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Purpose of the Study: This study demonstrates how a participatory action research approach was used to address the challenge of the early and effective detection of the deteriorating patient in the ED setting. The approach enabled a systematic approach to patient monitoring and escalation of care to be developed to address the wide-ranging spectrum of undifferentiated presentations and the phases of ED care from triage to patient admission. This paper presents a longitudinal patient monitoring system, which aims to provide monitoring and escalation of care, where necessary, of adult patients from triage to admission to hospital in a manner that is feasible in the unique ED environment., Methods: An action research approach was taken to designing a longitudinal patient monitoring system appropriate for the ED. While the first draft protocol for post-triage monitoring and escalation was designed by a core research group, six clinical sites were included in iterative cycles of planning, action, reviewing and further planning. Reasons for refining the system at each site were collated and the protocol was adjusted accordingly before commencing the process at the next site., Results: The ED Adult Clinical Escalation longitudinal patient monitoring system (ED-ACE) evolved through iterative cycles of design and testing to include: (1) a monitoring chart for adult patients; (2) a standardised approach to the monitoring and reassessment of patients after triage until they are assessed by a clinician; (3) the ISBAR (I=Identify, S=Situation, B=Background, A=Assessment, R=Recommendation) tool for interprofessional communication relating to clinical escalation; (4) a template for prescribing a patient-specific monitoring plan to be used by treating clinicians to guide patient monitoring from the time the patient is assessed until when they leave the ED and (5) a protocol for clinical escalation prompted by single physiological triggers and clinical concern., Conclusions: This tool offers a link in the 'Chain of Prevention' between the Manchester Triage System and ward-based early warning scores taking account of the importance of standardisation, while being sufficiently adaptable for the unique working environment and patient population in the ED., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Recently, a family of guanine nucleotide exchange factors have been identified in many cell types as important effectors of cyclic adenosine 3',5'-monophospahte (cAMP) signalling that is independent of protein kinase A (PKA). In the heart, investigation of exchange protein directly activated by cAMP (Epac) has yielded conflicting results. Since cAMP is an important regulator of cardiac contractility, this study aimed to examine whether Epac activation modulates excitation-contraction coupling in ventricular preparations from rat hearts. The study used 8-(4-chlorophenylthio)-2'-O-methyladenosine-3', 5'-cyclic monophosphate (cpTOME), an analogue of cAMP that activates Epac, but not PKA. In isolated myocytes, cpTOME increased Ca(2+) spark frequency from about 7 to 32/100 μm(3)/s (n = 10), P = 0.05 with a reduction in the peak amplitude of the sparks. Simultaneous measurements of intracellular Ca(2+) and isometric force in multicellular trabeculae (n = 7, 1.5 mmol/L [Ca(2+)]o) revealed no effect of Epac activation on either the amplitude of Ca(2+) transients (Control 0.7 ± 0.1 vs cpTOME 0.7 ± 0.1; 340/380 fura-2 ratio, P = 0.35) or on peak stress (Control 24 ± 5 mN/mm(2) vs cpTOME 23 ± 5 mN/mm(2), P = 0.20). However, an effect of Epac in trabeculae was unmasked by lowering extracellular [Ca(2+)]o. In these depotentiated trabeculae, activation of the Epac pathway increased myofilament Ca(2+) sensitivity, an effect that was blocked by addition of KN-93, a Ca(2+)/calmodulin-dependent protein kinase II (CaMK-II) inhibitor. This study suggests that Epac activation may be a useful therapeutic target to increase the strength of contraction during low inotropic states., (© 2015 Wiley Publishing Asia Pty Ltd.)

The heat liberated upon stress production in isolated cardiac muscle provides insights into the complex thermodynamic processes underlying mechanical contraction. To that end, we simultaneously measured the heat and stress (force per cross-sectional area) production of cardiac trabeculae from rats using a flow-through micromechanocalorimeter. In a flowing stream of O(2)-equilibrated Tyrode solution (∼22°C), the stress and heat production of actively contracting trabeculae were varied by 1) altering stimulus frequency (0.2-4 Hz) at optimal muscle length (L(o)), 2) reducing muscle length below L(o) at 0.2 and 2 Hz, and 3) changing extracellular Ca(2+) concentrations ([Ca(2+)](o); 1 and 2 mM). Linear regression lines were adequate to fit the active heat-stress data. The active heat-stress relationships were independent of stimulus frequency and muscle length but were dependent on [Ca(2+)](o), having greater intercepts at 2 mM [Ca(2+)](o) than at 1 mM [Ca(2+)](o) (3.5 and 2.0 kJ·m(-3)·twitch(-1), respectively). The slopes among the heat-stress relationships did not differ. At the highest experimental stimulus frequency, pronounced elevation of diastolic Ca(2+) resulted in incomplete twitch relaxation. The resulting increase of diastolic stress, which occurred with negligible metabolic energy expenditure, subsequently diminished due to the time-dependent loss of myofilament Ca(2+)-sensitivity.

It is generally agreed that changes in Ca(2+) cycling are often associated with heart failure, yet the impact of these changes on a beat-to-beat basis remains unclear. Measurements of isometric force and [Ca(2+)](i) were made at 37°C in left ventricular trabeculae from failing spontaneously hypertensive rat (SHR) hearts, and their normotensive Wistar-Kyoto (WKY) controls. At 1 Hz, peak stress was reduced in SHR (14.5 ± 2.4 mN mm(-2) versus 22.5 ± 6.7 mN mm⁻² for WKY), although the Ca(2+) transients were bigger (peak [Ca(2+)](i) 0.60 ± 0.08 μM versus 0.38 ± 0.03 μM for WKY) with a slower decay of fluorescence (time constant 0.105 ± 0.005 s versus 0.093 ± 0.002 s for WKY). To probe dynamic Ca(2+) cycling, two experimental protocols were used to potentiate force: (1) an interval of 30 s rest, and (2) a 30-s train of paired-pulses, and the recirculation fraction (RF) calculated for recovery to steady-state. No difference was found between rat strains for RF calculated from either peak force or Ca(2+), although the RF was dependent on potentiation protocol. Since SR uptake is slower in SHR, the lack of change in RF must be due to a parallel decrease in trans-sarcolemmal Ca(2+) extrusion. This view was supported by a slower decay of caffeine-induced Ca(2+) transients in SHR trabeculae. Confocal analysis of LV free wall showed t-tubules were distorted in SHR myocytes, with reduced intensity of NCX and SERCA2a labelling in comparison to WKY.

Aircraft maintenance is a highly regulated, safety critical, complex and competitive industry. There is a need to develop innovative solutions to address process efficiency without compromising safety and quality. This paper presents the case that in order to improve a highly complex system such as aircraft maintenance, it is necessary to develop a comprehensive and ecologically valid model of the operational system, which represents not just what is meant to happen, but what normally happens. This model then provides the backdrop against which to change or improve the system. A performance report, the Blocker Report, specific to aircraft maintenance and related to the model was developed gathering data on anything that 'blocks' task or check performance. A Blocker Resolution Process was designed to resolve blockers and improve the current check system. Significant results were obtained for the company in the first trial and implications for safety management systems and hazard identification are discussed. Statement of Relevance: Aircraft maintenance is a safety critical, complex, competitive industry with a need to develop innovative solutions to address process and safety efficiency. This research addresses this through the development of a comprehensive and ecologically valid model of the system linked with a performance reporting and resolution system.

Objective: This study examines the extent to which the contractile deficit of diabetic cardiomyopathy is due to altered Ca(2+) homeostasis., Research Design and Methods: Measurements of isometric force and intracellular calcium ([Ca(2+)](i), using fura-2/AM) were made in left ventricular (LV) trabeculae from rats with streptozotocin-induced diabetes and age-matched siblings., Results: At 1.5 mmol/l [Ca(2+)](o), 37 degrees C, and 5-Hz stimulation frequency, peak stress was depressed in diabetic rats (10 +/- 1 vs. 17 +/- 2 mN/mm(2) in controls; P < 0.05) with a slower time to peak stress (77 +/- 3 vs. 67 +/- 2 ms; P < 0.01) and time to 90% relaxation (76 +/- 7 vs. 56 +/- 3 ms; P < 0.05). No difference was found between groups for either resting or peak Ca(2+), but the Ca(2+) transient was slower in time to peak (39 +/- 2 vs. 34 +/- 1 ms) and decay (time constant, 61 +/- 3 vs. 49 +/- 3 ms). Diabetic rats had a longer LV action potential (APD(50), 98 +/- 5 vs. 62 +/- 5 ms; P < 0.0001). Western blotting showed that diabetic rats had a reduced expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2a, with no difference in expression of the Na(+)/Ca(2+) exchanger. Immunohistochemistry of LV free wall showed that type I collagen was increased in diabetic rats (diabetic 7.1 +/- 0.1%, control 12.7 +/- 0.1%; P < 0.01), and F-actin content reduced (diabetic 56.9 +/- 0.6%; control 61.7 +/- 0.4%; P < 0.0001) with a disrupted structure., Conclusions: We find no evidence to support the idea that altered Ca(2+) homeostasis underlies the contractile deficit of diabetic cardiomyopathy. The slower action potential and reduced SERCA2a expression can explain the slower Ca(2+) transient kinetics in diabetic rats but not the contractile deficit. Instead, we suggest that the observed LV remodeling may play a crucial role.

Background: At present, there is no consensus regarding how frequently BRCA mutation carriers should be screened for malignancies using breast imaging techniques. An interval malignancy is defined as a malignancy that becomes evident during the period between annual screening mammography scans; the finding of such a malignancy indicates that the malignancy either went undetected by the last breast imaging scan or developed during the interval since that last scan., Methods: The authors retrospectively reviewed the medical charts of all BRCA mutation carriers who were followed by the genetic counselor at the Columbia-Presbyterian Comprehensive Breast Center (New York, NY) between September 1995 and September 2002., Results: Thirteen BRCA mutation carriers elected to undergo close surveillance and thus were followed at our institution. Three of these 13 patients (23%) did not develop breast carcinoma, 4 (31%) developed breast carcinoma that was detected at the time of annual screening, and 6 (46%) developed palpable interval malignancies in less than 12 months. Among the six patients who developed interval malignancies, the mean time between the last screening mammogram and disease presentation was 5.1 months (range, 2-9 months); the average tumor size in this patient subgroup was 1.7 cm (range, 0.8-3 cm). Two of these six patients had ductal carcinoma in situ, whereas the remaining four had invasive breast carcinoma; three patients had positive lymph nodes at presentation. All six patients who developed interval disease exhibited dense breast tissue on the previous mammogram. Focused breast ultrasonography was able to identify the tumor mass in 3 of 4 patients (75%)., Conclusions: Nearly half of all BRCA-positive women who chose to undergo close surveillance in the current study developed malignant disease less than a year after exhibiting normal findings on screening mammography. Half of these interval malignancies were positive for lymph node involvement. These results suggest that strong consideration should be given to screening BRCA-positive women at more frequent intervals and to using additional imaging techniques, such as breast ultrasonography and/or breast magnetic resonance imaging, as a part of this screening., (Copyright 2004 American Cancer Society.)