologies with wide variation in their dimension [48], [51], [52], [53] and [54]. Together, these findings demonstrate the remarkable differences in crystal size and direction of growth toward a particular axis, depending on the

preparation conditions. The solubility of calcium phosphates can be estimated by measuring the degree of supersaturation (DS) with respect to particular

calcium phosphate phases [55], [56] and [57]. Table 2 shows the DS values Y-27632 research buy in the supernatant after soaking dicalcium phosphate dihydrate (DCPD), OCP, β-TCP, and HA in alpha essential minimal medium (α-MEM) for 72 h at 37 °C, as previously reported [58]. The DS can be expressed by dividing the ionic product by the solubility product from the objective calcium phosphate [55], [56] and [57]. The DS is usually calculated using the analytical results, including the concentration of calcium (Ca2+) and inorganic Methane monooxygenase phosphate (Pi) ions as well as the pH of the solution [55], [56], [57] and [59]. The results showed that α-MEM was supersaturated with HA and OCP before the introduction of calcium phosphate materials, but undersaturated with DCPD, suggesting that α-MEM has the potential to form HA and OCP if seeded with crystals. The composition of α-MEM after the introduction of DCPD became saturated with respect to DCPD, and the introduction

of OCP induced a slight supersaturated condition. In addition, the introduction of β-TCP and HA induced a relatively higher supersaturated condition with respect to OCP and HA. In particular, β-TCP induced a supersaturated condition that was higher than that of the α-MEM alone. Thus, calcium phosphates seeded in α-MEM may be deposited with newly formed HA and possibly OCP [58], although the crystal growth may also be affected by the kinetics of the specific calcium phosphate phase associated with the inhibitory effect of some of the ionic regulators, such as small amounts of magnesium and other factors [55], [60], [61], [62] and [63]. It is of great interest to determine whether calcium phosphate ceramics positively promote osteogenesis, because recent studies have shown that some calcium phosphate ceramics have osteoinductive properties [64], [65] and [66], including the capability to induce ectopic bone formation.

6 mm internal diameter polytetrafluoroethylene (PTFE) column (PC Inc., Potomac, MD). The value of β ranged from 0.5 at the inner part of the column Sotrastaurin purchase to 0.85 at the outside of the column. The total volume of the column

was 325 mL. The column was rotated at 850 rpm. Samples were introduced using a 16-mL loop injector (PC Inc.) with the aid of a Waters (Milford, MA) pump. Melting points (in °C) were determined using a Mettler melting point apparatus (Mettler–Toledo, Leicester, UK). Absorption spectra in the ultraviolet region were collected with a Shimadzu-2550 dual beam UV–visible spectrophotometer (Shimadzu, Kyoto, Japan), as described by Mabry, Markham, and Thomas (1970), with modifications. The phenolic constituents were dissolved in ethanol (0.1%) and analysed by scanning over the range λ = 500–200 nm, both before and after the addition of AlCl3 and

HCl, or NaOAc and H3BO3. Absorption spectra in the infrared region (IR) were obtained with a Prestige-21 spectrometer (Shimadzu) using KBr pellets. The 1H and 13C NMR spectra were collected on a 400 MHz Bruker AVANCE DRX spectrometer (Bruker Biospin, Rheinstetten, Germany). The gHMQC, gHMBC and COSY contour maps were collected on a 500 MHz Varian (Palo Alto, CA) spectrometer equipped with a Z-axis gradient multinuclear probe. Tetramethylsilane (TMS) Neratinib nmr was used as an internal reference for all NMR experiments. The molecular masses of the compounds were determined using the positive ionisation mode in MALDI-TOF mass spectrometry (Microflex LT, Bruker), using alpha-cyano-4-hydroxycinnamic acid as the matrix. The in vitro antioxidant activity experiments were monitored by UV–visible spectrophotometry Aspartate using a dual beam Shimadzu-2550 instrument. The radical-scavenging experiment was observed at λ = 517 nm, and the reducing power experiment was observed at λ = 700 nm. G. brasiliensis Mart. fruits were collected from the campus of the Federal University of Viçosa-MG,

Brazil, in February (summer) of 2010. The botanical identification of the samples was confirmed by Dr. João Augusto Alves Meira Neto of the Horto Botânico of the Federal University of Viçosa. A voucher specimen (number VIC2604) was deposited at the Herbarium of the Federal University of Viçosa. Epicarps from G. brasiliensis fruit were air-dried at 40 °C for 8 days with continuous moisture monitoring. After the material was completely dry, it was pulverised in a knife grinder, producing 1052 g of ground sample. The dried, ground epicarps were subjected to exhaustive extraction in a Soxhlet apparatus using an increasing polarity solvent system, with n-hexane and ethyl acetate as solvents for 24 h each. The extracts were then concentrated at reduced pressure, yielding 60.2 g of hexane epicarp extract (EHE) and 102.2 g of ethyl acetate epicarp extract (EAEE). The chemical analysis of the EHE fraction, which contains the polyprenylated benzophenones 7-epiclusianone and garciniaphenone, has been previously reported (Derogis, 2008).

The steep water was then drained off, and the slurry was ground in a laboratory blender. The ground slurry was screened through a 200-mesh sieve. The material remaining on the sieve was washed thoroughly with distilled water. The filtrate slurry was allowed to stand for 3 h. The supernatant was then removed, and the settled starch layer was resuspended in distilled water and centrifuged in wide-mouthed cups at 1200g for 20 min. The upper non-white layer was scraped off. The white layer was resuspended in distilled water and centrifuged at 1200g for 15 min. The upper non-white layer was scraped off

again, and the starch was collected and dried in an oven at 40 °C ISRIB concentration for 12 h. The starch isolation yield was approximately 24%, and the protein, ash and lipid contents in the native starch were approximately 0.43%, 0.14% and 0.19%, respectively, on a dry basis. Starch oxidation was performed according to the method described

by Wang and Wang (2003), with some modifications. A 35% starch slurry was prepared by adding deionised water to 200 g of starch (dry basis) to a final weight of 571 g in a 2 l reaction vessel and mantle. The starch slurry was maintained at 35 °C by occasionally turning off the mantle heating power, and the pH level was adjusted to 9.5 with 0.5 N NaOH. Twenty grams of sodium hypochlorite (1 g of active chlorine and 200 g of starch resulting in 0.50% active chlorine, w/w) was slowly added to the starch slurry over a period of 30 min while maintaining the pH level at 9.5 with 1 N HCl. After the addition of sodium hypochlorite, the pH value Quizartinib of the slurry was maintained at 9.5 with 1 N NaOH for an additional 50 min. The slurry was then adjusted to a pH value of 7.0 with 1 N HCl, filtered by suction with a Buchner filter funnel (Whatman filter No. 4), washed

with a twofold volume of deionised water and dried in a convection oven at 40 °C for 24 h. The same procedure was applied for different active chlorine concentrations (0.50%, 1.0% and 1.5%; w/w). The carbonyl content was determined old according to the titrimetric method as described by Smith (1967). A starch sample (2 g) was added to 100 ml of distilled water in a 500-ml flask. The suspension was gelatinised in a boiling water bath for 20 min, cooled to 40 °C, and adjusted to a pH value of 3.2 with 0.1 N HCl. A hydroxylamine reagent (15 ml) was then added to the mixture. The flask was stoppered and placed in a 40 °C water bath for 4 h with slow stirring. The excess hydroxylamine was determined by rapidly titrating the reaction mixture to a pH value of 3.2 with standardised 0.1 N HCl. A blank determination with only the hydroxylamine reagent was performed in the same manner. The hydroxylamine reagent was prepared by first dissolving 25 g of hydroxylamine hydrochloride in 100 ml of 0.5 N NaOH, before the final volume was adjusted to 500 ml with distilled water.

The dough (60 g) was placed into paper muffin cups and baked in a preheated oven at 180 °C for 20 min. After baking, the muffins were cooled to room temperature and packed in polypropylene pouches. They were then sealed until sensory and texture analysis. Other muffins intended for chemical analysis were frozen, freeze-dried, ground into a fine powder, and stored at −18 °C in airtight vials. Recipe 1 (R1) consisted of only wheat flour, water, white beet sugar, and margarine with 80% fat content. The additional ingredients—namely, nonfat dry milk powder (in recipe R1M), baking powder (R1B), dry egg white powder (R1E),

salt (R1S), and all ingredients together (R1A)—were added to the R1 recipe in the ratio used for muffin preparation (Section 2.2). Recipe 2 (R2) contained all

PF-02341066 in vivo the ingredients listed above (Section 2.2). However, the effects of the following different types of sugar were examined: glucose (in recipe R2G), fructose (R2F), white (refined) beet sugar (R2Bs), and raw (unrefined) cane sugar (R2Cs). In these recipes, margarine (80% fat content) was the fat source. The effects of different types of fat were determined by replacing the margarine with HDAC inhibitor olive oil (in recipe R2OO), rapeseed oil (R2RS), rice bran oil (R2RB), and grapeseed oil (R2GS), with white beet sugar as the sugar source. Model samples of recipes R1 and R2 were prepared with a 20% addition of GP to determine the associated effect of food ingredients with phenolic compounds from the GP on CML concentration. The CML measuring method employed here is adapted from Peng et al. (2010). Following defatting, ifenprodil protein reduction, hydrolysis, and derivatization using o-phthaldialdehyde, CML determination was performed using a Waters Alliance high-performance liquid chromatography (HPLC System 600, Milord, MA, USA) with a fluorescence detector (Waters 474). The HPLC system was equipped with a Waters Sun Fire C18 column (150 × 4.6 mm, 5 μm; Milord, MA, USA). The flow rate

was 1.0 ml/min and the injection volume was 10 μl. The mobile phases were acetate buffer and acetonitrile (9:1, v/v) (solvent A) and 50% acetonitrile (solvent B). Detection was at 340 nm (excitation) and 455 nm (emission). The peaks for CML-derivatives in the muffin samples were confirmed by comparison with an authentic sample of CML provided by PolyPeptide Laboratories France SAS (Strasbourg, France). Identified compounds were quantified using the external standard calibration procedure. The limit of detection (LOD) was 0.42 ng, the limit of quantification (LOQ) was 1.29 ng, the recovery of the analyte compared to the internal standard was ∼100% (SD = 10.03%), and the repeatability (method precision) was 3.65% (coefficient of variations). Phenolic compounds were extracted from muffins and GP with methanol/water/formic acid solution (70:29.7:0.3 v/v/v), using the procedure described by Wang and Zhou (2004).

The gas-line and lead were connected to the “Y” connector of the PIL, which was tunneled under the rectus sheath to an exit site located on the abdomen. A driver was attached to the patient connector

and a programmer was used to adjust cuff inflation volume and timing of inflation and deflation in relation to the cardiac cycle to optimize the counterpulsation effect (Figure 1B). Balloon inflation was timed via the programmer to begin right after the dicrotic notch, while deflation started during the pre-ejection phase and continued during the ejection phase of systole in such a way that 70 ± 10% of the balloon Selleck AZD5363 was deflated at the start of ejection. Patients were discharged from the hospital once heart failure medications were re-established and the patients were ambulatory and able to demonstrate the ability to care for the exit site and manage the driver. Patients were scheduled to be seen by the heart failure clinician-investigator and study coordinator at 1, 3, 6, and 12 months post-implant. During the primary period of follow-up (the first 6 GW-572016 price months), the C-Pulse System was intended to be used at least 20 h per day.

The non–blood contacting feature of the C-Pulse System allows the device to be intermittently turned off as tolerated. This enables the patient to be “untethered” from the device, allowing freedom for personal hygiene and convenience. Follow-up visits included a repeat of baseline tests: physical examination, medication summary, and assessment of NYHA functional class, QoL as measured by the Minnesota Living with Heart Failure questionnaire and the Kansas City Cardiomyopathy Questionnaire, 6MWD, and pVO2 (repeated at 6 months only). Safety data, including adverse events, was collected continuously. The CT was repeated at 6

months only. Data were collected via electronic data capture screens referred to as e-case report forms and independently monitored. Core laboratories were used to provide data on CT scans (Cardiovascular Core Labs, Washington, DC), echocardiograms (Cardiovascular Core Labs, Washington, DC), and pVO2 testing (Henry Cediranib (AZD2171) Ford Health System, Detroit, Michigan). Functional status assessments and QoL testing (NYHA functional classification and QoL scoring, respectively) were conducted using standardized and validated approaches and questionnaires 1 and 17. Adverse events were recorded by the clinical sites and adjudicated by an independent Clinical Events Committee (see the Online Appendix). Adverse event definitions were based on Version 2.2 adverse event definitions for the Intermacs registry 2 and 18. This feasibility study was designed to assess the safety and potential benefit of the C-Pulse System in patients with NYHA functional class III-ambulatory functional class IV heart failure. As with most Investigational Device Exemption feasibility studies, the primary focus of the U.S.