Control of ventricular unloading using an electrocardiogram-synchronized Thoratec paracorporeal ventricular assist device

OBJECTIVE: Current pulsatile ventricular assist devices operate asynchronous with the left ventricle in fixed-rate or fill-to-empty modes because electrocardiogram-triggered modes have been abandoned. We hypothesize that varying the ejection delay in the synchronized mode yields more precise control of hemodynamics and left ventricular loading. This allows for a refined management that may be clinically beneficial. METHODS: Eight sheep received a Thoratec paracorporeal ventricular assist device (Thoratec Corp, Pleasanton, Calif) via ventriculo-aortic cannulation. Left ventricular pressure and volume, aortic pressure, pulmonary flow, pump chamber pressure, and pump inflow and outflow were recorded. The pump was driven by a clinical pneumatic drive unit (Medos Medizintechnik AG, Stolberg, Germany) synchronously with the native R-wave. The start of pump ejection was delayed between 0% and 100% of the cardiac period in 10% increments. For each of these delays, hemodynamic variables were compared with baseline data using paired t tests. RESULTS: The location of the minimum of stroke work was observed at a delay of 10% (soon after aortic valve opening), resulting in a median of 43% reduction in stroke work compared with baseline. Maximum stroke work occurred at a median delay of 70% with a median stroke work increase of 11% above baseline. Left ventricular volume unloading expressed by end-diastolic volume was most pronounced for copulsation (delay 0%). CONCLUSIONS: The timing of pump ejection in synchronized mode yields control over left ventricular energetics and can be a method to achieve gradual reloading of a recoverable left ventricle. The traditionally suggested counterpulsation is not optimal in ventriculo-aortic cannulation when maximum unloading is desired.

Time to admission in acute ischemic stroke and transient ischemic attack

BACKGROUND AND PURPOSE: The effect of thrombolysis depends on the time from stroke onset to treatment and therefore also on the time when patients come to the hospital. This study was designed to analyze the variables that influence the time from symptom onset to admission (TTA) to the stroke unit. METHODS: We evaluated the medical records of 615 consecutive stroke or transient ischemic attack (TIA) patients admitted to our neurological department within 48 hours after symptom onset. RESULTS: The median TTA was 180 minutes. Referral by emergency medical services (EMS; P<0.001), high National Institutes of Health Stroke Scale (NIHSS) scores (P<0.001), strokes in the carotid territory (P<0.001), and strokes not attributable to small vessel disease (P<0.001) were associated with shorter prehospital delays. The TTA was adjusted for travel times (adjTTA), and all these variables remained significantly associated with time to admission. In addition, patients with previous experience with stroke or TIA had longer adjTTA (P=0.028). Regression analysis confirmed the independent association between referral by EMS (P=0.010), high NIHSS scores (P<0.001), carotid territory stroke (P<0.001), and first-ever cerebrovascular event (P=0.022) with shorter adjTTA. CONCLUSIONS: Factors such as NIHSS scores and stroke location influence the time to admission but, unlike referral pathways, cannot be modified. Educational programs and stroke campaigns should therefore not only teach typical and less common stroke symptoms and signs but also that EMS provides the fastest means of transportation to a stroke unit and the best chances to get treatment early.

Nerve excitability changes in critical illness polyneuropathy

Patients in intensive care units frequently suffer muscle weakness and atrophy due to critical illness polyneuropathy (CIP), an axonal neuropathy associated with systemic inflammatory response syndrome and multiple organ failure. CIP is a frequent and serious complication of intensive care that delays weaning from mechanical ventilation and increases mortality. The pathogenesis of CIP is not well understood and no specific therapy is available. The aim of this project was to use nerve excitability testing to investigate the changes in axonal membrane properties occurring in CIP. Ten patients (aged 37-76 years; 7 males, 3 females) were studied with electrophysiologically proven CIP. The median nerve was stimulated at the wrist and compound action potentials were recorded from abductor pollicis brevis muscle. Strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle (refractoriness, superexcitability and late subexcitability) were recorded using a recently described protocol. In eight patients a follow-up investigation was performed. All patients underwent clinical examination and laboratory investigations. Compared with age-matched normal controls (20 subjects; aged 38-79 years; 7 males, 13 females), CIP patients exhibited reduced superexcitability at 7 ms, from -22.3 +/- 1.6% to -7.6 +/- 3.1% (mean +/- SE, P approximately 0.0001) and increased accommodation to depolarizing (P < 0.01) and hyperpolarizing currents (P < 0.01), indicating membrane depolarization. Superexcitability was reduced both in patients with renal failure and without renal failure. In the former, superexcitability correlated with serum potassium (R = 0.88), and late subexcitability was also reduced (as also occurs owing to hyperkalaemia in patients with chronic renal failure). In patients without renal failure, late subexcitability was normal, and the signs of membrane depolarization correlated with raised serum bicarbonate and base excess, indicating compensated respiratory acidosis. It is inferred that motor axons in these CIP patients are depolarized, in part because of raised extracellular potassium, and in part because of hypoperfusion. The chronic membrane depolarization may contribute to the development of neuropathy.

Help-seeking pathways in early psychosis

INTRODUCTION: Understanding the help-seeking pathways of patients with a putative risk of developing psychosis helps improving development of specialised care services. This study aimed at obtaining information about: type of health professionals contacted by patients at putative risk for psychosis on their help-seeking pathways; number of contacts; type of symptoms leading to contacts with health professionals; interval between initial contact and referral to a specialised outpatient service. METHOD: The help-seeking pathways were assessed as part of a prospective study in 104 patients with suspected at-risk states for psychosis. RESULTS: The mean number of contacts prior to referral was 2.38. Patients with psychotic symptoms more often contacted mental health professionals, whereas patients with insidious and more unspecific features more frequently contacted general practitioners (GPs). CONCLUSIONS: GPs have been found to under-identify the insidious features of emerging psychosis (Simon et al. (2005) Br J Psychiatry 187:274-281). The fact that they were most often contacted by patients with exactly these features calls for focussed and specialised help for primary care physicians. Thus, delays along the help-seeking pathways may be shortened. This may be of particular relevance for patients with the deficit syndrome of schizophrenia.

Point Process Methodology for On-line Spatio-temporal Disease Surveillance

The AEGISS (Ascertainment and Enhancement of Gastrointestinal Infection Surveillance and Statistics) project aims to use spatio-temporal statistical methods to identify anomalies in the space-time distribution of non-specific, gastrointestinal infections in the UK, using the Southampton area in southern England as a test-case. In this paper, we use the AEGISS project to illustrate how spatio-temporal point process methodology can be used in the development of a rapid-response, spatial surveillance system. Current surveillance of gastroenteric disease in the UK relies on general practitioners reporting cases of suspected food-poisoning through a statutory notification scheme, voluntary laboratory reports of the isolation of gastrointestinal pathogens and standard reports of general outbreaks of infectious intestinal disease by public health and environmental health authorities. However, most statutory notifications are made only after a laboratory reports the isolation of a gastrointestinal pathogen. As a result, detection is delayed and the ability to react to an emerging outbreak is reduced. For more detailed discussion, see Diggle et al. (2003). A new and potentially valuable source of data on the incidence of non-specific gastro-enteric infections in the UK is NHS Direct, a 24-hour phone-in clinical advice service. NHS Direct data are less likely than reports by general practitioners to suffer from spatially and temporally localized inconsistencies in reporting rates. Also, reporting delays by patients are likely to be reduced, as no appointments are needed. Against this, NHS Direct data sacrifice specificity. Each call to NHS Direct is classified only according to the general pattern of reported symptoms (Cooper et al, 2003). The current paper focuses on the use of spatio-temporal statistical analysis for early detection of unexplained variation in the spatio-temporal incidence of non-specific gastroenteric symptoms, as reported to NHS Direct. Section 2 describes our statistical formulation of this problem, the nature of the available data and our approach to predictive inference. Section 3 describes the stochastic model. Section 4 gives the results of fitting the model to NHS Direct data. Section 5 shows how the model is used for spatio-temporal prediction. The paper concludes with a short discussion.

Low awareness of transient ischemic attacks and risk factors of stroke in a Swiss urban community

BACKGROUND AND PURPOSE: Time delays from stroke onset to arrival at the hospital are the main obstacles for widespread use of thrombolysis. In order to decrease the delays, educational campaigns try to inform the general public how to act optimally in case of stroke. To determine the content of such a campaign, we assessed the stroke knowledge in our population. METHODS: The stroke knowledge was studied by means of a closed-ended questionnaire. 422 randomly chosen inhabitants of Bern, Switzerland, were interviewed. RESULTS: The knowledge of stroke warning signs (WS) was classified as good in 64.7%. A good knowledge of stroke risk factors (RF) was noted in 6.4%. 4.2% knew both the WS and the RF of stroke indicating a very good global knowledge of stroke. Only 8.3% recognized TIA as symptoms of stroke resolving within 24 hours, and only 2.8% identified TIA as a disease requiring immediate medical help. In multivariate analysis being a woman, advancing age, and having an afflicted relative were associated with a good knowledge of WS (p = 0.048, p < 0.001 and p = 0.043). Good knowledge of RF was related to university education (p < 0.001). The good knowledge of TIA did not depend on age, sex, level of education or having an afflicted relative. CONCLUSIONS: The study brings to light relevant deficits of stroke knowledge in our population. A small number of participants could recognize TIA as stroke related symptoms resolving completely within 24 hours. Only a third of the surveyed persons would seek immediate medical help in case of TIA. The information obtained will be used in the development of future educational campaigns.

Non-invasive neurally adjusted ventilatory assist in rabbits with acute lung injury

OBJECTIVE: Neurally adjusted ventilatory assist uses the electrical activity of the diaphragm (EAdi)-a pneumatically-independent signal-to control the timing and pressure of the ventilation delivered, and should not be affected by leaks. The aim of this study was to evaluate whether NAVA can deliver assist in synchrony and proportionally to EAdi after extubation, with a leaky non-invasive interface. DESIGN AND SETTING: Prospective, controlled experimental study in an animal laboratory. ANIMALS: Ten rabbits, anesthetized, mechanically ventilated. INTERVENTIONS: Following lung injury, the following was performed in sequential order: (1) NAVA delivered via oral endotracheal tube with PEEP; (2) same as (1) without PEEP; (3) non-invasive NAVA at unchanged NAVA level and no PEEP via a single nasal prong; (4) no assist; (5) non-invasive NAVA at progressively increasing NAVA levels. MEASUREMENTS AND RESULTS: EAdi, esophageal pressure, blood gases and hemodynamics were measured during each condition. For the same NAVA level, the mean delivered pressure above PEEP increased from 3.9[Symbol: see text]+/-[Symbol: see text]1.4[Symbol: see text]cmH(2)O (intubated) to 7.5[Symbol: see text]+/-[Symbol: see text]3.8[Symbol: see text]cmH(2)O (non-invasive) (p[Symbol: see text]<[Symbol: see text]0.05) because of increased EAdi. No changes were observed in PaO(2) and PaCO(2). Increasing the NAVA level fourfold during non-invasive NAVA restored EAdi and esophageal pressure swings to pre-extubation levels. Triggering (106[Symbol: see text]+/-[Symbol: see text]20[Symbol: see text]ms) and cycling-off delays (40[Symbol: see text]+/-[Symbol: see text]21[Symbol: see text]ms) during intubation were minimal and not worsened by the leak (95[Symbol: see text]+/-[Symbol: see text]13[Symbol: see text]ms and 33[Symbol: see text]+/-[Symbol: see text]9[Symbol: see text]ms, respectively). CONCLUSION: NAVA can be effective in delivering non-invasive ventilation even when the interface with the patient is excessively leaky, and can unload the respiratory muscles while maintaining synchrony with the subject's demand.

Investigating the effect of construction management strategies on project greenhouse gas emissions using interactive simulation

The challenges posed by global climate change are motivating the investigation of strategies that can reduce the life cycle greenhouse gas (GHG) emissions of products and processes. While new construction materials and technologies have received significant attention, there has been limited emphasis on understanding how construction processes can be best managed to reduce GHG emissions. Unexpected disruptive events tend to adversely impact construction costs and delay project completion. They also tend to increase project GHG emissions. The objective of this paper is to investigate ways in which project GHG emissions can be reduced by appropriate management of disruptive events. First, an empirical analysis of construction data from a specific highway construction project is used to illustrate the impact of unexpected schedule delays in increasing project GHG emissions. Next, a simulation based methodology is described to assess the effectiveness of alternative project management strategies in reducing GHG emissions. The contribution of this paper is that it explicitly considers projects emissions, in addition to cost and project duration, in developing project management strategies. Practical application of the method discussed in this paper will help construction firms reduce their project emissions through strategic project management, and without significant investment in new technology. In effect, this paper lays the foundation for best practices in construction management that will optimize project cost and duration, while minimizing GHG emissions.

Meta-analysis in medical research: potentials and limitations

Meta-analysis, the statistical combination of results from several studies to produce a single estimate of a treatment effect or size of an association, continues to attract controversy. We illustrate and discuss the promises and limitations of meta-analysis. Meta-analysis of clinical trials can prevent delays in the introduction of effective treatments or lead to the timely identification of adverse effects. However, meta-analyses are liable to numerous biases, both at the level of the individual study and the selection of studies for inclusion in meta-analysis. The biases and confounding factors that threaten the validity of individual studies will also affect meta-analyses of observational studies. We argue that meta-analyses should only be performed within the framework of systematic reviews that have been prepared using methods that minimize bias and address the combinability of studies.

Subject-ventilator synchrony during neural versus pneumatically triggered non-invasive helmet ventilation

OBJECTIVE: Patient-ventilator synchrony during non-invasive pressure support ventilation with the helmet device is often compromised when conventional pneumatic triggering and cycling-off were used. A possible solution to this shortcoming is to replace the pneumatic triggering with neural triggering and cycling-off-using the diaphragm electrical activity (EA(di)). This signal is insensitive to leaks and to the compliance of the ventilator circuit. DESIGN: Randomized, single-blinded, experimental study. SETTING: University Hospital. PARTICIPANTS AND SUBJECTS: Seven healthy human volunteers. INTERVENTIONS: Pneumatic triggering and cycling-off were compared to neural triggering and cycling-off during NIV delivered with the helmet. MEASUREMENTS AND RESULTS: Triggering and cycling-off delays, wasted efforts, and breathing comfort were determined during restricted breathing efforts (<20% of voluntary maximum EA(di)) with various combinations of pressure support (PSV) (5, 10, 20 cm H(2)O) and respiratory rates (10, 20, 30 breath/min). During pneumatic triggering and cycling-off, the subject-ventilator synchrony was progressively more impaired with increasing respiratory rate and levels of PSV (p < 0.001). During neural triggering and cycling-off, effect of increasing respiratory rate and levels of PSV on subject-ventilator synchrony was minimal. Breathing comfort was higher during neural triggering than during pneumatic triggering (p < 0.001). CONCLUSIONS: The present study demonstrates in healthy subjects that subject-ventilator synchrony, trigger effort, and breathing comfort with a helmet interface are considerably less impaired during increasing levels of PSV and respiratory rates with neural triggering and cycling-off, compared to conventional pneumatic triggering and cycling-off.

Control of recycle processes using neural networks combined with PID controller

This thesis is focused on the control of a system with recycle. A new control strategy using neural network combined with PID controller was proposed. The combined controller was studied and tested on the pressure control of a vaporizer inside a para-xylene production process. The major problems are the negative effects of recycle and the delays on instability and performance. The neural network was designed to move the process close to the set points while the PID accomplishes the finer level of disturbance rejection and offset reductions. Our simulation results show that during control, the neural network was able to determine the nonlinear relationship between steady state and manipulated variables. The results also show the disturbance rejection was handled by PID controller effectively.

TIME LAPSE SEISMIC OBSERVATIONS AND EFFECTS OF RESERVOIR COMPRESSIBILITY AT TEAL SOUTH OIL FIELD

One of the original ocean-bottom time-lapse seismic studies was performed at the Teal South oil field in the Gulf of Mexico during the late 1990’s. This work reexamines some aspects of previous work using modern analysis techniques to provide improved quantitative interpretations. Using three-dimensional volume visualization of legacy data and the two phases of post-production time-lapse data, I provide additional insight into the fluid migration pathways and the pressure communication between different reservoirs, separated by faults. This work supports a conclusion from previous studies that production from one reservoir caused regional pressure decline that in turn resulted in liberation of gas from multiple surrounding unproduced reservoirs. I also provide an explanation for unusual time-lapse changes in amplitude-versus-offset (AVO) data related to the compaction of the producing reservoir which, in turn, changed an isotropic medium to an anisotropic medium. In the first part of this work, I examine regional changes in seismic response due to the production of oil and gas from one reservoir. The previous studies primarily used two post-production ocean-bottom surveys (Phase I and Phase II), and not the legacy streamer data, due to the unavailability of legacy prestack data and very different acquisition parameters. In order to incorporate the legacy data in the present study, all three poststack data sets were cross-equalized and examined using instantaneous amplitude and energy volumes. This approach appears quite effective and helps to suppress changes unrelated to production while emphasizing those large-amplitude changes that are related to production in this noisy (by current standards) suite of data. I examine the multiple data sets first by using the instantaneous amplitude and energy attributes, and then also examine specific apparent time-lapse changes through direct comparisons of seismic traces. In so doing, I identify time-delays that, when corrected for, indicate water encroachment at the base of the producing reservoir. I also identify specific sites of leakage from various unproduced reservoirs, the result of regional pressure blowdown as explained in previous studies; those earlier studies, however, were unable to identify direct evidence of fluid movement. Of particular interest is the identification of one site where oil apparently leaked from one reservoir into a “new” reservoir that did not originally contain oil, but was ideally suited as a trap for fluids leaking from the neighboring spill-point. With continued pressure drop, oil in the new reservoir increased as more oil entered into the reservoir and expanded, liberating gas from solution. Because of the limited volume available for oil and gas in that temporary trap, oil and gas also escaped from it into the surrounding formation. I also note that some of the reservoirs demonstrate time-lapse changes only in the “gas cap” and not in the oil zone, even though gas must be coming out of solution everywhere in the reservoir. This is explained by interplay between pore-fluid modulus reduction by gas saturation decrease and dry-frame modulus increase by frame stiffening. In the second part of this work, I examine various rock-physics models in an attempt to quantitatively account for frame-stiffening that results from reduced pore-fluid pressure in the producing reservoir, searching for a model that would predict the unusual AVO features observed in the time-lapse prestack and stacked data at Teal South. While several rock-physics models are successful at predicting the time-lapse response for initial production, most fail to match the observations for continued production between Phase I and Phase II. Because the reservoir was initially overpressured and unconsolidated, reservoir compaction was likely significant, and is probably accomplished largely by uniaxial strain in the vertical direction; this implies that an anisotropic model may be required. Using Walton’s model for anisotropic unconsolidated sand, I successfully model the time-lapse changes for all phases of production. This observation may be of interest for application to other unconsolidated overpressured reservoirs under production.

Information processing in long delay memory-guided saccades: further insights from TMS

The performance of memory-guided saccades with two different delays (3 s and 30 s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delays.

Time-dependent hierarchical organization of spatial working memory: a transcranial magnetic stimulation study

The performance of memory-guided saccades with two different delays (3 and 30 s of memorization) was studied in seven healthy subjects. Double-pulse transcranial magnetic stimulation (dTMS) with an interstimulus interval of 100 ms was applied over the right dorsolateral prefrontal cortex (DLPFC) early (1 s after target presentation) and late (28 s after target presentation). Early stimulation significantly increased in both delays the percentage of error in amplitude (PEA) of contralateral memory-guided saccades compared to the control experiment without stimulation. dTMS applied late in the delay had no significant effect on PEA. Furthermore, we found a significantly smaller effect of early stimulation in the long-delay paradigm. These results suggest a time-dependent hierarchical organization of the spatial working memory with a functional dominance of DLPFC during the early memorization, independent from the memorization delay. For a long memorization delay, however, working memory seems to have an additional, DLPFC-independent component.

The systemic angiogenic response during bone healing

INTRODUCTION: Angiogenesis is known to be a critical and closely regulated step during bone formation and fracture healing driven by a complex interaction of various cytokines. Delays in bone healing or even nonunion might therefore be associated with altered concentrations of specific angiogenic factors. These alterations might in turn be reflected by changes in serum concentrations. METHOD: To determine physiological time courses of angiogenic cytokines during fracture healing as well as possible changes associated with failed consolidation, we prospectively collected serum samples from patients who had sustained surgical treatment for a long bone fracture. Fifteen patients without fracture healing 4 months after surgery (nonunion group) were matched to a collective of 15 patients with successful healing (union group). Serum concentrations of angiogenin (ANG), angiopoietin 2 (Ang-2), basic fibroblast growth factor (bFGF), platelet derived growth factor AB (PDGF-AB), pleiotrophin (PTN) and vascular endothelial growth factor (VEGF) were measured using enzyme linked immunosorbent assays over a period of 24 weeks. RESULTS: Compared to reference values of healthy uninjured controls serum concentrations of VEGF, bFGF and PDGF were increased in both groups. Peak concentrations of these cytokines were reached during early fracture healing. Serum concentrations of bFGF and PDGF-AB were significantly higher in the union group at 2 and 4 weeks after the injury when compared to the nonunion group. Serum concentrations of ANG and Ang-2 declined steadily from the first measurement in normal healing fractures, while no significant changes over time could be detected for serum concentrations of these factures in nonunion patients. PTN serum levels increased asymptotically over the entire investigation in timely fracture healing while no such increase could be detected during delayed healing. CONCLUSION: We conclude that fracture healing in human subjects is accompanied by distinct changes in systemic levels of specific angiogenic factors. Significant alterations of these physiologic changes in patients developing a fracture nonunion over time could be detected as early as 2 (bFGF) and 4 weeks (PDGF-AB) after initial trauma surgery.