The invention is directed to a process for preparing a Class-A surface, fiber reinforced molded article. The process broadly requires the use of two separate fiber surfacing veils with a fiber reinforcement sandwiched therebetween. A polyurethane reaction system is injected into the mold. The system requires the presence of specified hindered amines.

Reaction injection molding (RIM) has become an important process for the manufacture of a wide variety of moldings. The RIM process is a process which involves the intimate mixing of a polyisocyanate component and an isocyanate-reactive component followed by the injection (generally under high pressure) of the mixture into a mold with subsequent rapid curing. U.S. Pat. No. 4,218,543 describes one particularly commercially significant RIM system, which requires the use of a specific type of aromatic amine as a crosslinker/chain extender. The preferred amine described in the '543 patent is diethyl toluene diamine (DETDA).
In the automotive industry, the application of RIM technology has been primarily to produce vertical parts (e.g. fenders and fascias) and has typically not been used in the production of horizontal body parts (e.g., trunks, hoods and roofs). In order to be useful for the production of horizontal body parts, the molded product 1) must have high stiffness, 2) must have a high quality surface, and 3) must be able to withstand the heat generated during further processing of the part (e.g., painting and curing the paint). Typically, such a part must have a flexural modulus of 750,000 psi or higher.
Fiber glass reinforcement of polyurethane RIM parts is known. See, e.g., U.S. Pat. Nos. 4,435,349, 4,792,576, and 4,871,789. When utilizing such fiber glass reinforcement, several problems are generally encountered, not the least of which is the production of a smooth surface (see, e.g., U.S. Pat. Nos. 4,610,835, 4,644,862, 4,781,876, 4,810,444, 4,952,358, 4,957,684, and 5,009,821).
Recently, a process was developed for preparing Class A surface, fiber-reinforced molded articles (U.S. Pat. No. 5,391,344 issued on Feb. 21, 1995, based on U.S. application Ser. No. 159,891, filed on Dec. 1, 1993 which is a Continuation-in-Part of U.S. patent application Ser. No. 07/798,479, filed on Nov. 26, 1991 now abandoned). The process broadly comprised injecting a specific formulation into a mold, allowing the formulation to fully react and removing the molded part from the mold. The formulation broadly required the use of a polymethylene poly(phenyl isocyanate) and a mixture of hydroxyl functional materials. While adequate for many applications, the formulation tended to blister after being subjected to further heat treatment at 150.degree. C. (which is typical for curing of the paint).
Hindered amines are known for a variety of use in the polyurethane art (see, e.g., U.S. Pat. Nos. 4,146,688, 4,595,742, 4,631,298 and 5,059,634).

Injection molding fibers embedded in polyurethane with hindered amine


Computer-assisted surgical systems and methods provide intraoperative playback of and interaction with recorded video images and/or a 3D model while displaying current video images. The methods and related surgical systems involve capturing, by a two-dimensional (2D) or three-dimensional (3D) video camera, current video images and recording the captured video images. A user interface displays the current video images and the recorded video images and/or the 3D model and enables a user to interact with either or both of them.

Computer-assisted surgical systems, which may include image-guided surgical systems (e.g., systems for performing video-assisted thoracoscopic surgery (VATS)), and robotic surgical systems (e.g., systems for performing robot-assisted thoracoscopic surgery (RATS)), have allowed surgeons to more effectively treat tissue in a minimally invasive manner. Some computer-assisted surgical systems utilize three-dimensional models of a patient's anatomy, which may be based on pre-operative or intra-operative medical imaging (e.g., x-ray computed tomography (CT) or magnetic resonance imaging (MRI)). And some computer-assisted surgical systems are used in conjunction with other objects in the surgical field (e.g., surgical instruments, robotic manipulators, or end effectors). The computer-assisted surgical systems have also revolutionized the way in which surgeons plan for surgical procedures and provide the surgeon with much-needed feedback during the course of a surgical procedure.

Systems and methods for displaying medical video images and/or medical 3D models


In order to produce a window-actuator drive having assembly and service friendliness, particularly by providing a design which enables the gearbox unit to be easily exchanged, the drive is designed as two functionally separate units. A gear housing, a worm gear, and a housing cover which is sealed off from them both makes up a first unit. A cable housing with a cable pulley makes up a second unit. The subassemblies of the first and second unit can be assembled by means of notched, snap-fit connections.

This invention relates to control drives in general and more particularly to a window-actuator drive for motor vehicles which includes two separate units to be assembled together.
In a prior art control drive of this type, the first unit, which is on the side of the motor, comprises at least a cup-shaped housing with an axle mounted in its cup-shaped base, and a driving disk rotatably supported on the axle, which is driven by a driving motor. The second unit, which is on the driven side, comprises at least a second housing with an driven disk rotatably supported therein. When the units are assembled together, the driven disk can be supported on the axle protruding axially out of the first unit. Such a control drive is disclosed in the DE-02-35 19 056.
In the window-actuator drive unit disclosed in the DE-02 35 19 056, a worm gear acting as a driving gear and a cable pulley acting as an driven drive, as well as a separate adapter piece provided between them to effect a reciprocal rotational-slave relationship, are all rotatably supported on an axle. this axle has its axial ends supported in bearing bushings, one of which is secured in the housing base of the cup-shaped gear housing and the other in a flat wall section. This flat wall section can be bolted to the gear housing, with a ring-shaped cable pulley housing structure interposed. When the total drive unit is in its assembled state, the cable pulley housing structure is used as a seal for the cup-shaped gear housing, which otherwise is open. To hold the subassemblies of each unit together, only the worm gear is mounted on the axle in the first subassembly, which is on the side of the motor. In the assembly on the driven side, the bearing bushing for the axle is provided with a radial, peripheral collar. Between this collar and the flat wall section, both the separate driving disk, as well as the cable pulley, are fit in a concentric bearing arrangement into a corresponding radial recess on the bearing bushing.
In a cable window-actuator drive for a motor vehicle disclosed in the DE-A1-34 38 254, the driving gear and the cable pulley subassembly are accommodated in a common housing made of two half-shell shaped housing halves. The open sides of the housing halves lie opposite each other. One housing half encloses (in a cup shape) the worm shaft, which is driven by a flanged electric motor, as well as the worm gear which mates with this worm shaft. The other housing half encloses (in a cup shape) the cable pulley, which has a cable looped around it.
in view of the prior art, there is a need for a control drive for a motor vehicle, in particular a window-actuator drive of the type mentioned in the beginning, which is has improved assembly and service friendliness, particularly with regard to the ease of assembly and disassembly of the gearbox unit.

Control drive particularly a window-activated drive for motor vehicles


Handheld devices are described herein with display portions and with key input portions having curved form factors. The key input portions have form factors that are concave or convex with respect to a plane formed by two edges of a surface of the display portion.

A form factor is the physical size and shape of a device or of a component of a device. A key input form factor is the physical size and shape of a keyboard, for example. As handheld devices, such as cell phones, personal digital assistants (PDA), smart phones, etc., become increasingly popular for mobile communications and mobile data access, key input form factors for handheld devices must meet the physical biomechanics of the human users and must be adapted to accommodate the limited amount of space provided.

Curved key input form factors of handheld devices


A method for transmitting a reference signal by a base station in a wireless communication system is provided. The method includes transmitting configuration information for a reference signal to a terminal, performing a scrambling operation which multiplies the reference signal by a sequence on the basis of a beam group identifier for each of at least two beam groups set on a single cell, and transmitting the reference signal, to which the scrambling operation has been performed on the basis of the configuration information, to the terminal.

In order to meet traffic demands of wireless data which is continuously increasing, the wireless communication system has been developed in a direction for supporting higher data transmission rates. A 4th generation (4G) wireless communication system sought to develop a technology that mainly improves a spectral efficiency to increase the data transmission rate. However, it is difficult to satisfy heavily increasing wireless data traffic demands only with a frequency efficiency improving technology.
Accordingly, research on the use of a very wide frequency band is actively being processed at present. In general, a frequency band currently used for a mobile communication cellular system is equal to or smaller than 10 GHz. Now, it is very difficult to secure a wider frequency band and, accordingly, it is required to secure a broadband frequency in a higher frequency band. However, as the frequency band for wireless communication is higher, a propagation path loss increases and thus a propagation arrival distance becomes relatively short and service coverage becomes reduced. Accordingly, a beamforming technology is currently raised as one of the main technologies to mitigate the propagation path loss and increase the propagation arrival distance.
The beam forming may be classified into transmission beamforming performed at a transmitting end and reception beamforming performed at a receiving end. In general, the transmission beamforming increases directivity by concentrating a radio wave arrival area in a particular direction through a plurality of antennas. At this time, the form in which the plurality of antennas are arranged may be referred to as an antenna array, and each antenna included in the array may be referred to as an array element. The antenna array may be configured in various types, such as a linear array and a planar array. Further, when the transmission beamforming is used, the signal directivity increases and thus a signal transmission distance also increases. In addition, since the signal is hardly transmitted in another direction other than the directed direction, the receiving end gives significantly reduced signal interference to another receiving end.
The receiving end may perform the beamforming on received signals through a reception antenna array. The reception beamforming concentrates reception of radio waves in a particular direction to increase received signal sensitivity incident from the corresponding direction and excludes signals incident from directions other than the corresponding direction from the received signals, so as to provide a gain of blocking an interference signal.
As described above, in order to secure the wide frequency band, an ultra-high frequency, that is, a millimeter wave system is expected to be introduced, in which case the beamforming technology is being considered to overcome the propagation path loss.
However, in the beamforming technology, a base station has to transmit a reference signal in all transmission-available beam directions one or more times and a user equipment has to receive the reference signal in all reception-available beam directions, so that a reference signal transmission efficiency is reduced.
The above information is presented as background information only to assist with an understanding of the present disclosure. No determination has been made, and no assertion is made, as to whether any of the above might be applicable as prior art with regard to the present disclosure.

Method and apparatus for transmitting and receiving reference signal through beam grouping in wireless communication system


A method for purifying a cumene recycle stream by removing 2-phenyl-2-propanol and cumene hydroperoxide before the cumene is distilled and recycled to the peroxidation reactor which comprises reacting the recycle cumene in the presence of an acid treated montmorillonite clay of the formula: EQU M.sub.x/n.sup.n+.sub..y H.sub.2 O(Al.sub.4-x Mg.sub.x) (Si.sub.8)O.sub.20 (OH).sub.4. or in the presence of a catalyst comprising phosphoric acid on silica.

1. Field of the Invention
This invention relates to an improved method for purification of a cumene recycle stream and more particularly this invention relates to methods for removing cumene hydroperoxide and 2-phenyl-2-propanol impurities from a cumene recycle stream in order to reduce the loss in selectivity to cumene hydroperoxide resulting from peroxidation of recycle cumene containing impurities. The impurities can be removed by treatment with a clay catalyst in one embodiment and, in another embodiment are removed by a catalyst comprising phosphoric acid on silica.
2. Description of Related Art
The cumene process is used to manufacture more than 90% of the phenol produced today. In the process, propylene is reacted with benzene to produce cumene. ##STR1## After purification, the cumene is reacted with either air or oxygen to produce cumene hydroperoxide. ##STR2##
Careful adjustment of reaction conditions is necessary to obtain good reaction rates without loss of yield. In most industrial processes, the conversion of cumene to products is held to 20-40%. Under the best conditions yields of over 90% to cumene hydroperoxide may be obtained.
Most of the unconverted cumene is removed from the oxidation product by vacuum distillation and recycled to the oxidation reactor. The concentration of cumene hydroperoxide is then 75-85%.
The next stage in the process is the cleavage of the peroxide to phenol and acetone which can be represented as follows: ##STR3##
The product from the cleavage stage contains phenol, acetone, cumene, acetophenone, 2-phenyl-2-propanol and other minor byproducts. Phenol and acetone are separated by distillation.
The cumene present in the cleavage step is distilled but still contains impurities. It is combined with the cumene isolated from the concentration step. This combined product is recycled to the oxidation reactor, but contains various impurities such as cumene hydroperoxide, 2-phenyl-2-propanol, acetophenone, .alpha.-methyl styrene and phenol. .alpha.-Methyl styrene and phenol are especially detrimental in the oxidation. These two impurities are difficult to remove by distillation since 2-phenyl-2-propanol decomposes to give .alpha.-methyl styrene and cumene hydroperoxide may decompose to give phenol and acetone during distillation.
There is an overview of the technology and economics relating to the production of phenol in Chem. Systems Report No. 79-2, September, 1979, p. 155. It is noted that an important factor influencing the oxidation rate is the purity of the cumene feed, since small amounts of inhibitors, such as sulfur compounds, phenols, aniline or styrenes present in the feed may break the reaction chain by tying up free radicals. Other compounds that catalyze the decomposition of the hydroperoxide are soluble compounds of copper, cobalt and manganese. Acceptable oxidation and conversion rates can be achieved with normal industrial cumene without extensive feed pretreatment, but this generally leads to lower conversion efficiencies and increased side reactions. In the market recently the requirements for improved conversion efficiencies have resulted in the tightening of cumene feed specifications. Purities as high as 99.9 weight percent are now commonly required for the production of chlorination-grade phenol. An alkali wash cumene feed pretreatment is also generally beneficial.
In Kirk-Othmer Encyclopedia of Chemical Technology, 7, 373(1982) there is a discussion of various methods for producing phenol and of the economic aspects related thereto. At page 380, second paragraph it is noted that the USP specification for phenol requires a phenol content of not less than 98%.
The following early patents provide background for the oxidation of aromatic hydrocarbons:
U.S. Pat. No. 2,447,400 PA1 U.S. Pat. No. 2,547,400 PA1 U.S. Pat. No. 2,632,772 PA1 U.S. Pat. No. 2,632,773 PA1 1. An acidic clay catalyst PA1 2. A phosphoric acid on silica catalyst
to produce products such as acetophenone, peroxides of alkylbenzenes, etc.
U.S. Pat. No. 2,706,708 discloses a process for separating cumene from cumene hydroperoxide, wherein the hydroperoxide is made substantially free of dialkylarylmethane by stripping the dialkylarylmethane from dialkylaryl methyl hydroperoxide and passing it through a separation zone.
An improvement in a method for producing cumene hydroperoxide is disclosed in U.S. Pat. No. 3,049,477. The improvement comprises fractional distillation of the oxidation reaction mixture in a still to obtain an overhead fraction comprising cumene, water and organic acids and a bottoms product comprising cumene hydroperoxide which occurs in a concentration higher than it occurred in the oxidation mixture, the improvement comprising recycling the total overhead fraction and recycling at least the cumene to the oxidation step and adding to the still as a liquid reflux a fresh cumene characterized by being substantially dry and having a pH not less than 5.
U.S. Pat. No. 3,092,587 demonstrates the use of thin film and reflux measures to produce high percentage solutions of organic peroxides from low percentage solutions of alkylated aromatic hydrocarbon organic peroxides.
It was disclosed in U.S. Pat. No. 3,141,046 that an effective catalyst for the oxidation of cumene to hydroperoxide is an alkali salt of a carboxylic acid of the general formula: ##STR4## where R.sub.1 represents an alkyl or aryl group and R.sub.2 represents a straight or branched-chain trivalent saturated aliphatic hydrocarbon group. The invention disclosed in this patent comprises oxidizing cumene by treatment at an elevated temperature with molecular oxygen in the presence of the above-described alkali metal salt of a carboxylic acid.
U.S. No. 3,290,384 discloses a method for the oxidation of aralkyl hydrocarbons such as isopropyl benzene to aralkyl hydroperoxides in the presence of a specific class of heavy metal catalysts.
In U.S. No. 3,519,690 there is disclosed a process for the separation of aliphatic or aromatic organic hydroperoxides from their liquid mixtures by thermal diffusion.
In the invention of U.S. No. 3,647,886 certain hydrocarbyl hydroperoxides are formed by contacting a hydrocarbyl hydrocarbon with an oxygen-containing gas in the presence of KF.
There is disclosed in U.S. No. 3,833,663 a process for the oxidation of cumene to cumene hydroperoxide in which cumene is contacted in the liquid phase in the presence of cumene hydroperoxide at a temperature in the range of 40.degree. to 140.degree. C. with a gas containing free oxygen over a catalyst comprising a fluoride of an alkali or alkaline earth metal.
In Liquid Phase Oxidation of Hydrocarbons, Emanual, N. M., et al., Plenum Press (1967), Chapter IX, titled "The Oxidation of Individual Hydrocarbons", it is noted at page 314 that benzoic acid accelerates the decomposition of the hydroperoxide into radicals. Apparently the addition of certain acids inhibits the oxidation of cumene, causing decomposition of the peroxide into phenol and acetone. As little as 0.02% by weight of formic acid almost completely inhibits the oxidation of cumene, Ibid., p. 315.
It was found the pH of the medium had an additional influence on the kinetics of the oxidation of cumene. For example, alkali-containing compounds were found to have an accelerating action. In addition, the inhibiting action of phenol on the oxidation is greatly weakened in the presence of alkali, Ibid.
Emanual, et al. provided evidence to indicate that in the presence of an alkali, decomposition takes place by the overall equation: EQU RH+ROOH.fwdarw.2ROH
It was concluded that the accelerating effect of alkali is connected, not only with the neutralization of acidic products, but also with an increase in the rate of initiation of the chains.
In a strongly alkaline medium (5-10% NaOH) the oxidation of cumene does not go selectively, although the rate is high and the yield of hydroperoxide does not exceed 50% of the oxygen absorbed. Acids formed in the oxidation of cumene at 85.degree. C. in an aqueous emulsion lower the pH of the emulsion and retard the reaction. At a pH of about 4-7(neutral or acidic) oxidation takes place slowly, similar to homogeneous oxidation at this temperature.
It would be a substantial advance in the art in this field if an efficient method were available which would provide a way to remove 2-phenyl-2-propanol and cumene hydroperoxide from the cumene recycle stream so that subsequent distillation would allow production of the recycle cumene essentially free of detrimental impurities.


A wheel assembly, for use on an off-highway vehicle, includes a generally cylindrical wheel hub extending axially from a first end to a second end around an inner volume. A hub adapter is secured to the second end of the wheel hub, the hub adapter including a peripheral shoulder, which has a first shoulder surface axially facing in a direction extending from the second end towards the first end. A first wheel rim is mounted to the peripheral shoulder of the hub adapter at the first shoulder surface.

Off-highway vehicles ("OHVs"), such as mining vehicles used to haul heavy payloads, usually employ motorized wheels for propelling or retarding the vehicle in an energy efficient manner. This efficiency is typically accomplished by employing a large horsepower diesel engine in conjunction with an alternator, a main traction inverter, and a pair of wheel drive assemblies housed within the rear tires of the vehicle. The diesel engine is directly associated with the alternator such that the diesel engine drives the alternator. The alternator, in turn, powers the main traction inverter, which supplies electrical power having a controlled voltage and frequency to electric drive motors of the two wheel drive assemblies. Each wheel drive assembly houses a planetary gear transmission that converts the rotation of the associated drive motor energy into a high torque low speed rotational energy output which is supplied to the rear wheels.
Typical operating loads in an OHV may exceed one hundred tons, while the gross vehicle weight and load may be several hundred tons. Indeed, the weight of a single wheel drive assembly can be in excess of ten tons, while the gross weight exerted on each tire may exceed sixty tons. As will be appreciated, it is desirable to provide reliable attachment of each tire/wheel rim to its corresponding wheel drive assembly. Tires are wear parts, however, that require periodic replacement. As such, is it also desirable to provide for efficient removal and replacement of tires from a wheel drive assembly of an OHV. Additionally, all components in an OHV are weight-controlled and it is therefore desirable to provide for attachment of tires to wheel drive assemblies using a low-weight attachment mechanism.


Optimized remoting cloning is disclosed, including: receiving data from a source storage system associated with an ongoing replication process of a snapshot; and prior to the completion of the replication process of the snapshot, generating a set of metadata associated with a clone of the snapshot, wherein at least a portion of data comprising the snapshot that has been received at the destination storage system can be read using the clone while the replication process of the snapshot is ongoing.

Typically, when moving data from one storage system to another, the data must be fully copied at the destination storage system before it can be accessed by clients of the destination storage system. Also, typically, portions of the data to be replicated are sent from the source storage system to the destination storage system in a relatively static order.


A method for monitoring cardiac output (pulmonary blood flow) of a subject, the method including: measuring a first net pulmonary uptake or elimination of a breathed gas species by the subject and a first partial pressure of the gas species at a first time, and at a second time later than the first time, determining a first pulmonary blood flow of the patient at the first time, and determining a pulmonary blood flow of the subject at the second time on the basis of the first pulmonary blood flow, the first net pulmonary uptake or elimination, the second net pulmonary uptake or elimination, the first partial pressure, and the second partial pressure.

Cardiac output (pulmonary blood flow) is the rate at which blood is pumped by the heart to the body. Along with the blood pressure, it fundamentally reflects the degree of cardiovascular stability and the adequacy of perfusion of vital organs. Knowledge of the cardiac output will not itself provide a diagnosis of a patient's condition, but can provide information useful in making a diagnosis. Monitoring cardiac output is most important where cardiovascular instability is threatened, such as during major surgery and in critically ill patients. In these situations "moment to moment" or continuous monitoring is most desirable, since sudden fluctuations and rapid deterioration can occur, for instance, where sudden blood loss complicates an operation.
Continuous monitoring of cardiac output is still not performed routinely during anaesthesia and critical care due to the absence of a convenient, safe, non-invasive and accurate method. The established techniques for measuring cardiac output, such as pulmonary thermodilution via a pulmonary artery catheter, are invasive and associated with occasional but serious complications, such as pulmonary artery rupture, and/or are time consuming and heavily operator dependent, as in the case of Doppler echocardiography. Other indicator dilution techniques are available, but are invasive and poorly adapted to routine clinical monitoring requirements. Improvements in this field are taking place, such as the development of pulse contour techniques, transpulmonary thermodilution, and improved thoracic bioimpedance devices, but these all have limitations, such as poor accuracy under clinical conditions, the need for repeated calibration, invasive central or peripheral cannulation, and/or are simply unsuitable for patients during surgery and critical care who are intubated or ventilated.
Techniques based on pulmonary gas exchange measurement are among the oldest methods used for cardiac output measurement, and are attractive because of their potentially non-invasive nature. Recent refinements have produced systems or devices based on inert gas uptake (Innocor, Innovision, Denmark), partial CO2 rebreathing (NICO, Respironics, USA) and differential lung ventilation via a double lumen endobronchial tube (the throughflow method). (Gabrielsen et al 2002, Capek and Roy 1988, Robinson et al 2003). However, none of these alternatives allows truly continuous and non-invasive cardiac output monitoring. It follows that it would be useful to provide an automated, non-invasive, continuous measurement method and system suitable for routine use in patients undergoing general anaesthesia or in intensive care.
Non-shunt ("effective") pulmonary capillary blood flow {dot over (Q)}c is that part of the total pulmonary blood flow (cardiac output, {dot over (Q)}t) which engages in gas exchange with an inspired gas mixture in the lung.
The Fick equation, based on the principle of conservation of mass, when applied to elimination of carbon dioxide (CO2) by the lungs, states that{dot over (Q)}t(CaCO2−C vCO2)={dot over (V)}CO2  Equation (1)where {dot over (V)}CO2 is the rate of uptake or elimination of CO2 by the lungs, and C vCO2 and CaCO2 respectively are the (dimensionless) contents of CO2 in mixed venous blood and arterial blood.{dot over (Q)}c can be related to measured {dot over (V)}CO2 by a variation of the Fick equation:
                                          Q            .                              c                =                                                            V                .                                            CO                2                                                    (                                                Cc                                      CO                    2                                    ′                                -                                  C                                                                              v                      _                                                              CO                      2                                                                                )                                .                                    Equation                                                            (          2          )                    where Cc′CO2 and C vCO2 are the fractional contents of CO2 in pulmonary end-capillary and mixed venous blood, respectively. Since the pulmonary end-capillary blood and alveolar gas can be considered to be in equilibrium with one another, Cc′CO2 can be related to the content of CO2 in the alveolar gas mixture if the solubility of CO2 in blood is known, so that
                                          Q            .                              c                =                                            V              .                                      CO              2                                            (                                                            S                                      CO                    2                                                  ·                                                      P                                          A                                              CO                        2                                                                                P                    B                                                              -                              C                                                                      v                    _                                                        CO                    2                                                                        )                                              Equation                                                            (          3          )                    where PACO2 is the alveolar partial pressure of CO2, and PB is the atmospheric pressure corrected for the presence of water vapour at body temperature (47 mmHg at 37° C.). SCO2 is the blood-gas partition coefficient of CO2, a constant representing the solubility of CO2 in blood under the conditions present in the patient at that time.
To permit non-invasive measurement, measured partial pressure of CO2 in end-tidal gas (PE′CO2) is used as an approximation of PACO2 so that Equation (3) can be rewritten as:
                                          Q            .                              c                =                                            V              .                                      CO              2                                            (                                                            S                                      CO                    2                                                  ·                                                      P                                          E                                              CO                        2                                            ′                                                                            P                    B                                                              -                              C                                                                      v                    _                                                        CO                    2                                                                        )                                              Equation                                                            (          4          )                    {dot over (Q)}c can be determined non-invasively by application of the differential Fick principle (Capek and Roy, 1988). This combines two simultaneous versions of Equation (4) where {dot over (Q)}c and C vCO2 are assumed to be constant, as follows:
                                          Q            .                              c                =                                                            V                .                                            CO                                  2                                    i                                                      -                                          V                .                                            CO                                  2                                    j                                                                                S                                  CO                  2                                                            P                B                                      ·                          (                                                P                                      E                                          CO                                              2                                                i                                                              ′                                                  -                                  P                                      E                                          CO                                              2                                                j                                                              ′                                                              )                                                          Equation                                                            (          5          )
The variables in this equation are measured at two points in time (i and j), before and after inducing a change in the alveolar minute ventilation, which alters both {dot over (V)}CO2 and PE′CO2 acutely. This can be achieved by a number of means. The first method used in the past is to make a stepwise change in the respiratory rate (Gedeon et al 1980). An alternative method, referred to as partial CO2 rebreathing, is to introduce a change in the serial deadspace, while holding tidal volume constant, thereby effectively reducing the alveolar ventilation (Capek and Roy, 1988). This is the technique used by the NICO device (Respironics, USA). This approach obviates the need to know the mixed venous CO2 content (C vCO2), which could otherwise only be directly measured by invasive mixed venous blood sampling via a pulmonary artery catheter. {dot over (Q)}c requires correction using an estimate of pulmonary shunt fraction ({dot over (Q)}s/{dot over (Q)}t). This estimate can be obtained by a number of means, including non-invasively (Peyton et al 2004). This then permits the determination of total pulmonary blood flow (cardiac output, {dot over (Q)}t), as follows:
                                          Q            .                              t                =                                            Q              .                                    c                                1            -                                                            Q                  .                                                s                                                              Q                  .                                                t                                                                        Equation                                                            (          6          )
The acute change in {dot over (V)}CO2 and PE′CO2 rapidly levels out as washin or washout of CO2 from alveolar gas and lung tissue stores briefly approaches a new steady state level (Gedeon et al 1980, Capek and Roy, 1988). However, the change in alveolar ventilation begins to alter the content of CO2 in the mixed venous blood, Importantly, stability in both C vCO2 and {dot over (Q)}c is required for equation (6) to be accurate, and the measurement cannot be repeated more frequently than once every 3-4 minutes to allow C vCO2 to stabilise prior to the next measurement. For this reason it has not been previously possible to provide accurate continuous (breath-by-breath) monitoring of cardiac output.
Orr et al (U.S. Pat. No. 6,217,524 B1) have described an approach to the provision of continuous (breath to breath) monitoring of cardiac output, by the ongoing measurement of {dot over (V)}CO2 with each breath, following an initial baseline measurement of cardiac output and {dot over (V)}CO2. Their approach makes the assumption, based on the well-known fact that CO2 stores in the body are very large, that the arterio-venous CO2 content difference (CaCO2−C vCO2) will remain constant for some time following a change in cardiac output. From this assumption, it follows that, if {dot over (Q)}t at a breath i ({dot over (Q)}ti) changes on a subsequent breath k to {dot over (Q)}tk, then {dot over (Q)}tk can be derived from two simultaneous versions of equation (1), in which the arterio-venous CO2 content difference (CaCO2−C vCO2) cancels out, giving{dot over (Q)}tk=F·{dot over (V)}CO2k  Equation (7a)where {dot over (V)}CO2k is {dot over (V)}CO2 at breath k, and F is a scaling factor given by
                    F        =                                            Q              .                                                  t              i                                                          V              .                                      CO                              2                                i                                                                        Equation                                                            (                      7                        b                    )                    where {dot over (V)}CO2i is {dot over (V)}CO2 measured at breath i. This method determines an estimate of cardiac output on a breath-by-breath basis from a previous measurement of CO2 elimination by the lungs and a previous measurement of cardiac output, such as might be obtained from equation (5) above.
However, experimental testing of the Orr et al method by the inventor has found it to be unacceptably inaccurate. Continuous breath-by-breath estimations of cardiac output made using the Orr method were compared on a breath by breath basis with simultaneous measurements made by a "gold standard" in vivo measurement device, an indwelling ultrasonic flow probe placed on the ascending aorta or pulmonary artery in six ventilated sheep ranging in weight from 35-45 kg. The sheep were anaesthetised with isoflurane in oxygen-air, and their cardiac output was manipulated using a dobutamine infusion alternating with esmolol boluses. {dot over (V)}CO2 was measured at the mouth with each breath using a calibrated measurement system incorporating a pneumotachograph and sidestream rapid gas analyser. A single initial calibration cardiac output was measured by introducing a step change in tidal volume for 30 seconds and applying equation (5). Cardiac output was then followed breath-by-breath for up to 100 minutes. The results are shown in FIGS. 7 and 9.
Overall mean bias for {dot over (Q)}t (Orr et al—flow probe) was −0.34 L/min [95% confidence limits: ±0.04 L/min]. The standard deviation of the difference was 1.16 L/min, giving upper and lower limits of agreement of +1.9 and −2.6 L/min Intraclass correlation coefficients (ICC) over successive 5 minute intervals were 0.65 for agreement in {dot over (Q)}t, and 0.55 for agreement in changes in {dot over (Q)}t. From this it can be determined that only approximately 30-40% of the actual variation in cardiac output measured by the flow probe was reflected in the corresponding changes estimated by the method of Orr et al. This level of agreement with the gold standard was not improved by nominating the {dot over (Q)}t measured by the flow probe at the initial calibration point as {dot over (Q)}ti.
The method described by Orr et al produces an overdamped or "flat" response to real changes in {dot over (Q)}t. The origins of this flat responsiveness lie in the assumption underlying the method of Orr et al that the arterio-venous CO2 content difference is unaffected in the short term by changes in {dot over (Q)}t. This assumption implies a simple linear relationship between changes in {dot over (Q)}t and changes in {dot over (V)}CO2, which is not borne out by the experimental data shown in FIG. 7.
The consequence of Orr et al's assumption is a tendency to "normalise" the estimated cardiac output toward the initial baseline measurement, despite significant actual changes in {dot over (Q)}t. The clinical consequences of this are potentially serious, where the magnitude of a sudden deterioration in a patient's condition during anaesthesia for surgery, or in critical care, is underestimated, potentially resulting in an inadequate response by treating clinicians.
It is desired, therefore, to provide a method and system for monitoring cardiac output of a subject that alleviate one or more difficulties of the prior art, or at least to provide a useful alternative.

System and method for monitoring cardiac output