A system for detecting/quantifying the conductance of a right-to-left cardiac shunt includes a mouthpiece assembly, a solenoid-driven vacuum/pressurization assembly; a controller for operating the solenoid-driven vacuum/pressurization assembly; and a monitor for displaying the instructions from the controller. A microbubble counting cell and digital image sensor are combined with software-based image analysis to determine a number of microbubbles contained in a microbubble counting zone. A monitor enables operator specification of total volume of contrast agent to be injected into the patient. One or more first Doppler ultrasound transducer arrays are positioned adjacent to targeted intracranial arteries at one side of the skull or a pair of first Doppler ultrasound transducer arrays positioned adjacent to targeted intracranial arteries at both sides of the skull. A second Doppler ultrasound transducer is positioned on the precordium of the patient to detect the arrival of microbubble-containing contrast agent in the right atrium of the patient.

Cryptogenic strokes and transient ischemic attacks ("TIAs") are those in which no obvious cause is found by patient history, carotid Doppler studies, or cardiac conditions such as atrial fibrillation, myocardial infarction, or valve diseases. Patent foramen ovale ("PFO"), which is a small flap-valve hole in the heart, has been associated with cryptogenic stroke allowing paradoxical embolism from the veins to the brain through a right-to-left shunt ("RLS"). Normally, blood returning to the heart from the veins is re-oxygenated when it is pumped from the right side of the heart and then through the lungs. However, in people with PFO, the venous blood, which may contain clots, may instead travel through the hole (i.e., the PFO) between the upper chambers of the heart and into the arterial blood, bypassing the lungs where the clots would normally be filtered out. When this blood goes to the brain, a clot may cause a stroke or stroke-like symptoms. Hereinafter, the term "right-to-left shunt" refers to an abnormal pathway between the right side and the left side of the heart (e.g., an abnormal pathway or communication between the right atrium and the left atrium of the heart through the wall of the intervening septum). The most common abnormal pathway or communication between the right atrium and the left atrium of the heart is known as a PFO. A PFO is also the most common form of a right-to-left shunt. Normally, blood returning to the heart from the veins is re-oxygenated when it is pumped from the right side of the heart and then through the lungs as it proceeds to the left atrium. However, in subjects with a PFO, the venous blood, which may contain one or more emboli, may instead travel through the hole or pathway (e.g., a PFO) between the upper chambers of the heart and into the arterial blood, bypassing the lungs where the emboli would normally be filtered out. When venous blood bypasses the filtering benefit of the lungs and proceeds to the left side of the heart, that portion of the venous blood that proceeds to the brain may contain one or more emboli, thereby causing a stroke or stroke-like symptoms. In approximately 40 percent of stroke cases, the underlying cause is difficult to determine and the stroke is called "cryptogenic". Evidence now suggests that when a person has a stroke, and its cause is undetermined, the person is about twice as likely as the normal population to have PFO.
The presence of a PFO is found in all ages with diameters as large as 18 mm. Cryptogenic stroke patients, assessed with transcranial Doppler ultrasound ("TCD"), have a much higher likelihood of having a large PFO compared to subjects that have not experienced a stroke. Also, migraine patients, especially those experiencing migraine with aura, have a greater likelihood of having a PFO compared to subjects that do not experience migraine.
The presence of a PFO appears to be the source of silent or subclinical brain infarcts (SBIs) and small cortical infarcts. SBIs are associated with a 2×-increased risk of dementia and stroke. In this regard, see Bang, O., et al., Patent Foramen Ovale and Stroke—Current Status. Journal of Stroke 2015; 17(3): 229-237. In addition, paradoxical embolism has been identified as the main mechanism for SBI in otherwise healthy population. The consequences of SBI include mobility/gait disturbances, dementia, mild cognitive impairment, psychiatric disorders, e.g., bipolar disorder and depression (see Fanning, J., et al., Emerging Spectra of Silent Brain Infarction. Stroke 2014; 45: 3461-3471). In another clinical study of 1,103 patients, 31% of subjects exhibited SBI at MRI; of these 31%, 51% exhibited RLS upon examination by TCD. Prevalence of SBI in subjects with RLS is the same as the prevalence of cryptogenic stroke in subjects with RLS (see Kim, S., et al., Paradoxical Embolism as the Cause of Silent Brain Infarctions in Healthy Subjects: the ICONS Study. European Journal of Neurology 2013; 20 [2]: 353-360). The incidence of SBI (also known as microinfarcts) is 2× greater in subjects who died with dementia than those who died without dementia. Based on multiple studies, smaller and more numerous SBIs may be a stronger contributor to and causative factor for dementia (see Smith, E., et al., Cerebral Microinfarcts: The Invisible Lesions. Lancet Neurology 2012; 11 [3]: 272-282).
The existence of spontaneous cerebral emboli (SCE) were found to predict a more rapid progress of dementia in a study of 99 patients, 58 with Alzheimer's Disease (AD) and 41 with Vascular Dementia (VaD). SCE was detected in 44% of dementia patients and also was associated with the presence of significant PFO upon examination by TCD. The number of detected SCE significantly correlated with cognitive deterioration over 2 years of follow-up of Alzheimer's Disease and Vascular Dementia patients (see Purandare, N., et al., American Journal of Psychiatry. 2012; 169: 300-308). Also, Deep White Matter Hyperintensities (Deep WMH) were significantly associated with PFO in Alzheimer's Disease (AD), but not vascular dementia (VaD). Significant RLS (>15 microbubbles detected using TCD method) was associated with more severe deep WMH in Alzheimer's Disease and appears to be associated with the etiology of AD (Purandare, N., et al., Paradoxical Embolization and Cerebral White Matter Lesions in Dementia. British Journal of Radiology 2008; 81: 30-34).
Of 180 patients having a PFO that was detectable without any provocative maneuver (to increase right atrial pressure) exhibited an increased frequency of multiple ischemic brain lesions on magnetic resonance imaging as well as previous recurrent stroke, previous peripheral arterial embolism and migraine with aura (see Rigatelli, G., et al., Permanent Right-to-Left Shunt Is the Key Factor in Managing Patent Foramen Ovale. Journal of the American College of Cardiology 2011; 58 [21]: 2257-2261).
In view of the complications associated with presence of a PFO, especially a PFO exhibiting a larger shunt fraction (i.e., the fraction of blood flow through a PFO as compared with the magnitude of the overall blood flow through the heart), minimally invasive and non-invasive methods for detecting the presence of a PFO have evolved over the past two decades. Unfortunately, there is currently no available method suitable for widespread screening for the presence of an quantifying the conductance of a PFO when the patient experiences early warning signs signaling an ischemic incident, or the patient exhibits or is exposed to an elevated risk of a stroke. Consequently, the "at risk" fraction of the population with a right-to-left shunt is most often resigned to the possibility of experiencing a stroke before definitive right-to-left shunt testing is performed. Only then are methods such as transesophageal echocardiography (TEE) performed to detect the presence of a previously undiagnosed right-to-left shunt. If detected, the patient may elect to be treated with anti-clotting agents or elect to undergo transcatheter right-to-left shunt closure or the more conventional open-heart procedure for right-to-left shunt closure.
Transesophageal Echocardiography (TEE) in conjunction with the injection of agitated saline contrast agent containing very small, air filled "microbubbles" is considered the clinical "gold standard" for determining the presence of a right-to-left cardiac shunt. In this regard, see Shariat, A., et al., Comparison of Agitated Saline Mixed with Blood to Agitated Saline Alone in Detecting Right-to-Left Shunt during Contrast-Transcranial Doppler Sonography Examination. Acta Neurology Taiwan 2011; 20:182-187. In carrying out this test, microbubble filled contrast agent, produced by the agitation of a saline/air mixture with the optional addition of a small amount of the subject's blood, is injected into a vein (e.g., antecubital vein) leading to the right side of the heart. As this is underway, the somewhat sedated patient is required to bear down with their abdominal muscles (as during defecation) to perform a Valsalva strain, the release of which will momentarily reverse the pressure differential between the right and left atria and cause a PFO, if present, to open, while an ultrasound transducer, positioned in the esophagus at the level of the heart, is used to record the possible passage of microbubbles into the left atrium. Because of gagging problems, the patient is partially anesthetized. Typically, patients experience discomfort, and it is hardly suited for screening. The TEE test requires a physician with specialized training as well as an anesthesiologist or anesthetist. Attempts to perform semi-quantitative TEE tests have been shown to only correlate with PFO size if the microbubble-containing contrast agent was administered via femoral vein whereas poor correlation has been observed with PFO size when the contrast agent was administered via an antecubital vein (see Schuchlenz, H., et al., Transesophageal Echocardiography for Quantifying the Size of Patent Foramen Ovale in Patients with Cryptogenic Cerebrovascular Events. Stroke January, 2002; 33 [1]: 293-296). Hence, not only is TEE unsuitable for screening patients for the presence of a PFO but it is incapable of quantifying the shunt fraction or conductance (also referred to as the "size") of a right-to-left shunt.
A related test is referred to as transthoracic echocardiography (TTE). Again, a microbubble containing contrast agent is injected into a vein (e.g., antecubital vein) leading to the right side of the heart. Since the ultrasound detectors are positioned externally over the chest wall in a TTE, the Valsalva maneuver for this procedure is performed by having the patient blow forcefully into a small tube, sometimes connected to a manometer, while echocardiography recordings are made using ultrasound imaging through the chest wall. This procedure exhibits relatively poor sensitivity due the intervening distance between the transducer and the heart. Some clinical studies report a sensitivity of only 60% corresponding to a false-negative rate of 40%. For a comprehensive description of the exhalation-based Valsalva maneuver, see Pfleger, S., et al., Haemodynamic Quantification of Different Provocation Manoeuvers by Simultaneous Measurement of Right and Left Atrial Pressure: Implications for the Echocardiographic Detection of Persistent Patent Foramen Ovale. European Journal of Echocardiography 2001; 2: 88-93. In regard to the performance of a Valsalva maneuver, also see Spencer, M. S., et al., Power M-Mode Transcranial Doppler for Diagnosis of Patent Foramen Ovale and Assessing Transcatheter Closure. American Society of Neuroimaging 2004; 14: 342-349 and Zhao, E., et al., A Comparison of Transthroracic Echocardiograpy andTranscranial Doppler With Contrast Agent for Detection of Patent Foramen Ovale With or Without the Valsalva Maneuver. Medicine October 2015; 94(43):1-5. In addition to its poor sensitivity, the TTE method is incapable of quantifying the shunt fraction or conductance (also referred to as the "size") of a right-to-left shunt.
A third test, incorporating transcranial Doppler (TCD) technology, also uses microbubbles as a contrast agent along with a Valsalva maneuver. Regarding transcranial Doppler technology and method, see Spencer, M., et al., Power M-Mode Transcranial Doppler for Diagnosis of Patent Foramen Ovale and Assessing Transcatheter Closure. Journal of Neuroimaging 2004; 14:342-349). Ultrasonic transducers are positioned unilaterally or bilaterally on the skull to measure embolic signals produced by any microbubbles transiting the middle cerebral artery. The TCD method exhibits a relatively high sensitivity as compared with the TEE and TTE ultrasound methods. By way of example, U.S. Pat. No. 7,771,358, incorporated herein by reference, describes such systems and methods for grading microemboli flowing in targeted intracranial arteries using a Doppler Ultrasound method. Using intravenous injections of agitated saline, which provide an ultrasonic contrast agent of saline filled with a million or more microbubbles, the suspended bubbles pass through the PFO from the right atrium to the left atrium and are readily detected by the TCD ultrasound generated microembolic spectra emanating from the targeted cerebral arteries. The generated microbubbles within the agitated saline contrast agent do not pass through the lungs and into the left atrium. Therefore a shunt between the venous system and the arterial system that bypasses the lungs is the only way for bubbles to be seen on the arterial side of circulating blood. A provocative maneuver such as a Valsalva strain (forced expiratory effort against a closed glottis) or a breath-hold based Valsalva maneuver facilitates passage of the microbubbles through the PFO by raising the pressure in the right atrium over that of the left atrium.
As a further example of the use of the prior art TCD method described in U.S. Pat. No. 7,771,358 for the detection and quantification of the conductance of a right-to-left cardiac shunt, all embolic tracks (ETs) are counted in the bilaterally insonated intracranial arteries from a depth range of approximately 40 mm to 75 mm. Typically, all ETs are counted visually. Because the beams overlap at the midline at a depth of 75 mm, ETs are not counted at depths beyond 75 mm. Based on the number of ETs counted, a grade may be determined according to a six-level logarithmic grading scale to rate the degree of RLS: grade 0=0 ETs, grade I=1-10 ETs, grade II=11-30 ETs, grade III=31-100 ETs, grade IV=101-300 ETs, and grade V>300 ETs. The example six-level grading scale does not predict the physical size of the opening but does correspond to the conductance or ability of the right-to-left shunt to transmit emboli from the venous circulation to the arterial circulation of the brain.
The number of detected embolic tracks in the targeted cranial arteries following the injection of microbubbles into the venous circulation (e.g., injection at the antecubital vein of the subject) represents a quantifiable metric referred to hereinafter as the "conductance" of a right-to-left shunt. The measured number of embolic tracks detected in cranial arteries is dependent on many factors including [a] the right-to-left shunt flow distribution to the anterior circulation of the brain, the size of the foramen ovale that temporarily opens when the exhalation pressure exerted by the subject abruptly ends (i.e., the end of the Valsalva maneuver), the length of the pathway through the wall of the heart separating the venous and arterial circulation of blood within the heart (e.g., the length of the pathway through the septum located between the right and left atria), the tortuosity of the pathway length, the right-to-left pressure gradient during the brief period when the foramen ovale is open and the total number of microbubbles contained in the volume of injected contrast agent.
In the case of the unilateral TCD detection method, the number of ETs counted are doubled based on the assumption of an equal distribution of blood flowing through the left and right hemispheres of the brain. The resulting number of ETs is then applied to the six-level grading scale described above. Although the use of TCD provides greater accuracy for the detection or ruling out of right-to-left shunts as well as an improved grading scale for determining the functional conductance of PFO, it is not without significant limitations. For example, current TCD devices and methods require the services of a trained neurosonographer to perform the time-consuming process of visually analyzing TCD generated ultrasound spectra and counting of the ETs detected during examination. Additionally, counting the number of ETs for the higher grades, such as grades VI and above in the above example, is difficult as visually distinguishing between individual ETs on the recorded ultrasound spectra. As a result, the grading process, specifically for right-to-left shunts such as PFO is susceptible to operator-dependent counting errors.
Another significant limitation of the use of existing TCD devices and methods to quantify the conductance of a right-to-left shunt is the inconsistency of operator-prepared agitated saline mixtures to produce the microbubble-containing contrast agent as a circulatory tracking indicator. In current practice, microbubbles are created just prior to use by filling a first syringe with, by way of example, 8.0 ml of sterile isotonic saline, 1.0 ml of air and 0.5 to 1.0 ml of blood withdrawn from the patient. This mixture is then rapidly transferred into an initially empty second syringe and, after which, the saline/air/blood mixture within the second syringe is rapidly injected back into the first syringe to complete one mixing cycle. This process causes the air to be dispersed within the saline and blood liquid mixture in the form of small bubbles. Alternatively, microbubbles are created just prior to use by filling a first syringe with, by way of example, 9.0 ml of sterile isotonic saline and 1.0 ml of air. This mixture is then rapidly transferred into an initially empty second syringe and, after which, the saline/air mixture within the second syringe is rapidly injected back into the first syringe to complete one mixing cycle. This process causes the air to be dispersed within the saline liquid in the form of small bubbles. This mixing cycle process is typically repeated six to ten times in rapid succession resulting in a mixture containing millions of microbubbles typically having a mean diameter of about 25 microns (i.e., micrometers). Unfortunately, the microbubbles generated using the above described manual agitation process [a] vary in total number per unit volume of contrast agent and [b] are highly unstable during the time domain of performing a TCD test procedure.
The size of the microbubbles in contrast agents used for the detection of right-to-left shunts using TCD methods is important. The saline agitation method described above generates microbubbles whose diameter is at least 10 microns for more than 99% of the microbubbles generated. The preferred size microbubbles for TCD as well as Transthoracic Echocardiography (TTE) and Transesophageal Echocardiography (TEE) is greater than 10 microns and typically the generated microbubbles have a geometric mean diameter of 25 to 29 microns. The vast majority of the microbubbles produced by the manual agitation of a saline/air mixture as well as saline/air/blood mixture are too large to cross the pulmonary vasculature (see Stewart, M, Contrast Echocardiography. Heart 2003; 89:342-348).
By way of example, a first contrast agent study reports a geometric mean microbubble diameter of 28.9 microns with a range of 10 to 338 microns for saline/air/blood mixtures prepared with 8.0 ml saline, 1.0 ml air and 0.5 ml of patient's blood. In this first study, the microbubble diameter ranged from 12.5 to 78.7 microns for 1% to 99% of the population with the smallest microbubble at least 10 micron in diameter. In the inter-investigator comparison in this first study, the geometric mean microbubble diameter was 26.7 microns and 28.7 microns for Investigator 1 and 2, respectively, for the above-specified saline/air/blood mixture. For further information regarding this first study, see Sastry, S., et al., Is Transcranial Doppler for the Detection of Venous-to-Arterial Circulation Shunts Reproducible? Cerebrovascular Disease 2007; 23: 424-429.
In another example, a second contrast agent study reports on the characteristics of an agitated saline mixture containing 8.0 ml saline, 1.0 ml air and 1.0 ml blood. The agitated saline contrast agent prepared with this particular mixture yielded an average microbubble size of 26.7 microns with a standard deviation of 7.2. For further information regarding this second study, see Jeon, D., et al., The Usefulness of a 10% Air-10% Blood-80% Saline Mixture for Contrast Echocardiography: Doppler Measurement of Pulmonary Artery Systolic Pressure. Journal of American College of Cardiology 2002; 39 [1]: 124-129.
In yet another example, a third contrast agent study reports on the characteristics of an agitated saline mixture containing 9.0 ml saline, 1.0 ml without any addition of blood withdrawn from the subject. The agitated saline contrast agent prepared with this particular mixture yielded an average microbubble size of 31.6 microns with a standard deviation of 8.2 microns For further information regarding this third study, also see Jeon, D., et al., The Usefulness of a 10% Air-10% Blood-80% Saline Mixture for Contrast Echocardiography: Doppler Measurement of Pulmonary Artery Systolic Pressure. Journal of American College of Cardiology 2002; 39 [1]: 124-129.
Although the mean microbubble diameter was similar in the three example studies referenced above, the range of microbubble diameters was somewhat greater in the first study. However and importantly, the number of microbubbles produced was significantly different between the three example studies. By way of example, in a first study using a contrast agent prepared with 8.0 ml saline, 1.0 ml air and 0.5 ml of patient's blood, the geometric mean number of bubbles was 451/mm3 with a range (95% Confidence Interval) from 409/mm3 to 498/mm3 after six mixing cycles. After 18 mixing cycles, the geometric mean number of bubbles was 857/mm3 with a range (95% Confidence Interval) from 757/mm3 to 926/mm3 (see Sastry, S., et al., Is Transcranial Doppler for the Detection of Venous-to-Arterial Circulation Shunts Reproducible? Cerebrovascular Disease 2007; 23: 424-429).
In a second study using a contrast agent prepared with 8.0 ml saline, 1.0 ml air and 1.0 ml of patient's blood, the geometric mean number of bubbles was 2,285/mm3 with a standard deviation of 704/mm3 after 10 mixing cycles. In contrast, in a third study using a contrast agent prepared with 9.0 ml saline and 1.0 ml air, but without the addition of any patient's blood, the geometric mean number of bubbles was 193/mm3 with a standard deviation of 153/mm3 after 10 mixing cycles. In regard to the second and third study, see Jeon, D., et al., The Usefulness of a 10% Air-10% Blood-80% Saline Mixture for Contrast Echocardiography: Doppler Measurement of Pulmonary Artery Systolic Pressure. Journal of American College of Cardiology 2002; 39 [1]: 124-129.
A comparison of the first and second studies describe above reveals that the two-fold larger amount of added blood for the saline/air/blood mixture in the first study resulted in a three-fold larger number of microbubbles. More significantly, for the case of the third study in which the contrast agent was prepared with 9.0 ml saline, 1.0 ml air without the addition of the patient's blood, the geometric mean number of bubbles was only 193/mm3, a factor of about twelve-fold lower than the number of microbubbles generated when the patient's blood is added to the saline/air mixture.
In addition to significant variations in the number of microbubbles generated per unit volume of manually prepared contrast agent, as describe in the three example studies cited above, there is also a significant variation in the number of microbubbles per unit volume of contrast agent depending on the elapsed time between the completion of the last agitation cycle and the injection of the contrast agent into the venous blood stream of the subject. The half-life values for microbubbles prepared by two different methods involving agitation of saline and air with and without the addition of blood have been reported (see Jeon, D., et al., The Usefulness of a 10% Air-10% Blood-80% Saline Mixture for Contrast Echocardiography: Doppler Measurement of Pulmonary Artery Systolic Pressure. Journal of American College of Cardiology 2002; 39 [1]: 124-129). The measured and reported half-life values of the generated microbubbles range from 4.2 seconds (for saline/air mixture) to 4.9 seconds (for saline/air/blood mixture). Hence, if the operator delays the start of injection by about 4 to 5 seconds rather than injecting immediately after the last agitation cycle, then the number of injected microbubbles will decrease by a two-fold factor.
By way of example, if a typically used 10 ml volume of agitated saline/air/blood mixture (80%/10%/10% composition) is injected immediately after the 10th mixing cycle, the estimated number of microbubbles injected will be 2,285 bubbles/mm3×1,000 mm3/ml×10 ml or 22.85 million microbubbles. If the operator performing a TCD test delays the start of the injection of this agitated saline mixture by 5.0 seconds, the estimated number of microbubbles injected will be 14.97 million microbubbles in a 10 ml volume of injected agitated saline contrast, a nearly two-fold lower number of microbubbles. In another example, if the operator performing TCD test delays the start of the injection of this agitated saline mixture by 10.0 seconds, the estimated number of microbubbles injected will be only 4.31 million microbubbles in a 10 ml volume of injected agitated saline contrast, a five-fold lower number of microbubbles as compared with the number of microbubbles in the contrast agent when it is injected immediately after the last agitation cycle. In this regard, see Jeon, D., et al., The Usefulness of a 10% Air-10% Blood-80% Saline Mixture for Contrast Echocardiography: Doppler Measurement of Pulmonary Artery Systolic Pressure. Journal of American College of Cardiology 2002; 39 [1]: 124-129.
In yet another example and in contrast to the case of a saline/air/blood agitated saline mixture, if a 10 ml volume of agitated saline/air mixture without the addition of blood (e.g., 9 ml saline+1.0 ml air) is injected immediately after the 10th mixing cycle, the estimated number of microbubbles injected will be 193 bubbles/mm3×1,000 mm3/ml×10 ml or 1.93 million microbubbles. If the operator performing TCD test delays the start of the injection of this agitated saline mixture by 5.0 seconds, the estimated number of microbubbles injected will be 890,000 microbubbles in a 10 ml volume of injected agitated saline contrast, a number of microbubbles that is more than two-fold lower than if the contrast agent is injected immediately and about 17× smaller than for the case of the saline/air/blood agitated saline mixture. If the operator performing a TCD test delays the start of the injection of this agitated saline mixture by 10.0 seconds, the estimated number of microbubbles injected will be 350,000 microbubbles in a 10 ml volume of injected agitated saline contrast, a number of microbubbles over 12× smaller than for the case of the saline/air/blood agitated saline mixture. In this regard, also see Jeon, D., et al., The Usefulness of a 10% Air-10% Blood-80% Saline Mixture for Contrast Echocardiography: Doppler Measurement of Pulmonary Artery Systolic Pressure. Journal of American College of Cardiology 2002; 39 [1]: 124-129.
The significance of these differences in the total number of microbubbles contained in the injected contrast agent is that [a] the composition of the contrast agent (e.g., composition with or without the addition of blood), [b] the number and forcefulness of the agitation cycles and [c] delays in the start of injection of the agitated saline/air/blood or agitated saline/air mixtures significantly affect the absolute number of embolic tracks (ETs) counted for right-to-left shunts. The number of detected ETs during a TCD shunt test is essential to distinguishing between large (Grade IV, 101-300 ETs), medium (Grade III, 31-100 ETs), small (Grade II, 11-30 ETs) and very small (Grade I, 1-10 ETs) shunt conductances (see Spencer, et al., Power M-Mode Transcranial Doppler for Diagnosis of Patent Foramen Ovale and Assessing Transcatheter Closure. Journal of Neuroimaging 2004; 14:342-349). By way of example, for an actual Grade III shunt using agitated 80% saline/10% air/10% blood mixture, assume the number of microbubble-induced ETs detected in the middle cerebral artery (MCA) using TCD could be 40 ETs if the operator injected the contrast agent immediately after the last of 10 agitation cycles corresponding to a medium or Grade III shunt conductance. However, if the operator delayed the start of injection of the contrast agent (containing the same initial number of microbubbles) by 10.0 seconds, the predicted number of microbubbles and associated number of ETs would be reduced by a factor of 5.3× due to the disappearance of microbubbles, thereby resulting in the number of microbubble induced ET detected in the middle cerebral artery (MCA) using TCD of only 8 ETs corresponding to a very small or Grade I shunt conductance.
By way of a second example illustrating the effect of the agitated saline mixture used and for the case of an actual Medium or Grade III shunt using agitated 80% saline/10% air/10% blood mixture, assume the number of microbubble-induced ETs detected in the middle cerebral artery (MCA) using TCD for a subject is 70 ETs corresponding to a medium or Grade III shunt for the case in which the operator injected the contrast agent immediately after the last of 10 agitation cycles. However, if the operator alternatively used an agitated 90% saline/10% air mixture and again injected the contrast agent immediately after the last of 10 agitation cycles, the predicted number of microbubbles and associated number of detected ETs would be reduced correspondingly by a nearly twelve-fold factor due to the much smaller number of generated microbubbles in the 10 ml injected saline/air contrast agent. As a consequence, the measured the number of microbubble-induced ETs detected in the middle cerebral artery (MCA) using TCD in combination with an agitated saline/air mixture would be only 6 ETs corresponding to a very small or Grade I shunt conductance.
In summary, prior art Transcranial Doppler methods for attempting to quantify the conductance of a right-to-shunt into categories of Grade I (Very Small), Grade II (Small), Grade III (Medium) and Grade IV (Large) are unavoidably limited by significant variations in the numbers of microbubbles contained in the manually prepared and injected bolus of contrast agent even when the injected bolus size is maintained at a consistent volume of 10 ml. This unavoidable limitation becomes even more important for determining the residual conductance of right-to-left shunts after medical interventions to close or "seal" a right-to-left shunt such as atrial septal defect (ASD) or a patent foramen ovale (PFO).
For example, multiple clinical studies have demonstrated the benefits of percutaneous PFO closure with regard to [a] the reduction in occurrence of primary or secondary stroke and/or [b] the reduction or complete cessation of migraine attacks. However, most of the prior clinical trials fail to reach the expected threshold of improvement with statistical significance. Clinical studies have consistently reported residual or recurring shunt levels ranging from 9% to 40% within one year following assumed PFO closure during a percutaneous procedure. It is essential that PFO closure be achieved to the greatest possible extent, even if it requires some period of time post-closure to affect the complete closure of the PFO. During this post-closure sealing period, depending on the detected level of residual shunt conductance, anticoagulant therapy may be indicated to minimize the possibility of cerebrovascular accidents and/or minimizing the frequency and severity of migraines. However, due to the risks of anticoagulant therapy (e.g., hemorrhagic stroke and other internal bleeding complications), anticoagulant therapy with drugs such as warfarin should only be administered if the shunt conductance is sufficiently high to warrant such medical therapy. Likewise, this strategy necessarily requires ongoing monitoring of the patient following closure to determine when prophylactic anticoagulant therapy can be terminated.
However, as seen in the examples presented above, the number of microbubbles contained in the injected bolus of contrast agent can vary by factors of at least seventeen-fold (based on the measured average number of generated microbubbles per cubic millimeter) depending on the agitated saline composition, agitation technique and delay between the last agitation cycle and the start of the injection of the contrast agent into the venous blood circulation of the subject. If the variation in the number of microbubbles generated relative to the average number of microbubbles generated for 63% of the population, the number of microbubbles contained in the injected bolus of contrast agent can vary by factors of more than fifty-fold. Consequently, there is currently no current method for accurately quantifying the conductance of a right-to-left shunt, either prior to or following the percutaneous closure of a right-to-left shunt based on the unknown and significantly varying number of microbubbles contained in the injected bolus of contrast agent, even when the same operator and same agitated saline composition is used for a TCD measurement of shunt conductance.
In addition to the unknown and significantly varying number of microbubbles contained in the injected bolus of contrast agent, there are other factors that can affect the measured number of ETs using the TCD method. These other factors can cause a significant variation in the numbers of detected ETs for a given subject and shunt conductance, even if the number of microbubbles in the injected contrast agent was accurately known and/or controlled. One of these other factors is the adequacy of the provocative maneuver used to briefly increase the pressure in the right atrium to a level that is higher than the pressure in the left atrium. Normally, the localized blood pressure within the left atrium is higher than the right atrium. By way of example, during normal activities that do not involve any provocations such as exertion, straining or coughing, the presence of a right-to-left shunt will result in blood flow, if any, only from the left atrium of the heart to the right atrium of the heart and, accordingly, pose no risk of embolic ischemia since there is no blood flow directly from the right atrium to the left atrium across the atrial septum. However, during provocative activities such as lifting, straining during defecation, physical sports, coughing and scuba diving, the pressure in the right atrium can briefly become larger than the pressure in the left atrium, thereby allowing a portion of the venous blood flowing through the right atrium to briefly flow directly from the right atrium to the left atrium, thereby circumventing the filtering benefit provided by the lungs. Under the conditions of such provocations, any embolus or emboli (viz., tiny blood thrombus or thrombi) in the right atrium during the period of a positive right-to-left atrial pressure gradient can be transported directly to the left atrium. Once in the left atrium, the embolus or emboli can follow any of the normal arterial circulatory pathways which include pathways leading to the brain or the coronary arteries of the heart. Those pathways allowing any embolus or emboli to reach the brain or heart can lead to stroke or heart attack, respectively.
Several types of provocative maneuvers have been reported that can create the required right-to-left pressure gradient to purposely induce the flow of an injected indicator or contrast agent through a right-to-left shunt, if present. Alternative provocative maneuvers include the Valsalva maneuver, Valsalva strain and coughing. The most widely used type of Valsalva maneuver is a breathing procedure involving the following three-steps: [1] inspiration (i.e., deep breath) to fill the lungs with air, [2] generation of exhalation pressure to a predetermined pressure level of about 40 mm Hg into a closed mouthpiece (usually incorporating a pressure sensing device) for a minimum period of five seconds and [3] abrupt release of exhalation pressure followed by normal breathing. Published clinical studies involving humans have demonstrated that a Valsalva maneuver performed according to the above three steps provides the most consistent method for inducing the right-to-left pressure gradient required to induce a temporary blood flow through any right-to-left shunt (e.g., PFO) that may be present in the heart and thereby reveal the presence of a right-to-left shunt by any of the aforementioned detection methods. These published clinical studies also have confirmed that the right-to-left pressure gradient required to induce blood flow across a shunt (if present) [a] only starts upon the release or end of the Valsalva maneuver and [b] only persists for two or three heart beats or about two to three seconds following the Valsalva release. Consequently, it is important that the release or end of the exerted exhalation pressure occurs when the contrast agent arrives in the right atrium of the heart, since the right-to-left pressure gradient persists for only two to three seconds beyond the release of the Valsalva exhalation pressure. Further background on provocative maneuvers including Valsalva maneuvers and coughing maneuvers is found in the following articles: [a] Pfleger, S. et al. Hemodynamic Quantification of Different Provocation Maneuvers by Simultaneous Measurement of Right and Left Atrial Pressure: Implications for the Echocardiographic Detection of Persistent Foramen Ovale. European Journal of Echocardiography 2001; 2: 88-93, [b] Dubourg O, et al., Contrast echocardiographic visualization of cough-induced right-to-left atrial shunt through a patent foramen ovale. Journal of American College of Cardiology 1984; 4: 587-594 and [c] Droste D W, et al., Contrast Transcranial Doppler ultrasound in the detection of right-to-left shunts: comparison of different procedures and different contrast agents. Stroke 1999; 30:1827-1832.
In addition to the critical timing of the release of the Valsalva exhalation pressure that is coincident with the time when an injected contrast agent arrives in the right atrium, it is also important to account for the differences in transit time between the site of injection (e.g., antecubital vein fossa in the arm) and the right atrium. This transit time is critical since the contrast agent needs to arrive at right atrium during the brief two to three second period that the right-to-left pressure gradient persists (immediately after the release of the Valsalva maneuver) in order to cross directly into the left atrium during that brief period. A further complication confronting methods employing contrast agent based shunt detection methods is the variability in the transit time due to differences in the venous volume in the pathway between the antecubital vein and the right atrium associated with subjects of varying size. Even if the contrast agent and flushing solution is injected at a nominally constant rate, the transit time between the antecubital vein and the right atrium can vary by as much as three seconds or more due to vascular differences as well as levels of cardiac output between subjects being tested.
In order to compensate for known transit time differences, it is advantageous to release the Valsalva maneuver to induce a positive right atrial-to-left atrial pressure gradient at the precise time when the contrast agent substantially arrives and fills the right atrium. If the contrast agent arrives more than several seconds before the release of the Valsalva maneuver and the associated creation of the essential right-to-left pressure gradient, then most or all of the contrast agent will proceed along the normal pathway through the lungs and into the left atrium since the right-to-left shunt will effectively be "closed" when the contrast agent arrives. As a consequence, any right-to-left shunt that may be present may not be detected resulting in a false negative shunt test result. Likewise, if the contrast agent arrives too late relative to the release of the Valsalva exhalation pressure, the essential right-to-left pressure gradient will have ended and consequently essentially all of the contrast agent will proceed along the normal pathway through the lungs and into the left atrium again resulting in a negative shunt test result.
In addition to achieving the correct timing of the release of the Valsalva maneuver coincident with the arrival of the contrast agent in the right atrium, the ability to accurately detect the presence of a right-to-left shunt in the heart also depends on performing a provocative maneuver of both adequate intensity (viz., exhalation pressure of at least 40 mm Hg, preferably at least 40 mm Hg) and adequate duration (viz., exhalation exertion for at least 5 seconds).
By way of example, a system and method for measuring exhalation pressure to determine abdominal pressure surrounding the bladder is disclosed by de Menezes in U.S. Publication Number US 2010/0234758. The system and method includes a pressure monitor with display, tubing extending from the pressure monitor to a mouthpiece and a mouthpiece. The subject exhales into the mouthpiece and the exhalation pressure level is displayed. Other methods currently used in the conduct of Valsalva maneuvers include attaching a length of tubing to a pressure gauge or mercury manometer. The patient exhales into the tube and the exhalation pressure is dynamically displayed.
Both of the above methods allow the exhalation pressure to be dynamically measured. As stated above, it is essential that the provocative maneuver be adequate to create a positive right-to-left atrial pressure gradient sufficient to induce blood flow directly from the right atrium to the left atrium (in the event a right-to-left cardiac shunt is present). In addition, it is also essential that the contrast agent arrives in the right atrium during the brief 2 to 3 second period when the positive right-to-left pressure gradient persists so that indicator may traverse the atrial wall (septum) and reveal the presence of a right-to-left shunt. The timing of the arrival of the contrast agent in the right atrium is critical since the time period during which the requisite right-to-left pressure gradient persists is less than about two seconds. In this regard, also see Karttunen, V., et al. Dye Dilution and Oximetry for Detection of Patent Foramen Ovale. Acta Neurol Scand 1998; 97:231-236.
As stated above, the accurate quantification of the conductance of a right-to-left shunt is important to identifying subjects at risk of an ischemic stroke, both a first stroke as well as recurrent strokes caused by the passage of emboli through a patent right-to-left shunt, emboli that would otherwise have been trapped and filtered from the blood stream as a result of the normal flow of blood through the vasculature of the lungs. In addition to minimizing the risk of strokes, there are other significant adverse consequences of right-to-left shunts, especially larger right-to-left shunts (e.g., PFOs and ASDs) exhibiting higher shunt conductances. By way of example of other adverse consequences, the association between migraineurs with aura and ischemic stoke has been reported to be statistically significant based on a six year follow-up of 459 subjects that were 45 years or older (see Androulakis, X., et al., Ischemic Stroke Subtypes and Migraine with Visual Aura in the ARIC Study. Neurology 2016; EPub Nov. 9, 2016). As another example, a report including 20 observational studies involving 1,194 subjects, 10% to 83% reported complete cessation of migraine and 14% to 83% reported reduction in migraine symptoms (see Tariq, N., et al., Patent Foramen Ovale and Migraine: Closing the Debate—A Review. Headache 2016; 56 [3]: 462-478). In the PREMIUM Trial of 220 subjects with 117 receiving PFO closure, 10.8% of migraineurs with aura experienced complete remission of migraine headaches following PFO closure while only 1.5% experienced complete remission without PFO closure (see Reisman, M., et al., Migraine Reduction after Transcatheter Closure of Interatrial Septal Defects: Another Brick in the Wall? Journal of Structural Heart Disease 2016; 2 [5]: 231-233). In yet another example, the PRIMA Trial showed a significant reduction in migraine symptoms during 12-month follow up after PFO closure compared to medical treatment alone (Tarantini, G., et al., Patent Foramen Ovale Closure and Migraine Time Course: Clues for Positive Interaction. Int. Journal of Cardiology 2015; 195:235-236). In yet another clinical trial, it has been reported at three months after PFO closure that 40% of patients with only aura had complete resolution of symptoms while 25% of migraineurs with aura had complete resolution of symptoms (see Khessali, H., The Effect of Patent Foramen Ovale Closure on Visual Aura without Headache or Typical Aura with Headache. Journal of American College of Cardiology: Cardiovascular Interventions 2012; 5: 682-687). In yet another clinical trial in which complete PFO closure was confirmed, 15 of 16 patients experienced complete remission of migraine symptoms after closure (see Yoon, J., et al., Intermediate and Long-Term Results of Transcatheter Closure of Patent Foramen Ovale Using Amplatzer Patent Foramen Ovale Occluder: One Case of Pulmonary Embolism Irrespective of Patent Foramen Ovale Closure. Korean Circulation Journal 2011; 41: 356-362).
In addition to minimizing the risk of stroke and debilitating affects of severe migraine, clinical studies have also confirmed the adverse neurological impact of the cardiac shunt-related emboli burden on an otherwise asymptomatic population. The results of clinical studies indicate that a significant cause of dementia in the elderly population may be due to the presence of a right-to-left shunt since the cumulative effect of subclinical or silent microinfarcts appears likely to be a principal cause of progressive dementia and possibly even Alzheimer's Disease. The dementia and Alzheimer's Disease syndrome is now considered by many clinicians to be a sufficient reason to prophylactically close known PFOs assuming closure can be safely and effectively accomplished. In this regard, see [a] Bang, O., et al., Patent Foramen Ovale and Stroke—Current Status. Journal of Stroke 2015; 17(3): 229-237, [b] Hassell, M., et al., Silent Cerebral Infarcts Associated with Cardiac Disease and Procedures. Nature Reviews Cardiology 2013; 10: 696-706 and [c] Purandare, N., et al., American Journal of Psychiatry 2012; 169: 300-308.
The detection of the presence of a clinically significant right-to-left shunt in a patient routinely enables the attempted closure of the shunt using one of a number of alternative transcatheter closure devices. However, clinical trials have demonstrated that complete closure of the identified right-to-left shunt often is not achieved, especially in the first three to twelve months after closure, resulting in residual shunting. By way of example of the differing levels of achieved closure with alternative closure devices, the level of residual shunting after ASD closure in 217 patients at 12 months post closure was clinically significant with 40%, 22% and 9% residual shunting observed upon post-closure examination using TEE for CardioSEAL/STARFlex, Helex and Amplatzer closure devices, respectively (see Zdradzinski, M., et al., Contributors TO and Impact of Residual Shunting After Device Closure of Atrial Septal Defects. American Heart Journal 2016; 177: 112-119). In yet another example, a significant number of recurrent and residual right-to-left shunts were observed in a 120 patient cohort using the TCD method at an average of five years after PFO closure with 17% exhibiting residual shunting and 29% exhibiting recurrent shunting, i.e., the residual shunting decreased significantly and then subsequently increased significantly suggesting failure of the closure device (see Cheli, M., et al., Recurrent and Residual Shunts After Patent Foramen Ovale Closure: Results from a Long-Term Transcranial Doppler Study. Journal of Interventional Cardiology 2015; 28: 600-608).
The above examples of the prevalence of residual shunting, as well as recurrent shunting, extending for post-closure periods of a year or more, confirm the need for an accurate method for quantifying the conductance of residual and recurrent shunting after the intended closure. The accuracy of the post-closure method for quantifying the conductance of a residual or recurrent shunt is important for three reasons. First, the level of residual or recurrent shunting following "closure" guides the clinician's selection of anticoagulant therapy, if needed, and the duration of its use following closure. Once the conductance of the shunt following closure is confirmed to have been sufficiently reduced (e.g., reduced from a large Grade IV shunt to a very small Grade I shunt), then the use of high risk anticoagulants such as warfarin can be terminated and replaced with, at most, aspirin therapy. Second, the level of residual or recurrent shunting following "closure" allows the assessment of the efficacy of the closure device and the suitability of its continued clinical use.
Third, the level of residual or recurrent shunting following "closure" enables the conduct of meaningful clinical trials so that the inability to achieve the expected outcome (e.g., reduction in the occurrence of strokes or migraine symptoms) can be interpreted based on extent to which shunt closure was actually achieved. In spite of the demonstrated sensitivity to detect the presence of a right-to-left shunt, prior art Transcranial Doppler apparatus, systems and methods are incapable of accurately quantifying the conductance of right-to-left shunts. This inherent limitation is the consequence of multiple and uncontrolled operator dependent functions including [a] the interpretation of ultrasound images of embolic tracks (currently performed manually and subject to individual interpretation), [b] the accurate positioning of ultrasound traducers over the Middle Cerebral Artery on one or both sides of the subject's head adjacent to the targeted intracranial arteries, [c] the timing of the arrival of the injected agitated saline ultrasound contrast agent (i.e., microbubble mixture) in the right atrium relative to the timing of the Valsalva Maneuver release and [d] the very large (20× or more) variability in number of microbubbles injected due to the operator's preparation method and variable delays before injection causing microbubbles to collapse since their half-life has been measured to be in the range from about 4 to 5 seconds depending on the contrast agent composition.
In summary and in view of the fact that over 20% of the adult population has a right-to-left shunt, the capability to accurately quantify the conductance of a right-to-left shunt is clinically beneficial for a number of reasons as described above. The clinical benefits of providing an accurate method for quantifying the conductance of a right to left shunt include identifying subjects whose right-to-left shunt is sufficiently large to warrant intervention with transvascular closure or anticoagulant therapy to minimize [a] the risk of initial or recurrent ischemic strokes, [b] the frequency and severity of migraine headaches and [c] the risk and severity of dementia and Alzheimer's Disease. In addition, providing an accurate method for quantifying the conductance of a right-to-left shunt is essential for ongoing clinical follow-up and guiding medical therapy following transcatheter closure of a right-to-left shunt as well as characterizing the efficacy of alternative closure devices and method used.
An object of the present disclosure is therefore to provide a Transcranial Doppler (TCD) ultrasound method, apparatus and system to accurately measure the conductance of a right-to-left shunt with a high level of repeatability. In order to achieve the conductance measurement accuracy and repeatability required, it is an object of the present disclosure to incorporate a method, apparatus and system to detect when the contrast agent substantially arrives in the right atrium of the heart. Another object of the present disclosure is to provide a method, apparatus and system to assure a Valsalva maneuver whose exhalation pressure level and duration are within predetermined limits (e.g., a pressure of at least 40 mm Hg and at least 5.0 seconds in duration). Another object of the present disclosure is to provide a method, apparatus and system to automatically induce the release (i.e., end) of the Valsalva maneuver when the arrival of the contrast agent in the right atrium is detected. Yet another object of the present disclosure is to incorporate a controlled leak in the exhalation mouthpiece so that the patient creates the required Valsalva maneuver pressure using their diaphragm and not their cheek muscles. The creation of pressure using only the cheek muscles will not create the hemodynamic conditions necessary to effect a right-to left pressure gradient. A further object of the present disclosure is to provide a mouthpiece component that can be manufactured at sufficiently low cost to enable its single use thereby avoiding cross-contamination and pathogen transfer between patients. Yet another object of the present disclosure is to incorporate a method, apparatus and system to automatically count the number of microbubbles contained in a sampled portion of the agitated saline/air/blood mixture so that the number of embolic tracks measured using Transcranial Doppler ultrasound can be adjusted according to the total number of microbubbles injected estimated using a sampled volume of contrast agent. Still yet another object of the present disclosure is to incorporate a method, apparatus and system to automatically determine the number of embolic tracks using a software algorithm based on [a] the number of countable embolic tracks and/or [b] an ultrasound signal intensity as an equivalent metric for the number of microbubbles transported within the targeted intracranial artery, thereby eliminating the time consuming and user dependent manual counting methods currently use to analyze the ultrasound spectra generated by Transcranial Doppler apparatus and systems.

Apparatus, system and method for the detection and quantification of conductance of right-to-left cardiac shunts


A transport device (2, 50, 56, 88) for transporting a coil (4), comprising a coil transport cart (6) having a chassis (8) and having a coil support (10), which is height-adjustable relative to the chassis (8). In order to enable secure transport of the coil (4), the transport device (2, 50, 56, 88) has a movable fastening device (12) having a clamping unit (22) for pressing the coil (4) to be transported against the coil support (10). The clamping unit (22) being height-adjustable relative to the coil support (10) and being able to be at least partly inserted into a coil eye (42) of the coil (4). The fastening device (12) being fastened to the coil support (10) or to the chassis (8) of the coil transport cart (6). The coil support (10) having a cut-out (40), into which the clamping unit (22) can be at least partly lowered. Further disclosed is a use of such a transport device (2, 50, 56, 88), to a coil-processing system (70, 118) having such a transport device (2, 50, 56, 88), and to a method for transporting a coil (4).

In the metal industry, it is customary to transport a rolled product, such as a metal strip or a metal wire, as a bundle, i.e., wound up. Such a bundle of wound-up rolled product is also called a coil in technical circles.
For the transport of a coil, one may use a coil transport cart, for example, which is fitted with a coil support on which the coil can be placed.
A coil in which the wound-up rolled product has high strength and/or large thickness may have a tendency to bounce up from a coil support of a coil transport cart or to fall down from the coil support, since the coil acts like a spiral spring on account of its material stiffness. The bouncing of a coil carries the risk of injuring persons in the vicinity of the coil and/or damaging equipment components.
In order to hinder bouncing of a coil, especially during its transport, after the rolled product is wound up, the coil can be closed with one or more strapping bands.
Moreover, it is known how to take a sample from a coil in a sampling station in order to monitor its quality.
For purposes of the sampling, the coil is usually partly unwound in the sampling station. Any strapping bands which are present must be first removed. After the sampling, the remaining coil is completely wound up and typically closed again with one or more strapping bands.
If any strapping bands that are present are removed in a separate band removal station located upstream from the sampling station, there is a danger that a coil with a tendency to bounce up will bounce up during its transport from the band removal station to the sampling station. Likewise, if a coil with a tendency to bounce is again strapped in a strapping station located downstream from the sampling station, the coil may bounce under certain circumstances during its transport from the sampling station to the strapping station.
Furthermore, in the case of a coil having a narrow width and a large diameter and which is transported in such a way, resting on a coil transport cart, that its coil axis is oriented horizontally during the transport, there is a high danger that the coil will tip over during the transport, especially when it starts to move and/or when the coil transport cart is braked. The transport of such narrow coils with large diameters thus likewise carries the risk of persons being injured in the vicinity of the coil and/or equipment components getting damaged.
DE 10 2011 080 410 A1 discloses a transport device for transporting of a coil, wherein the device has a coil transport cart and a height-adjustable coil support. A movable fastening device provides a height-adjustable clamping unit for pressing the coil to be transported against the coil support, and the clamping unit can be introduced at least partly into a coil eye of the coil.

Transport device and method for transporting a coil


According to one embodiment, a wet-area device includes a main part, a first layer, and a second layer. The first layer is provided on an outer surface of the main part. The second layer is provided on an outer surface of the first layer. A hardness of the second layer is greater than a hardness of the first layer. The first layer includes a first unevenness at a side of the outer surface of the first layer. The first unevenness includes a plurality of recesses and a plurality of protrusions. The second layer includes a second unevenness at a side of an outer surface of the second layer. The second unevenness includes a plurality of recesses and a plurality of protrusions. The second unevenness is arranged along the first unevenness. An average height of the first unevenness is less than an average length of the first unevenness.

Metal plating on the outer surface of a main part for ensuring the strength of a wet-area device such as a faucet apparatus or the like is known (e.g., JP-A 2008-106487). The outer surface of such a wet-area device has a highly glossy appearance due to the plating when struck by light.
On the other hand, matting of the outer surface of a plated wet-area device for suppressing the glossy appearance of the outer surface is known. For example, such matting is performed by forming a fine unevenness in the outer surface of the wet-area device (the plating) by shot blasting, etc.
However, when matting is performed by shot blasting or the like, there are cases where the height (the depth) of the unevenness formed in the outer surface of the wet-area device undesirably becomes too large. When the height of the unevenness formed in the outer surface of the wet-area device is too large, it is difficult to remove the water that collects in the unevenness, and the adhesion of grime to the outer surface of the wet-area device easily becomes a problem.

Wet-area device and method for manufacturing wet-area device


A method for selective detection of volatile and non-volatile explosives in a mass spectrometer or ion mobility spectrometer at a parts-per-quadrillion level without preconcentration is disclosed. The method comprises the steps of ionizing a carrier gas with an ionization source to form reactant ions or reactant adduct ions comprising nitrate ions (NO3−); selectively reacting the reactant ions or reactant adduct ions with at least one volatile or non-volatile explosive analyte at a carrier gas pressure of at least about 100 Ton in a reaction region disposed between the ionization source and an ion detector, the reaction region having a length which provides a residence time (tr) for reactant ions therein of at least about 0.10 seconds, wherein the selective reaction yields product ions comprising reactant ions or reactant adduct ions that are selectively bound to the at least one explosive analyte when present therein; and detecting product ions with the ion detector to determine presence or absence of the at least one explosive analyte.

Current state of the art trace detection for explosives, chemical threat agents, and other threat agent signatures have remained long-standing goals of modern instrument platforms. However, analytical techniques for direct vapor detection of threat agents remain limited because significant improvements in sensitivity must yet be attained if automated technologies are to be of practical use. For example, equilibrium vapor pressures (saturated) of RDX explosive at 25° C. provide a concentration of ˜6 parts-per-trillion (ppt) or 6 in 1012. Because real-world analyses must achieve detection below saturation levels, sensitivity must be substantially better than this 6 ppt threshold. To complicate matters, improvements in sensitivity without improvements in selectivity are counterproductive, as increasing sensitivity effectively raises the chemical noise, which offsets improvements to upstream components. Thus detection of threat agent vapors requires significant increases in sensitivity along with subsequent increases in selectivity. While some sensitivity and selectivity improvements have been achieved with mass spectrometry (MS)-based analytical approaches including, e.g., Selected Ion Flow Tube (SIFT) Mass Spectrometry (MS) or (SIFT-MS); Proton Transfer Reaction Mass Spectrometry (PTR-MS); and Atmospheric Pressure Chemical Ionization Mass Spectrometry (APCI-MS), none of these approaches provides selective determination of vapors from explosives and other threat agents. Nor do these approaches achieve sensitive and selective trace level detection of threat agents in real-time.
Accordingly new systems and processes are needed that enable real-time trace level detection of explosives and other threat agents at a parts-per-trillion level or better. The present invention addresses these needs.

Method for selective detection of explosives in mass spectrometer or ion mobility spectrometer at parts-per-quadrillion level


A ladder adjustment apparatus (10) which is designed to be secured to the rungs (101) of a ladder (100) whereby the apparatus (10) may be laterally shifted on the rungs (101) to position the apparatus (10) adjacent either leg (102) of the ladder without the need for physically detaching the apparatus (10) from the ladder (100).

This invention was the subject matter of Document Disclosure Program Registration No. 221581 which was filed in the U.S. Patent and Trademark Office on Mar. 6, 1989.
As can be seen by reference to the following U.S. Pat. Nos.: 3,554,321; 4,143,742; 4,607,726; and 2,969,126; the prior art is replete with myriad and diverse ladder extension apparatus that are intended to level a ladder on an uneven surface.
While all of the aforementioned prior art constructions are more than adequate for the basic purpose and function for which they have been specifically designed, these devices are also limited in their basic design in that they fall into one of two categories. The most common category being the plural legal adjustment variety wherein both legs of the ladder can be adjusted independently; and the other category being the single leg exterior mounted variety wherein a detachable adjustment mechanism can be mounted on the outboard surface of either of the legs of the ladder.
In the first instance the plural leg adjustment devices are very costly to incorporate into the ladder structure, and usually contain a large number of components which are subject to structural failure which will render the ladder inoperative for uneven surfaces.
In the second instance the single leg variety is typically mounted on the outboard surface of the ladder legs which of necessity extends the width of the ladder, and the outwardly projecting portions of the adjustment mechanism tend to bump into movable and stationary surfaces as the ladder is being moved to and from a job site.
Furthermore there are certain instances wherein the standard width of a ladder is unsuitable for either variety of adjustment mechanism due to the narrowness and/or uneven contour of the workplace.
As a consequence of the foregoing situation there has existed a longstanding need for a new type of ladder adjustment mechanism that will overcome the shortcomings of the prior art constructions and provide a ladder adjustment device that is both adjustable and laterally translatable relative to the rung of a ladder. The provision of such a construction is a stated objective of the present invention.


Disclosed are systems and methods for presenting media access patterns to a user. Requests are received for a media item from consumers located in a first geographic area, or media access information is otherwise collected. A first plurality of media accesses are recorded in a logging database associated with consumers who requested the media item and who are located in the first geographic area. Requests are received for the media item from consumers located in a second geographic area. A second plurality of media accesses associated with consumers who requested the media item and who are located in the second geographic area are recorded in the logging database. A first graphical representation of the first plurality of media accesses is displayed on a map. A second graphical representation of the second plurality of media accesses is also displayed on the map.

1. Field
This disclosure relates to online media access. In particular, this disclosure relates to systems and methods for providing visual indications of media access patterns to users.
2. Background
Media consumers are increasingly accessing media, such as music and video, through the World Wide Web, and the Internet in general. As the Internet becomes the new forum for artist's success, media access patterns in the Internet have become more important. Record labels, artists, and media producers in general are now more focused than ever on media access of consumers on the Internet. In addition, consumers also want to know what media other consumers are listening to, viewing, and accessing online.

Systems and methods for presenting visualizations of media access patterns


A projector includes a light source, an information acquisition section adapted to obtain information of designating light intensity of light emitted by the light source, an arithmetic section adapted to calculate time for which the light source can be used with the light intensity represented by the information obtained by the information acquisition section, and a notification section adapted to give notification of the time calculated by the arithmetic section.

1. Technical Field
The present invention relates to a projector, and a method of controlling a projector.
2. Related Art
As a projector for displaying an image with a desired amount of light, there is a projector disclosed in, for example, JP-A-2015-129783. The projector detects a changing state of a light source with an optical sensor, then generates a table, which has the luminance of the light source and the value of a current for driving the light source so as to correspond to each other, based on the detection result, and then control the light source using the table thus generated.
The light source used in the projector deteriorates due to use. As the deterioration of the light source progresses, display with the desired brightness becomes unachievable. In order to prevent the display with the desired brightness from becoming unachievable, it is preferable for the user to figure out the deterioration of the light source in advance.

Projector and method of controlling projector


A stylus pen cap has at least one camera disposed at least partially therein. The pen cap can further include a light source (such as an infrared light source) that directs light outwardly of the pen cap to the stylus. The pen cap can further include an electrical connector that operably couples to the camera(s) and conveys captured-image data to an outboard device of choice. The pen cap can include a pocket clip that comprises the electronic connector. The pocket clip can include a flexible joint (such as but not limited to a universal joint) to thereby permit the camera(s) to be oriented and aimed as desired even while electrically connected to an outboard device.

Stylus-based user interfaces are known in the art. Generally speaking, a stylus comprises a hand-held writing utensil that often (but not exclusively) has a pencil-like elongated form factor and that includes at least one pointed end configured to serve as a writing tip by interacting with a scribing/writing surface. Using a stylus offers a variety of advantages over a fingertip including the opportunity for increased precision as well as an expression modality that accords with the user's own past experience with a pencil or pen.
Some styli are operationally passive while others are active and interact with a stylus-location sensor in some non-passive way. Generally speaking, stylus readers usually accommodate only a very limited application setting as regards use of the stylus itself. For example, use of the stylus may be limited to only a specific scribing surface or area. In cases where such a limitation does not apply, the stylus itself often includes considerable circuitry and programming to permit the stylus itself to be self-monitoring in these regards. Accordingly, typical prior art stylus solutions tend to be either highly limiting with respect to where and how a user can employ the stylus and/or represent a technically complicated and relatively expensive solution.


A user is able to appropriately select character data such as a watermark, and importance of the document is able to be effectively recognized by an addressee using a language which is different from that of a user who sends the document. A setting accepting portion accepts setting of a first language describing a first character indicated by the first character data, and setting of a second character which is a translation of the first character to a second language; a data generating portion generates a composite image data in which the image data is combined with the first character data indicating a first character which is a translation of the second character to the first language; and an apparatus control portion controls the image forming apparatus to cause the image forming apparatus to execute image forming processing of the composite image data.

When printing a document, conventionally, a watermark has been used to show importance of the document. The watermark is a character printed on a document such as "(URGENT)", "(CONFIDENTIAL)", "(IMPORTANT)", and "(TOP SECRET)". A function to print such watermarks on documents is included in a printer driver as standard specifications. Further, it is possible to print arbitrary characters input by a user on a document as a watermark.
However, in such a case, a language of a watermark which can be used by the user is the language that has been selected by the user as a using language when installing a printer driver in a computer. For example, when the user selects Japanese at the time of installing the printer driver, the language of the watermark to be printed on a document will be Japanese.
Then, when a document on which a watermark in Japanese is printed is sent by FAX, mail, an electronic mail, etc. to a dealer or a production factory in a country in which English, Korean or Portuguese is spoken, a local staff member who is the addressee of the document cannot recognize the importance of the watermark, and the case where the watermark does not function as intended may thus occur.
As the result, the document on which the watermark, "(URGENT)" is printed may be delayed to be received by a person in change, handling of the document may be left until later, or the document on which the watermark, "(TOP SECRET)" is printed may be left on a desk, thus causing a trouble in business.
It might be helpful if a user can directly input characters used as a watermark in the language that can be understood by the local staff member, however, it is expected that there is a small number of users who know the expressions in Korean, Portuguese, etc.
Furthermore, even when expressions in those languages are known by a user, when the OS (operating system) of a computer is provided in a Japanese version, or when a keyboard is a Japanese keyboard, there occurs a problem that the OS needs to be set up so that characters in such a language can be input, input of Hangul characters or characters with accent marks is difficult, and the like.
Japanese Laid-Open Patent Publication No. 2006-279098 shows a translation apparatus which, in order to transmit to a user who cannot understand Japanese at all that a document should be dealt as a secret, extracts from data security information which is an image indicating that the document should be dealt as a secret, and translates the security information into a target language.
However, the translation apparatus of Japanese Laid-Open Patent Publication No. 2006-279098 is used in a case where the security information has already been printed on a document, and not used prior to the printing of the document. Therefore, the type of the security information to be printed on a document cannot be selected by a user.
That is to say, the translation apparatus of Japanese Laid-Open Patent Publication No. 2006-279098 is not the apparatus in which in order to solve the problem due to a language used in a destination country, when a user has decided a watermark to be added to the document while the document to which the watermark is added has not yet been printed, appropriate processing is performed for the document, and has a background art and a purpose of development which are totally different from such an apparatus.

Apparatus control method and control apparatus


A method of improving data security or privacy in a computing environment includes providing a group identifier value to at least a first user of one or more users and associating a first pseudonym with the first user. The method further includes encrypting a first data set according to a private key and marking the encrypted first data set according to the group identifier and the first pseudonym. The method also includes performing a first operation on the encrypted first data set and transforming the encrypted first data set into an encrypted second data set according to the first operation performed and the first pseudonym, decrypting the encrypted second data set using the private key, and analyzing the decrypted second data set.

The present invention is directed to homomorphic encryption, and more specifically to improvements to computer data privacy and security in fully homomorphic encryption.
Data aggregation is highly desirable in many computer systems and schemes. However, data aggregation currently poses the challenge of how to protect the privacy of the participants, parties, or users, especially when the participants do not trust each other and other computer-based entities such as a data aggregator or decryptor. Typically, the aggregator is a separate entity to the decryptor.
Homomorphic encryption is a cryptographic concept or mechanism that allows certain computations on encrypted data, generating an encrypted result which, when decrypted, matches the result of the same operations performed on the plaintext data. Computer-based verification of the operations performed via evaluation of homomorphic encryption schemes is a desirable capability particularly in settings where multiple distrusting users, parties, or entities are involved. Existing fully or partially homomorphic computer-based encryption schemes have limited privacy. Therefore, current homomorphic encryption schemes have weak security and privacy guarantees because of a lack of reliable, computer-based verification measures. This has necessitated a certain level of trust among the distrusting parties, which may not be desirable or practical, especially in settings where competitors are collaborating and sharing their encrypted data for homomorphic encryption evaluations.

Privacy preserving fully homomorphic encryption with circuit verification


A dishwasher, wherein a duct system has a function describing a pressure difference in dependence on the rotational speed of the circulating pump and having a lower rotational speed range in which the pressure difference changes at most in proportion to the rotational speed of the circulating pump and an upper rotational speed range in which the pressure difference changes more than in proportion to the rotational speed of the circulating pump; and wherein the control device has a first rinsing program in which the circulating pump is operated at a normal cleaning rotational speed for normal cleaning of the rinsing stock and a second rinsing program in which the circulating pump is operated at an intensive cleaning rotational speed higher than the normal cleaning rotational speed and lying in the upper rotational speed range for intensive cleaning of the rinsing stock.

The present invention relates to a dishwasher, particularly a household dishwasher, comprising a control device for carrying out a rinsing process for cleaning rinsing stock on the basis of a rinsing program, a rinsing chamber for receiving the rinsing stock during the rinsing process, a circulating pump for circulating a rinsing liquid present in the rinsing chamber, the rotational speed of the pump being variable by the control device, a first spray element for action on a first region of the rinsing chamber by the circulated rinsing liquid, a second spray element for action on a second region of the rinsing chamber by the circulated rinsing liquid and a duct system for conducting the circulated rinsing liquid from the circulating pump to the first spray element and the second spray element, the duct system having a first branch conducting the rinsing liquid to the first spray element and a second branch conducting the rinsing liquid to the second spray element.
A dishwasher of that kind is known from practice. In the known dishwasher it is not always possible to optimally match the cleaning action to the loading of the dishwasher.

Dishwasher with improved cleaning effect


An automatic transmission brake adapter for use in high performance vehicle drag racing. In electronic controlled automatic transmission, the transmission is held in both reverse and drive allowing the engine to accelerate without movement of a vehicle. Release of the reverse gear and associated rapid acceleration of the vehicle in drive is accomplished by a modular transmission brake adapter using the existing electronic automatic transmission control system without extensive modification thereto.

1. Technical Field
This invention relates to transmission brakes for vehicles in which the transmission is held in place by engaging both drive and reverse gears simultaneously allowing the engine to be accelerated without moving the vehicle until the reverse gear is released. Such devices are used in high performance automobile drag racing in which it is important to get the fastest start possible when utilizing an automatic electronic controlled transmission.
2. Description of Prior Art
Prior art devices of this type have been directed to a variety of ways in which automatic transmissions can be selectively locked into a braking position for drag racing purposes when released, see for example U.S. Pat. Nos. 4,883,151, 5,148,720, 5,622,088 and 6,050,384.
In U.S. Pat. No. 4,883,151 a transmission brake is disclosed for automatic transmissions in which the conventional gear selector is modified in the vehicle with two gear engagement positions by modifying the existing manual selecting switch shift valve.
U.S. Pat. No. 5,148,720 discloses a lock-up solenoid assembly that is universal that closes off a fluid passageway allowing pressure to build up in a control chamber moving a valve element so that the front portion of the torque converter can empty itself, effectively locking the transmission.
An automatic transmission for racing is set forth in U.S. Pat. No. 5,622,088 which has a reverse gear piston that is engageable to act as a transmission brake.
U.S. Pat. No. 6,050,384 is directed to a method and device for rapid transmission brake release in which a modification to the automatic transmission is made applicable to Turbo Hydromatic 400 Transmissions. A pressure release passageway is provided in the servo cover so that it can be selectively blocked and unblocked by a solenoid.

Automatic transmission brake for racing vehicles


An alert broadcast method includes wirelessly transmitting a first message from a first cellular communication device to a central transceiver. The first message has a characteristic identifying the first message as an alert message. A location of the first cellular communication device is determined. A plurality of second cellular communication devices that are within a proximity of the first cellular communication device are identified. A second message is transmitted from the central transceiver to the second cellular communication devices. The second message is dependent upon the first message.

1. Field of the Invention
The present invention relates to apparatuses and methods for broadcasting alert messages to groups of people within a geographic area.
2. Description of the Related Art
In response to some recent events in which gunmen have been on college campuses, the colleges have put into place a central facility for transmitting text messages to an entire campus body. A problem with this approach is that it necessitates finding out and keeping track of the phone numbers of each telephone near the campus. Another problem with this approach is that it includes no mechanism for contacting people who are merely passing through the area or who are just visiting the area for the day.
What is neither disclosed by nor obvious in view of the prior art is a close proximity broadcast message system that can alert anyone within a several miles of the system of a dangerous situation, or a situation that they may be interested in. What is also neither disclosed by nor obvious in view of the prior art is a system that enables a user to call an alert number such that anyone within a specified distance of the system may receive the message without the system having to know the person's specific phone number. Nor does the prior art disclose or make obvious a system that allows a cellular (or Bluetooth) device to receive broadcast messaging based on a device's proximity to the caller. Further, the prior art does not disclose or make obvious a system that enables a cellular or Bluetooth device to directly transmit to another cellular or Bluetooth device based on proximity global positioning system (GPS) coordinates or Bluetooth radio frequency range for alert communications.

Close proximity alert messaging system and method


A method for reducing interference to wireless communication devices is described. A handoff request is received from a wireless communication device. A femto access point that is a hand-in target of the handoff request is determined. A handoff information message is sent to the femto access point. The method may be performed by a core network apparatus.

Wireless communication systems have become an important means by which many people worldwide have come to communicate. A wireless communication system may provide communication for a number of mobile stations, each of which may be serviced by a base station.
It may be beneficial to use localized base stations that provide service to a select group of mobile stations. These localized base stations may use less power and have smaller coverage areas than normal base stations. The localized base stations may then provide a mobile station with active voice/data access. As localized base stations continue to improve, more localized base stations will become prevalent.
Examples of localized base stations include femtocells and picocells. Localized base stations may be referred to as femto access points without loss of generality. These localized base stations may be controlled by a user. For example, a localized base station may be purchased by an end user and placed in their home or office to increase wireless coverage. A localized base station may also be controlled by a service provider. For example, a service provider may place a localized base station in a public area with high traffic.
As a mobile station approaches a localized base station, the mobile station may detect the localized base station and attempt to access it by sending a registration request. The localized base station may then determine whether to allow access to this mobile station for different services such as a voice/data connection with the mobile station. Mobile stations that are near these localized base stations but not part of the select group may receive strong interference from the localized base stations. This strong interference, in some instances, may prevent a mobile station from obtaining access to a normal base station. As such, benefits may be realized by minimizing the interference of localized base stations on mobile stations.

Minimizing interference to non-associated users


A user interface is provided allowing a user to simulate mouse hovering with the user's finger on a touch-sensitive display. When a finger or other stylus touches the touch-sensitive display adjacent to a display cursor, a control appears that enables the user to drag the cursor about the display by dragging the control. Manipulation of the control instead of the cursor allows the user to see the cursor while it moves, making it easier to accurately target small objects that were previously difficult to target directly. In addition, a tap or other user touch input is funneled from the control to the location of the cursor itself. For example, if the user taps on the control, the tap causes an event such as a left mouse button down event to be generated at the location of the cursor as opposed to the location of the tap, thereby improving accuracy.

Touch-sensitive surfaces are rapidly becoming more common in computing devices. They are very convenient as they allow a user to make natural gestures familiar to the user in other contexts, such as by entering handwriting using a special stylus such as an elongated pen-like object having a pointed tip. Many of these devices also allow input to be provided by user's fingertip. The term touch-sensitive surface or device will be used herein to refer to such surfaces or devices that are configured to detect the touch of any type of "stylus" such as a specially-design stylus device or a user's finger. One disadvantage of using a finger or other broad-tipped stylus with a touch-sensitive device is that it is more difficult to accurately target where the finger will and will not touch. For instance, where the touch-sensitive device is combined with a display (thus, a touch-sensitive display), it is difficult to use a finger to target small displayed objects so that they may be selected and/or manipulated. There is therefore a need to provide a way for users to be able to use a touch-sensitive device with their fingers or other inherently imprecise styluses, while maintaining a reasonable level of accuracy.
In addition, various pointing devices such as mice and man-made pen-type stylus digitizers provide for a hover function, meaning that the user may position the cursor over an area without generating a click. However, few if any touch-sensitive displays have this capability when used by a human finger. There is therefore a need to provide a way for users to hover the cursor using only their finger on a touch-sensitive display.


A slide door-carrying cab is provided which includes a slide door capable of forming a sufficient clearance between a rear portion of the cab and a back of an operators seat, reclining the back at a sufficient angle, and giving an excellent comfortableness to an operator. The cab is provided in the position on a turntable which is offset from the center of a swinging movement thereof. An outer side portion of the cab has an outwardly bulging surface, and the slide door which moves along the curved surface is provided at a front section of the outer side portion. A rear portion of the cab is made of outwardly bulging two-dimensionally bent rear curved glass, and an outer edge of the rear portion is made to stay within a turning radius of an outer edge portion of the turntable.

1. Field of the Invention
This invention relates to a slide door-carrying cab for construction machines.
2. Description of the Related Art
The known slide door-carrying cabs for construction machines include the cab for construction machines disclosed in, for example, Japanese patent publication (JP-A-2001-49696), pages 3 to 4, FIGS. 2 and 7. According to this patent publication, a turntable is provided on a traveling gear which is at a lower portion of a construction machine, and a cab in the position on the turntable which is offset from the center of a swinging movement thereof. The cab is formed so that an outer side portion thereof bulges outward curvilinearly. The outer side portion of the cab is provided with a slide door, and a radius of curvature of a rear half section of the outer side portion is set smaller than that of a front half section thereof. Consideration is given to the slide door so that an orbit of an outer edge portion of the slide door in opening and closing movements thereof stays within a turning radius of an outer edge portion of the turntable.
FIG. 3 is a perspective view of the cab disclosed in this patent publication. The construction of the cab will be described in detail on the basis of what is shown in FIG. 3. The cab 20 is provided with a front portion 21, a top plate portion 22, an inner side portion 23, a rear portion 24, and an outer side portion 25 having a slide door 30 in a front half section 27 thereof and a wall surface portion in a rear half section 26 thereof. The slide door 30 is slidingly moved with the slide door 30 guided by an intermediate guide rail 31, an upper guide rail 32 and a lower guide rail 33 which are provided on the outer side portion 25. The outer side portion 25 is formed so as to have an outwardly bulging curvilinear surface, and the radius of curvature of the rear half section 26 of the same portion 25 is set smaller than that of the front half section 27 thereof, i.e. the slide door 30. The front portion 21 is provided with front glass 21a, the inner side portion 23 flat side glass 23a, the rear portion 24 flat rear glass 24a, and the rear half section 26 of the outer side portion 25 two-dimensional curved glass 26a respectively.
This patent publication says that, when the slide door 30 is opened, the lateral size of a rear half portion of the cab 20 can be widened owing to the above-described structure to as great an extent as possible without causing a rear end portion of the slide door 30 to project to the outside of the turning radius of a swinging movement of an outer edge of the turntable, and that an effective space in the cab can thereby be enlarged limitlessly.
FIG. 4 is a side view of a rear-end small-turn type power shovel 1, an example of a construction machine on which the cab disclosed in the above patent publication is mounted. A turntable 3 swingably mounted on a traveling gear 2 is mounted with the cab 20. A front end portion of the turntable 3 is mounted on a working machine 4. According to what is shown in FIG. 7 in this patent publication, a rear portion of the cab 20 is made of a flat vertical wall.
FIG. 5 is a sectioned side view of a mode of embodiment to which an operator's seat 40 is added of the cab 20 disclosed in the above patent publication, and FIG. 6 is a plan view of the same embodiment. Referring to FIGS. 5 and 6, the cab 20 is fixed in the position on the turntable 3 which is offset from the center C of a swinging movement thereof 3, and an outer edge (a broken line shows a turning circle of the slide door 30 being opened) of a turning circle of the slide door 30 being opened and closed stays within a turning radius R of the outer edge of the turntable 3. The cab 20 is provided with a total of five support posts 34a, 34b, 34c, 34d, 34e in the four left and right corners thereof and at an intermediate section of the portion thereof which is on the side of the slide door 30. In the interior of the cab 20, an operator's seat 40 having a back 41 against which the back of an operator can be reclined is provided.
In this structure, flat vertical rear glass 24a is provided in the rear portion 24 of the cab 30, so that a clearance M between the back 41 of the operator's seat 40 and the rear glass 24a is narrow. The clearance M is really too narrow to place, for example, a tool box therein, and proves inconvenient. Moreover, in order to recline the back 41, a reclining angle β cannot be set large, and an operator therefore cannot take a break in a comfortable posture during a rest period.