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Objectives: The authors reconfigured the emergency care system of Addenbrookes Hospital, Cambridge. The medical admissions unit and the emergency department (ED) have been combined into one emergency assessment unit. This paper aims to determine if reconfiguration has reduced non-elective hospital admissions and reduced mortality for non-elective admissions., Design: A retrospective 'before and after' study in a teaching hospital. Routinely collected data were used to evaluate the effectiveness of this approach. Setting One acute trust in the UK. Main outcome measures Inhospital mortality rates and standardised admission ratios (SAR) between 2003 and 2009., Results: There was a significant trend towards improved survival, both for non-elective admissions and deaths in the ED (z=-3.92; p>0.001), despite the age and acuity of patients increasing. There was a marked decrease in the SAR. Formal complaints, incident reports and the proportion of patients leaving before treatment declined, whereas the proportion of patients re-admitted as an emergency within 28 days did not change., Conclusions: Integrating emergency care within a hospital reduces hospital admissions, is associated with reduced inhospital mortality and a better quality of care.

Clinical trial results support the hypothesis that implantable hemodynamic monitoring (IHM) systems may reduce hospitalizations among patients with chronic heart failure (HF). The Reducing Decompensation Events Utilizing Intracardiac Pressures in Patients With Chronic Heart Failure (REDUCE hf  ) study was a prospective, randomized, multicenter, single-blinded trial that enrolled patients with New York Heart Association class II or III symptoms, an indication for an implantable cardioverter-defibrillator (ICD), and a previous HF hospitalization. A combination IHM-ICD was implanted and patients were randomly assigned to a treatment group in which hemodynamic information was used or a control group in which hemodynamic information was not available. Patients were followed for 12 months to evaluate the primary efficacy end point of HF hospitalizations, emergency department visits, or urgent clinic visits. The trial was designed to enroll 1300 patients, but stopped at 400 patients because of IHM lead failures experienced from previous trials. A total of 202 treatment patients and 198 controls were randomized for 12-month follow-up. The primary safety end point was met, but the rate of HF equivalents was not different between groups. REDUCE hf was unable to test clinical efficacy end points adequately. The device combining IHM-ICD technology was safe and functioned appropriately. Patients at high risk for decompensated HF have high baseline filling pressures and demonstrate consistent increases as the process of congestion worsens to the time of hospitalization., (© 2011 Wiley Periodicals, Inc.)

Background: Cardiac output (CO) is an important determinant of the hemodynamic state in patients with congestive heart failure (CHF). We tested the hypothesis that CO can be estimated from the right ventricular (RV) pressure waveform in CHF patients using a pulse contour cardiac output algorithm that considers constant but patient specific RV outflow tract characteristic impedance., Method: In 12 patients with CHF, breath-by-breath Fick CO and RV pressure waveforms were recorded utilizing an implantable hemodynamic monitor during a bicycle exercise protocol. These data were analyzed retrospectively to assess changes in characteristic impedance of the RV outflow tract during exercise. Four patients that were implanted with an implantable cardiac defibrillator (ICD) implementing the algorithm were studied prospectively. During a two staged sub-maximal bicycle exercise test conducted at 4 and 16 weeks of implant, COs measured by direct Fick technique and estimated by the ICD were recorded and compared., Results: At rest the total pulmonary arterial resistance and the characteristic impedance were 675 ± 345 and 48 ± 18 dyn.s.cm(-5), respectively. During sub-maximal exercise, the total pulmonary arterial resistance decreased (Δ 91 ± 159 dyn.s.cm(-5), p < 0.05) but the characteristic impedance was unaffected (Δ 3 ± 9 dyn.s.cm(-5), NS). The algorithm derived cardiac output estimates correlated with Fick CO (7.6 ± 2.5 L/min, R(2) = 0.92) with a limit of agreement of 1.7 L/min and tracked changes in Fick CO (R(2) = 0.73)., Conclusions: The analysis of right ventricular pressure waveforms continuously recorded by an implantable hemodynamic monitor provides an estimate of CO and may prove useful in guiding treatment in patients with CHF.

Background: The purpose of this study was to develop an automated surveillance system, using pressure-based hemodynamic factors that would detect which patients were making the transition from compensated to decompensated heart failure before they developed worsening symptoms and required acute medical care., Methods and Results: Intracardiac pressures in 274 patients with heart failure were measured using an implantable hemodynamic monitor (IHM) and were analyzed in a retrospective manner. An automated pressure change detection (PCD) algorithm was developed using the cumulative sum method. The performance characteristics of the PCD algorithm were defined in all patients who developed a heart failure-related event (HFRE); patients without HFRE served as controls. Optimal PCD threshold values were chosen using a receiver operator curve analysis. Each of the pressures measured with the IHM were evaluated using the PCD analysis. All had sensitivities ≥80% and false-positive rates <4.7/patient-year; however, estimated pulmonary artery diastolic pressure (ePAD) had the best performance. An ePAD based on the optimized PCD threshold of 6.0 yielded a sensitivity of 83% and a false-positive rate of 4.1/patient-year for detecting patients making the transition from compensated to decompensated heart failure. These performance characteristics were not significantly different for patients with an ejection fraction > vs. <50%, estimated glomerular filtration rate > vs. <60 mL/min/1.73 m(2), or age > vs. <60 years., Conclusions: The automated PCD algorithm had high sensitivity and acceptable false-positive rates in detecting the development of decompensated heart failure before the patient developed worsening symptoms and required acute medical care. These data support the development of a prospective study to examine the utility of adding an automated PCD algorithm to IHM-based management strategies to prevent decompensated heart failure., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine which pressure-based hemodynamic factor was most closely associated with the transition from chronic compensated to acute decompensated heart failure., Methods and Results: Intracardiac pressures were retrospectively examined in 274 heart failure patients using an implantable hemodynamic monitor. The relationship between the development of a heart failure-related event (HFRE) and 3 pressure variables were analyzed: peak estimated pulmonary artery diastolic pressure (ePAD) at the time of an HFRE, change in ePAD from baseline to peak pressure, and the product of ePAD pressure and time (P×T) calculated as the area under the pressure-versus-time curve from baseline to peak pressure. Patients without an HFRE served as control subjects. Peak ePAD and change in ePAD were not closely associated with the development of an HFRE. In patients with an HFRE, P×T was 221 ± 130 mm Hg·days with only 4% of the P×T values <60 mm Hg·days. In contrast, in patients without an HFRE, the P×T was 5 ± 23 with only 4% of the P×T values >60 mm Hg·days., Conclusions: The product of small increases in pressure that occur over an extended period of time (P×T) is the pressure-based hemodynamic factor most closely associated with the transition to acute decompensated heart failure., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Intracardiac pressures in heart failure (HF) have been measured in patients while supine in the hospital but change at home with posture and activity. The optimal level of chronic ambulatory pressure is unknown. This analysis compared chronic intracardiac pressures to later HF events and sought a threshold above which higher pressures conferred worse outcomes., Methods and Results: Median pressures were measured every 24 hours from continuous 8-minute segments for 6 months after implantation of hemodynamic monitors in 261 patients with New York Heart Association class III-IV HF in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure Study. Baseline and chronic daily medians of estimated pulmonary artery diastolic, right ventricular systolic, and right ventricular end-diastolic pressures were compared with HF event rate. The group median for chronic 24-hour estimated pulmonary artery diastolic pressure was 28 mm Hg (excluding 7 days before and after events). Despite weight-guided management, events occurred in 100 of 261 (38%) patients. Event risk increased progressively with higher chronic 24-hour estimated pulmonary artery diastolic pressure, from 20% at 18 mm Hg to 34% at 25 mm Hg and 56% at 30 mm Hg, with similar relations for right ventricular pressures. Among patients with baseline day median estimated pulmonary artery diastolic pressures of ≥25 mm Hg, event risk was 1.10/6 mo when they remained chronically ≥25 mm Hg, but risk fell to 0.47 when 24-hour pressures declined to <25 mm Hg for more than half of the days., Conclusions: Despite current management, many patients with advanced HF live on a plateau of high filling pressures from which later events occur. This risk is progressively higher with higher chronic ambulatory pressures. It is not known whether more targeted intervention could maintain lower chronic ambulatory pressures and better outcomes.

The root cap has a central role in root growth, determining the growth trajectory and facilitating penetration into the soil. Root cap cells have specialized functions and morphologies, and border cells are released into the rhizosphere by specific cell wall modifications. Here, we demonstrate that the cellular maturation of root cap is redundantly regulated by three genes, SOMBRERO (SMB), BEARSKIN1 (BRN1), and BRN2, which are members of the Class IIB NAC transcription factor family, together with the VASCULAR NAC DOMAIN (VND) and NAC SECONDARY WALL THICKENING PROMOTING FACTOR (NST) genes that regulate secondary cell wall synthesis in specialized cell types. Lateral cap cells in smb-3 mutants continue to divide and fail to detach from the root, phenotypes that are independent of FEZ upregulation in smb-3. In brn1-1 brn2-1 double mutants, columella cells fail to detach, while in triple mutants, cells fail to mature in all parts of the cap. This complex genetic redundancy involves differences in expression, protein activity, and target specificity. All three genes have very similar overexpression phenotypes to the VND/NST genes, indicating that members of this family are largely functionally equivalent. Our results suggest that Class IIB NAC proteins regulate cell maturation in cells that undergo terminal differentiation with strong cell wall modifications.

In this review, we analyze progress in understanding the mechanisms of root meristem development and function. The formation of embryonic and lateral roots, together with the remarkable regenerative ability of roots, seems to be linked to an auxin-dependent patterning mechanism, the "reflux loop," that can act at least partly independently of cellular context. A major feature of root formation is the production of the "structural initials," the center of the developing root. These cells form an organizing center (OC), the quiescent center (QC), which is needed for meristem activity. The exact role of the QC remains somewhat unclear, though it maintains a stem cell (SC) state in adjacent cells and acts as a long-term SC pool itself. SCs in the root can be defined on an operational basis, but a molecular definition for SC identity remains elusive. Instead, the behavior of cells in the proximal root might better be understood as the result of a "potential" gradient in the meristem, which confers cellular characteristics with respect to proximity to the QC. This potential gradient also seems to be auxin-dependent, possibly as a result of the effect of auxin on the expression of PLETHORA genes, key regulators of meristem function. Only in the root cap (RC) has distinct SC identity been proposed; but increasingly, evidence suggests that regulation of RC development is rather different from that in the proximal meristem; interestingly, a similar dichotomy can also be observed in the shoot meristem. Cell cycle progression must lie at the core of meristematic activity, and recent work has begun to uncover how hormonal regulation feeds forward into various aspects of the cell cycle. The emergent picture is one of coordinate regulation of cell division and elongation by a hormonal signaling network that is integrated by the auxin reflux loop to control root growth., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Nearly half of all patients with chronic heart failure (HF) have a normal ejection fraction (EF), and abnormal diastolic function (ie, diastolic heart failure [DHF]). However, appropriate management of DHF patients remains a difficult and uncertain challenge., Methods and Results: The Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial was designed to evaluate whether an implantable hemodynamic monitor (IHM) was safe and effective in reducing the number of heart failure-related events (HFRE) in patients with chronic HF. The current study presents data on a prespecified and planned subgroup analysis from the COMPASS-HF trial: 70 patients with an EF > or =50% (ie, DHF). As such, this represents a subgroup analysis of the COMPASS-HF Trial. DHF patients were randomized to IHM-guided care (treatment) vs. standard care (control) for 6 months. All 70 patients received optimal medical therapy, but the hemodynamic information from the IHM was used to guide patient management only in the treatment group. The HFRE rate in DHF patients randomized to treatment was 0.58 events/6 months compared with DHF patients randomized to control, which was 0.73 events/6 months; this represented a 20% nonsignificant reduction in the overall HFRE rate in the treatment group (95% CI = -46, 56, P = .66). There was a 29% nonsignificant reduction in the relative risk of a HF hospitalization in the DHF patients randomized to treatment compared with DHF patients randomized to control (95% CI = -69, 70, P = .43)., Conclusions: The IHM was shown to be safe and was associated with a very low system-related and procedure-related complication rate in DHF patients. However, in this subgroup analysis limited to 70 DHF patients, the addition IHM-guided care did not significantly lower the rate of HFR events. The results of this subgroup analysis in DHF patients, for whom there are currently no proven, effective management strategies, will be used to design future studies defining the effects of IHM-guided care in patients with DHF.

Background: Approximately half of all patients with chronic heart failure (HF) have a decreased ejection fraction (EF) (systolic HF [SHF]); the other half have HF with a normal EF (diastolic HF [DHF]). However, the underlying pathophysiological differences between DHF and SHF patients are incompletely defined. The purpose of this study was to use echocardiographic and implantable hemodynamic monitor data to examine the pathophysiology of chronic compensated and acute decompensated HF in SHF versus DHF patients., Methods and Results: Patients were divided into 2 subgroups: 204 had EF <50% (SHF) and 70 had EF >or=50% (DHF). DHF patients had EF of 58+/-8%, end-diastolic dimension of 50+/-10 mm, estimated resting pulmonary artery diastolic pressure (ePAD) of 16+/-9 mm Hg, and diastolic distensibility index (ratio of ePAD to end-diastolic volume) of 0.11+/-0.06 mm Hg/mL. In contrast, SHF patients had EF of 24+/-10%, end-diastolic dimension of 68+/-11 mm, ePAD of 18+/-7 mm Hg, and diastolic distensibility index of 0.06+/-0.04 mm Hg/mL (P<0.05 versus DHF for all variables except ePAD). In SHF and DHF patients who developed acute decompensated HF, these events were associated with a significant increase in ePAD, from 17+/-7 to 22+/-7 mm Hg (P<0.05) in DHF and from 21+/-9 to 24+/-8 mm Hg (P<0.05) in SHF. As a group, patients who did not have acute decompensated HF events had no significant changes in ePAD., Conclusions: Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.

Tracking changes in stroke volume or cardiac output (CO) can be useful in the diagnosis and treatment of various cardiac illnesses. Existing arterial pressure waveform based pulse contour CO algorithms perform poorly during altered systemic hemodynamics. In this study, a right ventricular pressure waveform based pulse contour CO algorithm was developed to estimate the amplitude and duration of a hypothetical triangular flow waveform in the pulmonary artery. This algorithm was tested against gold standard blood flow measurements in ten canines during acute perturbations to preload (inferior vena caval occlusion (IVCO), rapid saline infusion), afterload (descending aortic occlusion (DAO), serotonin, angiotensin II, sodium nitroprusside infusion), and cardiac contractility (dobutamine and propranolol infusion). The algorithm correctly predicted the changes in CO (r2 = 0.82) that varied from - 45 to 31% of the baseline levels. To explain this finding both the pulmonary arterial (PA) and the ascending aortic (AA) input impedances were modeled as three element windkessels. In the AA the peripheral resistance (from - 61 to 191%), characteristic impedance (from - 59 to 20%) and total arterial compliance (from - 49 to 34%) varied significantly with these perturbations. In contrast, these parameters in the PA changed little. In particular, except serotonin infusion, the characteristic impedance of the PA deviated only 6% (SD/mean) from baseline values. This suggests right ventricular pressure waveform based estimate of CO is possible during acute changes in left ventricular hemodynamics.

Axillary meristems allow the production of secondary growth axes in the shoot systems of plants. As such they make a large contribution to the plastic developmental potential of plants, allowing them to alter their architecture to suit the prevailing environment conditions. This review focuses on the formation and activity of axillary meristems, across several model species. Current topics and problems in the field are discussed.

Background: Plants achieve remarkable plasticity in shoot system architecture by regulating the activity of secondary shoot meristems, laid down in the axil of each leaf. Axillary meristem activity, and hence shoot branching, is regulated by a network of interacting hormonal signals that move through the plant. Among these, auxin, moving down the plant in the main stem, indirectly inhibits axillary bud outgrowth, and an as yet undefined hormone, the synthesis of which in Arabidopsis requires MAX1, MAX3, and MAX4, moves up the plant and also inhibits shoot branching. Since the axillary buds of max4 mutants are resistant to the inhibitory effects of apically supplied auxin, auxin and the MAX-dependent hormone must interact to inhibit branching., Results: Here we show that the resistance of max mutant buds to apically supplied auxin is largely independent of the known, AXR1-mediated, auxin signal transduction pathway. Instead, it is caused by increased capacity for auxin transport in max primary stems, which show increased expression of PIN auxin efflux facilitators. The max phenotype is dependent on PIN1 activity, but it is independent of flavonoids, which are known regulators of PIN-dependent auxin transport., Conclusions: The MAX-dependent hormone is a novel regulator of auxin transport. Modulation of auxin transport in the stem is sufficient to regulate bud outgrowth, independent of AXR1-mediated auxin signaling. We therefore propose an additional mechanism for long-range signaling by auxin in which bud growth is regulated by competition between auxin sources for auxin transport capacity in the primary stem.

Grafting provides a simple way to generate chimeric plants with regions of different genotypes, and thus to assess the cell autonomy of gene action. The technique of grafting has been widely used in other species, but in Arabidopsis, its small size makes the process rather more complicated. However, there are now several well-established grafting procedures available, which we described here, and their use has already contributed greatly to understanding of such processes as shoot branching control, flowering, and disease resistance.

Information from an implantable hemodynamic monitoring system (IHM) aids in management of patients with heart failure. This study identified which components of 24-hour IHM data best estimate resting conditions. Thirty-two patients with heart failure received an IHM in the right ventricular (RV) outflow tract. RV hemodynamics were divided into seven components of a 24-hour recording and were compared with resting supine values. Ambulatory pressures approximating rest were then compared with acute invasive catheterization values. Resting RV pressures from the IHM averaged 41+/-16/10+/-6 mm Hg and estimated pulmonary artery diastolic pressure was 21+/-8 mm Hg. Nighttime (midnight to 4 a.m.) minimum pressures from the IHM best approximated supine resting conditions. RV and pulmonary artery pressures during catheterization were higher than the nighttime minimum, although RV diastolic pressure was not statistically different. Minimum RV and pulmonary artery pressures during nighttime approximate observed resting conditions; invasive catheterization pressures are higher than IHM resting values.

Background: Care and management of patients with congestive heart failure (CHF) is a major health-care challenge. The value of acute hemodynamic data in assessing heart failure has been questioned in some studies, while more intensive hemodynamic monitoring has been reported to improve patient care in others. A series of patient studies are reported here that were conducted to identify device requirements and verify the feasibility of continuous hemodynamic monitoring in CHF patients and devices for remote transfer and use of these data., Methods and Results: The results of four separate studies in 68 CHF patients who received systems for chronic hemodynamic monitoring between 1992 and the present are reviewed. One early study was with five patients followed for 7-16 months and another study was with nine patients followed for 4-22 months. A third study included 21 patients followed up to 39 months, and the fourth study included 32 patients implanted in 1998-99 with many of them still in follow-up. These studies support the technical feasibility of implanted devices and the external instrumentation required to transfer and manage the collected data. They also support the long-term stability and accuracy of these systems. Three additional acute studies conducted with 30 patients and chronic data from 53 of the 68 patients with the implanted systems are presented that support the feature included in the newer monitors--the ability to reliably estimate pulmonary artery diastolic pressures from the right ventricular pressure signal., Conclusions: Development of implantable technology to measure several hemodynamic variables in ambulatory CHF patients is feasible. External instrumentation needed to remotely acquire data from the implanted devices has been verified. The potential to eliminate the uncertainties associated with the use of acute, invasive hemodynamics and the ability to evaluate long-term ambulatory hemodynamic patterns is provided. These findings set the stage for determining the potential clinical value of these systems in impacting the care of chronic CHF patients.

Background: We describe the performance of an implantable hemodynamic monitor (IHM) that allows continuous recording of heart rate, patient activity levels, and right ventricular systolic, right ventricular diastolic, and estimated pulmonary artery diastolic pressures. Pressure parameters derived from the implantable monitor were correlated to measurements made with a balloon-tipped catheter to establish accuracy and reproducibility over time in patients with chronic heart failure (CHF)., Methods and Results: IHM devices were implanted in 32 patients with CHF (left ventricular ejection fraction, 29% +/- 11%; range, 14%-62%) and were tested with right heart catheterization at implantation and 3, 6, and 12 months later. Hemodynamic variables were digitally recorded simultaneously from the IHM and catheter. Values were recorded during supine rest, peak response of Valsalva maneuver, sitting, peak of a 2-stage (25-50 W) bicycle exercise test, and final rest period. The median of 21 paired beat-to-beat cardiac cycles was analyzed for each intervention. A total of 217 paired data values from all maneuvers were analyzed for 32 patients at implantation and 129 paired data values for 20 patients at 1 year. The IHM and catheter values were not different at baseline or at 1 year (P >.05). Combining all interventions, correlation coefficients were 0.96 and 0.94 for right ventricular systolic pressure, 0.96 and 0.83 for right ventricular diastolic pressure, and 0.87 and 0.87 for estimated pulmonary artery diastolic pressure at implantation and 1 year, respectively., Conclusions: The IHM and a standard reference pressure system recorded comparable right heart pressure values in patients with CHF. This implantable pressure transducer is accurate over time and provides a means to precisely monitor the hemodynamic condition of patients with CHF in a continuous fashion.