Forewarning of hypotensive events using a Bayesian artificial neural network in neurocritical care.

Traumatically brain injured (TBI) patients are at risk from secondary insults. Arterial hypotension, critically low blood pressure, is one of the most dangerous secondary insults and is related to poor outcome in patients. The overall aim of this study was to get proof of the concept that advanced statistical techniques (machine learning) are methods that are able to provide early warning of impending hypotensive events before they occur during neuro-critical care. A Bayesian artificial neural network (BANN) model predicting episodes of hypotension was developed using data from 104 patients selected from the BrainIT multi-center database. Arterial hypotension events were recorded and defined using the Edinburgh University Secondary Insult Grades (EUSIG) physiological adverse event scoring system. The BANN was trained on a random selection of 50% of the available patients (n = 52) and validated on the remaining cohort. A multi-center prospective pilot study (Phase 1, n = 30) was then conducted with the system running live in the clinical environment, followed by a second validation pilot study (Phase 2, n = 49). From these prospectively collected data, a final evaluation study was done on 69 of these patients with 10 patients excluded from the Phase 2 study because of insufficient or invalid data. Each data collection phase was a prospective non-interventional observational study conducted in a live clinical setting to test the data collection systems and the model performance. No prediction information was available to the clinical teams during a patient's stay in the ICU. The final cohort (n = 69), using a decision threshold of 0.4, and including false positive checks, gave a sensitivity of 39.3% (95% CI 32.9-46.1) and a specificity of 91.5% (95% CI 89.0-93.7). Using a decision threshold of 0.3, and false positive correction, gave a sensitivity of 46.6% (95% CI 40.1-53.2) and specificity of 85.6% (95% CI 82.3-88.8). With a decision threshold of 0.3, > 15 min warning of patient instability can be achieved. We have shown, using advanced machine learning techniques running in a live neuro-critical care environment, that it would be possible to give neurointensive teams early warning of potential hypotensive events before they emerge, allowing closer monitoring and earlier clinical assessment in an attempt to prevent the onset of hypotension. The multi-centre clinical infrastructure developed to support the clinical studies provides a solid base for further collaborative research on data quality, false positive correction and the display of early warning data in a clinical setting.

KidsBrainIT: A New Multi-centre, Multi-disciplinary, Multi-national Paediatric Brain Monitoring Collaboration.

OBJECTIVES: Validated optimal cerebral perfusion pressure (CPP) treatment thresholds in children do not exist. To improve the intensive care unit (ICU) management of the paediatric traumatic brain injury (TBI) population, we are forming a new paediatric multi-centre collaboration to recruit standardised ICU data for running and reporting upon models for assessing autoregulation and optimal CCP (CPPopt). MATERIALS AND METHODS: We are adapting the adult BrainIT group's approach to develop a new Paediatric Brain Monitoring and Information Technology Group (KidsBrainIT), which will include a repository to store prospectively collected high-resolution physiological, clinical, and outcome data. In the first phase of this project there are 7 UK Paediatric Intensive Care Units, 1 Spanish, 1 Belgium, and 1 Romanian Centre interested in participating. In subsequent phases, we plan to open recruitment to other centres both within Europe, US and abroad. We are collaborating with the Leuven Group and plan to use their LAx (low-frequency autoregulation index), DATACAR (dynamic adaptive target of active cerebral autoregulation), CPPopt and visualisation methodologies. We also plan to use the continuous diffuse optical monitoring and tomography technology developed in Barcelona as an acute surrogate end-point for optimising brain perfusion. This technology allows non-invasive continuous monitoring of deep tissue perfusion and oxygenation in adults but its clinical application in infants and children with TBI has not been studied previously. RESULTS: We report on the current status of setting up this new collaboration and also on pilot analyses in two centres which are the basis of our rationale for the need for a prospective validation study of CPPopt in children. Specifically, we demonstrated that CPPopt varied with time for each patient during their paediatric intensive care unit (PICU) stay, and the median overall CPPopt levels for children aged 2-6 years, 7-11 years and 12-16 years were 68.83, 68.09, and 72.17 mmHg respectively. Among survivors and patients with favourable outcome (GOS 4 and 5), there were significantly higher proportions with CPP monitoring time within CPPopt (p = 0.04 and p = 0.01 respectively). CONCLUSIONS: There is a need and an interest in forming a multi-centre PICU collaboration for acquiring data and performing analyses for determining validated CPPopt thresholds in the paediatric TBI population. KidsBrainIT is being formed to meet that need.

Plasticity, elasticity, and adhesion energy of plant cell walls: nanometrology of lignin loss using atomic force microscopy.

The complex organic polymer, lignin, abundant in plants, prevents the efficient extraction of sugars from the cell walls that is required for large scale biofuel production. Because lignin removal is crucial in overcoming this challenge, the question of how the nanoscale properties of the plant cell ultrastructure correlate with delignification processes is important. Here, we report how distinct molecular domains can be identified and how physical quantities of adhesion energy, elasticity, and plasticity undergo changes, and whether such quantitative observations can be used to characterize delignification. By chemically processing biomass, and employing nanometrology, the various stages of lignin removal are shown to be distinguished through the observed morphochemical and nanomechanical variations. Such spatially resolved correlations between chemistry and nanomechanics during deconstruction not only provide a better understanding of the cell wall architecture but also is vital for devising optimum chemical treatments.

Literature review and meta-analysis of translaminar pressure difference in open-angle glaucoma.

There is increasing evidence in the literature regarding translaminar pressure difference's (TPD) role in the pathophysiology of glaucoma. The optic nerve is exposed not only to intraocular pressure in the eye, but also to intracranial pressure (ICP), as it is surrounded by cerebrospinal fluid in the subarachnoid space. Although pilot studies have identified the potential importance of TPD in glaucoma, limited available data currently prevent a comprehensive description of the role that TPD may have in glaucomatous pathophysiology. In this review, we present all available qualified data from a systematic review of the literature of the role of TPD in open-angle glaucoma (OAG). PubMed (Medline), OVID Medline, ScienceDirect, SpringerLink, and all available library databases were reviewed and subsequent meta-analysis of pooled mean differences are presented where appropriate. Five papers including 396 patients met criteria for inclusion to the analysis. Importantly, we included all observational studies despite differences in ICP measurement methods, as there is no consensus regarding best-practice ICP measurements in glaucoma. Our results show that not only TPD is higher in glaucoma patients compared with healthy subjects, it is related to structural glaucomatous changes of the optic disc. Our analysis suggests further longitudinal prospective studies are needed to investigate the influence of TPD in OAG, with a goal of overcoming methodological weaknesses of previous studies.

Effects of feeding fiber-fermenting bacteria to pigs on nutrient digestion, fecal output, and plasma energy metabolites.

Inclusion of feedstuffs with higher plant cell wall (fiber) content in swine diets has increased in recent years due to greater availability and lower cost, especially coproduct feeds, such as corn distillers dried grains with soluble (DDGS). Limitations of feeding higher fiber diets include increased fecal output, which can exceed manure storage volumes, and decreased energy density, which can decrease growth performance; dietary treatments that ameliorate these limitations would benefit pork producers. Grower pigs (n = 48; 61.1 kg initial BW) were used to establish the effects of supplementation of fiber-fermenting bacteria in a 2 × 4 factorial, consisting of 2 diets (standard and high fiber) and 4 bacterial treatments (A, no bacteria; and B, C, and D bacterial supplements). Increased fiber came from inclusion of soybean hulls (10%) and corn DDGS (20%) in the diet. The 3 bacterial supplements (all Bacteroides strains) were isolated from fecal enrichment cultures and selected for their fiber-fermenting capacity. The high fiber diet increased fecal output, blood cholesterol, and triglyceride concentrations, and digestibility of NDF, ADF, and S; CP digestibility decreased (P ≤ 0.10). The improved fiber digestibility and altered energy status of pigs fed the high fiber diet was primarily due to fermentation of soybean hulls, resulting in increased short-chain fatty acid production and absorption, and decreased dietary starch content. Overall, pigs fed the bacterial treatments had only increased blood cholesterol concentrations (P = 0.10). When individual bacterial treatments were compared, pigs fed Bacteria B had decreased fecal output (P ≤ 0.10) and both blood glucose and cholesterol concentrations were increased (P ≤ 0.10) compared with the other 3 treatments, indicating an improved energy status. Pigs fed Bacteria B increased both CP and ADF (P ≤ 0.10), and tended (P = 0.16) to have increased NDF digestibilities compared with pigs fed no bacteria (Treatment A), whereas pigs fed the other 2 bacterial treatments did not differ from pigs fed Bacteria B for nutrient digestibility. Both had similar fecal outputs to pigs fed no bacteria. This is the first report of reduction in fecal output and increased fiber digestibility with pigs fed live bacteria. Successful application of this bacterial treatment could result in improved pig performance and decreased manure volumes, both of which would improve profitability of producers.

Clinical assessment of noninvasive intracranial pressure absolute value measurement method.

OBJECTIVE: To assess prospectively the accuracy and precision of a method for noninvasive intracranial pressure (ICP) measurement compared with invasive gold standard CSF pressure measurement. METHODS: Included were 62 neurologic patients (37 idiopathic intracranial hypertension, 20 multiple sclerosis, 1 Guillain-Barré syndrome, 1 polyneuropathy, and 3 hydrocephalus). The average age was 40 ± 12 years. All patients had lumbar puncture indicated as a diagnostic procedure. ICP was measured using a noninvasive ICP measurement method, which is based on a two-depth high-resolution transcranial Doppler insonation of the ophthalmic artery (OA). The OA is being used as a natural pair of scales, in which the intracranial segment of the OA is compressed by ICP and the extracranial segment of the OA is compressed by extracranial pressure (Pe) applied to the orbit. The blood flow parameters in both OA segments are approximately the same in the scales balance case when Pe = ICP. All patients had simultaneous recording of noninvasive ICP values and invasive gold standard CSF pressure values. RESULTS: Analysis of the 72 simultaneous paired recordings of noninvasive ICP and the gold standard CSF pressure showed good accuracy for the noninvasive method as indicated by the low mean systematic error (0.12 mm Hg; confidence level [CL] 0.98). The method also showed high precision as indicated by the low SD of the paired recordings (2.19 mm Hg; CL 0.98). The method does not need calibration. CONCLUSION: The proposed noninvasive ICP measurement method is precise and accurate compared with gold standard CSF pressure measured via lumbar puncture.

Early warning of EUSIG-defined hypotensive events using a Bayesian Artificial Neural Network.

BACKGROUND: Hypotension is recognized as a potentially damaging secondary insult after traumatic brain injury. Systems to give clinical teams some early warning of likely hypotensive instability could be added to the range of existing techniques used in the management of this group of patients. By using the Edinburgh University Secondary Insult Grades (EUSIG) definitions for -hypotension (systolic arterial pressure <90 mmHg OR mean arterial -pressure <70 mmHg) we collected a group of ∼2,000 events by analyzing the Brain-IT database. We then constructed a Bayesian Artificial Neural Network (an advanced statistical modeling technique) that is able to provide some early warning when trained on this previously collected demographic and physiological data. MATERIALS AND METHODS: Using EUSIG defined event data from the Brain-IT database, we identified a Bayesian artificial neural network (BANN) topology and constructed a series of datasets using a group of clinically guided input variables. This allowed us to train a BANN, which was then tested on an unseen set of patients from the Brain-IT database. The initial tests used a particularly harsh assessment criterion whereby a true positive prediction was only allowed if the BANN predicted an upcoming event to the exact minute. We have now developed the system to the point where it is about to be used in a two-stage Phase II clinical trial and we are also researching a more realistic assessment technique. KEY RESULTS: We have constructed a BANN that is able to provide early warning to the clinicians based on a model that uses information from the physiological inputs; systolic and mean arterial pressure and heart rate; and demographic variables age and gender. We use 15-min SubWindows starting at 15 and 30 min before an event and process mean, slope and standard deviations. Based on 10 simulation runs, our current sensitivity is 36.25% (SE 1.31) with a specificity of 90.82% (SE 0.85). Initial results from a Phase I clinical study shows a model sensitivity of 40.95% (SE 6%) and specificity of 86.46% (SE 3%) Although this figure is low it is considered clinically useful for this dangerous condition, provided the false positive rate can be kept sufficiently low as to be practical in an intensive care environment. CONCLUSION: We have shown that using advanced statistical modeling techniques can provide clinical teams with useful information that will assist clinical care.

Trigger characteristics of EUSIG-defined hypotensive events.

BACKGROUND: Hypotension is a recognized -secondary insult after traumatic brain injury (TBI). There are many definitions of hypotension, an often cited example being the Brain Trauma Foundation's current (2007) "Guidelines for the Management of Severe Traumatic Brain Injury," which defines hypotension as systolic pressure <90 mmHg. However, this same document declares "The importance of mean arterial pressure, as opposed to systolic pressure should also be stressed, …." Our work shows that when using the Edinburgh University Secondary Insult Grades (EUSIG) definitions, which require monitoring of both systolic and mean arterial pressures, that most hypotensive events are in fact triggered by a breach of the mean arterial level of 70 mmHg. We suggest that close monitoring of mean arterial pressure would enable clinical teams to avoid more potentially damaging hypotensive events. MATERIALS AND METHODS: An analysis of 100 patients from the Brain-IT database was performed. Using the EUSIG definitions, 2,081 events can be obtained by analyzing the systolic and mean blood pressures on a minute by minute basis. A software program was written to identify and classify the trigger pattern for each event. A categorical analysis of these triggering patterns has been carried out. KEY RESULTS: Our analysis shows that most events are triggered by a drop in mean arterial pressure. In fact a large number of events (91%) occur where the mean arterial pressure is below the threshold limits whereas the systolic pressure does not cross the 90 mmHg limit at all. CONCLUSION: We suggest that more emphasis should be placed on closely monitoring mean arterial pressure as well as systolic pressure when trying to guard against hypotensive problems in traumatically brain injured patients. In future work we will study the underlying physiological mechanisms and attempt to further classify concomitant conditions that may be contributing to the onset of a hypotensive event.

Nanometrology of delignified Populus using mode synthesizing atomic force microscopy.

The study of the spatially resolved physical and compositional properties of materials at the nanoscale is increasingly challenging due to the level of complexity of biological specimens such as those of interest in bioenergy production. Mode synthesizing atomic force microscopy (MSAFM) has emerged as a promising metrology tool for such studies. It is shown that, by tuning the mechanical excitation of the probe-sample system, MSAFM can be used to dynamically investigate the multifaceted complexity of plant cells. The results are argued to be of importance both for the characteristics of the invoked synthesized modes and for accessing new features of the samples. As a specific system to investigate, we present images of Populus, before and after a holopulping treatment, a crucial step in the biomass delignification process.

The use of hyperventilation therapy after traumatic brain injury in Europe: an analysis of the BrainIT database.

OBJECTIVE: To assess the use of hyperventilation and the adherence to Brain Trauma Foundation-Guidelines (BTF-G) after traumatic brain injury (TBI). SETTING: Twenty-two European centers are participating in the BrainIT initiative. DESIGN: Retrospective analysis of monitoring data. PATIENTS AND PARTICIPANTS: One hundred and fifty-one patients with a known time of trauma and at least one recorded arterial blood-gas (ABG) analysis. MEASUREMENTS AND RESULTS: A total number of 7,703 ABGs, representing 2,269 ventilation episodes (VE) were included in the analysis. Related minute-by-minute ICP data were taken from a 30 min time window around each ABG collection. Data are given as mean with standard deviation. (1) Patients without elevated intracranial pressure (ICP) (< 20 mmHg) manifested a statistically significant higher P(a)CO(2) (36 +/- 5.7 mmHg) in comparison to patients with elevated ICP (> or = 20 mmHg; P(a)CO(2): 34 +/- 5.4 mmHg, P < 0.001). (2) Intensified forced hyperventilation (P(a)CO(2) < or = 25 mmHg) in the absence of elevated ICP was found in only 49 VE (2%). (3) Early prophylactic hyperventilation (< 24 h after TBI; P(a)CO(2) < or = 35 mmHg, ICP < 20 mmHg) was used in 1,224 VE (54%). (4) During forced hyperventilation (P(a)CO(2) < or = 30 mmHg), simultaneous monitoring of brain tissue pO(2) or S(jv)O(2) was used in only 204 VE (9%). CONCLUSION: While overall adherence to current BTF-G seems to be the rule, its recommendations on early prophylactic hyperventilation as well as the use of additional cerebral oxygenation monitoring during forced hyperventilation are not followed in this sample of European TBI centers. DESCRIPTOR: Neurotrauma.

Production of ethanol from carbohydrates from loblolly pine: a technical and economic assessment.

Ethanol from lignocellulosic biomass has the potential to contribute substantially to bioethanol for transportation. We have evaluated the technical and economic feasibility of producing ethanol from the carbohydrates in loblolly pine. In the process evaluated, prehydrolysis with dilute sulfuric acid was employed to hydrolyze hemicellulose and make the cellulose more accessible to hydrolysis by enzymes. Residual biomass from hydrolysis and extraction of carbohydrates was burned in a CHP plant to generate power and process steam. Our analysis indicates that ethanol can be produced at a cost of dollars 1.53/gal, based on a delivered wood cost of $63.80/dry metric ton and 75% conversion of the carbohydrates in wood to sugars for ethanol production. Improving the conversion of wood carbohydrates to sugars to 95% would reduce the production cost to dollars 1.29/gal. These values are for a plant producing 74 million gal/yr and 93 million gal/yr, respectively. At current feedstock prices, ethanol produced from loblolly pine would be competitive with ethanol produced from corn or other lignocellulosic biomass. Based on our analysis, discounted cash flow rates of return would be 18% and 25%, respectively for plants of this capacity.

Clinical study of craniospinal compliance non-invasive monitoring method.

BACKGROUND: The ability to quantify non-invasively the effect of posture on intracranial physiology by using cine phase-contrast MRI may lead to the development of new diagnostic tests to evaluate such functions as regulation of CBF and ICP, and the effect of pathologies on these functions. METHODS: Results similar to MRI technology can be obtained using non-invasive ultrasonic method (Vittamed) for intracranial blood volume pulse wave (IBVPW) measurement and intracraniospinal compliance (ICC) monitoring. FINDINGS: IBVPW have been investigated in supine and upright positions of healthy volunteers using Vittamed technology. A group of 13 healthy volunteers (nine females, four males, mean age 25.1 +/- 3.4) was studied. More than 3,000 IBVPW were analysed in order to show the difference of shape and amplitude in supine and upright positions. Averaged shape of ten IBVPW waves was presented in the normalized window with dimensions 1.0 x 1.0. CONCLUSIONS: The results show significant difference between averaged IBVPW shapes in upright (highest intracraniospinal compliance) and supine (lower intracraniospinal compliance) body positions. Body posture caused IBVPW subwave P2 and P3 changes deltaP2 = 18% and deltaP3 = 11%. Amplitude of IBVPW in upright body position was significantly higher than in the supine one. The value of IBVPW amplitude's ratio in supine and upright positions was 1.55 +/- 0.61.

BrainIT: a trans-national head injury monitoring research network.

BACKGROUND: Studies of therapeutic interventions and management strategies on head injured patients are difficult to undertake. BrainIT provides validated data for analysis available to centers that contribute data to allow post-hoc analysis and hypothesis testing. METHODS: Both physiological and intensive care management data are collected. Patient identification is eliminated prior to transfer of data to a central database in Glasgow. Requests for missing/ ambiguous data are sent back to the local center. Country coordinating centers provide advice, training, and assistance to centers and manage the data validation process. RESULTS: Currently 30 centers participate in the group. Data collection started in January 2004 and 242 patients have been recruited. Data validation tools were developed to ensure data accuracy and all analysis must be undertaken on validated data. CONCLUSION: BrainIT is an open, collaborative network that has been established with primary objectives of i) creating a core data set of information, ii) standardizing the collection methodology, iii) providing data collection tools, iv) creating and populating a data base for future analysis, and v) establishing data validation methodologies. Improved standards for multi-center data collection should permit the more accurate analysis of monitoring and management studies in head injured patients.

The clinical application of non-invasive intracranial blood volume pulse wave monitoring.

An ultrasonic method was used to non-invasively measure intracranial blood volume (IBV) pulse waveforms. This technology has previously shown a strong association between invasively recorded ICP pulse waves and non-invasively recorded IBV pulse waves. The objective of the present study was to investigate the diagnostic value of non-invasively measured IBV pulse waves in the cases of different pathologies. A total of 75 patients were examined and these included cases of acute, chronic and stabilized hydrocephalus, spinal cord injury and terminal blood flow. These were compared to a control group of 53 healthy volunteers. The object of comparison was normalized and averaged IBV pulse waves. Pathological IBV pulse waveforms were compared with IBV pulse waveforms of the normal group using sub-wave values, the area under waveform curve and the Euclidean distance calculation. The non-invasively measured IBV pulse waveform is not significantly dependent on acoustic path, gender or age. A detectable change in IBV pulse waveform shape was observed in situations when disturbance in intracranial hydrodynamics was present, e.g. during hypoventilation tests, in cases of terminal blood flow and hydrocephaly, depicting the level of hydrocephalus activity and the patient's compensatory capabilities as well as the effect of treatment.

Survey of traumatic brain injury management in European Brain-IT centres year 2001.

BACKGROUND: The aim of this study was to obtain basic knowledge about the current local conditions and neurointensive care of traumatic brain injury (TBI) in the new multi-centre collaborative BrainIT group. MATERIALS AND METHODS: The survey comprised a background part on local policies (Part A), and a case study section (Part B). The information was gathered by questionnaire followed by telephone interviews. Twenty-three BrainIT centres participated in the survey and answers from two respondents were available from 18 of the sites. RESULTS: The average proportion of agreement between duplicate respondents was 0.778 (range 0.415-1.00). All BrainIT centres monitored ICP. The treatment protocols seem to have a pattern concerning escalation of treatment of intracranial hypertension: 1/ evacuation of mass lesions and head elevation; 2/ increased sedation and mannitol; 3/ hyperventilation; 4/ ventricular drainage; 5/ craniectomy and barbituates. CONCLUSIONS: There seemed to be an agreement on neurointensive care policies within the BrainIT group. The suggested order of treatment was generally in accordance with published guidelines although the suggested order and combinations of different treatments varied. Variation of treatment within the range of prescribed standards provides optimal conditions for an interesting future analysis of treatment and monitoring data in reality using the BrainIT database.

Innovative non-invasive method for absolute intracranial pressure measurement without calibration.

A new absolute ICP (aICP) measurement method was designed which does not need calibration. In this study we compared a new method with invasive aICP method in ICU on the patients with closed severe traumatic brain injury. A new method is based on two-depth TCD technique for aICP and external absolute pressure aPe comparison using the eye artery (EA) as natural "balance". The intracranial segment of EA is compressed by aICP and the extracranial segment is compressed by aPe applied to the tissues surrounding the eye. The blood flow parameters in both EA segments are approximately the same when aPe = aICP. Two-depth TCD device is used as an indicator of balance aPe = aICP when the pulsatility index of blood flow velocity waveform in intracranial and extracranial segments are the same. Fifty seven simultaneous invasive and non-invasive aICP measurements were performed in aICP range from 3.0 to 37.0 mmHg. Bland Altman plot of the differences between simultaneous invasive and non-invasive aICP measurements shows the negligible mean difference (mean = 0.94 mmHg) with a standard deviation of 6.18 mmHg. This validation study shows that it is possible to measure aICP non-invasively without calibration of the system with 95% confidence interval of 12 mmHg.