text:
|Publication number
|Publication type
|Application number
|Publication date
|Jun 24, 2003
|Filing date
|Dec 21, 2001
|Priority date
|Apr 10, 1998
|Fee status
|Also published as
|Publication number
|Aureliu M. Porumbescu
|Original Assignee
|Proactive Metabolics, Co.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (20), Non-Patent Citations (1), Referenced by (29), Classifications (14), Legal Events (12)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a divisional of U.S. Pat. application No. 09/290,094, now pat. No. 6,368,272 B1, filed Apr. 12, 1999; which claims the benefit of U.S. Provisional Application No. 60/081,290, filed Apr. 10, 1998. Each of these applications is hereby incorporated by reference in their entireties, including all figures and tables.
The invention described herein was made in the performance of work under National Institutes of Health (Contract Number LR43 DR47730-01A2) and Department of Defense (Contract Number DASG60-97-M-0066) contracts. The federal government may have certain rights in this invention.
In health, all events taking place inside living bodies are controlled by a myriad of minute processes, each having outcomes preordained by their DNA templates. One such process is the blood glucose metabolism, which is optimized to achieve normoglycemia even for wide swings in the predominant effect inputs, food and physical exercise. Illness, on the other hand, is characterized by the body's inability to maintain control over one or more biological processes. Unless correctable by surgery, medication, or other means, the out-of-control condition extends to other processes and results in poor patient prognosis. The only alternative left to people suffering from "incurable" afflictions is disease management, that is, careful monitoring of the parameters of interest, coupled with corrective actions such as insulin injections, dialysis, etc.
For example, diabetes patients have little or no endogenous blood glucose (BG) control capability, and many must inject insulin to compensate for swings outside the acceptable serum glucose range. Similarly, end-stage renal disease patients have lost the ability to control their nitrogen metabolism, and must undergo dialysis, typically for the rest of their lives. The reader will appreciate that many other situations sadly exist, however, because they are representative of this entire class of problems, we will limit the examples presented here to glucose control and diabetes, and their spin-off, long-term weight management.
Diabetes mellitus is a significant chronic disease with no cure, affecting more than 16 million Americans and 100 to 150 million people worldwide. In the U.S. it is the fourth-leading cause of death each year. (National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases: Diabetes in America/Second Edition, NIH Publication No. 95-1468 (1995)) Its incidence rate among children and teenagers in the U.S. increased several fold during the last thirty years, and more than 30,000 new cases are identified each year. It is a $156 billion problem for the US economy.
A problem of this magnitude naturally generates intense efforts to alleviate it, and one landmark study has altered the course of treatment. The results of the Diabetes Control and Complications Trial (DCCT) indicate that tight control of blood glucose levels results in a dramatic reduction of complications, including 76% lower incidence of diabetic retinopathy, 60% less neuropathy, and as much as 56% fewer cases of nephropathy. The costs to society could be drastically reduced, but at the expense of intensive management (more frequent blood sugar measurements, multiple daily injections).
Technological advances have made it possible for patients to administer insulin at home, and to monitor the blood glucose levels (self monitoring of blood glucose, or SMBG) with equipment that costs less than $100; test strips and accessories run about $2,000 per year per patient, but of course this expense will double with intensive management as suggested by the DCCT results. To further improve ease of control, intense product development efforts have led to the introduction of a new, rapid insulin (HUMALOG™), and non-invasive blood glucose measurement equipment could be marketed within the next few years.
However, currently available equipment does not take into account the blood glucose dynamics, and invasive blood glucose measurement techniques discourage frequent testing. The blood glucose values are therefore known only to a minute extent, because even the most compliant patients will only draw blood and test the glucose concentration less than ten times a day. The data available is therefore much too far from the Nyquist sampling rate, and very little in formation results from the individual blood tests. Again, intense product development efforts have led to the introduction of statistical process control concepts in blood glucose meters, and many now can store several hundred measurements, including the time of day and date each value was measured. For a rigid regimen, whereby the patient always eats the same meals at the same time, and injects the same amounts and types of insulin every day at the same time, the statistical information thus gathered helps with the metabolic control and gives the physician the means to assess the patient compliance and adequacy of the regimen. The main draw-back of this methodology is that it is all after the fact, while also severely restricting the patients ' freedom of action in the most basic are as, such as food and exercise, and rest.
This too has a solution, albeit an imperfect one: the "gold standard" in diabetes nutrition is carbohydrate counting, a method that allows the patients with insulin-dependent diabetes to eat any higher carbohydrate meal, so long as the equivalent amount of insulin is administered. There are problems with this also, the two most important being that most patients cannot do the conversion, and that not all carbohydrates are equal in terms of their speed of conversion to blood glucose. (An extensive amount of information exists on the glycemic index of different types of food.)
Intense efforts to introduce non-invasive blood glucose testers will soon bring to market equipment that will make frequent testing convenient, but still no predictive capability will be added by non-invasive SMBG. The burden of understanding the temporal characteristics of the physiological mechanisms of glucose regulation depends on the patients.
Those equipped with the knowledge and willingness to devote time are able to achieve a good overall level of control, but most patients are overwhelmed and find themselves unable to understand what has caused the lack of blood glucose control. For patients who are not equipped with the ability to understand such issues, the only way to stay in control is to adhere to a very stringent schedule of daily insulin, food and exercise that does not vary from one day to another. Such a regimen poses serious compliance and lifestyle problems. For these patients, solutions based on mathematical modeling are available:
The body of a healthy person has the endogenous control capability to minimize the glycemic challenge to the body, but the diabetes patient has little or no endogenous control capability. Maintaining blood glucose levels within normal limits can be treated as a control systems engineering problem, which was, and continues to be the object of much research. Those who published their work in this field (Heinonen, Porumbescu, etc.) considered the body's blood glucose system a classic control system, consisting of a plant whose aim is to maintain control over an output (Blood Glucose), in the presence of zero or non-zero inputs (food, physical exercise, insulin), and of perturbations (emotional status, illness). The euglycemic output is achieved by feedback: continuously measuring the output values, comparing them to the desired state (set point), and initiating compensatory action. By contrast, in diabetes this is an open-loop system, in need of an external feedback loop, therefore attempts were made to provide it through mechanical means.
After more than twenty years of trying, it can be safely said that attempts to devise mathematical models for blood glucose metabolism have failed. The reasons are numerous, but one of the most important is that models that will work properly for an entire population are very complicated and include nonlinear equations. Some degree of success has been reported with developing adaptive individual-specific models, which will work in conjunction with a strict regimen that does not vary from one day to another.
For example, U.S. Pat. No. 5,840,020 (Heinonen et al.) addresses the adaptive model shown in FIG. 4, whereby the error between a predicted value and the actually measured value is used to optimize (converge) a dynamical model in a recursive fashion, using Widrow's Adaptive Least Means Square algorithm.
Similarly, Porumbescu et al. ("Patient Specific Expert System For IDDM Control" in Proceedings of the Fourth Conference of the International Federation of Automatic Control/System Structure and Control, October 1997) report on the development of an Expert Equipment that optimizes a dynamical model using Kalman recursive filtering.
The rapid spread of increasingly affordable high speed computers gives this type of research more impetus, and several researchers have recently reported significant progress. One commercial software package, based on a very simple prediction model has been introduced in 1995 (Insulin Therapy Analysis, by ITA Software Inc.). The AIDA Interactive Diabetes Advisor, which uses a similar modeling and prediction approach is available over the internet. Yet another system, KADIS, is in use in Germany as a model-aided education tool for IDDM patients.
What all these solutions have in common is the inability to process the information and generate predictions in an on-going manner. For this reason they are more in the nature of educational tools, than of assistive devices. While they may, to some extent, be able to generate sufficiently accurate predictions, those predictions apply only to a known and very rigid, set of inputs. And, while with a good model, the patient will likely be able to generate a close enough prediction for one different input one time, the performance cannot generally be repeated several times in a row, because the initial conditions have changed.
The complicating factor is that to achieve contemporaneous control, the modeled external feedback loop must include not only static corrections, but also predictive elements relative to the dynamics of the patient's body.
The present invention relates to decision support equipment and improved methods for providing individuals with means to proactively control their health. The invention subject also relates to computing equipment suitable for processing data to simulate the dynamics of the metabolic processes and their inputs, in order to generate real time predictions of the metabolic status. The subject invention further relates to knowledge-based apparata used in controlling management-intensive medical conditions, including apparata for noninvasive assays of metabolic analytes.
FIG. 1: A flow chart and block diagram of the software and steps involved.
FIG. 2: Diagram showing the system, including software, hardware, and patient.
FIG. 3: Graph illustrating the differences in glucose bio-availability for different types of food, computed according to the invention.
FIG. 4: Prior art illustration of "static" adaptive model.
FIG. 5: Principle of operation of the wedge-and-Strip position-sensitive detector (prior art): The centroid position computation in Wedge-and-Strip patterns is based on the following property of the wedge-and-strip inter-digital pattern: An electron cloud, having diameter larger than the pitch, lands on the pattern. With the collected charges Qs, Qw as shown, and Q0 for the substrate, the [X,Y] coordinates of the centroid of the cloud are simply computed as:
FIG. 6: Optical Spectroscopy apparatus having a wedge-and-strip array as photodetector.
Decreasing costs for computers and communications and increasing pressures to contain health care costs promote technology-intensive proactive approaches to health care, especially in diabetes, but the invention is also applicable to any other medical condition where measurements are routinely made. The main benefit is that the patient has the ability to implement proactive actions that do not affect his or her life style in a major way, which leads to greatly improved health outcomes and compliance.
The invention puts control ahead of measurement, giving people the means to understand what is happening with their bodies with respect to a set of parameters of interest, relying on the fact that proactive control is more desirable than the current test-fix-test (an approach with which one is instinctively comfortable). To that end, the invention provides a group of software programs and ancillary equipment to compute an individual patient's profile and make contemporaneous accurate predictions regarding how the patient's biological system will respond to individual stimuli: predictions are communicated in real time, enabling plans for future actions by verification of good control status, or signaling the need for corrective action. Thus, contemporaneous decision support is provided to the patient.
The subject invention provides for customizing traditional population-based solutions to an individual patient's needs and adding the time dimension (i.e., attaching a time function to each variable of interest). This approach is superior because it allows prevention-driven proactive care at the health care consumer level, when the consumer needs the information, not after the fact. It is also more accurate and effective:
The invention is based on three basic concepts: 1) Control is more relevant than measurement. Devices of the future, which will mimic life itself, must target the overall success of metabolic control—keeping the parameters of interest within the target range—to know any value with accuracy and precision is less relevant. A patient-specific system model converges much quicker to "good enough" approximations of the outputs of the real system than one that only uses general population data; 2) Proactive control mimics life. In control systems parlance, these are "feedforward" systems as opposed to measure-and-correct, or "feed back" that we accept instinctively. Unlike current devices that test something and generate a value that must be processed to generate information, our noninvasive measurement devices aim to use the prior knowledge about the dynamics of the system being measured, in order to generate "heads up, in or out of control" signals, usable directly by the consumer; and 3) Living things reflect the dynamics of their inputs—this is borne by research in system control theory, which indicates that stable feedforward systems have structures that are actually governed by the dynamics of their input functions.
Ultimately, these basic concepts mean that the invention addresses the problem from a duality point of view: Dualities between control and estimation problems are useful concepts in optimal control theory because by demonstrating a duality, the solution to one set of problems can be applied also to the dual set of problems. As discussed by Bernhardsson et al. "A duality is demonstrated between optimal feedforward control and optimal deconvolution, or input estimation. These two problems are normally discussed separately in the literature, but have close similarities." Managing a management-intensive disease such as diabetes involves an individual about whom considerable knowledge exists, and knowing when to test is usually more important than the test results. With careful consideration of all major inputs and outputs, total system models can predict much of what is occurring; therefore total system individual-specific modeling is as important as the measurement method, be it invasive or noninvasive.
Blood glucose and interstitial fluid glucose dynamics are dominated by smooth time functions that describe the temporal transformation of a food input to glucose (the output): To that end, using carbohydrate counting to simulate the system input in conjunction with a feedback model, no matter how accurately the carbohydrates are counted, is like hitting a radio with a hammer and calculating its Dirac pulse response in order to understand how it's built.
The methodology to describe the exogenous glucose dynamics for various foods which is part of this invention is the direct result of this challenge. Rather than aiming for measurement accuracy and precision, the objective of the invention is to provide the individual with sufficient information to achieve proactive metabolic control, including the optimal timing and specifics of key activities such as insulin injections, blood glucose measurements, meals, exercise, etc. That is, to pursue regimen flexibility instead of rigidity. Using the models for the input dynamics results in a drastic simplification of the complexity of the models of the metabolic system.
Progress in the area of non-invasive SMBG will complement the methodology by providing more frequent clinical data points and thus helping the model converge to a sufficient prediction accuracy within a shorter time period. For IDDM patients who will not be able to afford the non-invasive SMBG equipment, the use of predictive technology in conjunction with a HUMALOG™ (lispro) type of insulin will be able to achieve euglycemia.
The subject invention provides methods of generating ongoing status predictions for improved decision support in metabolic control, comprising at least one of the following steps:
(a) entering ongoing information from the user-patient and from biomedical assay equipment according to an interactive, time-stamped mode which includes at least one of the following sub-steps:
(a)(1) selecting and specifying inputs to the living system being controlled, plus specific descriptors and quantifiers of said inputs, wherein the said inputs may include nutrients, medication, physical activity, illness, or hormonal challenges;
(a)(2) recording individual-specific anthropometrical, medication prescriptions, and treatment regimen data, wherein the said treatment regimen data also includes physician-prescribed metabolic control guidelines, including rules that define the "in-control range" and "sufficiently close" terms;
(a)(3) selecting output parameters and entering their measured values; and
(a)(4) selecting hypothetical inputs, wherein the user can evaluate a course of action over other possible actions.
(b) accepting or rejecting said input and output values and storing the information contained therein in appropriate memory areas, wherein each associated time stamp is properly stored as well;
(c) assigning to each said specified input an appropriate time function describing its dynamic characteristics and computing the predicted values thereof in an ongoing manner, starting said predictions from the time of the appropriate time stamp data;
(d) assigning to each said output parameter a mathematical model describing its dynamic interactions with the said inputs and improving said mathematical model by making it individual-specific by the following sub-steps:
(d)(1) accepting individual-specific anthropometrical data and storing the information contained therein in appropriate memory areas;
(d)(2) performing appropriate computations, wherein said anthropometrical data is incorporated in each said output parameter mathematical model;
(e) generating ongoing metabolic status predictions by combining all previous relevant said inputs with said individual-specific mathematical models, wherein the accuracy of the said predictions is improved by one or more of the following substeps:
(e)(1) selecting from the universe of possible mathematical models only those that meet physiologically meaningful periodicity criteria, wherein they reflect circadian, menstrual and other applicable cycles that affect the process; and
(e)(2) further improving the said mathematical models by selecting from the universe of possible mathematical models only those that lead to predicted values that are "sufficiently close" to the actual measured values.
(f) recording, revising and storing the prescribed individual-specific medication and control parameter limits, wherein a health practitioner sets boundaries on the type of actions the patient can take; and
(g) communicating to the patient the need for proactive corrective action, wherein any such need is determined by considering steps (e) and (f).
The subject invention also provides methods for estimating the ongoing "dynamic bio-availability" of metabolites subject to control, comprising at least one of the following steps:
(a) dividing the intake matter into distinct components, whereas each component is uniquely characterized by the dynamics of its transformation into a metabolite;
(b) assigning each said distinct component to an elementary category, wherein each category is described mathematically by a category-specific time function;
(c) calculating the time functions corresponding to the said distinct components, by accounting for all relevant quantifiers available for the intake matter; and
(d) calculating the combined effect of said elementary components as a function of time.
The intake matter may be food, and the metabolites are "exogenous glucose" from food. Category-specific time functions are described by a time function having a general form such as would be required to describe mathematically the output from a chain of N compartments connected with one-way fluxes of the same rate a, given for example by, but not limited to, the expression:
wherein "EG(t)" is elementary food component glucose activity time function; "t" is a length of time measured from the time stamp of entered data, such as the time the food was consumed; "a" is the flux rate of elementary food categories; and "N" is the number of compartments. In various embodiments, "a" is a population averaged value, "a" is specific for a given individual, or a=12 for all sugars, a=1/1.5 for starchy glucose, a=1/2 for starchy galactose, a=1/3 for starchy fructose, a=1/5 for protein, and a=1/8 for fats and N=1 to 5. Some embodiments provide for N=4.
Elementary food categories are simple sugars, starches, protein, and fat, wherein each of the said elementary categories is described by a unique pair of coefficients a and N. The elementary food categories are further refined by executing at least one of the following steps:
(a) dividing each food category into sub-categories, each said sub-category being described by its unique pair of coefficients a and N;
(b) dividing the food category "starches" into three sub-categories corresponding to glucose-based, galactose-based, and fructose-based carbohydrates; and
(c) adjusting the values of any said pair of coefficients a and N to reflect any individual-specific differences in ability to process the said category or sub-category of food.
Contemporaneous decision support in metabolic control may be achieved for diabetes, by pursuing two or more of the following steps:
(a) generating time functions describing the time course of the exogenous glucose following a meal, according to the methods provided herein;
(b) generating time functions describing the time course of the exogenous insulin following an injection or infusion pump action, according to the following method:
(b)(1) generating specific time functions having a general form such as would be required to describe mathematically the output from a chain of N compartments connected with one-way fluxes of the same rate by, given for example by, but not limited to, the expression:
wherein "I(t)" is an exogenous insulin time function; "t" is a length of time measured from the time stamp of entered data, such as the time the particular insulin was injected; "a" is the flux rate of various insulin types; and "N" is the number of compartments. In various embodiments, "b" is a population averaged value, "b" is specific for a given individual, or b=1.0 for regular insulin, b=0.5 for NPH insulin, b=0.25 for lente insulin, and b=0.2 for ultralente insulin. N can be a value from 1 to 5. Some embodiments provide for N=4;
(b)(2) refining said exogenous insulin time functions by accounting for the differences in insulin bio-availability experienced by the patient depending on the injection site; and
(b)(3) refining said exogenous insulin time functions by accounting for the differences in insulin bio-availability experienced by the patient depending on the patient's degree of insulin resistance.
(c) generating time functions describing the time course of the physical exercise and other manually-entered inputs, according to the following method:
(c)(1) generating specific time functions having a general form such as would be required to describe mathematically the output from a chain of N compartments connected with one-way fluxes of the same rate c, given for example by, but not limited to, the expression:
wherein c takes specific values for each different type of exercise, and d is a delay factor; and
(c)(2) refining said physical exercise time functions by accounting for the differences in insulin bio-availability experienced by the patient depending on the injection site; and
(c)(3) accounting for the additive or subtractive effect of illness, medication, or hormonal challenges by correcting the insulin input information accordingly.
The subject invention also provides a personal assistive apparatus for contemporaneous metabolic control, wherein a health practitioner programs the prescription and limits the type and extent of actions a patient is allowed to take by means of a hierarchical software structure. The invention also provides an apparatus for computing the bioavailability of exogenous glucose and other nutrients contained in food, consisting of:
(a) an interface and control device that accepts user input and provides information for the assessment and control of the ongoing metabolic state of the individual user;
(b) a data storage device containing an addressable food data base, and software wherein each element in the said food data base is decomposed vectorially into elementary food categories;
(c) a data storage device that contains a plurality of coefficient values and time function formats, wherein such coefficients and time functions appropriately describe the expected variation in time of one or more metabolites in vivo, under certain input conditions; and
(d) software and means for computing and storing the predicted input time functions for the characteristics of the specified inputs.
The personal assistive apparatus for contemporaneous metabolic control may further comprise a means for determining the current values for at least one output parameter, such as the blood glucose level, wherein such determination results from direct input by the individual patient, or from direct download from an instrument measuring the concentration of said blood glucose; software and means for computing the estimated current values for the said blood glucose level; software and means for comparing the estimated current values for the said blood glucose level with their contemporaneous measured correspondent values, in order to optimize the mathematical model of the metabolic control system; software and means for predicting values for the future state of the blood glucose level, including means to decide if and when said blood glucose values are expected to fall outside the range defined by the "in-control" rules; and/or a means for alerting the user whenever any such predicted output parameter values fall outside the range defined by the "in-control" rules. The device may also present information to the user, through a graphical user interface, a color-coded or pictorial representation of the time course of the blood glucose, enabling the user to assess how every new action taken will modify the said representation.
The personal assistive apparatus for contemporaneous metabolic control may further comprise a means to compute and store functions indicative of the degree of control achieved by the individual patient over a period of time, such functions consisting typically of the aggregation of the severity-weighted time integrals of all out-of-control situations likely to have been experienced by the patient over the reporting period. Additionally, the personal assistive apparatus for contemporaneous metabolic control can further comprise at least one of the following devices: an insulin infusion pump; a blood glucose meter; a modem for communicating with other computers; wireless communication means for emergency situations; a meter that can test both glucose and fructosamine in the blood; a non-invasive blood glucose meter; a minimally-invasive blood glucose meter; a transdermal glucose measurement system. Alternatively, the personal assistive apparatus for contemporaneous metabolic control may further comprise an intelligent sensor consisting of at least: an optical spectroscopy apparatus employing at least one Wedge-and-Strip Position-Sensitive Photo-Detector, including means to detect the location of light pulses by employing analog decoding means; a means to illuminate a portion of a patient's body and onward the said Wedge-and-Strip Position-Sensitive Photo-Detector with light in certain portions of the infrared spectrum, wherein such illumination may be applied in a pulsatory fashion; a means to synchronize such light pulses with certain biological events, such as the heart beats; a means to accumulate the pulses read by the Wedge-and-Strip Position-Sensitive Photo-Detector into a histogram; means to calibrate the said optical spectroscopy apparatus by correlating the number of counts per second recorded in a certain portion of the histogram with the glucose concentration; a means to modify the duration of the measurement; and/or software for adapting the duration of the measurement according to the degree of prior knowledge about the analyte.
The personal assistive apparatus for contemporaneous metabolic control can further comprise software for optimizing the peritoneal dialysis prescription of patients with diabetes who suffer from kidney disease or for optimizing the metabolic control regimen of pancreatic or protected beta-cells transplantation patients. The software can be optimized for the metabolic control regimen of newly diagnosed diabetes patients in a hospital or clinic setting. Alternatively, the software for optimizing the metabolic control regimen of astronauts during space flights or for optimizing the metabolic control regimen of people with special glucose metabolism needs, including but not limited to patients under intensive care, patients who have suffered trauma, premature babies, or people involved in performance sports.
The term "acceptable serum glucose range" is intended to mean glucose levels above 50 mg/dl and below 300 mg/dl more preferably 80 mg/dl to 200 mg/dl and most preferably about 100 mg/dl. It will be understood by those skilled in the art that levels of about 50 mg/dl are considered low and that levels of about 300 mg/dl are considered high, although acceptable in the sense that these levels are generally not fatal.
Insulin Dependent Diabetes Mellitus, or IDDM is a syndrome of disordered metabolism, leading to hyperglycemia due to an absolute deficiency of insulin secretion. The only known way to prevent the patient's death is by administering insulin.
The term "metabolism" is used here in its general sense, and it summarizes the activities each living cell carries on.
The term "dynamic bio-availability" reflects the time course of a certain metabolite, typically expressed as the changes in its quantity in blood.
The term "exogenous blood glucose" means glucose appearing in the blood stream as a result of the steps involved in assimilating food.
The term "in-control range" is a patient-specific term, reflecting the physician's assessment of the range of values within which a patient must try to maintain the metabolite being controlled.
Insulin Dependent Diabetes Mellitus, or IDDM is a syndrome of disordered metabolism, leading to hyperglycemia due to an absolute deficiency of insulin secretion. The only known way to prevent the patient's death is by administering insulin.
Normoglycemia is a patient-specific state, which can be thought of as a metabolic set point of 100 mg/dl, within a "normal range of 60 to 120 mg/dl. The specificity means that, for example, a person's blood glucose may never exceed 120 mg/dl, while another's may exceed 150 after every meal due to that person's increased resistance to the counter-regulatory hormone insulin, or it may go below 50 mg/dl every day, due to some prolonged physical strain at work, or due to over-excretion of insulin.
The term "sufficiently close" is used here in the following sense: a confidence band of physiologically-significant width around the measured metabolite values, that must contain all the predicted values for that metabolite for the same time stamp and input history combinatoin
The term "time-stamped", as used in conjunction with information events entered into the device, means associating each such event with the correct time it has occurred, either through mechanical means or by having the user actually enter the correct time into the device.
While there have been described what are believed to be the preferred software and hardware embodiments of the invention, those skilled in the art will recognize that other and further motifications may by made hereto without departing from the spirit of the invention, and it is intended to claim all such embodiments as fall within the true scope of the invention.
U.S. Patent Documents:
U.S. Pat. No. 5,840,020 Nov. 24, 1998 Heinonen et al.
U.S. Pat. No. 4,731,051 Feb. 15, 1983 Fischell, R.
Other References:
Bernhardsson, B.; Sternad, M.; "Feedforward Control is Dual to Deconvolution" in International Journal of Control (February 1993).
Porumbescu, A.; Dobrescu, R.; Jora, B.; Popeea, C.; "Patient Specific Expert System For Iddm Control" in Proceedings of the Fourth Conference of the International Federation of Automatic Control/System Structure and Control (October 1997).
Salzsieder, E.; Albrecht, U.; Freise, E.; "Kinetic Modeling of the Glucoregulatory System to Improve Insulin Therapy" in IEEE Trans. In Biomedical Engineering BME-32, 846-855 (1985).
Berger, M.; Rodbard, D.; "Computer Simulation of Plasma Insulin and Glucose Dynamics after Subcutaneous Insulin Injection" in Diabetes Care 12(10), 725—736 (1989).
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|Infusion pump system with disposable cartridge having pressure venting and pressure feedback
|Aug 14, 2009
|Jun 24, 2014
|The University Of Toledo
|Neural network for glucose therapy recommendation
|May 29, 2012
|Sep 23, 2014
|Tandem Diabetes Care, Inc.
|Infusion pump with activity monitoring
|Jul 29, 2010
|Jan 6, 2015
|Tandem Diabetes Care, Inc.
|Infusion pump system with disposable cartridge having pressure venting and pressure feedback
|May 22, 2012
|Feb 24, 2015
|Tanden Diabetes Care, Inc.
|Insulin pump having a food database
|Aug 7, 2009
|Mar 24, 2015
|Tandem Diabetes Care, Inc.
|Two chamber pumps and related methods
|May 22, 2014
|Jul 7, 2015
|The University Of Toledo
|Neural network system and uses thereof
|Jul 29, 2010
|Dec 15, 2015
|Tandem Diabetes Care, Inc.
|Infusion pump system with disposable cartridge having pressure venting and pressure feedback
|Jul 30, 2015
|Jun 6, 2017
|Tandem Diabetes Care, Inc.
|Temporary suspension for closed-loop medicament therapy
|Feb 24, 2014
|Dec 5, 2017
|Tandem Diabetes Care, Inc.
|Insulin pump based expert system
|Jan 9, 2002
|Mar 27, 2003
|Paul Brazhnik
|Method and apparatus for computer modeling diabetes
|Aug 20, 2002
|Mar 18, 2004
|Piet Moerman
|Wireless diabetes management devices and methods for using the same
|Jun 22, 2004
|Mar 10, 2005
|Dave Arndt
|Method and apparatus for managing data received from a medical device
|Oct 7, 2004
|Jun 16, 2005
|Entelos, Inc.
|Simulating patient-specific outcomes
|Jan 3, 2006
|Jul 27, 2006
|Giacomo Vespasiani
|Method for interactively managing of data concerning a self-controlled insulin therapy for a diabetic patient, and system for carrying out said method
|Jun 6, 2005
|Dec 7, 2006
|Galley Paul J
|System and method providing for user intervention in a diabetes control arrangement
|Mar 31, 2008
|Mar 12, 2009
|Entelos, Inc.
|Method and Apparatus fo Computer Modeling Diabetes
|Oct 7, 2004
|Dec 23, 2010
|Entelos, Inc.
|Simulating patient-specific outcomes
|Dec 17, 2010
|Apr 14, 2011
|Erchonia Corporatin
|Method for Treatment of Diabetes and Prediabetes with Low-Level Laser Therapy
|Aug 14, 2009
|Sep 15, 2011
|University Of Toledo
|Multifunctional Neural Network System and Uses Thereof
|U.S. Classification
|International Classification
|Cooperative Classification
|European Classification
|Apr 25, 2002
Owner name: PROACTIVE METABOLICS COMPANY, FLORIDA
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Year of fee payment: 4
|May 25, 2007
|Surcharge for late payment
|Jan 31, 2011
|Maintenance fee reminder mailed
|Jun 10, 2011
|Surcharge for late payment
Year of fee payment: 7
|Jun 10, 2011
|Fee payment
Year of fee payment: 8
|Jan 30, 2015
|Maintenance fee reminder mailed
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Owner name: PORUMBESCU, AURELIU M, FLORIDA
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|Surcharge for late payment


text:
MARCH sees a return of a display all about Midhurst at the town's museum in Knockhundred Row.
It includes many pictures showing how most of the buildings have only changed their fronts and are still recognisable today.
A newly-acquired picture shows a Sentinel steam wagon outside the works in Shrewsbury waiting to be delivered to Isidore Livingstone Stent who ran a builders' merchant and coal yard and at one time had three railway coal wagons, four horses and nine lorries.
The gas works featured in another picture is a reminder that coal arrived by barge to The Wharf where the gas works was built.
With the demise of the canals, coal came by rail and had to be transported to the gas works. The library is shown in its previous use as four cottages.
Also on show is Midhurst crested china which holidaymakers took back as a memory of their visit.

subset: commoncrawl


text:
Wednesday, December 12, 2012
Helping The Poor
Are you tired of people becoming dependent upon outside gifts or entitlements to live? Don't you think that everyone has a responsibility to at least 'try' to provide for themselves? This year I want to help end the cycle by doing more than just giving someone money. Read on…
Denise and I have discovered something that many missionaries have written about. I have been engaged in world missions for over 20 years, and actually on the mission field for five. In that time, I have seen how a blessing can become a problem. Let me explain.
Often, on the mission field, ministry is dependent upon the missionary, and the missionary is dependent upon money from the USA. This is a good thing because it allows so many people to participate in missions. It is Biblical. It is how we take the gospel to new places and minister to the poor. World evangelism needs not only those who go. We must have those who can send. So what is the problem?
You and I agree that while it is virtuous to help others, it is harmful to create a welfare mentality. Yet this is what happens in missions, sadly to say more often than not. The current method of doing missions is a system where the national church's dependence upon the missionary's dependence upon the sending church/people can spell the end of ministry. There is a cycle in world missions. Missionaries travel to other lands, establish churches and ministries to help the poor and needy, then after as little as a year to as much as a few decades, the missionary returns home.
What happens to the ministry now? What happens to the ministry of the national if it is dependent upon the missionary who is dependent upon the sending group…when either the sending group of the missionary breaks the chain?
This is what happens. The ministry stops. It ends. It is over. We have created a culture of subsistence missionaries that sadly produce subsistence evangelism because, when the pipeline of cash from the sending church/people ends, so does the ministry. So, there are two problems to overcome for long-term impact. We have to somehow give without creating a welfare mindset, and at the same time learn how to by-pass the dependency upon the missionary.
The solution, when it is economically possible, is job creation. More than once I have had people ask me, both in person and on Facebook, how they can give to the poor without 'hurting them'. How can you help the poor without your short term help actually hurting them in the long-term? We believe that sustainable growth is only possible when the growth is not dependent upon outside factors. We know that this functions in the real world. That is why we try to use job creation in our own country (the States) to help the overall economy. I actually have a donor who has told me that he will give me $1,000 as soon as I have a clean water micro-enterprise project ready to go. It is in the planning phases now, but he knows that providing clean water is vital, and if we can do it in a manner that also stimulates economical viability and provides jobs, it is a home run.
We agree with him and believe that the best way to help the poor is to provide opportunities for them. We want to not only give them material assistance; we want to lead them to a point where they can help others. We want to provide jobs and business opportunities to impoverished Christians and through those jobs provide not only a way out of poverty, but also an income string to fund ministry.
We want Bolivian Christians to fund Bolivian Ministry with Bolivian money earned in Bolivian business ventures.
Our goal is to start small businesses that will be 100% non-profit. The businesses will provide good jobs and benefits to Bolivian church leaders (99% of Bolivian pastors are bi-vocational). We will provide slightly better than market salary/benefit packages to improve the quality of lives for these church leaders. These businesses will also provide money so that ministry to the poor such as helping orphans, providing food and shelter to the homeless, clean water projects, building homes, starting and constructing churches, etc., can happen without a dependency upon the missionary or the sending groups. If we can start businesses that create jobs and provide money for ministry, all "in-house", then the ministry is no longer tied to a simple love offering or an expense item in a missionary's budget. Ministry is now open-ended, multi-generational and avoids the welfare mentality.
This is the purpose of this letter. We are looking for start up capital to begin these businesses. Our current plans are to open a guesthouse, coffee shop, language school, and a hamburger fast food restaurant. The profit generated by our businesses will be used to fund local ministries. Imagine what would happen in your hometown if the owner of a Burger King, a Starbucks, a Private School, and a small hostel all donated 100% of their net profit to Christian ministry! We will not be franchised, but this is a good illustration of our vision. We want to start private industries providing honest employment, sustainable growth, and monies to invest in God's Kingdom.
This is where we need you to make a high impact and eternal difference in Bolivia!
We need like-minded Christians such as you to invest in lives. Here is how you can do it.
First of all, there are some of you that are receiving this letter that have a large sum of money to invest. We are looking for people that can give us a "no to low" interest loan. We will return your start up capital at the agreed upon interest rate. This way you can take the money that you currently have in money market or low yielding mutual and invest it in the Kingdom, in lives, and in eternity while receiving both an eternal and temporal return. We are looking for people that can invest $10,000 to $25,000 for up to three years.
This probably doesn't describe most of you. However, we are also looking for people that can simply give a lump sum gift of $1,000 to $5,000 for us to use as start up funds. The goal is to invest the money in a business, then as it becomes self-sustaining to take out the initial investment and use it in another start up. Your gift could be multiplied in maybe ten different ventures, giving us constant start up capital. This money is tax deductible and should be sent to Ripe For The Harvest, Holmans, Project #340. For more information on how to give the way that you want to, go to www.Ripeforharvest.org and click on the donate tab.
I don't know how you can become involved in this exciting venture, but God does and He will reveal it to you. Please pray and join us in changing lives both here and forever.
In Jesus,
Joe Holman
Director Of Central And South America,
Ripe For The Harvest World Outreach
P.S. Please contact me directly with questions about how you can help or for more information on the project. email@example.com
pps (as per IRS regulations) Contributions are solicited with the understanding that Ripe For The Harvest has total discretion and control over donated funds. Leia Mais…
Monday, December 3, 2012
Christmas--Big Deal Or Not?
Saturday, November 17, 2012
Holman Newsletter Part One
Check out what God has been doing! Thanks for being a part of it.Leia Mais…
Holman Newsletter
Part Two of the Newsletter...I could only add four pages of photos at a time. :)Leia Mais…
Thursday, August 9, 2012
Slice Of Life
Here is a video that just gives a quick glimpse at our lives. If you want to download it for use at your church, small group, missions event or whatever, just message me and I will send you a link to my cloud.Leia Mais…
Holman Newsletter
Here are photos of my newest newsletter. You won't be able to click the links, but I will upload the Slice of Life Video in just a moment, it is also on Youtube, my account is Bolivianjoe. At the bottom is a link to download the pdf file from my cloud if you need larger images.
Leia Mais…
Tuesday, May 15, 2012
First Podcast
Here is a try for my first podcast. I have signed up for Itunes, but it may take up to a week before they have me officially listed. I soon expect to have at least two subscribers, counting me and Denise.
It is not a video, but it automatically puts my podcast photo in the window. You can simply stare at me and wish you looked like me, or just listen and wish you sounded like me. :)
Seriously, I don't know how to change the photo, so please don't label me narcissistic.
Wednesday, May 2, 2012
Cut Finger Or Compassionate Heart
Leia Mais…
Monday, April 9, 2012
Going North American--Or Am I Already There?
Friday, April 6, 2012
Another Lesson About Going North American
Wednesday, April 4, 2012
Lessons From Going North American...
Thursday, March 22, 2012
Tearful Reminder
It hit me out of the blue. When I preach, I like to use graphics and photos to support what I am saying. This Sunday, I am telling a story about my dad, shortly before he died. I think I might write it out in a blog after this one…anyway, I was looking through old photos to find a photo of him. Before we came to Bolivia, we took all of our photo albums and sent them to a company in California. This company scanned them so that we could have them electronically. We had six thousand photos. Yep, six thousand photos!
Leia Mais…


text:
Lions in Four is a globally minded, socially conscious luxury fashion brand. They combine the highest standards in materials and production with native dying techniques from artisans in Kerala, India. Lions in Four strives to empower all women; from those who design and create products to those who wear them. Collaborating with the founders, I helped develop positioning, strategy, naming, identity and interactive while guiding and collaborating with the design team through art direction, branding, web design, and launch. The rich, elegant system leverages the cultural story of Lions in Four with muted tones and luxurious photography accentuated by ink patterns to create an ethereal visual language.
Together, the team concluded that Lions in four is the brand of choice for the woman who moves through the world with a grace, confidence and a style they can call their own. They care about being noticed without being ostentatious. Like the women they speak to, Lions in Four is exquisite, unique in details that may go unnoticed at first, but surface upon further exploration. Their clientele attract people with their strength and emotional depth; an old souls with a dash of playfulness and wit, living in the moment.
The mark represents the four asiatic lions of India's national emblem. Each lion is integrated and together they rememble a textile block pattern, alluding the hand-made ink processes. Supplemental geometric icons were developed from the mark's intersection to visually and symbolically represent one of four traits each lion signifies.
A startup, Lions in Four had limited resources and much of our concepting relied on prototyping and storytelling. Their textiles are sourced from and utilize printing and dying techniques that are products of India's cultural heritage. In partnership with WeCare of India NFP, they have established a training center to educate disadvantaged women with these employable skills. They fuel a sustainable system of training, fair employment and empowerment through a percentage of Lions in Four's profits. We used their history to tell this story through their brand.
The emblem of India is four asiatic lions standing back to back – symbolizing power, courage, pride, and confidence. The lions face all directions, looking out for one another. "Lions in Four" alludes to this, creating intrigue and begins telling a story where it starts–in India. The team developed the name through rapid ideation sessions with stakeholders that culminated in hundreds of potential names on sticky notes. Names were narrowed incrementally until a handful were left to test. A highly collaborative process, ideas often built off one another creating patterns and common themes.
My Role: Strategy, Naming, Art Direction, Design, Web Design
Agency: DMH
Communication Arts, FRESH Feature
American Institute of Graphic Arts, (AIGA) A11 Awards, Brand + Identity
American Advertising Federation (AAF) National Addy Awards, Gold
American Institute of Graphic Arts, (AIGA) A10 Awards, Website


text:
Shoreline Arts Alliance launched a new outreach program titled ArtsNET90 in August. This is a 90-minute networking meeting that has six sessions scheduled for this fiscal year. The sessions reach across our region, bringing together senior staff, board members and volunteers, in a fast-paced, formatted agenda. The goal is to strengthen our relationship with the many organizations that we serve in our region; to build awareness of the many and varied art and cultural activities that are available; to encourage collaboration; and to learn of successes and challenges that this sector faces. By involving staff, board and volunteers many different perspectives and viewpoints are presented.
We have hosted four ArtsNET90 meetings thus far and have engaged an energetic worker who is doing much of the outreach to artists and organizations to encourage them to take advantage of this sector building program. Our first meeting (August 2) brought 18 representatives together. By our fourth meeting, we had over forty sign up to attend. The rapid growth in attendance, the number of returning attendees and the new connections made has far exceeded our expectations this early in the development of the project.
Shoreline Arts Alliance has a Board member who has committed to being our representative at all of the sessions. Through his attendance and efforts we have been able to engage Board members from other organizations to participate. Each meeting is scheduled at a Member Organization's facility thus adding another level of awareness for the hosting organization.
Our first priority is to seek a new or additional facility to conduct business and support our mission to Educate, Encourage, Enrich and Engage our communities through the arts, culture, heritage and humanities. The current office has worked for many years but no longer meets our needs as we continue to build the business and seek a permanent home. The current location has little to no visibility in the community and because of limited space requires that most of our business be conducted off-premise. This decreases the amount of time the staff is in the office, increases the expense for time and travel, and leaves the office frequently under-staffed. Efforts continue to find a location that will meet our goals of developing a Regional Cultural Center and a permanent location for Shoreline Arts Alliance. Additionally, though we are currently bound by a confidentiality agreement, we have entered into a partnership with a major CT company to include many other services and programs in our strategic business plan, which will contribute significantly to our mission and our sustainability and be a strong consideration for a permanent location. We have also formed an alliance with the University of New Haven with the Department of Business, Marketing and Quantitative Analysis, the Department of Communication, Media and Film, and with UNH's recently acquired Lyme Academy College of Fine Arts. This collaboration continues to support to our organization in the form of scholarships and continuing education opportunities for students (almost $500,000 awarded this year), social media engagement and expansion (an increased presence on Facebook, Twitter, Instagram), and marketing and technology assistance for better outreach and communication (students are reviewing and working on marketing and branding ideas). In return, Shoreline Arts Alliance is able to engage some of the most talented regional high school artists to exhibit at the UNH-LACFA campus, offer guidance and direction for independent projects in Business, Marketing and Quantitative Analysis, and work collaboratively with the Communication, Media and Film on specific projects. This relationship is directed primarily at engaging our audience/donor base, expanding our visibility and building our brand, all of which support our mission and our efforts to develop a cultural hub (Regional Cultural Center) encouraging and supporting creativity and innovation. Short term new space with increased visibility will require considerably higher expenses but ultimately provide a more conducive environment in which to conduct and expand the business. Once identified and leased the organization will begin the relocation process to include: renovations and upgrades, physical move, installation, reconfiguring and trouble-shooting technology, notification to our constituents of new location and reviewing, revamping or creating new office procedures and protocols and orienting staff, board, volunteers and visitors to new space.
With strengthening and growth as our three year goal, it is essential that we invest in a user-friendly, comprehensive content management system (CMS) that meets the increased needs, expansion and diversification of the organization. Our current data base was purchased in 2008 and organizational growth in 8 years has surpassed the capabilities of this CMS. Investing in a new CMS or upgrading the current system is vital to improving tracking and communications with our current donors and participants and to identifying and raising funds from diverse sources, generating earned income, garnering in-kind donations, effectively soliciting and managing volunteers, and providing accurate demographic and reporting data. We have invested a significant amount of time in research, review and negotiations in an effort to select the system that will best meet our current needs and provide substantial growth potential. Essential components of an RFP are: in-depth analysis of current system identifying those components that are specific to our business; on-site training with staff and key board members; readily available technical support to address questions, issues, etc. Existing data base needs to be reviewed for accuracy, consistency and levels of participation so that data migration into a new or upgraded system will be compatible and comprehensive. This will require the hiring of the Development Coordinator and Development Associate as soon as possible to undertake this assignment and to identify and prioritize the data to be uploaded to a new CMS. This transition will occur in multiple phases over two years. New donors will be immediately entered into the new system. The Development Associate working directly with the CEO/Executive Director and Board of Directors will research donors for giving history, event/program participation and special interests to then schedule meeting(s) to outreach to the donor, update them on SAA's strategic short and long-term plans, engage or re-engage them in the organization. By having donor history, opening channels of communication and providing the donor opportunities to identify their areas of interest will lay the framework for the discussion and capital campaign for the creation of a Regional Cultural Center.
The Shoreline Arts Alliance is responsible for serving the broad cultural sector within the region and making the arts part of the daily fabric of community life: Educate, Encourage, Enrich, and Engage!
Provide Business support and leadership to Arts, Culture and Heritage Organizations as will as individuals in those fields.
Upon the arrival of a new CEO/Exec Dir. in the late summer of 2011, SAA recognized the need to reconfigure its vision and strategic plans for the future. After attending a capacity building program sponsored by Community Foundation of Greater New Haven with Chuck Loring in 2012, the Board and CEO Eric Dillner realized the need to determine a new vision for the organization, including a new case statement that more effectively encompassed the primary activities and functions of this vision. After reviewing the functions of the organization in its current state, the Board and CEO concluded that service was the chief component of all activities and roles of SAA. Through SAA's membership service, its function as a local arts agency in the state of Connecticut, and its programming, the most visible component of its operations are its services provided to member organizations, non-member local arts organizations, professional artists, budding artists, and community members that attend SAA programming. Thus, the model to educate, encourage, engage and enrich through the arts became the guiding force of the organization and the lens through which to rebrand and cultivate a newly framed non-profit.
SAA serves residents/visitors in the central coastal region of CT from East Haven to the CT River, as a CT Local Arts Agency in 24-towns. Jurried competitions and FREE programs draw economically challenged individuals/families/seniors of diverse social/racial background of below median income from state/region.
Eric Dillner held positions such as Artistic Producing Director of Tampa Bay Performing Arts Center, Managing Director of Skylight Opera Theatre, Artistic and General Director of Shreveport Opera and held faculty positions at LIU-C.W. Post, University of Missouri-Columbia, Sherrill MilnesV.O.I.C. Experience at Walt Disney World and was vocalogist with the otolaryngology clinic at University of Missouri Hospitals and Clinics. He is a frequent Master Class presenter in New York City and judge of competitions such as the Metropolitan Opera Competition and the New York International Opera Project in the United States and in Beijing, China. He performed the lyric tenor repertoire for such companies as New York City Opera, Opera Theatre of St. Louis, Sarasota Opera, Chautauqua Opera, Virginia Opera and with symphonies including the Milwaukee Symphony Orchestra, Louisiana Philharmonic, Orchestra of New Orleans, New Jersey State Opera Orchestra and Annapolis Symphony. He has sung with Swedish Radio Orchestra at Berwald Hall in Stockholm, Sweden, Brussels Festival Orchestra, at Cathédrale St-Michel, Bruxelles, Belgium, Concertgebouw in Amsterdam, Holland and numerous other halls throughout Sweden, Denmark, Germany, and Belgium. He is recording artist for the Music Masters Classics for BMG and appeared in PBS "Live from Lincoln Center" broadcast of Paul Bunyan (New York City Opera). His professional directing credits include Die Fledermaus, Cosí fan tutte, The Magic Flute, The Tender Land, Il Barbiere di Siviglia, Carmen, L'elisir d'amore and Dialogues of the Carmelites as well as the world premiere children's opera Wonderland. He commissioned Michael Ching and Hugh Moffatt to create Corps of Discovery, a Musical Journey and What is Freedom. Educational commissions-Why Dinosaurs Don't Smoke, Why Dinosaurs Don't Litter in partnership with Louisiana Governor Kathleen Blanco and Herman the Horse, a Healthy Tail. All three were National Endowment for the Arts grant recipients.
SAA works with many long-standing, local organizations to produce its programs and services in various locations throughout the region. These collaborative partners include:
Indirect Public Support HelpIndirect public support represents revenue received through solicitation campaigns. This includes funding United Way and other federated fundraising organizations, but does not include donor designated contributions.
Earned Revenue HelpEarned revenue represents income generated in direct exchange for a product or service.Earned income includes income from government contracts.
Greater New Haven is home to a thriving arts community that includes theatre, music, dance and the visual arts. It is invested in its museums, historic preservation and the celebration of its members' ethnic and cultural diversity.
70 Audubon Street
New Haven, CT 06150
(203) 777-2386 firstname.lastname@example.com
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text:
Original Gangstas
"This may be the best book ever written about the hip hop world." –S. Leigh Savidge, co-writer and Oscar nominee, Straight Outta Compton
"A provocative, multifaceted portrait of essential rap pioneers…As raw, authoritative, and unflinching as the music Westhoff's narrative chronicles." –Kirkus (starred review)
"[Adds] fresh detail to the oft-told stories …[A] history that won't settle for easy heroes or villains." –Rolling Stone
"My favorite book of the year" — Sermons Domain
"An impressive and exhaustive look inside the real world of the pioneering group" N.W.A. –People
Now in its second printing and translated into Japanese, German, and Hungarian, Original Gangstas: The Untold Story of Dr. Dre, Eazy-E, Ice Cube, Tupac Shakur, and the Birth of West Coast Rap is based on five years of research and reporting. It's the definitive history of L.A. gangsta rap, revealing how a cohort of then-unknown rappers, including Eazy-E, Dr. Dre, Ice Cube, Snoop Dogg, and Tupac Shakur, grappled with rivalries, crime, drugs, gangs, racist cops and bad record deals to create the defining music of a generation. The book is now available at Amazon, Barnes & Noble, and your local bookseller.
In the late 1980s the emergence of a new genre, gangsta rap, shifted the epicenter of hip-hop from New York to Los Angeles. Award-winning journalist Ben Westhoff shows how N.W.A's shocking success led to rivalries among members and clashes between Eazy's Ruthless Records and Suge Knight's Death Row; backlash from the FBI, politicians, and police; and eventually an all-out war between East and West Coast rappers that would turn deadly. In the process, hip-hop burst into mainstream America at a time of immense social change.Original Gangstas includes revelations about seminal events, including the death of Eazy-E from AIDS, Suge Knight's ascent at Death Row, the whereabouts of rappers – including Tupac Shakur – during the 1992 L.A. riots, the events that led to the East Coast / West Coast feud, and the murders of Shakur and the Notorious B.I.G, among many others.
Packed with insights from original interviews with Ice Cube, Dr. Dre, MC Ren, Snoop Dogg, D.O.C., Mopreme Shakur, Ice-T, and dozens more – including rappers, girlfriends, family members, and industry professionals – Ben Westhoff's Original Gangstas is a monumental work of music history.
Shea Serrano, New York Times bestselling author of The Rap Year Book says:
"I trust Ben Westhoff. I trust him to report a story and I trust him to tell a story, and that's exactly what he's done here in Original Gangstas. He's taken what's always felt like an almost impossibly knotted string of storylines and plot points in gangsta rap, the most turbulent version of the most popular music on the planet, and turned them into an airtight and unflinching book. Original Gangstas is as resolute as the people and ideas it sets out to profile, and that is no small feat."
Greg Mack, hip-hop radio godfather and host of "The Greg Mack Show" says:
"Original Gangstas is as real as it gets if you want to know the so-called 'gangsta rap' scene. Ben Westhoff refrains from using rumors and innuendos, and instead reports the facts, and he tells all sides of this music movement. The book goes into depth about many stories I'd only previously heard via the streets. As the first DJ to play almost everyone mentioned in the book, I found Original Gangstas compelling reading. Thank you, Ben Westhoff, for this great book!"
Stephen Witt, author of How Music Got Free, says:
Literary Agent
Ethan Bassoff
Lippincott Massie McQuilkin
Phone: 212 352 2055
Email: email@example.com
Marisol Salaman
Phone: 212 364 1226
Email: firstname.lastname@example.com
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text:
"You don't just call someone 'little girl' when they're just short and not really a small girl, you know." I said quietly and looked around, not wanting to talk to him.
He shrugged, "And you don't just call someone 'tall boy' just because they're not little."
Skeeter Sanchez never thought she'd be able to have friends, experience pranking, or even just hang out with someone when her Dad and she moved into the neighborhood until Colt Summers, school's heartthrob and bad boy, chased her before classes start.
Tyler Peterson, Colt's best friend, thought his life wouldn't get more interesting until he saw his best friend chase a girl he was sure he's never seen before.
"You're special to him," he said, smirking. "He never chases any girl."
She glared at him as she tried to breathe, "he'll never catch me. I'll be dead if he did."
Copyright © 2013 All Rights Reserved, including the right
- boy
- colt
- football
- friends
- girl
- highschool
- letitgo
- lewis
- little
- love
- newgirl
- romance
- skeeter
- tall
- tyler


text:
Crossed Keys Estate
Crossed Keys Estate has all the elements of an exquisite wedding venue: a charming Juliette balcony for tossing your bouquet; an elegant bride's room to get ready for your big day; a tree-lined drive for your arrival to the ceremony; lush meadows as the backdrop for your photos; a gorgeous reception tent; and a country-style B&B breakfast of homemade breads, pastries, gourmet entrees, fresh local fruits and dairy products for guests who stay the night. Explore the beauty of Crossed Keys Estate.
The Grounds
Around the Estate
The Big White Tent
The Ceremony
The Firepit
The Gardens
The Playhouse
Reserve Your Wedding Date Today
Contact us today to book a tour, or to save the date for your wedding day. At Crossed Keys Estate, every detail matters. Join us for the perfect outdoor wedding destination.


text:
By Anonymous - / Friday 2 November 2012 19:46 / Netherlands - Delft
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Top comments
By DomDomxoxo | 16
That's pretty harsh, at least you tried it out for her. I know some guys who always expect head and don't give anything back...
By neurodoc | 1
Don't worry. Practice makes perfect. Keep on trying ! Eventually you'll start to savor the fish taco. :P
BossPathfinderGM | 14
Still, it would benefit her to teach him what she likes rather than insult the man trying to please her. Everyone likes different things; communication is key for a satisfying sex life.
ositoakaluis | 16
Technically she didn't say anything, but the boyfriend did assumed the girlfriend was giving him a death stare when that could have been her pleasure face
adamcichuttek | 2
38 - does your user name mean Petered?
MikeFoxtrot01594 | 11
Maybe it was because OP stopped that he got the death-glare.
AllThingsBright_ | 11
Fish taco? I don't quite understand why everyone thinks women taste like/ smell like fish/fish tacos down there... I sure as hell don't. Going down on a woman, they should faintly taste a little salty but if it's fishy you should tell her to get her shit checked out.
kyleekay | 25
1- Agreed. From what I've gathered in my experience, as well as from talking to my friends, most guys don't get it right the first time. Every woman is different and should be treated as a learning experience; hopefully OP's girl stops acting like a bitch, and helps him out for round two.
AllThingsBright_ | 11
Not SALTY. It almost tastes like nothing with a hint of salt. Like tears? It's hard to describe.
xx1988 | 15
The ph of a normal, healthy vagina is around 4 - slightly acidic and therefore slightly sour-tasting. There may be some sodium in the secretions so the taste may also be slightly salty. Normal vaginas do not smell like fish unless they have a bacterial infection, which are common and can often be otherwise asymptomatic.
vip3r20 | 8
How bout she said that to him for stopping? She was probably about to climax and he looked up at the perfect wrong time. So he deserves it.
meganfoxissexy | 0
97- well you're cool....
98. I'm stating it because she's trying to explain to me what a fucking pussy tastes like. Get off your high horse.
Laurenlou | 24
A woman's diet will really effect the way they smell/taste down there. Red meat makes any body order smell not so pleasant, so that explains why a lot of women slightly have a smell. Fruits and veggies can even that out though! I've been a vegetarian for 3 years now and I've never smelled at all down there since. (Plus proper washing of course.)
strawberrystar | 4
Prob retarded,which looks stupid,idk why he made that his user name
blcksocks | 19
You are not supposed to eat it. Wait I mean, not literally...
Probably didn't grind his teeth on her clitoris enough. That's what really makes the ladies scream.
iBiteRoses | 22
That's what I wanted to know!!! I'm dying of curiosity.
BeaterOfTheDrums | 15
48: that's why they scream.
Karalela44 | 15
I like how people are side-tracking in this reply section xD
angeluv_2014 | 22
There was aabout to be a "what yhe fuck did you do?" if you hadn't put this comment.
DrainedOfSanity | 4
This why men are useless...
green2go | 14
Or op could have aspergers and is in capable of reading body language like myself
PlayWithElmo | 7
There are different severities of Aspergers, and everyone has different symptoms of it. No need to be rude.
By DomDomxoxo | 16
That's pretty harsh, at least you tried it out for her. I know some guys who always expect head and don't give anything back...
rsunshine2020 | 13
Yeah kudos for trying and Practice does make perfect ;)
AKGirlinSD | 20
I agree but the girlfriend didn't have to be a bitch about it. She should have told him politely that what he was doing wasn't working and she would love to give a few pointers.
By Church_Vii | 4
Ask her to show you what she prefers, and try not to be too..over zealous.
By sutianneli | 13
It took you a minute or two to realize she wasn't enjoying it? Well that answers the question.
windfuelsfire | 10
Amateur, but not "professionnal", where fake-titted, completely pubeless platinum blondes fake orgasms as easily as they take off clothes
windfuelsfire | 10
Haha! nuke, touché.
jbwlifefml | 0
alessiaxxooo | 3
So he can learn moves by watching some fake tits and drugged up guys with hard ons that last for like an hour? Oh and not to mention hurt the girl?Alrighty then.
By doubledee93 | 6
even though OP was doing something wrong didnt mean the girlfriend had to be a bitch....
bethrocksya | 9
Exactly what I was thinking! What a mean girlfriend! ):
JC_1218_Forever | 2
Hurts just thinking about it!
heather_rugby | 9
I've been squirming since I read that
By windfuelsfire | 10
If you can't identify where the clitoris is, I understand why she reacted, but she has a pretty bad attitude.. I think her mistake is worse than the one you made. Keep your chin up OP, learn well and maybe get to satisfy a girl that doesn't act like a bitch?
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I Use Sex as My Defense Armor — And I'm Totally OK with That
How pretty stuff makes people really happy.
It's time for straight white men to quit blaming women for their loneliness and to start finding solace in each other's company.
I want to be the type of person who makes other people feel comfortable, but how am I supposed to do that if I can barely hug my boyfriends?


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The artist Keyezua, known for her intricate collages that challenge so many critical notions of societal "normalcy", tactfully uses art as a tool.
Taking a solution seeking approach to creation, she approaches life's disappointments, both personal and universal, with the future in mind. She says that her art is a direct investment in the future of her generation of artists.
At times disillusioned with the horrors of our world, she transforms anger into artwork, giving us, her admirers emotionally moving series like Stone Women where she explores female genital mutilation.
Keyezua moves us to consider and perhaps even try to understand the hardships of our peers. Her art is a therapy as much as it is for her anger as it is for our biases.
We talk to the artist about her work below.
What does art mean to you?
Today for me, art means a direct investment to the future of my generation as artists are reinventing and bringing solutions for our people. We are waking up the power that was sleeping for years and I have been waiting for this moment where African artists understand how they can individually or even as a group change enough to emphasise the importance of having institutions and governments financially supporting culture making it a priority for artists to individually continue to represent new African stories inside and outside of Africa.
Where do you find inspiration?
After working for one year in Luanda, Angola. Inspiration is everywhere, I am daily confronted with issues that upset me. My inspiration starts with an inner feeling of anger and it continues transforming this anger into an artwork. It is important to not just walk but feel the inspiration in the people that you meet on your day to day activities. Often, you see people walking like zombies, they have to go to work, school or just hustle to survive especially now during the crisis. I try somehow to place an invisible blanket around me to be able to hear their stories, to catch their pain and make it mine, to touch their skin and wonder why it feels rough, to study the smell coming out of the corners of the streets, to see the sweat running through the bodies that stay in heat for hours just to have tea and bread for dinner.
Why did you choose to deal with topics on African Culture, sex and religion?
I have no choice! The manifestation is something that I can't control. For now I am confronted with an Angolan culture that feels like a little child and sometimes this child falls in the hands of the wrong people.
People who are responsible for change and education such as politicians, designers, teachers, leaders, companies and institutions still take eurocentrism to rebuild Angola…. they still look up to European designers, inventors and artists to look for inspiration while our books and our ancient stories are left in traditional markets, left to dust containing beautiful stories about pure African design, African inventions and even medicine before and after the colonisation of Angola.
Being sexual is something that manifested in me after hearing what I should be as a little girl and woman. What I should wear, when I should give birth to children and with which age I should get married. All these expectations never contained sexual information and sexual freedom and education is actually what takes women out of dangerous situations and avoids miscommunications between the female and male body bringing issues such as early child marriage, child abuse or even adult sexual assaults to debate.
To exhibit this type of work it continues to be my attempt to destroy the walls that camouflaged all the important information that makes our little girls ready to face the world and all of what that the world's tries to insist that our body should be and how we should feel as women.
I always fail to understand religion but I do believe in a God and I am looking for this God. As Africans we should continue to look for our Gods, the ancient Gods and not just Jesus and not just what the bible said but also what our own history says. Often we are afraid to worship our ancestors. I show this interest in my latest work I am not a demon. Who am I?
There is a God born in me every single day, I do believe in a God but I don't believe that it had a white son with blond hair and blue eyes so my search continues although you can find me in church to one day come to a conclusion about the God that they blindly follow in Angola.I refuse to blindly follow religion and in this following disrespect and crucify how someone further develops their personality. One of the reasons why a lot of people are in trouble today is because of the misunderstanding of religion somehow there is an "us versus them" mentality.
I am still searching for answers and this research is exhibited as an artwork.
Since you exposed your art to the world, what has been your most memorable moment?
Having an exhibition in the Dutch Parliament during the Museum Night in the Hague is a story I will have to share once a month with my children. I was the only artist invited for this exhibition. FACTICIUS is an artwork that I graduated with and during my graduation I was not nominated and I had a 6 as a grade with a very interesting comment from one teacher "You made it but you are a failure". It hurts, but you need to handle what causes pain and insecurity with success and persistence.
When I got the first phone call I started to jump around the house, first there was fear but in this fear I found the strength to believe in myself even when the grade "6" was considered a failure in my class. It was a good example of how you should never become somebody else´s opinion but your own and if you honestly believe in yourself despite all the struggle and rejections as an artist someday, soon very soon somebody will open a window and invite you to jump in. I took the opportunity and exhibited FACTICIUS, sculptures reflecting on the current situation in the Netherlands. Each nationality that arrives in the Netherlands brings its own religion, culture, tradition, beliefs and values. When placed as one image and not separated as a different group, one creates a rich cultural society, making FACTICIUS aesthetically strong enough to demand existence and exhibit a society that does not discriminate because of our language, culture, religion, habits and history differences.
How do you feel your culture and your environment influence your work?
Since I moved to Luanda I changed. What I believed I knew about my people no longer exists and the day to day steps that we all make together to see Angola grow is what changes you.
It gives you power but also the responsibility to not just create art to make beautiful things, make money and become famous. I now have a bigger responsibility and the steps I make will decide if our government will create more possibilities for artists to develop their art and design making it a priority and even part of the annual debate to have a bigger investment in our culture as the more they invest in us the more we can contribute for the empowerment of our people. My culture is strong, the beautiful women, men that are sellers are my family, I want to be part of them so I let them influence my body and its reaction to their inventions but also to their struggles. The people that are daily hustling or facing difficulties but still play loud music on Saturdays to celebrate life, that´s is a beautiful! This is our Angolan spirit and this happiness boosts a lot of power into you. When you see all these chances to have exhibitions not only in Africa but also in other continents. You know is your duty to represent your brothers and sisters not only as victims but also as survivors, inventors and storytellers.
Who are some of your favourite artists?
I have a lot of favourite artists it changes daily. I respect those that are doing it to change the way the rest of the world interacts with Africa. It is in our hands to represent and insist respect. As artists we go to places where our politicians will never be invited to. We have artists exploring techniques that examine what is behind the African Mask, the mask is/was a huge inspiration for all artists, we all played with it, intensely thought about it and now we are finding more techniques, materials and stories to talk about our Africa and to represent ourselves in different parts of the worlds with group exhibitions or even solo exhibitions. This is just the start!
Can you tell us a bit about your artwork , Female Genital Mutilation, FGM?
Stone Orgams, that is my WOMEN! This is an artwork that placed me where I had to be today to feel that what I was doing was not just a "tumblr thing" but something serious, you want to gain respect of your thoughts otherwise they are just thoughts if you don't manifest them into something that you share with the world for the world to feel uncomfortable regard their silence around Female Genital Mutilation.
I posted all my anger online and took the responsibility to talk for women that are going through a very difficult life journey. I don't know the pain, sometimes I wish I could feel it so I could even exaggerate more. I often experience new stories that makes these work unstoppable. It continues to be unstoppable as I created new WOMEN in 2016. It is one of the works that I decided to produce yearly as I don't want my WOMEN to sleep I want them to continue to be exhibited and I want them to continue to grow until they are 100 and I can finally have an exhibition where I give all the money to an organisation that will continue our fight.
The female body is not just a body but a temple and all these things humans do to it in the name of culture or religion should be exhibited to force our minds to question why we continue to be quiet about this when women, especially little girls in rural areas are FGM victims. Victims in developed countries also have to face this practice and quietly heal the physical and psychological damage. Stone Orgasms was my first work presented in the Lagos Photo Festival and this year they continue their journey in Addis Ababa for the Addis Photo Festival starting in December 2016.


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My previous three Holland America cruises had all been on the smaller ships (Ryndam, Volendam and Veendam). I was worried that what made HAL my favorite cruise line would be lost with the move to larger ships. As it turns out, I shouldn't have wasted the time. Our Cabin Our … [Read more...]
December 21, 2014: Disembarkation
My brother had taken advantage of the luggage express program so he had disembarkation around 7:30 if all went smooth. We had coffee at 6 (really it came about 10 minutes early because they had so many orders but we were all awake). After catching up on email and watching a … [Read more...]


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- Product 480899
EBS Evolution ProLine 212 Pro Cabinet
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The EBS Evolution ProLine 212 cabinet is built with the finest quality 13-ply Finnish Birch combining with advanced technology and natural materials ...Click To Read More About This Product
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A jury found a Temecula man guilty of first degree murder at the Southwest Justice Center in connection with the beating death of his niece Monday, Nov. 16.
Manuel Englis Quinanola, 67, also received a sentencing enhancement for use of a deadly weapon during the commission of a felony.
Superior Court Judge John Monterosso ordered Quinanola, who had been out on $1 million bail, back into custody.
Court documents say Quinanola told investigators he had beaten his niece, 52-year-old Mary Grace Bungato, with a bat because she had ignored him during a discussion about finances.
He is scheduled for sentencing in January.
Quinanola's defense attorney, Christopher Wagner, said he had hoped for Quinanola to receive a lesser manslaughter charge, especially givenQuinanola's diagnosis of autism.
"It was a tough issue," Wagner said. "My client has autism and the issue is with regard to how that autism affected specific intent."
But Wagner said he accepts the jury's decision.
"They seemed to consider all the evidence," he said. "They asked for a read-back of two of the key jury instructions. … And that's all we can ask. We ask the jury for a fair trial."
One juror, Kim French, 65, said deliberations were tough, with a portion of the jury in favor of a second-degree conviction.
"At least three of the jurors were having great difficulty with the definitions of willful, deliberate and even premeditated at one time," he said. "We had to keep going over and over how this whole thing started."
French said he thought prosecutor Torey Nasif and the prosecution's investigator did a good job of convincing the jury that Quinanola's beating was an act of murder.
Decisive evidence, French said, was a combined video and transcript of Quinanola telling investigators about the incident.
"It was 35-to-40 minutes, start to finish, of him describing how he beat her," French said.
But he said he and the other jurors were thorough. They looked at every piece of evidence, from transcripts and testimony, to physical evidence.
"We wanted to see the baseball bat," he said. "We wanted to feel the bat and see how heavy it was."
French said the jury wasn't swayed by Quinanola's testimony that he had hit his niece in the head only once, and that the beating didn't continue outside his home.
"Nobody believed that either," French said. "The damage that was done to her head was telling. Nobody deserves to die that way."
Quinanola is scheduled to be sentenced Jan. 15.
Contact the writer: firstname.lastname@example.com


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Ted Staszak
Vestry 2015-2017, Stewardship
Ted Staszak and his wife Lisa live in Hamburg and have been coming to St. Mary's for 5 years since moving from Nutley, NJ. Ted is Director of Outside Operations at Cedar Hill Country Club in Livingston. He enjoys volunteering his time with other St. Mary's parishioners at the Eric Johnson House each month and in working with Family Promise. Ted is the coordinator of the St. Mary's Golf Group and enjoys spring, summer and fall fellowship with everyone participating in the group. He is also pleased to be Golf Chairman for the annual Jim Nye Memorial Golf Outing.


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Sukhwinder Singh: Mom wants me to get married
Sukhwinder Singh discusses his 'single' status and upcoming collaboration with AR Rahman. In this tete-a-tete, he talks about working on Rangoon and his independent projects
Sukhwinder Singh
I was being selective about film songs in the last few years because I am not comfortable with the excessive use of auto-tuner in music making," says Sukhwinder Singh (45), who kicked off 2017 with hit songs like Udi Udi Jaaye (Raees), O Re Rangreza (Jolly LLB 2), Tippa and Chori Chori (Rangoon). He says he has recorded several tracks over the last couple of months after successfully convincing music directors to use his raw voice.
"The [auto-tuner] technology was adopted from the West for occasional use, but it became integral for most composers, except Vishal Bhardwaj and AR Rahman," he explains. Elaborating how his natural style of singing helps him, Sukhwinder says, "I recorded Udi Udi Jaaye with Ram Sampath in just 20 minutes. I have also started working with newer composers."
In this tete-a-tete, he talks about working on Rangoon and his independent projects.
How was the experience of working with Vishal Bhardwaj in Rangoon?
I recorded the title song of Rangoon six years ago. I have seen Rahman listen to Vishal's tracks while travelling in his car across Chennai. He is also a fan of Vishal's work. Rahman and Vishal have one thing in common — both are brilliant with orchestration and composition. Vishal's way of making music is very international. He loves taking on a challenge. Music is integral to Rangoon, and I am sure when the songs will be seen on screen, they will seem as if a painter created them.
Tell us about your upcoming film songs.
I have recorded songs for Toilet: Ek Prem Katha and Laali Ki Shaadi Mein Laddoo Deewana. I am working with Rahman for a Boney Kapoor movie, and with young composer Vishal Mishra for a Mahesh Manjrekar film.
Any indie projects in the pipeline?
I am working with Rahman on a single, which I recorded with students from his academy.
It should release by April. I have also conceptualised a series of 16 music videos that will release digitally around the same time. It will feature a bunch of singers, popular and new.
Do you plan to get married in the near future?
I want to get married this year. Whenever I meet Rahman, he spends the first 30 minutes convincing me to get married. My mom also wants me to find a life partner.