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An implantable monitoring device for monitoring a patient's heart rate variability over time. The device includes a cardiac electrogram amplifier, a sensing electrode coupled to an input of the amplifier, timing circuitry, processing circutry and a memory. The timing circuitry defines successive monitoring periods each extending over a period of hours, the monitoring periods together extending at least over a period of weeks and also defines successive shorter time periods during each monitoring period. The memory stores heart intervals between depolarizations of the patient's heart sensed by the amplifier during the shorter time periods. The processing circuitry calculates median intervals between depolarizations of the patient's heart sensed by the amplifier during the shorter time periods and calculates standard deviations of the median intervals calculated during each monitoring period. The processing circuitry may also reject heart intervals occurring during tachyarrhythmias and calculate median intervals based only on heart intervals not rejected.
1. An implantable device for monitoring a patient's heart rate variability over time to develop an index of heart rate variability, comprising:
a sensing electrode to detect a cardiac depolarization;
a sense amplifier coupled to the sensing electrode to produce a sigal indicative of a detected cardiac depolarization;
means for measuring intervals between detected cardiac depolarizations;
first timing means for defining successive monitoring periods;
second timing means for defining successive shorter time periods during each monitoring period;
a memory storing measured cardiac depolarization intervals occurring during a shorter time period;
means for calculating a median of the measured cardiac depolarization intervals occuring during a preceding shorter time period; and
means for calculating standard deviations of the calculated median measured cardiac depolarization intervals for a preceding monitoring period to produce an index of heart rate variability.
2. A device according to
3. A device according to
4. A device according to
5. A method of monitoring a patient's heart rate variability over time to develop an index of heart rate variability, comprising the steps of:
defining successive monitoring periods each extending over a first period of time;
defining successive shorter time periods during each monitoring period;
detecting cardiac depolarizations of the patient's heart;
measuring intervals between detected cardiac depolarizations;
storing the measured cardiac depolarization intervals occurring during the shorter time periods;
calculated a median measured cardiac depolarization interval for a preceding shorter time period; and
calculating standard deviations of the median cardiac depolarization intervals calculated during a preceding monitoring period to produce an index of heart rate variability.
6. A method according to
rejecting measured cardiac depolarization intervals occurring during tachyarrhythmias and wherein the calculating step comprises calculating median measured cardiac depolarization intervals based only on measured cardiac depolarization intervals not rejected.
7. A method according to
8. A method according to
binning stored measured cardiac depolarization intervals to form a histogram having multiple bins with each bin being associated with a measured cardiac depolarization interval range,
successively adding together the number of measured cardiac depolarization intervals stored in successive interval range bins until a sum is reached which exceeds one half of a total number of the measured cardiac depolarization intervals stored in the bins, and
responsive to the sum exceeding one half of the total number of measured cardiac depolarization intervals in the bins, designating as the median measured cardiac depolarization interval the interval range of the bin having the number of intervals stored therein most recently added to the sum that causes the sum to exceed one half of the total number of measured cardiac depolarization interval.
This application claims priorty from provisional application Ser. No. 60/123,145 filed Mar. 5, 1999.
The present invention relates generally to implantable medical devices and more particularly to implantable medical devices intended for use in monitoring a patient's heart rhythm.
Implantable pacemakers and cardioverters monitor the heart's rhythm in order to detect arrhythmias and deliver appropriate therapies to terminate detected arrhythmias. In conjunction with this function, the ability of the device is to store information with regard to monitored heart rhythms has dramatically increased over the past two years. Examples of implantable pacemakers and defibrillators which have the capability of storing information related to monitor heart rhythms include U.S. Pat. No. 4,223,678 issued to Langer et al., U.S. Pat. No. 5,722,999 issued to Snell, U.S. Pat. No. 5,513,645 issued to Jacobsen et al. and U.S. Pat. No. 5,312,446 issued to Holschbach et al. In addition, there have recently been developed subcutaneously implantable monitoring devices which do not deliver any anti-arrhythmia therapies to the heart but simply store information regarding a patient's heart rhythms for later uplink to an external device. Such devices are disclosed in U.S. Pat. No. 5,331,966 issued to Bennett et al., U.S. Pat. No. 5,135,004 issued to Adams and U.S. Pat. No. 5,497,780 issued to Zehender.
In conjunction with implantable devices as described above, information stored relating to a patient's heart rhythm may include information relating to heart rate trends over time, as disclosed as disclosed in U.S. Pat. No. 5,088,488 issued to Markowitz et al., U.S. Pat. No. 5,330,513 issued to Nichols et al. and U.S. Pat. No. 5,603,331 issued to Heemels et al., as well as information relating to heart rate variability over time, as disclosed in U.S. Pat. No. 5,749,900 issued to Schroeppel et. al., U.S. Pat. No. 5,466,245 issued to Spinelli et al., U.S. Pat. No. 5,411,131 issued to Yomtov et al. and U.S. Pat. No. 5,437,285 issued to Verrier et al.
Typically, measurements of heart rate variability in such devices is accomplished employing one of the standard measurements of heart rate variability such as the SDNN or SDANN indices, described in U.S. Pat. No. 5,749,900 issued to Schroeppel et al. and U.S. Pat. No. 5,411,031 issued to Yomtov, cited above. Unfortunately, obtaining clinically useful information employing the SDNN and SDANN indices traditionally requires the ability to correctly distinguish between normally conducted and ectopic beats, which may be difficult in some circumstances in the context of an implanted device.
The present invention is directed toward an implanted device having enhanced capabilities for monitoring a patient's heart rate and heart rate variability trends over extended periods of time. The information collected by the implantable device is stored and telemetered to an associated external device such as a device programmer for display and analysis. The collected information and calculated heart rate variability may also be employed to trigger an alarm or alert to the patient, in response to a measured calculation of heart rate variabilty or change in heart rate variability. Heart rates are measured by measuring the time intervals between sensed depolarizations of a chamber of the patient's heart and preceding sensed depolarizations or delivered pacing pulses. Intervals may be measured in the ventricle and/or atrium of the patient's heart. The measured intervals are referred to hereafter as "heart intervals".
In a preferred embodiment of the invention, the device is configured to allow for measurements of heart rate variability trends over extended time periods, employing a measurement of rate variability which does not require the device to accurately distinguish between normally conducted and ectopic beats. In this aspect of the invention, rather than calculating the mean values only of heart intervals beginning and ending in normally conducted beats, the device instead calculates the medians of the stored intervals over short periods of time, including heart intervals beginning or ending in ectopic beats, and calculates the standard deviation of the median values. This difference in calculation methodology produces a measurement of heart rate variability (SDMNN) similar in accuracy to the SDANN index, but without the requirement of unambiguously identifying ectopic beats and eliminating the heart intervals associated therewith.
In addition, particularly valuable in the context of an implanted device, the process for calculation of a median interval is substantially simplified as opposed to the process for calculating the mean values of the measured intervals with ectopic beats and associated measured intervals excluded. In a preferred embodiment of the invention, the process of calculation of the median is further simplified by first producing a histogram of the stored heart interval values, sorting the intervals into bins each associated with an interval range. The numbers of intervals in each bin are then successively added to one another until the total exceeds half of the total number of intervals binned and the rate range associated with the last bin added is employed to define the median interval value.
FIG. 1 illustrates an implantable pacemaker/cardioverter/defibrillator of a type useful in practicing the present invention, in conjunction with a human heart.
FIG. 2 illustrates an implantable pacemaker of a type useful in practicing the present invention, in conjunction with a human heart.
FIG. 3 illustrates an implantable monitor of a type useful in practicing the present invention.
FIG. 4 is a perspective view of a programmer of a type useful in practicing the present invention.
FIG. 5 is a functional schematic diagram of an implantable pacemaker/cardioverter/defibrillator of a type useful in practicing the present invention.
FIG. 6 is a functional schematic diagram of an implantable pacemaker of a type useful in practicing the present invention.
FIG. 7 is a functional schematic diagram of an implantable monitor of a type useful in practicing the present invention.
FIG. 8 is a functional schematic diagram of a programmer of a type useful in practicing the present invention.
FIG. 9 is a functional flow chart illustrating a method of monitoring heart rate variability which may be employed in conjunction with the present invention.
FIG. 1 illustrates a defibrillator and lead set of a type in which the present invention may usefully be practiced. The ventricular lead includes an elongated insulative lead body 16, carrying three mutually insulated conductors. Located adjacent the distal end of the lead are a ring electrode 24, an extendable helix electrode 26, mounted retractably within an insulative electrode head 28, and an elongated coil electrode 20. Each of the electrodes is coupled to one of the conductors within the lead body 16. Electrodes 24 and 26 are employed for cardiac pacing and for sensing ventricular depolarizations. At the proximal end of the lead is a bifurcated connector 14 which carries three electrical connectors, each coupled to one of the coiled conductors.
The atrial/SVC lead includes an elongated insulative lead body 15, also carrying three mutually insulated conductors. Located adjacent the J-shaped distal end of the lead are a ring electrode 21 and an extendible helix electrode 17, mounted retractably within an insulative electrode head 19. Each of the electrodes is coupled to one of the conductors within the lead body 15. Electrodes 17 and 21 are employed for atrial pacing and for sensing atrial depolarizations. An elongated coil electrode 23 is provided, proximal to electrode 21 and coupled to the third conductor within the lead body 15. At the proximal end of the lead is a bifurcated connector 13 which carries three electrical connectors, each coupled to one of the coiled conductors.
The coronary sinus lead includes an elongated insulative lead body 6, carrying one conductor, coupled to an elongated coiled defibrillation electrode 8. Electrode 8, illustrated in broken outline, is located within the coronary sinus and great vein of the heart. At the proximal end of the lead is a connector plug 4 which carries an electrical connector, coupled to the coiled conductor.
The pacemaker/cardioverter/defibrillator 10 includes a hermetic enclosure 11 containing the electronic circuitry used for generating cardiac pacing pulses for delivering cardioversion and defibrillation shocks and for monitoring the patient's heart rhythm. Pacemaker/cardioverter/defibrillator 10 is shown with the lead connector assemblies 4, 13 and 14 inserted into the connector block 12 which serves as a receptacle and electrical connector for receiving the connectors 4, 13 and 14 and interconnecting the leads to the circuitry within enclosure 11. An activity sensor 30 is illustrated schematically by broken outline, and may be an accelerometer or a piezoelectric transducer. Sensor 30 may be used for regulation of pacing rate based upon demand for cardiac output.
Optionally, insulation of the outward facing portion of the housing 11 of the pacemaker/cardioverter/defibrillator 10 may be provided or the outward facing portion may instead be left uninsulated, or some other division between insulated and uninsulated portions may be employed. The uninsulated portion of the housing 11 optionally serves as a subcutaneous defibrillation electrode, used to defibrillate either the atria or ventricles. Other lead configurations and electrode locations may of course be substituted for the lead set illustrated. For example, atrial defibrillation and sensing electrodes might be added to either the coronary sinus lead or the right ventricular lead instead of being located on a separate atrial lead, allowing for a twolead system.
FIG. 2 illustrates a cardiac pacemaker of a type appropriate for use in practicing the present invention in conjunction with its associated lead system, illustrated in relation to a patient's heart. The pacemaker 120 includes a hermetic enclosure 124 containing the electronic circuitry used for generating cardiac pacing pulses and for monitoring the patient's heart rhythm. An activity sensor 126 is illustrated schematically by broken outline, and may be an accelerometer or a piezoelectric transducer as discussed above in conjunction with FIG. 1. Mounted to the enclosure 124 is a header 122 which serves as a receptacle and electrical connector for receiving the connectors 132 and 134 of pacing leads 128 and 130 and interconnecting the leads to the circuitry within enclosure 124. Lead 128 is a ventricular lead provided with electrodes 140 and 142 for monitoring right ventricular heart signals. Also illustrated on lead 128 is a physiologic sensor 144 which may optionally be included in addition to or as an alternative to the activity sensor 126, and which may take the form of an oxygen sensor, pressure sensor, temperature sensor, other sensor of any of the various types employed for monitoring demand for cardiac output or for measuring heart hemodynamics. Sensor 124 may be used in conjunction with or as an alternative to the activity sensor 126 for rate responsive pacing. Atrial lead 130 carries electrodes 136 and 138 and is employed for sensing and pacing the patient's atrium.
FIG. 3 illustrates a subcutaneously implantable monitor of a type appropriate for use in practicing the present invention. The monitor shares the external configuration of the Medtronic Reveal� implantable monitor, and is provided with a hermetically sealed enclosure 104 containing the electronic circuitry used for generating cardiac pacing pulses and for monitoring the patient's heart rhythm and which carries a molded plastic header 108. The enclosure 104 and the header 108 each carry an electrode 102 and 106, respectively for monitoring heart rhythm. Also mounted in the header 108 is an antenna 110 for use in communicating between the device and an external programmer. Illustrated in broken outline at 112 is an internal activity sensor, of the type typically employed in the context of rate responsive cardiac pacemakers, taking the form either of an accelerometer or a piezo-electric transducer. Heart signals are detected between the electrodes 102 and 106 and measurements of physical activity are detected by sensor 112 for storage and analysis.
FIG. 4 is a plan view of an external programmer of a sort appropriate for use in conjunction with the practice of the present invention in conjunction with any of the devices of FIGS. 1-3. The programmer 420 is a microprocessor controlled device which is provided with a programming head 422 for communicating with an implanted device, a set of surface electrogram electrodes 459 for monitoring a patient's electrogram, a display 455 which is preferably a touch sensitive display, control buttons or keys 465, and a stylist 456 for use in conjunction with the touch sensitive screen 455. By means of the control keys 465 and the touch sensitive screen 455 and stylus 456, the physician may format commands for transmission to the implantable device. By means of the screen 455, the physician may observe information telemetered from the implantable device. The programmer is further provided with a printer 463 which allows for hard copy records of displays of signals received from the implanted device such as electrograms, stored parameters, programmed parameters and information as to heart rate variability trends according to the present invention. While not visible in this view, the device may also be provided with a floppy disk or CD ROM drive and/or a port for insertion of expansion cards such as P-ROM cartridges, to allow for software upgrades and modifications to the programmer 420.
In the context of the present invention, programmer 420 may serve simply as a display device, displaying information with regard to heart rate variability as calculated by the implanted device or instead may receive uplinked raw data related to heart intervals and may calculate the heart rate trends and heart rate variability values according to the present invention. It is believed that it is preferable for the implanted device to perform the bulk of the computations necessary to practice the invention, and in particular that it is preferable for the implanted device to at least calculate median rate values, to reduce the storage requirements within the implanted device. However, allocation of functions between the implanted device and the programmer may differ from the preferred embodiments and still result in a workable system.
FIG. 5 is a functional schematic diagram of an implantable pacemaker/cardioverter/defibrillator of the type illustrated in FIG. 3, in which the present invention may usefully be practiced. This diagram should be taken as exemplary of one type of anti-tachyarrhythmia device in which the invention may be embodied, and not as limiting, as it is believed that the invention may usefully be practiced in a wide variety of device implementations, including devices providing therapies for treating atrial arrhythmias instead of or in addition to ventricular arrhythmias, cardioverters and defibrillators which do not provide anti-tachycardia pacing therapies, anti-tachycardia pacers which do not provide cardioversion or defibrillation, and devices which deliver different forms of anti-arrhythmia therapies such nerve stimulation or drug administration.
The device is provided with a lead system including electrodes, which may be as illustrated in FIG. 1. Alternate lead systems may of course be substituted. If the electrode configuration of FIG. 1 is employed, the correspondence to the illustrated electrodes is as follows. Electrode 311 corresponds to electrode 1, and is the uninsulated portion of the housing of the implantable pacemaker/cardioverter/defibrillator. Electrode 320 corresponds to electrode 20 and is a defibrillation electrode located in the right ventricle. Electrode 310 corresponds to electrode 8 and is a defibrillation electrode located in the coronary sinus. Electrode 318 corresponds to electrode 28 and is a defibrillation electrode located in the superior vena cava. Electrodes 324 and 326 correspond to electrodes 24 and 26, and are used for sensing and pacing in the ventricle. Electrodes 317 and 321 correspond to electrodes 19 and 21 and are used for pacing and sensing in the atrium.
Electrodes 310 , 311, 318 and 320 are coupled to high voltage output circuit 234. Electrodes 324 and 326 are coupled to the R-wave amplifier 200, which preferably takes the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured R-wave amplitude. A signal is generated on R-out line 202 whenever the signal sensed between electrodes 324 and 326 exceeds the present sensing threshold.
Electrodes 317 and 321 are coupled to the P-wave amplifier 204. which preferably also takes the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured R-wave amplitude. A signal is generated on P-out line 206 whenever the signal sensed between electrodes 317 and 321 exceeds the present sensing threshold. The general operation of the Rwave and P-wave amplifiers 200 and 204 may correspond to that disclosed in U.S. Pat. No. 5,117,824, by Keimel, et al., issued Jun. 2, 1992, for an Apparatus for Monitoring Electrical Physiologic Signals, incorporated herein by reference in its entirety. However, any of the numerous prior art sense amplifiers employed in implantable cardiac pacemakers, defibrillators and monitors may also usefully be employed in conjunction with the present invention.
Switch matrix 208 is used to select which of the available electrodes are coupled to wide band amplifier 210 for use in digital signal analysis. Selection of electrodes is controlled by the microprocessor 224 via data/address bus 218, which selections may be varied as desired. Signals from the electrodes selected for coupling to bandpass amplifier 210 are provided to multiplexer 220, and thereafter converted to multi-bit digital signals by A/D converter 222, for storage in random access memory 226 under control of direct memory access circuit 228. Microprocessor 224 may employ digital signal analysis techniques to characterize the digitized signals stored in random access memory 226 to recognize and classify the patient's heart rhythm employing any of the numerous signal processing methodologies known to the art.
Telemetry circuit 330 receives downlink telemetry from and sends uplink telemetry to the patient activator by means of antenna 332. Data to be uplinked to the activator and control signals for the telemetry circuit are provided by microprocessor 224 via address/data bus 218. Received telemetry is provided to microprocessor 224 via multiplexer 220. The atrial and ventricular sense amp circuits 200, 204 produce atrial and ventricular EGM signals which also may be digitized and uplink telemetered to an associated programmer on receipt of a suitable interrogation command. The device may also be capable of generating so-called marker codes indicative of different cardiac events that it detects. A pacemaker with marker-channel capability is described, for example, in U.S. Pat. No. 4,374,382 to Markowitz, which patent is hereby incorporated by reference herein in its entirety. The particular telemetry system employed is not critical to practicing the invention, and any of the numerous types of telemetry systems known for use in implantable devices may be used. In particular, the telemetry systems as disclosed in U.S. Pat. No. 5,292,343 issued to Blanchette et al., U.S. Pat. No. 5,314,450, issued to Thompson, U.S. Pat. No. 5,354,319, issued to Wyborny et al. U.S. Pat. No. 5,383,909, issued to Keimel, U.S. Pat. No. 5,168,871, issued to Grevious, U.S. Pat. No. 5,107,833 issued to Barsness or U.S. Pat. No. 5,324,315, issued to Grevious, all incorporated herein by reference in their entireties, are suitable for use in conjunction with the present invention. However, the telemetry systems disclosed in the various other patents cited herein which are directed to programmable implanted devices, or similar systems may also be substituted. The telemetry circuit 330 is of course also employed for communication to and from an external programmer, as is conventional in implantable anti-arrhythmia devices.
The device of FIG. 5 may additionally is provided with an activity sensor 344, mounted to the interior surface of the device housing or to the hybrid circuit within the device housing. The sensor 344 and sensor present in circuitry 342 may be employed in the conventional fashion described in U.S. Pat. No. 4,428,378 issued to Anderson et al, incorporated herein by reference in its entirety, to regulate the underlying pacing rate of the device in rate responsive pacing modes.
The remainder of the circuitry is dedicated to the provision of cardiac pacing, cardioversion and defibrillation therapies, and, for purposes of the present invention may correspond to circuitry known in the prior art. An exemplary apparatus is disclosed for accomplishing pacing, cardioversion and defibrillation functions as follows. The pacer timing/control circuitry 212 includes programmable digital counters which control the basic time intervals associated with DDD, VVI, DVI, VDD, AAI, DDI, DDDR, VVIR, DVIR, VDDR, AAIR, DDIR and other modes of single and dual chamber pacing well known to the art. Circuitry 212 also controls escape intervals associated with anti-tachyarrhythmia pacing in both the atrium and the ventricle, employing, any anti-tachyarrhythmia pacing therapies known to the art.
Intervals defined by pacing circuitry 212 include atrial and ventricular pacing escape intervals, the refractory periods during which sensed P-waves and R-waves are ineffective to restart timing of the escape intervals and the pulse widths of the pacing pulses. The durations of these intervals are determined by microprocessor 224, in response to stored data in memory 226 and are communicated to the pacing circuitry 212 via address/data bus 218. Pacer circuitry 212 also determines the amplitude of the cardiac pacing pulses under control of microprocessor 224.
During pacing, the escape interval counters within pacer timing/control circuitry 212 are reset upon sensing of R-waves and P-waves as indicated by signals on lines 202 and 206, and in accordance with the selected mode of pacing on time-out trigger generation of pacing pulses by pacer output circuits 214 and 216, which are coupled to electrodes 317, 321, 324 and 326. The escape interval counters are also reset on generation of pacing pulses, and thereby control the basic timing of cardiac pacing fimctions, including anti-tachyarrhythmia pacing.
The durations of the intervals defined by the escape interval timers are determined by microprocessor 224, via data/address bus 218. The value of the count present in the escape interval counters when reset by sensed R-waves and P-waves may be used to measure the durations of R-R intervals, P-P intervals, PR intervals and R-P intervals, which measurements are stored in memory 226 and are used in conjunction with the present invention to measure heart rate variability and in conjunction with tachyarrhythmia detection functions.
Microprocessor 224 operates as an interrupt driven device, and is responsive to interrupts from pacer timing/control circuitry 212 corresponding to the occurrences of sensed P-waves and R-waves and corresponding to the generation of cardiac pacing pulses. These interrupts are provided via data/address bus 218. Any necessary mathematical calculations to be performed by microprocessor 224 and any updating of the values or intervals controlled by pacer timing/control circuitry 212 take place following such interrupts. Microprocessor 224 includes associated ROM in which the stored program controlling its operation as described below resides. A portion of the memory 226 (FIG. 2) may be configured as a plurality of recirculating buffers, capable of holding series of measured intervals, which may be analyzed in response to the occurrence of a pace or sense interrupt to determine whether the patient's heart is presently exhibiting atrial or ventricular tachyarrhythmia.
The arrhythmia detection method of the present invention may include any of the numerous available prior art tachyarrhythmia detection algorithms. One preferred embodiment may employ all or a suset of the rule-based detection methods described in U.S. Pat. No. 5,545,186 issued to Olson et al. or in U.S. Pat. No. 5,755,736 issued to Gillberg et al., both incorporated herein by reference in their entireties. However, any of the various arrhythmia detection methodologies known to the art might also usefully be employed in alternative embodiments of the invention.
In the event that an atrial or ventricular tachyarrhythmia is detected, and an anti-tachyarrhythmia pacing regimen is desired, timing intervals for controlling generation of anti-tachyarrhythmia pacing therapies are loaded from microprocessor 224 into the pacer timing and control circuitry 212, to control the operation of the escape interval counters therein and to define refractory periods during which detection of R-waves and P-waves is ineffective to restart the escape interval counters.
In the event that generation of a cardioversion or defibrillation pulse is required, microprocessor 224 employs the escape interval counter to control timing of such cardioversion and defibrillation pulses, as well as associated refractory periods. In response to the detection of atrial or ventricular fibrillation or tachyarrhythmia requiring a cardioversion pulse, microprocessor 224 activates cardioversion/defibrillation control circuitry 230, which initiates charging of the high voltage capacitors 246, 248 via charging circuit 236, under control of high voltage charging control line 240. The voltage on the high voltage capacitors is monitored via VCAP line 244, which is passed through multiplexer 220 and in response to reaching a predetermined value set by microprocessor 224, results in generation of a logic signal on Cap Full (CF) line 254, terminating charging. Thereafter, timing of the delivery of the defibrillation or cardioversion pulse is controlled by pacer timing/control circuitry 212. Following delivery of the fibrillation or tachycardia therapy the microprocessor then returns the device to cardiac pacing and awaits the next successive interrupt due to pacing or the occurrence of a sensed atrial or ventricular depolarization. In the illustrated device, delivery of the cardioversion or defibrillation pulses is accomplished by output circuit 234, under control of control circuitry 230 via control bus 238. Output circuit 234 determines whether a monophasic or biphasic pulse is delivered, whether the housing 311 serves as cathode or anode and which electrodes are involved in delivery of the pulse.
FIG. 6 is a functional schematic diagram of the pacemaker 120 illustrated in FIG. 2. The pacemaker of FIGS. 2 and 6 is essentially a set of subcomponents of the implantable pacemaker/cardioverter/defibrillator illustrated in FIGS. 1 and 5. Like the device of FIG. 5, the pacemaker is a microprocessor controlled device with microprocessor 189 operating under control of programming stored in Read Only Memory (ROM) 191. In the device as illustrated, electrodes 136 and 138, intended for location in the atrium of the patient's heart are coupled to an atrial amplifier 181 which may correspond to atrial amplifier 204 in FIG. 5. Similarly, ventricular electrodes 140 and 142 are coupled to ventricular amplifier 182, which may correspond to ventricular amplifier 200 in FIG. 5. The outputs of atrial and ventricular amplifiers 181 and 182 are input into timing and control circuitry 183 which conforms generally to the pacer timing and control circuitry 212 of FIG. 5, and which measures intervals between detected depolarizations and controls intervals between delivered pacing pulses as well as generating interrupts via data/address 192 to awake microprocessor 189 in response to delivery of a pacing pulse or sensing of a cardiac depolarization. Intervals between depolarizations measured by timing control circuitry 183 are stored in Random Access Memory (RAM) 190 until processed by microprocessor 189 to derive average heart rate values. Atrial and ventricular pacing pulses delivered according to one or more of the standard pacing modes described in conjunction with FIG. 5 are produced by atrial and ventricular pulse generator circuits 184 and 185 which may correspond to pulse generator circuits 215 ad 216 in FIG. 5.
The sensor illustrated in FIG. 6 may correspond to either an activity sensor 126 as described in conjunction with FIG. 2 above or to a hemodynamic sensor 140, as described in conjunction with FIG. 2. If the sensor is an activity sensor, then sensor processing circuitry 186 may correspond to sensor processing circuitry 342 discussed in conjunction with FIG. 5. However, if the sensor is a hemodynamic sensor, the sensor processing circuitry would correspond to the sort of processing circuitry typically associated with hemodynamic sensors. Telemetry circuitry 187 in conjunction with antenna 188 serves to transmit information to and receive information from an external programmer precisely as described above in conjunction with the device of FIG. 5, including information related to stored median interval values and heart rate variability measurements in RAM 190, as calculated by microprocessor 189.
FIG. 7 illustrates the functional organization of the subcutaneously implantable heart monitor 100 illustrated in FIG. 3. This device consists essentially of a set of subcomponents of the more complex embodiment of the invention disclosed in FIG. 5, and includes a sense amplifier 152 coupled to electrodes 102 and 106, illustrated in FIG. 1. Sense amplifier 152 may correspond to sense amplifier 204 or 200 in FIG. 5. Like the device of FIG. 5, the implantable monitor may be a microprocessor control device operating under control microprocessor 156 with its functionality controlled primarily by software stored in the read only memory associated therein. In this context, amplifier 152 detects the occurrence of heart depolarizations, with timing/control circuitry 154 serving to measure the durations between the detected heart depolarizations and to generate interrupts awakening microprocessor 156 so that it may store, analyze and process the detected intervals. Random Access Memory (RAM) 158 serves to store measured and calculated parameters including the calculated median heart rate and/or heart rate variability values for later telemetry to an external device. Like the device in FIG. 5, timing and control circuitry communicates with the microprocessor and the remaining circuitry by means of the address/data bus 168. Telemetry system 162 may correspond to telemetry system 330 in FIG. 5 and, via antenna 110 transmits and receives information from the external programmer, including transmitting information with regard to the calculated median rate values and heart variability values stored in RAM 158. Sensor 112 may correspond to sensor 344 in FIG. 5 and it may be a physical activity sensor as discussed above. The output of sensor 112 is passed through sensor processing circuitry 166 which may correspond to sensor processing circuitry 342 in FIG. 5.
FIG. 8 is a functional schematic of a programmer as illustrated in FIG. 4 appropriate for use in conjunction with the invention. Programmer 420 is a personal computer type, microprocessor-based device incorporating a central processing unit 450, which may be, for example, an Intel 80386 or 80486 or Pentium microprocessor or the like. A system bus 451 interconnects CPU 450 with a hard disk drive 452 storing operational programs and data and with a graphics circuit 453 and an interface controller module 454. A floppy disk drive 466 or a CD ROM drive is also coupled to bus 451 and is accessible via a disk insertion slot within the housing of the programmer 420. Programmer 420 further comprises an interface module 457 which includes digital circuit 458, non-isolated analog circuit 459, and isolated analog circuit 460. Digital circuit 448 enables interface module 457 to communicate with interface controller module 454.
In order for the physician or other care giver or user to communicate with the programmer 420, control buttons 465 or optionally a keyboard coupled to CPU 50 are provided. However the primary communication mode is through graphics display screen 455 of the well-known "touch sensitive" type controlled by graphics circuit 453. A user of programmer 420 may interact therewith through the use of a stylus 456, also coupled to graphics circuit 453, which is used to point to various locations on screen 455 which display menu choices for selection by the user or an alphanumeric keyboard for entering text or numbers and other symbols.
Graphics display 455 also displays a variety of screens of telemetered out data or real time data including measurements of heart rate variability and heart rate trends according to the present invention. Programmer 420 is also provided with a strip chart printer 463 or the like coupled to interface controller module 454 so that a hard copy of a patient's ECG, EGM, marker channel or of graphics displayed on the display 455 can be generated.
As will be appreciated by those of ordinary skill in the art, it is often desirable to provide a means for programmer 20 to adapt its mode of operation depending upon the type or generation of implanted medical device to be programmed. Accordingly, it may be desirable to have an expansion cartridge containing EPROMs or the like for storing software programs to control programmer 420 to operate in a particular manner corresponding to a given type or generation of implantable medical device. In addition, in accordance with the present invention, it is desirable to provide the capability through the expansion cartridge or through the floppy disk drive 66 or CD ROM drive.
The non-isolated analog circuit 459 of interface module 457 is coupled to a programming head 422 which is used to establish the uplink and downlink telemetry links between the pacemaker 410 and programmer 420 as described above. Uplink telemetered EGM signals are received in programming head 422 and provided to non-isolated analog circuit 459. Non-isolated analog circuit 459, in turn, converts the digitized EGM signals to analog EGM signals and presents these signals on output lines A EGM OUT and V EGM OUT. These output lines may then be applied to a strip-chart recorder 463 to provide a hard-copy printout of the A EGM or V EGM for viewing by the physician. Similarly, the markers be received by programming head 422 are presented on the MARKER CHANNEL output line from non-isolated analog circuit 459.
Isolated analog circuit 460 in interface module 547 is provided to receive external ECG and electrophysiologic (EP) stimulation pulse signals. In particular, analog circuit 460 receives ECG signals from patient skin electrodes 459 and processes these signals before providing them to the remainder of the programmer system in a manner well known in the art. Circuit 460 further operates to receive the EP stimulation pulses from an external EP stimulator for the purposes of non-invasive EP studies, as is also known in the art.
In order to ensure proper positioning of programming head 422 over the antenna of the associated implanted device, feedback is provided to the physician that the programming head 422 is in satisfactory communication with and is receiving sufficiently strong RF signals. This feedback may be provided, for example, by means of a head position indicator, e.g. a light-emitting diode (LED) or the like that is lighted to indicate a stable telemetry channel.
FIG. 9 is a functional flow chart illustrating the overall method of operation of a device according to the present invention in monitoring heart intervals and in calculating an index of heart rate variability for display on external programmer. In conjunction with the flow chart of FIG. 9, it should be understood that the operations illustrated are all presumed to take place in the implanted device, which is believed to be a preferred embodiment of the invention. In this context, it should also be understood that all calculations and processing of the measured heart intervals is performed by the microprocessor within the implanted device. However, in alternative embodiments, one or more steps of the method for determining an index of heart rate variability may be performed in the external device, based on information telemetered to the external device by the implanted device.
After initialization at 500, at 502 the device starts time period T1 which corresponds to a prolonged time period over which heart rate variability is to be determined, and typically will be a period of hours or days. Most preferably, it is believed that T1 should correspond to a period of a single day for ease in display and understanding of the calculated heart rate variability values. In conjunction with initiation of time period T1, the value of SUM 24 and SUM SQ24 are both reset to 0. SUM 24 is intended to reflect the sum of all calculated median values of heart intervals separating depolarizations of the chamber of the heart, e.g. atrial or ventricular depolarizations, over the 24 hour period. SUM SQ24 reflects a sum of the squares of the median values of the heart intervals taken over the 24 hour period. These values will be incremented with the expiration of each of a number of shorter time periods T2, and will be employed to calculate the observed heart rate variability over time period T1 using the SDMNN heart rate variability index according to the present invention. At 504, the device initiates the first of a sequence of shorter time periods T2 which may be, for example, periods of one to 20 minutes, preferably about 5 minutes. The median of value of the heart intervals between successive depolarizations during these 5 minute periods are employed to calculate the value of SUM24 and SUMSQ24, described above. In addition, at 504 the device resets the value N, corresponding to a bin of a histogram of stored heart intervals, to 1. This value will be incremented and employed in calculating the median interval during each of the shorter time periods T2, as discussed below. The value of TOTAL, also employed in calculating the value of the median interval as discussed below is also reset to zero at 504. During T2, in response to a sensed depolarization at 506, the device collects the heart interval ending with the sensed depolarization at 508. On expiration of T2 at 510, the device proceeds to determine whether a median value for the collected heart intervals during T2 can be usefully calculated, and if so, proceeds to calculate the median interval value. This is accomplished by first optionally discarding unwanted heart intervals at 512. Whether this step will be necessary or not is a function of the type of device employed to monitor heart rate variability and the status of the patient in whom the device is implanted. For example, in the case of a patient who is subject to atrial or ventricle tachycardia, wherein the device employing the present invention is an implantable pacemaker or pacemaker/cardioverter/defibrillator, it may be desirable to discard all intervals beginning with a paced depolarization. It may also be desirable to discard all heart intervals associated with detection and treatment of tachyarrhythmias. For example all heart intervals which meet tachyarrhythmia detection criteria due to their relatively short duration, all intervals obtained during charging of the output capacitors of such a device prior to delivery of a cardioversion or defibrillation shock and all intervals sensed during delivery of anti-tachyarrhythmia therapies such as anti-tachycardia pacing, cardioversion and defibrillation may be discarded. In addition or as an alternative, in cases in which the invention is embodied in the context of a dual chamber pacemaker capable of switching between various pacing modes in response to detected atrial tachyarrhythmias, it may be desirable to discard heart intervals measured during operation of the mode switch between pacing modes. In contrast, if the patient has a simple VVI type pacemaker, and is not subject to tachyarrhythmias, there may be no need to discard any collected heart intervals except those beginning in paced depolarizations. It should be noted that even if some or all of these heart intervals are to be discarded, selection of intervals to be discarded does not require the ability to distinguish between normally conducted and ectopic beats, but only the ability to either measure the durations between depolarizations and/or the underlying operative states of the device. At 514, the retained heart intervals are arranged into a histogram divided into a desired number of bins based on interval duration. For example, the histogram may be divided into 130 bins, each ten milliseconds wide, extending from 300 milliseconds through 1600 milliseconds. Intervals less than 300 milliseconds may be binned in the 300-310 millisecond bin, while intervals greater than 1600 milliseconds may be binned in the 1590-1600 milliseconds bin. In order to minimize data storage required for the histogram, the value of the number of intervals in a bin may optionally be limited to a maximum value, for example, 750.
After the device produces the histogram of intervals and stores it in the random access memory (RAM) of the device, the device at 516 adds the values of all binned intervals within the histogram. At 518, the device checks the value of the sum of the binned intervals against a preset total duration which may be a proportion of the value of the duration of time period T2. For example, the device may require that the total duration of the intervals within the histogram bins is at least 20% of the duration of time period T2. If the total duration binned heart intervals are less than this value, there is no calculation of a median for the preceding time period T2, and the device begins the timing of the next time period T2 at 504. If, however, the cumulative total of the binned intervals is sufficiently great at 518, the device then calculates a median interval value by first adding the number of intervals in bin N (previously initialized to 1) to the value of TOTAL (previously initialized to 0). At 524 the device checks to determine whether TOTAL is more than one half of the total number (NINT) of intervals binned. If not, the value of N is incremented to 520 and the number of intervals in the next bin are added to TOTAL at 522, until TOTAL exceeds half the total number of intervals binned. At this point, at 526, the rate range associated with bin N (the last bin whose intervals were added to the value of TOTAL) serves to define the median heart rate during the preceding time period T2. The lower end of the range of the bin, the upper end of the range of the bin, or more preferably the middle of the range associated with the bin may be employed as the median. At 528 the value of the calculated median is added to SUM 24. At 530 the value of the median is squared, and the square of the median is added to SUMSQ24 at 532.
If the longer time period T1 has not expired at 534, the device returns to restart timing of the next shorter period T2 at 504 and continues to collect heart rate intervals and calculate interval medians until expiration of the longer time period T1. Following the expiration of the longer time period T1 at 534, the device proceeds to calculate the index of heart rate variability SDMNN according to the present invention by first storing the calculated values of SUM24 and SUMSQ24 at 540. The value of SDMNN is calculated at 538, according to the formula SDMNN=(SUMSQ24−(SUM24)2/NINT)/(NINT−1). This value is then stored in the implanted device for later telemetry to an external device.
As noted above, it is believed that in some cases the allocation of functions between the external and internal device employed to practice the invention may be somewhat different. For example, instead of actually calculating the value of SDMNN according to the present invention, the implanted device may simply store the values of SUM24 and SUMSQ24, so that the external device may later perform the calculation of SDMNN according to the present invention. It is also possible that in some embodiments, the device may simply collect the values of undiscarded heart intervals, for later uplinking to external device wherein the calculation of median values and the heart rate variability index SDMNN may thereafter be undertaken. However, this embodiment is believed less desirable in that it requires substantial additional data storage base within the implanted device.
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Homestyle Dosa
- prep time 1 min
- total time 1 min
- serves 6
A basic homestyle dosa is prepared with a batter made from rice flour and soaked ground urad dal. The batter is left to ferment, and then poured out onto a griddle to make a bread that ranges in size from an eight-inch pancake (as in this recipe) to an enormous thin crepe (from 24 to 36 inches (60 to 85 centimetres) in diameter) that only a professional with a large griddle can make. No matter what the size, dosas are great to eat, and in predominantly vegetarian south India, they have the added benefit of combining complementary amino acids, from the grain and the dal.
Quick and Easy, Side, Lunch, Appetizer, Rice/Grain, Dinner, Vegetarian, Indian

subset: commoncrawl


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The Lake Barcroft community has experienced closed beaches and limited lake access four times this year due to sewage spills.
Fairfax County officials have taken steps to address the causes of each of the sanitary sewer overflows and test the water for contaminants, according to Department of Public Works spokeswoman Irene Haske.
The lake, created in the early 1900s as a reservoir by damming Holmes Run, is now privately owned and accessible only to members of the Lake Barcroft Association.
The first sewer overflow occurred during a major storm April 29 near the Holmes Run pumping station, where the county was doing maintenance on a sewer main, Haske said.
While an estimated 300,000 to 400,000 gallons was discharged from the sanitary sewer system, county officials believe most of that was rain water that entered the system.
During another storm on May 15 and 16, about 3,200 gallons was discharged from the sanitary sewer when the pumps failed to turn on. County maintenance crews were quickly able to get the pumps up and running again, Haske said.
Two days later, a different pump station failed, leading to a 3,900 gallon overflow. After that event, a backup communication system was installed at that pump station to ensure that any malfunctions are reported to county maintenance crews.
The most recent overflow was June 17 and also occurred in an area where county crews were doing maintenance. When crews noticed the leak, they shut off the pumps and began to work to correct the problem, but not before an estimated 6,000 gallons of sewage was discharged.
The beaches reopened following the latest spill June 19 after tests found no detectable levels of human bacteria near the beaches. One area of the water did show detectable bacteria levels, although below state limits, and that area remained closed to swimming for a longer period.


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Walter C Uhler » Russian History » Sergei Vasilievich Utechin, 1921-2004
Sergei Vasilievich Utechin, 1921-2004
Originally published in Slavic Review
The extraordinary life of Sergei Vasilievich Utechin, Professor Emeritus of Russian History at the Pennsylvania State University (1969-1984), ended on 11 July 2004, when he died at the Stanford University Medical Center from complications arising from a stroke suffered on 20 May.
S.V. Utechin was born on 18 December 1921 in the village of Tenki, near Kazan. His father became a teacher and principal after completing a theological seminary education that included Latin, Greek, and Church Slavonic. His father also had been active in the "small deeds" populist movement, in the February Revolution in Tenki volost and in delaying the Soviet takeover there until the summer of 1918. His father steadfastly refused to join the Communist Party. Sergei Vasilievich's mother was a teacher who had studied the higher women's courses at Kazan University, from which she received her diploma in 1917.
Although his parents came under increasing political pressure during the late 1920s and early 1930s, they were heartened by the educational reforms of the early 1930s. Looking back, Sergei Vasilievich credited those educational reforms, especially the return to the classics of Russian literature, for the intellectual and moral survival of his entire generation.
Nevertheless, political pressure and the "disappearance" of individuals from Kazan persuaded the Utechin family to move to Karaganda during the summer of 1934. Three years later, when Sergei Vasilievich contemplated refusal to join the Komsomol, his mother asked, "Do you want your father and me to be arrested?" He joined.
As one of the Soviet Union's secondary school "otlichniki" (standouts), Sergei Vasilievich was able to enter the History Faculty of Moscow State University in 1939 after an interview, not the oral examination required of less accomplished students. There he studied Russian history under K. V. Bazilevich (a student of S.V. Bakhrushin, who had studied under V. O. Klyuchevsky). Over the course of his life, Utechin would apply his gift for foreign languages to amass encyclopedic knowledge of Russian and world history.
But his studies were jeopardized in the summer of 1940, when he was summoned to Lubyanka for an interrogation that lasted several hours. It led to a failed attempt to expel him (in absentia) from the Komsomol in 1941
Nazi Germany's invasion of the Soviet Union did interrupt his studies and sent him south, where he, nevertheless, came under Romanian occupation in Anapa. On 31 August 1942, Sergei Vasilievich was accused of being the Russian soldier who was responsible for killing a Romanian soldier (in fact, his poor eyesight caused him to be rejected for military service three times). He avoided execution when another Russian confirmed that he was a teacher, not a soldier.
Two days later he was confronted by, but escaped from, two drunken German soldiers, one of whom suspected him of being a Jew who needed to be killed. But, in November 1943, Sergei Vasilievich was captured by the Nazis, transported to a camp in Germany, and forced to labor at the Krupp shipyards while surviving on meager rations designed to cause gradual starvation.
At war's end, Sergei Vasilievich heard rumors that repatriated Russians were being imprisoned in Siberia, which prompted him to hide in a Polish camp. Then he settled in Kiel, resumed his studies, and received a Doctorate of Philosophy from Kiel University in 1949.
During that same year, Utechin sought positions in Kiel and Berlin before receiving a scholarship to Oxford University, where he arrived in February 1950. But he soon returned to Berlin for a few months, during which time he became acquainted with Michael Josselson and Melvin Lasky. That summer he delivered a report about the prospects for freedom in the Soviet Union to the founding session of the Congress for Cultural Freedom.
At Oxford, Sergei Vasilievich became a friend (and informal student) of Sir Isaiah Berlin, but declined his formal invitation to spend a year reading analytic philosophy. Nevertheless it was precisely Berlin's philosophy of liberty and tragedy, as well as his critique of utopianism, that profoundly influenced Sergei Vasilievich's views and works for the rest of his life.
From 1953 to 1958 Utechin worked for the BBC's foreign broadcast service while laboring on what would become Everyman's Concise Encyclopedia of Russia (London, 1961). From 1958 to 1962, at the invitation of Leonard Shapiro, he lectured at the London School of Economics. In 1963, Utechin's translation (in collaboration with his wife, Patricia) of Vladimir Lenin's What Is To Be Done? (Oxford, 1963) was published. More significantly, 1963 also saw the publication of Sergei Vasilievich's most influential book, Russian Political Thought: A Concise History (Dent, 1963).
In 1965, Utechin moved to Scotland, where he became an editor of the University of Glasgow's journal, Soviet Studies. Between 1965 and 1969 he lectured at many institutions, including the University of Kansas and Indiana University, before accepting a faculty appointment at the Pennsylvania State University.
Until his retirement in 1984, Sergei Vasilievich's erudition and enthusiasm caused numerous unsuspecting and casual students of history at Penn State to be "bitten by the bug" of scholarship and Russian history. Consequently, such students usually found themselves "enrolled" permanently in his on-going graduate seminar/salon, normally conducted at his home.
Sergei Vasilievich was extremely demanding when it came to historical methods. As his friend and colleague, George Enteen, observed: "His course combined exacting standards as concerns the formal methods of research with a sense of the high purpose and dignity of historical investigation."
In 1984, Utechin moved to Menlo Park, California. It was from there that he devoted his last twenty years to scholarly life at Stanford, to Russian émigré politics as a member of the National Labor Organization (NTS), to visits, lectures and television appearances in Russia after the fall of communism, to attempts to publish Isaiah Berlin's work in Russia, and to the creation of a virtual university.
Sergei Vasilievich Utechin is survived by his second wife, Marina Pavlovna, and his son from his first marriage, Nicholas Sergeevich.
Filed under: Russian History · Tags: Sergei Vasilievich Utechin


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Health and Counseling
The Student Health Service and Monsour Counseling and Psychological Services are located in the Robert E. Tranquada Student Services Center, which is in front of Honnold Library. Both services are open each semester when classes are in session.
Student Health Service
The Student Health Service stresses preventative medicine and health awareness. Consultation and outpatient treatment by the physicians, nurse practitioners and nurses are available to students by appointment at no charge. There are minimal charges for walk-in visits, medications, x-rays, laboratory tests, special procedures and supplies. These charges do not have to be paid for at the time of service. Referral for subspecialty consultation, hospitalization and surgery can be arranged by the Student Health Service but will not be financed by the College—payment is the student's responsibility.
All students must have a health history and entrance physical on file to use the services. These forms are required for initial admission to Pomona College as a first year or transfer student. Forms completed by a family member/relative who is an M.D./nurse practitioner will not be accepted. All students' records are confidential. Medical records are not made available to anyone without the student's permission. The Student Health Service maintains a Website where more information about medical services can be accessed at www.cuc.claremont.edu/shs.
Monsour Counseling and Psychological Services
Monsour Counseling and Psychological Services helps students with personal and emotional problems. The Center provides brief individual therapy, medication evaluation, group therapy and referrals to other mental health resources. Workshops and groups are offered on topics such as sexual abuse, eating disorders, relationship issues, stress management, grief and self-esteem issues. Students who have personal concerns, psychological or emotional distress or who simply wish to talk with someone are welcome. There is no charge for the services of psychologists or a consulting psychiatrist at the center. It is understood that a relationship formed with the center is confidential.
The College does not assume responsibility for medical or psychological care of its students beyond the capacity of its health and counseling facilities. A student accident and sickness medical-expense insurance plan is available to students for purchase through the Claremont University Consortium (CUC). Effective fall 2008, all incoming students are automatically enrolled in the CUC Student Health Insurance Plan. Students may waive out of the plan by submitting proof of comparable insurance. International students are required to purchase the CUC plan. Designed to supplement the care provided by the health and counseling services, the CUC Student Health Insurance Plan includes benefits for psychological services, accidental injuries, hospitalization, surgery, doctor visits in the hospital, emergency care and ambulance services. Premiums for coverage are listed in an insurance-plan brochure mailed to each student. Information is also available from the Student Health Service.


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Year of publication
- 2009 (2) (remove)
- X-ray structure of the Na+-coupled Glycine-Betaine symporter BetP from Corynebacterium glutamicum (2009)
- Cellular membranes are important sites of interaction between cells and their environment. Among the multitude of macromolecular complexes embedded in these membranes, transporters play a particularly important role. These integral membrane proteins perform a number of vital functions that enable cell adaptation to changing environmental conditions. Osmotic stress is a major external stimulus for cells. Bacteria are frequently exposed to either hyperosmotic or hypoosmotic stress. Typical conditions for soil bacteria, such as Corynebacterium glutamicum, vary between dryness and sudden rainfall. Physical stimuli caused by osmotic stress have to be sensed and used to activate appropriate response mechanisms. Hypoosmotic stress causes immediate and uncontrolled influx of water. Cells counteract by instantly opening mechanosensitive channels, which act as emergency valves leading to fast efflux of small solutes out of the cell, therebydiminishing the osmotic gradient across the cell membrane. Hyperosmotic stress, on the other hand, results in water efflux. This is counterbalanced by an accumulation of small, osmotically active solutes in the cytoplasm, the so-called compatible solutes. They comprise a large variety of substances, including amino acids (proline), amino acid derivatives (betaine, ectoine), oligosaccharides (trehalose), and heterosides (glucosylglycerol). Osmoregulated transporters sense intracellular osmotic pressure and respond to hyperosmotic stress by facilitating the inward translocation of compatible solutes across the cell membrane, to restore normal hydration levels. This work presents the first X-ray structure of a member of the Betaine-Choline-Carnitine-Transporter (BCCT) family, BetP. This Na+-coupled symporter from Corynebacterium glutamicum is a highly effective osmoregulated and specific uptake system for glycine-betaine. X-ray structure determination was achieved using single wavelength anomalous dispersion (SAD) of selenium atoms. Selenium was incorporated into the protein during its expression in methione auxotrophic E. coli cells, grown in media supplemented with selenomethionine. SAD data with anomalous signal up to 5 Å led to the detection of 39 selenium sites, which were used to calculate the initial electron density map of the protein. Medium resolution and high data anisotropy made the structure determination of BetP a challenging task. A specific strategy for data anisotropy correction and a combination of various crystallographic programs were necessary to obtain an interpretable electron density map suitable for model building. The crystal structure of BetP shows a trimer with glycine-betaine bound in a three-fold cation-pi interaction built by conserved tryptophan residues. The bound substrate is occluded from both sides of the membrane and aromatic side chains line its transport pathway. Very interestingly, the structure reveals that the alpha-helical C-terminal domain, for which a chemo- and osmosensory function was elucidated by biochemical methods, interacts with cytoplasmic loops of an adjacent monomer. These unexpected monomer-monomer interactions are thought to be crucial for the activation mechanism of BetP, and a new atomic model combing biochemical results with the crystal structure is proposed. BetP is shown to have the same overall fold as three unrelated Na+-coupled symporters. While these were crystallised in either the outward- or inward-facing conformation, BetP reveals a unique intermediate state, opening new perspectives on the alternating access mechanism of transport.
- Improving methods for the study of membrane proteins by solid-state NMR (2009)
- Solid state NMR is a emerging method for the study of membrane proteins, which has received much interest in recent years. Limiting the study of many pharmacologically relevant targets, are the often long measuring times, required to obtain especially higher dimensional solid state NMR spectra of good quality. To address this problem, multiple methods where developed in this work, which can be categorized into two groups. The first set of methods aims at the quality of certain spectra, by implementing a spectral filter, which increases the fidelity of the measured data. The second set of methods, addresses the problem of long measuring times directly, by increasing the sensitivity per unit time, as could be shown, for example, on homo- and heteronuclear singlequantum-singlequantum correlation experiments. The gains in measuring time for the latter group of methods are typically in the order of 2-3, but some experiments allow multiple methods to be employed simultaneously, which can lead to a decrease in measuring time of a factor of up to 8. It is important to mention, that none of the methods introduced in this work require any equipment in addition to the conventional setup present in most sold state NMR laboratories and no changes or addition to the samples under study are required. Therefore the gains reported in this work come at no extra cost and require only minimal implementation effort on the side of the user.


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John McCain said something gracious and pointed at the same time just now:
I owe America more than she has ever owed me. And my friends, I've been an imperfect servant of my country for many years. I've never lived a day, good times or bad, when I wasn't proud — proud — of the privilege.
The point here is that McCain is a man who spent five and a half years in a hellish North Vietnamese prison, and therefore one might think whatever debt he may owe to his country he paid off in full long ago. The fact that he still speaks of his gratitude is notable.
And, of course, his words about being "proud" of the "privilege" to be her "servant" has to be seen in light of Michelle Obama's remark yesterday that until her husband's campaign of hopey-hope-hope, she had never felt "really proud" of her country. McCain is making it clear: He will run as the candidate of patriotism, and because of the attitude his wife's words inadvertently exposed, Obama is going to have trouble there.


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THE voter turnout in the Blunsdon and Highworth by-election is 32.56 per cent, which is average for a local election
ALL the ballot boxes for the police and crime commissioner election and the Blunsdon and Highworth by-election have now arrived at the count centres.
THE polling stations have now closed in the Wiltshire police and crime commissioner and Blunsdon and Highworth by-election.
There will be an opportunity to view the plans for the cloister-style extension at St Mary's Church in Devizes on Saturday.
Aspiring scientists took part in experiments and got a chance to look over a racing car from Castle Combe last week.
PEWSEY Vale manager Lewis Taylor says simple hard work has been the catalyst for his side's imperious recent form.
WEIGHTS were down in Sunday's Wilts Angling match on the Kennet & Avon Canal at Horton.
MP for Devizes, Claire Perry, welcomed the news that electrification of the rail line west of Newbury would be investigated.
DEVIZES Town assistant manager Justin Webster is confident that his side has what it takes to notch up positive results in the Toolstation League First Division after an up and down week at Nursteed Road.
A Pewsey mini-market lost hundreds of pounds in stock when a power cut ruined food chillers.
DAVE Turner reckons the Hellenic League Division One West title race is no simple two-horse race between his side and Brimscombe & Thrupp.
Diamond and pearl ear drops and a diamond and platinum watch worn by Holly-wood icon Elizabeth Taylor are on display in Marlborough.
SHELLEY Rudman has revealed how she is balancing short-term pain with long-term gain after finishing seventh in the opening round of the FIBT Skeleton World Cup series.
Six jobs stand to be lost if a public inquiry into Caffè Nero opening in Marlborough without planning permission upholds an enforcement notice issued by Wiltshire Council this week.
The position of Devizes Carnival Queen has become a thing of the past after the organising committee voted last week to end the 80-year tradition.
NORTH WILTS Ladies B side are through to the third round of the Over 60s women's double rinks competition.
Former soccer player Tristan Marsh, who is crippled by a rare illness, has moved into a new extension at his home.
Pursuant to the Trustee Act 1925 any persons having a claim against or an interest in the Estate of the aforementioned deceased, late of 184 Sheldon Road Chippenham Wiltshire, who died on 22/09/2012, are required to send particulars thereof in writing to the undersigned Solicitors on or before 25/01/2013, after which date the Estate will be distributed having regard only to claims and interests of which they have had notice.
Pursuant to the Trustee Act 1925 any persons having a claim against or an interest in the Estate of the aforementioned deceased, late of 9 Hastings Road Corsham Wiltshire SN13 9HQ, who died on 03/06/2012, are required to send particulars thereof in writing to the undersigned Solicitors on or before 25/01/2013, after which date the Estate will be distributed having regard only to claims and interests of which they have had notice.
Pursuant to the Trustee Act 1925 any persons having a claim against or an interest in the Estate of the aforementioned deceased, late of The Cedars High Street Purton Wiltshire SN5 4AF, who died on 15/10/2012, are required to send particulars thereof in writing to the undersigned Solicitors on or before 25/01/2013, after which date the Estate will be distributed having regard only to claims and interests of which they have had notice.
Among the fundraising events tomorrow are:
Schoolgirl Grace Canfield was quick off the mark in raising money for Children in Need, whose main sponsorship drive gets underway in earnest tomorrow. The seven-year-old, of Potterne Road, Devizes, organised her own fair at the skittle alley at the Southgate Inn on Saturday and it raised more than £300 for the fund. Family and friends helped make cakes and about 30 children attended in fancy dress while the Southgate provided free lollies and supermarkets donated prizes. Sarah Canfield, Grace's mum, said: "Grace was absolutely delighted with how it went. She was really surprised and shocked at how many people came along. The children were all dressed up and incredibly excited. Grace would like to thank everyone who attended, supported and donated." Among those who attended where Devizes Mayor and Mayoress Kelvin and Pam Nash, who chose the winners of the fancy dress. Fancy dress will undoubtedly be the theme for tomorrow, with many Pudsey supporters opting to don brightly coloured, spotty clothes to match his own attire. Schools across the region are holding mufti days to raise funds while office and factory workers are also getting in the spirit of the occasion, wearing wacky clothing. Chippenham Mayor Andy Phillips is going to be rolling up his trouser legs for the cause. At noon tomorrow he is going to have his legs waxed at his local One Stop shop in Sheldon Road. He said: "I must have had a brainstorm. I walked in one day and the lady in the shop suggested I have my legs waxed. I'm more than happy to help out for charity. Children in Need is a great cause. "I am looking forward to it with anticipation if not trepidation. I've never had it done before. I'm not worried about it, if it hurts, it hurts. It won't last for long." Staff at the Department for Work and Pensions in Chippenham are doing their bit for Children in Need. Their sports and social and well-being committees have organised a fun family event at the Air Dome Club, Bristol Road, Chippenham, tomorrow night. Teams will be competing on an inflatable obstacle course as part of an It's a Knockout-type challenge. Students at Pewsey Vale School will be throwing themselves into the fundraising with a variety of events that will see year 11 student Dan Eyles relieved of his flowing locks, with two teachers wielding the scissors. Those students who want to see Dan losing his hair on stage in the school hall will have to pay, with the money going towards the school's Children in Need donation. Other events at the Pewsey school tomorrow will include students playing a giant game of Twister; selling cakes they have made themselves and dressing up as their favourite character, celebrity or hero. Other fundraising activities will include nail painting and a library treasure hunt.
A traffic warden was forced to take refuge behind two parked cars after a driver blew his top when she gave him a parking ticket in Chippenham.
In Loving Memory of Leslie William Charles FORTUNE November 14, 1982 Silent memories keep you near, As time unfolds another year. Beautiful memories woven in gold, This is the picture we tenderly hold. Out of our lives you may be gone, But in our hearts you still live on. Always in our hearts never forgotten. All our love your wife Vera, children, grandchildren and great-grandchildren xxxxxxxxxx
Calls have been made for improvements to the A360 near Littleton Panell after a crash that left a 13-year-old boy fighting for his life and his mum in hospital.
Wiltshire Council is carrying out repairs to two roads in Devizes next week.
One of Wiltshire Conservatives' longest serving councillors Chris Humphries who represents Aldbourne and Ramsbury quit the party last night in a surprise move following his suspension for three months over controversial comments he was said to have made to a female officer.
The polls are open across Wiltshire today as the county goes to the polls to elect the county's first Police and Crime Commissioner.
Explorer David Hempleman-Adams will set off on Saturday on an expedition including three wounded soldiers on a charity trek to the South Pole.
Town councillor Sue Evans has launched a campaign to make the town look better by tidying up unsightly areas that are affecting its appearance and reputation. Coun Evans, who was mayor last year, alerted her fellow councillors to the collection of refuse bins that practically block off the top of The Brittox on Thursdays – market day – when the town is at its busiest. She told the Gazette: "This woman came up to me and took me to the top of The Brittox and I could only agree with her. These bins are put out first thing on Thursday morning but are not collected until the afternoon. The smell is terrible and it looks awful." Plastic barriers strapped to the bollards outside the Halifax, in Maryport Street, are also causing concern as they have been there such a long time.
A teenager has been cleaning up his act after being caught throwing eggs and flour at homes in Chippenham.
Champion Brian Liz, Sarah and Katie would like to thank all those who attended the funeral service and for all the kind messages and donations given in Brian's memory. Many grateful thanks to the Reverend Jennifer Haynes who conducted the service and to John Stuart Funeral Services for their kind attention and support.
REEVES To Matt and Kate Congratulations on the safe arrival of our grandson LOGAN LAWRENCE REEVES November 7, 2012. With all our love and best wishes Mum, Dad, Granny P and family.
BODMAN Phyllis A Your presence at the crematorium was very much appreciated, as were the many messages and cards. Special thanks to the Cedar Ward team and Dr. Jeffries at Chippenham Hospital for their excellent care and attention.
SKITTRALL Ivor 14th November 2011 If tears could build a stairway and memories a lane, we'd walk right up to Heaven and bring you home again. Forever in our hearts. Gillian, Mark and families.
RAMSAY Wendy November 19, 2009 Close in our hearts, Your memory is kept, To love and cherish, And never forget. Greatly missed and always in our thoughts. From the Ramsay and Unwin families xxx
RANDALL Gerard 10/06/1962 - 13/11/2007 Another year gone, but you are in our hearts forever. Love always Mum and brothers, wife and sons. xx
BYE Joan The family of Joan would like to thank everybody for their cards, kind messages and donations to Wiltshire Air Ambulance.
MIDGLEY Michael Mary, David and Sue would like to thank everyone who attended the service for Mike, and for all the kind messages and cards received. Also, for all the donations to Dorothy House Hospice.
EASTMOND Reg Maureen, Andrew and family would like to thank everyone for their kind messages of sympathy and support following the sad loss of Reg. Thank you also to those who attended the funeral service and for the generous donations to the Prospect Hospice and Ailesbury Ward, Savernake Hospital.
MILES Philip Sheila and Julie would like to thank everyone for their kind messages of sympathy and support following the sad loss of Philip. Thanks also to those who attended the funeral service and for the donations to Alzheimer's Support.
WICKS Trevor Jan and family thank everyone who attended the funeral and for all the cards and donations received.
Daylan Gleed ** Happy 40th Birthday ** November 21st All my love from Hong Kong Mum x
SUTCLIFFE Roy (Sam) Lots of love to a brilliant Dad and Grandad on your special day. Love from Kara, Shallot and Alice xxxxx
Grant Wall 12.7.77 - 24.9.12 Memorial Gathering November 24, 2012 At Poulshot 'Green Gardens' 12.00 - 3.00pm All friends invited. Voluntary collection towards 'Grant's Bench on the day.
MALONEY Douglas 10th November 1998 Still remembered by Eileen, Nigel, Kay, Matthew and Benjamin.
RANDALL James 24/11/1923 - 16/11/2010 In loving memory. Sadly missed by Jutta and sons xx
PENNEY Toots (Yvonne) We cannot bring the old days back when we were all together. But memories keep you close to us, and memories last forever. Love from Bunt, Sandra, Jayne, Iain, Lorraine and families xxxxx
WITTS Gary Robert Passed away suddenly at Bath RUH on November 6, 2012, aged 50 years. Loving wife to Donna, proud father to Amy, Jade, Alfie, Danny and Zara. Gary will be sadly missed by all who knew him. Funeral service to take place Wednesday November 21 at St Paul's Church, Chippenham at 1pm. Everyone welcome.
RUMMING Gladys Peacefully at home on November 6, 2012 aged 91 years. Beloved mother, grandmother and great grandmother. Funeral to be held on Tuesday November 20, 2.30pm West Wiltshire Crematorium, Semington. Family flowers only please, donations if desired to Dorothy House Hospice c/o E. Wootten and Son, 1 North Street, Calne, SN11 0HQ. Tel: 01249 812258


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Being among the most commonly used IM programs, MSN Messenger has consistently had a sizeable base of customers keen on creating add-on with which their favorite chat client could be personalized by them. Amateur engineering jobs programmers released add-on to detect who had removed you from their buddy list, to begin several MSN program, to record discussions… until MSN Plus! was started.
MSN Plus! Quickly became the most famous MSN plug-in, gathering together all of the additional choices customers could request into one application. Nonetheless Plus! Continues to be an outstanding bunch of resources definitely enhances your IM expertise and which which significant Messenger users consider as crucial. Throughout all these years it is able to adjust to each new Messenger version, including change of name, the and also the brand new software design. Actually Plus! Has become seamlessly incorporated into Live Messenger: it starts using the software and the sole way you'll be able to tell it can there be it by two small buttons in the primary software.
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When Plus! was started, its primary attribute was the capability to report "chat logs", that's, create text documents with all of your discussions and considered as a very effective verbal communication. Nevertheless, as this is currently contained within the IM application itself, Plus! Has received to broaden its scope of additional capabilities. These resources can be split into two groups: those committed to contact direction and those focused on speaking advancement. As for the very first team, you'll appreciate tabbed chat windows, assistance for custom text format and also the so-called fast messages, private keyboard shortcuts you'll be able to assign to phrases or expressions applied to a normal basis. The 2nd number of tools enables you to make custom status messages, have your favorite contacts right to the Windows computer and assemble a myriad of statistics about contacts, such as the past time they recorded on or if they have lately changed their moniker, that we personally find type of extreme, but hello, to each their own.
The great point though is you could make your own additional capabilities, in other words, if you understand the way to code scripts. Plus! Currently includes a nice group of these, enabling you to really show the complete name of the tune you are hearing, send screenshots, use sticky notes along with other good accessories.
Author's Bio
Philip Cole he has written many articles about topics related to technology education and some of the most interesting career info such as auto mechanic salary everything to know about paralegal salary and what does a neurologist do


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Tags summer, happy music, mermaids, lesley gore, sunshine lollipops and rainbows
Artists Lesley Gore, Javelin, Brenton Wood
April 15, 2012
summer summer summer
art by emmy cicierega
be happy! (yeah, you!) by iliketodisco
i don't care if the whole world knows what my secrets are.
happy, pop, girls, also the vamps
mfpoty by iliketodisco
(motherfucking party of the year).
summer, cher lloyd, princess jams
wanna see the way you move for me baby by iliketodisco
a girl power summer.
girls, and one direction apparently, summer, 2000s throwback
smiling faces, sometimes by iliketodisco
Not yet, anyway.
one direction big bangs, 70s spy + cult leader au, harry/louis


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Michael....PLEASE get your life back together. You're still young, you're SOOOOO talented, you're a shoe in for the next level.....it's all up to you. Make good choices young man, and....the NFL world will be your pearl! Good Luck.
Ya, well, I would think that the person that hit him represents the typical Alabama fan base, their eintire fan base, and, they don't even have shoes...
Ya, I think he's kinda poking fun at you guys....and by the way,some of you do think you have about 30 or so!
Not an Alabama fan. In fact, can't pull for them, don't know how....until the 3rd quarter of last night's game. WOW! That was the most DOMINATING defensive perforamce I have ever seen, at any level of any football game....anywhere. 7 minutes and 29 seconds left in the game....and mighty LSU finally reaches the 50! They don't cross it...the just reach it at that point. WOW. For the first tiime in 40 years, I pulled for Alabama. I wanted to see you shut them out. I saw the win coming, you dominaed them last time, but I didn't see total domination coming. Now....send your entire defense to the NFL please....everyone of them. Give us back Yeldon, and we'll see about next year!!!Congrats, you guys were amazing.
UHH, Shane...I haven't seen a playbook thrown at Alabama this year that did work...and that includes LSWHO, so....somehow I don't think it's Malzahn....
No, I think that's exactly what we've had the last 3 years....
No, and just like our defense, I think we need to send a search party out to look for them....
The same thing our problem has been on defense for the past 3 years. Take a look at our recruiting classes our Def. Coord. had to work with over the last 3 years, take a look at where our total defense ended up in those 3 years...this year included....answer looks pretty obvious to me. We have the talent, but not the results...coaching? Coordinator?
Love the screen name...but...I think we all know it counts.....well, unless you're CAUGHT!
WAREAGLE!!! You beat a full strength SC, at home, a team that showed on the field they were better than these bull puppies. Play good defense, you will have the same opportunity Saturday!
Charles, with his win against Florida, not LSU.....
Thank you.
You keep hoping, LSU. Not even a letter of inquiry, 2 years into this almost.....but they're "hot on some trail"...right? We define cheating? Really? seems to me it was around 1992 or so the last time we had serious issues with the NCAA. About 2 decades. And you guys? HMMMM. Typical Alabama fan, loves to point too what was......
Yes, Victory, the numbers don't lie. Interesting thing about that number if you dig a bit deeper....the difference between the first and 2nd number sure has been shrinking over the years. I'd say if you look at recent history, say 20 or 30 years of it, maybe not so good for you? Own us? If so, you "sold" a long time ago! Don't look back....we're coming!! WDE!!
This defense will be better each week, but.....I don't think we have many SEC wins left at this pace. We are getting hit right up the gut, where Auburn has been strong for decades. It's beginning to get a bit old....we are in the bottom tier of defese for the SEC for what appears to be every year Roof is in charge. I feel he's had enough time to get this defense back where it belongs, and if he can't soon.....?
I agree with rankings. I HOPE UTU was a wake up call for us......we'll find out in a few days!
Ya, Fred...typical. It's 2011, stay in the present my friend. I know it's hard for you guys...with all the "history" and stuff. We own the 200o's. We own the 90's...so you keep looking "back", that's probably your best bet.
Nature something Nurture who cares.
Alabama 2 Auburn 1
Aubrn 28 Alabama 27
Seems to me the 3rd stat means a whole lot more than the first 2....
Welcome Mr. Callahan! WAR EAGLE. We are STOCKPILING talent.
Rocky, same story with you just different verse. 5 wins? If we're lucky? Position by position, we have top (albeit raw) SEC talent. Agree winning the SEC or even West may be a long shot...but which "5 wins" or less do you see? We're going t be a little better than you think....think used liberally.
Heard it on 104.5 the Zone


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Below is the poem entitled My Inner Strength which was written by poet
Flach. Please feel free to comment on this poem. However, please remember, PoetrySoup is a place of encouragement and growth.
Read Poems by
Joe Flach
For Achilles it was his wounded heel
For Sampson his cut off hair
For me I would loss my inner strength
If you were no longer there
Like Stanley looking for Livingstone
Like Ponce de Leon searching for youth
I would scour the world looking for love
If you were gone – and that's the truth
Brutus was the end for Caesar
Waterloo for Napoleon
If ever you were to go away
I would cease to carry on
Throughout the pages of history
Are stories with which I relate
But as long as you stay here with me
I won't suffer a similar fate


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We asked you to create the perfect woman using the top nine ladies on Maxim's Hot 100 list, which include Marissa Miller, Scarlett Johansson, Jessica Biel, Eva Longoria Parker, Sarah Michelle Gellar, Elisha Cuthbert, Eva Mendes, Christina Aguilera (who won in the legs category by a landslide!), and Lindsday Lohan. You told us which of them had the fiercest legs, hottest face, sexiest midriff and best bottom. We tabulated your votes and photoshopped together the perfect woman. Tell us if you agree with the final results!
P.S. Scandalous Maxim Hot 100 news after the jump …
– Jeter, Mayer Have Bedded 10% of Maxim's 2008 girls
– Mini-Skirts Required at Maxim Hot 100 Party
– Maxim Hottie Tila Tequila Wants to "Screw" Jonathan Rhys Meyers


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Hang tight!
Recipe by Jana Thornton
"A vegan main dish soup that is hearty and tastes great with crusty bread."
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2 (14.5 ounce) cans
vegetable broth
1 (28 ounce) can
peeled and crushed tomatoes
2 large
carrots, coarsely chopped
1/2 cup
frozen green beans
1 stalk
celery, thickly sliced
1/3 cup
frozen pearl onions
2 cloves
garlic, minced
1 tablespoon
dried parsley
3/4 teaspoon
dried basil
bay leaf
1 cube
vegetable bouillon
1/2 cup
1 (15 ounce) can
kidney beans, drained
3 small
zucchinis, cubed
I've made this soup several times now and we always enjoy it. The first time I followed the recipe exactly but now I change it up to suit what's in our fridge and pantry on any given day. But that's the beauty of this soup, it's very versatile. Quick and healthy :) Today I made it with corn and I also threw in some ABC noodles. Mykids love this soup! :)
This was soup was meh. I substituted fresh tomatoes and green beans since I try to use canned food as little as possible. Regardless, it was nothing special.
56 Ratings
This is something I make almost weekly (sometimes more). It's really great for when all my veggies are starting to go bad. Very easy to customize...
Loved this as a low calorie, vegetarian, easy, filling meal. Soups are great to tweak to personal taste. My personal taste is to use 3 carrots and 2 zucchini and 3 cloves of garlic. I also used macaroni alphabet pasta to entice my kids. DO NOT substitute anything for pearl onions, nothing else will do.
Wonderful recipe and great for adapting to whatever veggies, beans or pasta you have on hand. I have made this 4 times now, and each time I play with ingredients following the basic recipe. Every time I have gotten great respnse from a very picky family!
Yum! Easy and quite tasty. I used orzo pasta instead of macaroni and doubled the garlic. Definitley a keeper!
I made this recipe but used chicken broth and chicken bouillon. I omitted the green beans because I didn't have any. And I used mini bow tie pasta and cooked it separately. This was a nice vegetable soup and easy to throw together. One can of kidney beans seemed a little sparse, so next time I'll add a second can. UPDATE 1/17/14: I made this again as follows: I used chicken broth and chicken bouillon as before, the tomatoes, 1 cup each of carrots, celery and pearl onions, no green beans, macaroni, or beans. I used two zucchini and one yellow summer squash. Great flavor and really low in calories!
i had to add a little more chicken broth. This is a very good low fat meal. And make a great left over. :)
* Percent Daily Values are based on a 2,000 calorie diet.
Italian Vegetable Soup
Serving Size: 1/6 of a recipe
Servings Per Recipe: 6
Amount Per Serving
Calories: 185
Calories from Fat: 11
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The firm, juicy texture of zucchini make them a perfect side to toss on the grill.
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COLUMBIA CITY — The warm, enjoyable football weather came to an end this week, as players took the field in rainy, 41-degree conditions.
Both Columbia City and Carroll faced the same muddy disadvantage Friday night at the Max Gandy Athletic Field — but the Eagles also carried the detriment of multiple sidelined starters, and fell 20-6 to the Chargers on senior night.
Garrett Vandersaul had a strong performance on the defensive end of the ball, forcing two fumbles, two sacks, two tackles for loss and five tackles overall.
The Eagles play their final regular season game next week at Northeast Hoosier Conference foe Norwell.
[1] http://www.thepostandmail.com/sites/default/files/DSC_5324.JPG


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