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Basic Physics of Nuclear Medicine/Dynamic Studies in Nuclear Medicine

Introduction
This is a developing chapter of a Wikibook entitled Basic Physics of Nuclear Medicine.

The metabolism of a substance in the human body is the result of a number of inter-related dynamic processes which include the absorption, distribution, utilization, degradation and excretion of the substance. The measurement of just one of these parameters can give a result which is indicative of a disease, but may not identify the actual cause of the disease. More detailed information about the cause may be determined when knowledge of the complete metabolic system is obtained. One method of gaining such knowledge is through mathematical simulation of the physiological system. The outcomes of this approach include generating a representation of the entire system as well as an understanding of interactions between its component parts. The approach typically involves:

1. obtaining experimental data following stimulation of the system by addition of a suitable tracer,

2. comparing experimental data with data predicted by the mathematical simulation, and

3. varying parameters of the simulation until the two sets of data agree as closely as possible using methods such as least squares, maximum likelihood and Monte Carlo simulation.

The general assumptions for this approach are that:

 * the addition of the tracer does not perturb the system,
 * the tracee (i.e. the substance under investigation) is conserved throughout the process,
 * the tracer is conserved throughout the process – allowing for radioactive decay, and
 * the system is in a steady state (i.e. the amount of tracee in each compartment of the system remains constant as does the exchange of tracee between each compartment).

There are two major types of mathematical model in use:

 * Deterministic: where analytical expressions are used to describe the exact behaviour of the tracer in each part of the system with time.  The mathematical expressions used are usually exponential or power functions,

 * Stochastic: where the behaviour of the system is determined by random processes which are described by probability functions.

Deterministic models are considered in some detail below.

Compartmental Analysis
This form of deterministic analysis involves dividing the physiological system into a number of interconnected compartments – where a compartment is defined as any anatomical, physiological, chemical or physical subdivision of a system. A basic assumption is that the tracer is uniformly distributed throughout a compartment. The simplest of such systems to consider is the single compartment model. We will start our treatment with this simple model and then extend it to more complex ones – the initial ones being considered simply to develop the framework with the later ones providing direct relevance to nuclear medicine dynamic studies; their acquisition and analysis.

There is an ImageJ plug-in available, named Compartments_TP, which provides simulations of a number of additional models.

Single Compartment Model
The flow of a tracer through a blood vessel following an ideal bolus injection is shown in the following figure as an illustration of a single compartment model. The compartment illustrated is closed except for the inflow and outflow of the tracee, and the tracer is injected as indicated. In these theoretical conditions, the tracer will mix immediately and uniformly throughout the compartment following its injection. And its quantity will reduce with time depending on the rate of outflow. The variables used in the figure are:

q: the quantity of tracer in the compartment at time, t, and

F: the outflow.

We can define the fractional turnover, k, as the ratio of these two parameters, i.e.

$$k = \frac{-dq/dt}{q}$$

which can be rewritten as:

$$\frac{dq}{dt} = -kq$$

Without going into the mathematical details (which are similar to the derivation of the radioactive decay law!), the solution to this equation is:

$$q = q_0\ exp(-kt)\,\!$$

where qo is the quantity of tracer present at time, t = 0.

This equation is plotted below to illustrate the influence of the value of the fractional turnover, k:

<

The graph indicates that the quantity of tracer in the compartment will decrease exponentially with time following injection at a rate dependent on the outflow, as might be intuitively expected.

Two Compartment Model – Closed System
A more complex, and yet still relatively simple, set of models are those based on two compartments. In a closed system the tracer simply moves between the two compartments without any overall loss or gain – see the following figure:

Therefore,

Since there is no loss of tracer from the system,

$$q_1 + q_2 = \text{constant} = q_0\,\!$$

Therefore,

$$\frac{dq_1}{dt} = -\frac{dq_2}{dt}\,,$$

indicating that as the quantity of tracer in Compartment #1 decreases, the quantity in Compartment #2 increases, and vice versa. Now, consider the situation illustrated in the figure above, where the tracer is injected into Compartment #1 at time, t = 0. At this time,

and, initially,

The solutions to these equations are:

$$q_1 = q_0 \left \lbrack 1 - \frac{k_{12}}{k_{12} + k_{21}} \left \lbrace 1 -\ \text{exp}\ - (k_{12} + k_{21}) t \right \rbrace \right \rbrack$$

and

$$q_2 = q_0 \left \lbrack \frac{k_{12}}{k_{12} + k_{21}} \left \lbrace 1 -\ \text{exp}\ - (k_{12} + k_{21}) t \right \rbrace \right \rbrack$$

and their behaviour in the special case when k12 = k21, and the volume of the two compartments is the same, is illustrated below:

Note that this model predicts that a steady state will be reached as the quantity of tracer in Compartment #1 decreases exponentially and the quantity in Compartment #2 increases exponentially, with the rate of each change controlled by the sum of the turnover rates.

Two Compartment Model – Open Catenary System
This is an extension of the single compartment model considered earlier with two compartments connected in series, as shown in the following figure:

In this model,

The solutions to these equations are:

$$q_1 = q_0\ \text{exp}(-k_{12}t)$$

and

$$q_2 = q_0 \frac{k_{12}}{k_{12} - k_{20}}\lbrack \text{exp}(-k_{20}t) - \text{exp}(-k_{12}t)\rbrack\,,$$

and the behaviour of q1 and q2 is shown in the figure below for the special case of k20 being three times the value of k12:

Note that the behaviour of q2 in this figure is similar to arterial tracer flow following an intravenous injection, and to the cumulated activity parameter used in radiation dosimetry.

Two Compartment Model – Open Mamillary System
This model is equivalent to the closed two compartment system considered above with the addition of an outflow from one compartment:

In this case,

At t = 0:

and, initially

The solutions to these equations are:

$$q_1 = q_0 \left \lbrack \frac{k_{21} - a_1}{a_2 - a_1} \text{exp}(-a_1t) + \frac{k_{21} - a_2}{a_1 - a_2}\text{exp}(-a_2t) \right \rbrack$$

and

$$q_2 = \frac{q_0 k_{12}}{a_2 - a_1} \lbrack \text{exp}(-a_1t) - \text{exp}(-a_2t) \rbrack$$

where

The behaviour of q1 and q2 is illustrated in the figure below:

This model has been widely adopted in the study of:

 * metabolism of plasma proteins, where Compartment #1 is the plasma and Compartment #2 is the extravascular space,
 * trapping of pertechnetate ion in the thyroid gland, where:
 * Compartment #1: the plasma,
 * Compartment #2: the thyroid gland,
 * k12: clearance rate from plasma into the gland, and
 * k21: leakage rate from the gland into the plasma.

Models with Three Compartments
The open mamillary model above has been extended to study iodine uptake using a third compartment which is fed by an irreversible flow, k23, from Compartment #2:

where:
 * Compartment #1: the plasma,
 * Compartment #2: the trapping of inorganic iodide in the thyroid gland, and
 * Compartment #3: iodide within the gland which has become organically bound as part of hormone systhesis processes.

The open mamillary type of model has also been applied to renal clearance with the system consisting of an intravascular compartment, with an extravascular compartment exchanging with it and connected irreversibly with a urine compartment:

The intravascular compartment (#1) in the figure above represents tracer which is exchangeable with the renal parenchyma and the extravascular space. The urine compartment (#2) represents tracer which has been cleared by the kidneys and is therefore associated with the renal pelvis and the bladder. The extravascular compartment (#3) represents the tracer which has not been cleared, e.g. tracer which becomes bound to other molecules or tracer in extrarenal tissues.

When the tracer is injected into the intravascular compartment via a peripheral vein, the initial distribution will not be uniform throughout the body – but this non-uniformity will even out as the blood circulates. For a highly vascular region, a plot of the quantity of tracer versus time will show an initial sharp rise which will rapidly fall off. The magnitude of this spike will vary with:
 * the anatomical region,
 * the site of the injection, and
 * the speed of the injection.

Compartmental analysis cannot therefore be applied to this phase of a renogram since the basic assumption of uniform tracer distribution, implicit in compartmental analysis, cannot be applied.

Following this phase, the quantity of tracer in the intravascular compartment begins to fall because of:
 * uptake by the kidneys – represented by k12 in the figure above,
 * diffusion into the extravascular space – represented by k13.

As the quantity of tracer in the extravascular compartment builds up, exchange in the opposite direction begins to occur (represented by k31), and so a maximum is reached before its quantity of tracer falls off. This is illustrated in the figure below for a situation where:

Ultimately, all the tracer will end up in the urine compartment.

The equations used for the figure above are:

$$q_1 = A_1\ \text{exp}(-l_1t) + A_2\ \text{exp}(-l_2t)\,\!$$

$$q_2 = A_3\ \text{exp}(-l_1t) - A_4\ \text{exp}(-l_2t)\,\!$$

$$q_3 = A_5\ \lbrack \text{exp}(-l_1t) - A_2\ \text{exp}(-l_2t)\rbrack\,\!$$

where l1 and l2 are constants related to the fractional turnovers, and A1 through A5 are also constants such that:

In practice, the renal clearance can be obtained by monitoring the quantity of tracer in the intravascular compartment, e.g. the blood plasma concentration, P, where:

$$P = \frac{\text{Quantity of Tracer in Intravascular Space}}{\text{Volume of Intravascular Space}}$$

The time dependence of this plasma concentration will vary in the same way as q1, so that:

$$P(t) = C_1\ \text{exp}(-l_1t) + C_2\ \text{exp}(l_2t)\,\!$$

where C1 and C2 are related to A1 and A2, respectively. The renal clearance, which is related to k12, can therefore be determined by characterizing the biexponential fall off in the quantity of tracer in the intravascular compartment.

Glomerular Filtration Rate
The Glomerular Filtration Rate (GFR) is generally regarded as one of the most important single indicator of renal function. It is particularly important in assessing the presence and severity of kidney failure.

There are three major methods of determining a patient's GFR:
 * Inulin clearance,
 * Creatinine clearance,
 * Radiotracer clearance.

Inulin clearance has been used for many years and is often regarded as the most reliable and accurate of the three methods. Its major disadvantages however include the need for continuous intravenous infusion, timed urine collections via a bladder catheter and protracted chemical analysis. Creatinine clearance has been widely used for routine GFR assessment as a result. However, while this method gives similar results as inulin clearance under normal conditions, the validity of its results is questionable in patients who have moderate to advanced renal failure because of an increasing significance of tubular secretion.

The third method, radiotracer clearance has been widely adopted using 51Cr-EDTA. This tracer is known to be physiologically inert, not bound to plasma proteins and not metabolized by erythrocytes or organs other than the kidneys. It is normally excreted within 24 hours of injection, 98% via the kidneys. 51Cr has a half-life of about 28 days and decays by 100% electron capture into stable vanadium, emitting monoenergetic (320 keV) gamma-rays in about 10% of the transformations. In addition, 51Cr-EDTA determination of GFR can be used in conjunction with OIH renal plasma flow assessment for the differential diagnosis of various renal conditions.

The typical radioactivity administered for 51Cr-EDTA clearance is 1-10 MBq and the radiopharmaceutical is generally administered via intravenous injection. This Single Shot technique assesses the GFR through venous blood sampling, in the simplest case, or by continuous external monitoring of the gamma-rays from 51Cr in the more sophisticated approach. When the patient counts are plotted against time on a log/linear axis, a curve is generated which falls off rapidly at first and thereafter decreases at a constant rate, representing the behaviors of q1 is our last figure. This initial fall-off arises as a result of the establishment of an equilibrium between the radiotracer and the extravascular, extracellular fluids. The slower second phase reflects renal excretion and contains the information necessary for GFR assessment.

A quick and simple technique is to obtain two blood samples from the patient, one at two hours and the other at four hours post injection. The counts per unit volume in the plasma of each sample are determined using a scintillation counter and compared with the counts from a standard solution. The standard solution is made by diluting an injection, identical to the patient's, in a known volume of water, e.g. 1 liter.

The slope, m, of the second portion of the above curve can be determined from:

$$m = \frac{\ln b_1 - \ln b_2}{t_2 - t_1}$$

where:
 * t1: time from injection for the first blood sample, usually 120 minutes,
 * b1: counts per milliliter (mL) in the plasma from the first sample (corrected for background counts),
 * t2: time from injection for the second blood sample, usually 240 minutes,
 * b2: counts/mL in the plasma from the second sample (also corrected for background).

We can now extrapolate this straight line back to the time of injection, t0, to determine what the plasma counts would be upon instantaneous mixing of the tracer throughout the patient's plasma compartment, i.e.

$$\ln b_0 = \ln b_1 + m(t_1 - t_0)\,\!$$

as illustrated in the following figure:

Therefore, we can write:

$$b_0 = \text{exp}\ \big(\ln b_1 + m(t_1 - t_0)\big)$$

The Dilution Principle can now be used to determine the volume of this plasma compartment by comparing the plasma counts with those from the standard solution, i.e.

$$V = \frac{S \cdot V_s}{b_0}$$

which results in

$$V = \frac{S \cdot 1000}{b_0}$$

when the standard injection is diluted in 1 liter. The clearance (in ml/min) is then given by the following equation:

$$\text{Clearance} = V \cdot m\,\!$$

Results for two patients are shown below to illustrate this technique.

Patient A

This patient's 51Cr-EDTA clearance was determined to be 38.8 mL/min. This result was assessed to be indicative of chronic renal failure, which was later found to be due to lupus nephritis. The patient was then placed on steroid therapy.

Two months later the patient was re-tested and the clearance was found to have risen to 52.7 mL/min. For the patient's age, this clearance was gauged as within the normal range indicating that the therapy was having a positive effect. The therapy was then ceased. Two months further, the patient was again tested having been without steroid therapy for this period. The result was 54.2 mL/min reflecting successful treatment.

Patient B

This patient had a high blood pressure and a renal involvement required confirmation. The clearance however was 117.3 mL/min, which is well within the normal range. The kidneys were therefore excluded from the investigation of this patient's condition.

Note that the number of blood samples is not limited to two, with some methods requiring three, four or more samples, and other methods using external monitoring of the clearance. Each method is nevertheless based on the form of analysis outlined above where the rate constant of the second phase of the clearance curve is determined along with the volume of distribution of the radiotracer. The timing of blood sampling is therefore after the first phase has finished, i.e. more than about two hours following injection, with the volume of distribution determined using a single-exponential fit to this later phase.

It is important to appreciate that the clearance of 51Cr-EDTA determined as described does not equate directly with the Glomerular Filtration Rate (GFR) since the method assumes a single exponential dependence. 51Cr-EDTA clearance results are therefore typically corrected by a factor, either empirically- or theoretically-derived, to force them to express the true GFR. Empirically-derived corrections include those of:

 * Chantler (1969), where the 51Cr-EDTA clearance is multiplied by a factor of 0.8;
 * Brien (1969), where clearances above 50 mL/min are multiplied by 0.82 and added to 6;
 * Brochner-Mortensen (1972), where a second-order polynomial is applied

to obtain the GFR. A correction based on a theoretical consideration of the relationship between true GFR and single-exponential clearance values based on compartmental analysis has been introduced (Fleming, 2007) which gives improved corrections, especially at high GFRs. This correction is of the form:

$$GFR = \frac{\text{Clearance}}{(1 + f \cdot \text{Clearance})}$$

where $$f$$ = 0.0017 min/mL.

As a final step, corrected clearance measurements are generally standardized to the body surface area (BSA) of the Standard Man, i.e. 1.73 m2. This is typically done using estimates of the BSA based on the patient's height and weight – as derived from DuBois (1916) or Haycock (1978), for instance. A single-exponential correction technique, based on BSA-scaled clearances has also been introduced (Jodal & Brochner-Mortensen, 2008) which is similar to that of Fleming (2007) but provides improved correction in paediatric studies.

Renography
It should be apparent from the discussion above that the urine compartment (#2) consists of the quantity of the tracer in the urine, without distinguishing whether the urine is in the renal pelvis, the ureters or the bladder. These anatomical spaces can be incorporated by extending the three compartment mamillary model to five compartments:

Note that the passage of the tracer through the renal parenchyma can be characterized by a transit time, t0, and that k56 is related to the rate of urine production.

The solutions to the resultant differential equations for the quantity of tracer in the renal parenchyma, the renal pelvis and the bladder incorporate consideration of the time delay, t0, so that:

 * When t < t0:

 * When t > t0:

where l3 is related to k56. The time course of the quantity of tracer in each compartment is shown below:

The quantity of tracer in the overall kidney can be obtained by summing the renal parenchyma and renal pelvis curves, so that:

$$q_{\text{kidney}} = q_4 + q_5\,\!$$

as shown below:

What is recorded in a renogram in practice is not just this kidney curve, but also the quantity of tracer in:

 * overlapping and underlying tissues, and in
 * the intravascular space of the kidney itself.

These contributions add a background upon which the true renogram is superimposed. The quantity of tracer in this background varies with time, but not in the same way as the true renal curve. The time course of this background is likely to behave in a manner similar to the sum of the intravascular (q1) and extravascular (q3) curves derived earlier using this five compartment model.

The following equation can be derived on this basis:

$$q_{\text{Bgd}} = b_1 q_1 + b_3 q_3\,\!$$

where b1 and b3 represent the contributions to the detected renogram curve from the tracer in the intravascular and extravascular spaces, respectively. For example, the curves below were generated using b1 = 0.05 and b3 = 0.02 and

$$q_{\text{Renogram}} = 0.5\,q_{\text{Kidney}} + q_{\text{Bgd}}\,\!$$

In practice, this background curve should be subtracted from the raw renogram data to obtain a curve which reflects the true quantity of tracer in the kidney (see the previous figure). This process is sometimes referred to as blood background subtraction – although you should now be able to appreciate that this is a bit of a misnomer!

The uncorrected and corrected curves are shown below to assist with direct comparison:

and an example from a patient's 99mTc-DTPA renogram is shown in the following figure, to assist you in comparing them with the predictions from compartmental analysis:

A final figure illustrates a form of analysis that can be used in 99mTc-MAG3 renography in a patient with obstructive uropathy:

Background Subtraction in Renography
In practice, the background activity in a renogram must be taken into account when interpreting a renogram. This is generally achieved by estimating the background activity and subtracting it from the raw renogram data. The question is: how can this background activity be measured?

One method has been based on recording the activity at nephrectomy sites in patients whose remaining kidney is being examined. However, it should be noted that removal of a kidney also removes an intravascular source of the background activity. As a result nephrectomy sites commonly appear colder than the extra-renal tissues in renogram images.

A potentially better method is to record the activity in the region of a non-functioning kidney.

In most patients, however, a non-renal region must be used for background estimation. Ideally, the choice of region should reflect the same intra- and extravascular background as the kidney itself. There appears to be no standardization in this area, with practices including the use of a region between the kidneys, above the kidneys, over the heart and below each kidney.

A comparison of such methods is provided in Taylor et al (1997) and results of a similar, but more basic, analysis are summarised below:

These renographic images were generated using Monte Carlo simulation and analysed using OsiriX. Split function was calculated using the Integral of counts in the 90-150 second time period. The Mean Absolute % Error was computed from a series of such simulated images where the left kidney to right kidney split function varied from 100%:0%, through 50%:50% to 0%:100% in steps of 5 percent.

It is seen that the Lateral RoIs yielded the lowest % Error and that the Central RoI, which was used in the early days of gamma-camera renography using 99mTc-DTPA, yielded a substantially greater error of ~12%. This is in line with current clinical practice where central RoIs are not longer used and lateral or oblique, or perirenal, RoIs are preferred.

In comparison, no background correction generated an error of 20.7%, which highlights the overall importance of background correction.

The variation of background activity is illustrated below for a real LK:RK split function ratio of 50%:50% and for the extremes of 100%:0% and 0%:100%. The first point to note is that the background curves vary with time in a manner which reflects the renal curves themselves, quickly rising during the uptake phase and falling slowly during the excretion phase. Secondly, note that the right kidney (RK) curves decrease more slowly that those of the left kidney (LK) – possibly as a result of retention of the MAG3 tracer in the liver. This is quite different to the assumption used in the earlier analytical model. The extent of liver involvement can be gauged from the Monte Carlo simulated AP renogram on the left where a reasonable view of the liver and its dynamics can be observed throughout the study. This is consistent with the pharmacokinetic model which was used to generate the virtual study.

Thirdly, note that the RK curves are of greater magnitude than those of the LK at 50%:50% and 0%:100%, while the opposite is the case at 100%:0%. This highlights the requirement to use separate background RoIs for each kidney.

The final point to note is in relation to the 90-150 second time window, where the Integral or Slope method is typically applied. It can be seen that both the sum of background counts (the Integral) and the rate of change in these counts (the Slope) vary during this period, which indicates that both methods will be influenced by these features of the background curves.

Once the background region is selected and the activity/time curves are generated, the background curve should be scaled by a factor dependent on the relative areas of the background and renal regions, prior to subtraction from the raw renogram curve. In addition, note that some practices also involve further scaling of the background curve depending on the kidney location. Finally, more sophisticated methods of background correction have been developed and include:
 * the generation of interpolated background regions from samples of the background around the kidney,
 * the estimation of background correction factors using extrapolation techniques, and
 * deconvolution analysis.

It should be noted that caution should be used in translating these results directly to real patient studies in that the raw data is derived from a two-dimensional representation of a compartmental model.

Relative Renal Function
The relative function of a patient's kidney is generally defined as that kidney's renal clearance rate expressed as a percentage of the patient's overall renal clearance rate, i.e.

where LK and RK refer to the left and right kidneys, respectively.

Suppose that:

 * NKidney(t): background corrected renal count rate, and

 * NBgd(t): count rate from an intravascular region of interest.

It should be apparent at this stage that:

We can therefore conclude that in the initial phase of the renogram, i.e. when t < t0:

$$N_{\text{Kidney}}(t) = UC \int_0^t N_{\text{Bgd}}(t) \cdot dt$$

where UC in the kidney uptake constant. This constant is related to that kidney's clearance rate, and we can therefore write:

$$\text{LK Relative Fn.} = \frac{\text{LK Update Constant}}{\text{LK} + \text{RK Uptake Constant}}$$

and

$$\text{RK Relative Fn.} = \frac{\text{RK Uptake Constant}}{\text{LK} + \text{RK Uptake Constant}}$$

However, we have already seen above that the background corrected renal count rate is directly related to the uptake constant and we can therefore conclude that:

Note that this analysis indicates that relative renal function can be determined from measurement of the relative counts in each kidney following the initial vascular spike but prior to the commencement of the excretion phase.

Kidney Depth Correction
Given that two kidneys can be at different depths within a patient, a correction for the difference in photon attenuation is generally applied. The conventional way of doing this is to acquire lateral views following a renogram so as to measure the depth of each kidney and to apply an exponential correction based on an assumed linear attenuation coefficient for the gamma ray energy (e.g. 0.153 cm-1 for 99mTc gamma rays).

The situation is illustrated by the following study where the right kidney is slightly over 1 cm deeper than the left. The study is actually of images generated by Monte Carlo simulation of a digital phantom (XCAT) which includes the effects of photon attenuation, scattering, limited spatial resolution and noise. The left kidney is positioned 7.31 cm deep while the right is at a depth of 8.64 cm, and the split function is 50:50.

Note that the two curves do not overlap, as would be expected for a 50:50 split function, as a result of the difference in attenuation. The split function estimated by the integral of counts between 90 and 150 seconds is 54:46. When this attenuation difference is corrected, however, the following curves are obtained and the split function estimate is now a more realistic 49:51.

Commercial renal analysis software typically provide options for the automatic computation of kidney depth based on empirically derived relationships between the patient's height and weight and the depth of each kidney. One such package provides the following options (with weight expressed in kg and height in cm):

A graphical representation of the difference in kidney depth generated by these equations for a broad range of weight-to-height ratios is shown in the figure below (note: an age of 50 years was assumed for the Emory formulae):

It can be seen that little change in depth is predicted by the Standard formulae and that derived attenuation corrections are likely to have little effect on relative function estimates. It can also be seen that the T.Itoh formulae indicate that the right kidney is always deeper than the left. The final two sets of formulae indicate that the right kidney is deeper for weight-to-height ratios of less than 0.6 to 0.7 and the left kidney is deeper above this ratio range. The overall range of depth differences predicted by these latter three formulae is seen to be no more than ±5 mm. Such differences yield an anticipated attenuation correction factors in the range 0.95 to 1.05.

The predictions of these formulae should be contrasted with the results of studies of kidney depth which have shown that differences of greater than 5 mm can be expected in about 60% of patients, and greater than 1 cm in about a third of patients. It can therefore be inferred that the above formulae will only provide sufficient attenuation correction in less than half of patients, and that attenuation correction factors as low as 0.6 can occasionally be expected.

It is therefore apparent that accurate kidney depth measurement is imperative for the proper interpretation of all renograms, and that automatic kidney depth formulae should be applied with caution.

Semi-Automatic Methods of 99mTc-MAG3 Renogram Analysis
Commercial software for renogram analysis generally provides a number of methods for what is called semi-automatic analysis – where some features of the analysis require user interaction (e.g. kidney identification) and others are performed automatically (e.g. computations) to determine split renal function and Effective Renal Plasma Flow (ERPF). Here the software might request the user to, for instance:
 * input the height and weight of the patient – so that body surface area and kidney depths can be computed using empirically-derived formulae, and
 * define regions of interest (RoIs) around each kidney – with background regions automatically placed adjacent to these kidney RoIs.

Counts/time curves are generated for each of these four RoIs. The counts in the background RoIs are then scaled automatically to those of background areas of the same size as the respective kidney RoI and the scaled background curves are subtracted from the kidney curves to generate a net renogram curve for each kidney.

The counts in a pre-defined time interval in the uptake phase of each renogram (e.g. 1 to 2 minutes post-injection) are then used to compute: for each kidney.
 * the sum of counts (called the Integral) and/or
 * the rate of increase in counts (called the Slope)

A comparison of these two methods was performed using the Lateral RoIs for background subtraction of the renographic series used earlier, and the 90 to 150 second period for analysis. Both methods yielded very similar results:

The Integral method, however, generated a mean absolute % error of just 2.6%, while the Slope method generated a substantially greater error of 9.4% - mainly due to inaccuracies at the lower and higher LK/RK ratios.

In comparison, no background correction generated an error of 20.7% using the Integral method while with the Slope method the error was just 9.2%. This highlights, once again, the importance of such corrections.

The Integral can be corrected for tissue attenuation using the computed depth of each kidney and an assumed linear attenuation coefficient for 99mTc gamma rays. Computation of the Integral in this manner is a major source of error in this form of analysis since the use of the patient’s height and weight (along with their age in one method) to determine kidney depth is likely to be inaccurate – see the previous section. In addition, no standard exists for the value of the linear attenuation coefficient (μ) in the renographic scanning situation, with values such as 0.12, 0.14 and 0.153 per cm in clinical use. For a kidney depth of 6 cm, for instance, these values of μ would result in correction factors of between 2 and 2.5 being applied, i.e. to give a variation of ~20%.

Split Function can be determined from the percentage contribution of each kidney’s Attenuation-Corrected (AC) Integral to the sum of the two kidneys’ AC Integrals.

In addition, Kidney Uptake can be determined by expressing the AC Integrals as a percentage of the injected dose.

Effective Renal Plasma Flow (ERPF) may then be calculated on the basis of empirically-derived formulae such as: Left Kidney ERPF (mL/min) = -21.579 + (11.621*Left Kidney Uptake) and ERPF Value (mL/min) = 14.98 * (Left Kidney Uptake + Right Kidney Uptake) + 8.28

Alternatively, a Washout Coefficient can be defined as: 0.48026*(exp(1.35315*Sum of Kidney Uptakes)/100)-1 to be multiplied by an estimate of the Plasma Volume, such as: Body Surface Area * 1,000 + 0.608 mL to give the Total MAG3 Clearance. This final factor is used to calculate the Total ERPF (mL/min) using the formula: 1.25821* (Total MAG3 Clearance) + 18.34451

A figure of 0.53 has also been used as an ERPF Conversion Factor, i.e. to convert from ERPF to MAG3 Clearance. However, it should be noted that values of this Factor between 0.61 and 0.9 have been reported.

As an alternative to these Integral-based methods, the slopes of the curves for each kidney during the uptake phase of the renogram have been used to define a Slope Index for each kidney, based on the Slope of each renogram, attenuation-corrected for kidney depth, and expressed as a percentage of the injected dose multiplied by 106! Split Function can then presumably be obtained by relating the Slope Index for each kidney to the sum of Slope Indices – and the Total MAG3 Clearance calculated using the formula:

(12.725 * Sum of Kidney Slope Indices + 6.24)/Body Surface Area

Body Surface Area (BSA) estimation is another source of variation in these computations. It is widely used to reference a patient’s ERPF to a standard BSA, e.g. 1.73 m2. It is also used within calculations using formulae such as the one above. At least two BSA computation methods are used in this field, as detailed below:

Du Bois Formula: BSA = 0.007184 * W0.425 * H0.725 and Haycock Formula: BSA = 0.024265 * W0.5378 * H0.3964

where W is the patient’s weight in kg and H is their height is cm, to give the BSA in m2. These formulae give reasonably similar BSA estimates for adults, e.g. a difference of ~2%, for a 69 kg, 163 cm patient, and their choice as a result is reasonably inconsequential in this application, irrespective of their accuracy.

In summary, commercial semi-automatic renal analysis software is generally based on one of the following two approaches:
 * determine the absolute uptake of MAG3 for each kidney and relate these uptakes to the ERPF using empirical relationships derived from limited patient studies (36 presumably-Japanese patients in the case of Itoh et al. for instance);
 * determine the rate of MAG3 uptake for each kidney and relate these rates to MAG3 clearances empirically-derived from limited patient studies (12 presumbly-Japanese patients in the case of Oriuchi et al. ).

An evaluation of the accuracy of these methods is warranted given the strong empirical features which are evident and the very limited number of patients surveyed. Such an evaluation can be conducted using Monte Carlo simulated renograms and results of such are shown in the following table:

For this evaluation, the formulae for the Itoh ERPF (MAG3), Inoue (MAG3 Without Samples) and Oriuchi Clearance (MAG3) methods were used to calculate the MAG3 Clearance and Split Function for each renogram using spreadsheet software. The values of these parameters for the ERPF Modified Schlegel and ERPF Modified Gates methods were calculated using the manufacturer's software package directly and assumed an ERPF Conversion Factor of 0.76 (i.e. the mean value of Oriuchi’s study ) – as did the Itoh method.

It is apparent that no correlation in any of the results exists except, for instance, that when the MAG3 Clearance is halved from 260 to 130 mL/min, the computed clearances also reduce – although the results for the Modified Schlegel method are quite reasonable in some situations. A second point is that the variation in split function estimates is likely to result in part from the use of (potentially inaccurate) automatic methods of kidney depth determination.

So.... should these automatic computations be used clinically without, for instance, a confirming set of kidney depth measurements from lateral scans, post-renogram, or from an ultrasound scan? This question was answered in 1985 but unfortunately has not yet seemed to infiltrate the psyche of producers of modern renal analysis software.

Another question: should conjugate imaging be considered for renogram analysis in commercial dual-headed gamma camera software packages?

Conjugate Imaging in Renography
The principle of conjugate imaging is based on computing the Geometric Mean of activity measurements from two opposing detectors and is illustrated in the following diagram where a homogeneous medium (yellow rectangle) containing a point source of radioactivity (red dot). The thickness of the medium is d and the point source is a distance t1 from Detector #1 and a distance t2 from Detector #2.

The activity detected by Detector #1, assuming no scatter is detected, is given by:

$$ A_1 = A \exp(-\mu*t_1)$$

while that detected by Detector #2 is given by:

$$ A_2 = A \exp(-\mu*t_2)$$.

The Geometric Mean, GM, of the detected activities is given by:

$$GM = \sqrt{A_1*A_2}$$

so that:

$$GM = \sqrt{A\exp(-\mu*t_1)*A\exp(-\mu*t_2)}$$

and, therefore:

$$GM = \sqrt{A\exp(-\mu*t_1)*A\exp(-\mu*(d-t_1))}$$

and, as a result:

$$GM = \sqrt{A \exp(-\mu*d)}$$

This final equation indicates that the Geometric Mean is dependent solely on the thickness of the medium, d, which contains the point source and not on the distance of the source from either detector.

Translating this to renography implies that imaging with opposing gamma camera heads (as with a dual camera SPECT system) would provide spilt function measurements which are independent of renal depth.

Conjugate imaging in renography is illustrated by the following images of Monte Carlo simulated renograms acquired simultaneously using anterior-posterior (AP) and posterior-anterior (PA) projections. The simulations had renal depths of 7.31 cm on the left and 8.64 on the right and the real LK/RK split function ratio was 50%:50%.

These images were used to compute the Geometric Mean using ImageJ and the resultant images were analysed using OsiriX. Image computation involved multiplying the AP and PA renograms and taking the square root of the result, at 32-bit accuracy. Computed images were the converted to 16-bit for DICOM storage. The resultant Geometric Mean renogram (see the centre panel above) provided an LK/RK split function estimate of 51%:49%, while the PA-only data, not corrected for renal depth, provided an inferior estimate of 54%:46%.

It is apparent from the above illustration that conjugate imaging may have a role in clinical renography and may not be reliant on renal depth measurements for attenuation correction. However, it should be noted that the method assumes that the activity is located in a homogeneous medium with a spatially-uniform linear attenuation coefficient, μ, which indicates that the method may suffer in real patients from aberrations generated by sources such as digestive gases overlying the kidneys.

It should be noted, as a concluding remark, that conjugate counting is well established in quantitative renal analysis using static 99mTc-DMSA images.

Blood Pool Compensation for Split Function Determination
A recent publication has introduced the technique of Blood Pool Compensation for split function determination in renography. Here the activity in each kidney and the liver is measured over time. The liver activity is assumed to represent blood pool activity during the uptake phase of the renogram. A linear fit to a plot of liver activity versus kidney activities is then back-extrapolated to zero liver activity to determine the kidney activity with zero blood pool contribution. The split function is then calculated using the relative contributions at this zero activity.

This simple method is illustrated in the following figures. Three regions of interest (RoIs) defined for the liver, the left kidney and the right kidney are shown in the top left panel and the three resulting curves are shown in the top right panel of the table for a Monte Carlo-simulated renogram with 50/50 split function. A liver counts versus kidney counts plot for the uptake phase is shown in the bottom left panel, where an intercept of 17,281 counts is found for the left kidney and an intercept of 18,719 counts for the right kidney. Split function is then estimated to be 48% on the left and 52% on the right.

The bottom right panel shows the Mean Absolute % Error, computed from a series of such simulated images where the left kidney to right kidney split function varied from 100%:0%, through 50%:50% to 0%:100% in steps of 5 percent, to be 7.5%.


text:
GIMP/Layers

Layers in the GIMP are a powerful tool allowing you to do many things. A good way to think of them is as layers of glass stacked up. Layers can be transparent, translucent or opaque.

The Layer Dialog
Go to Windows > Dockable Dialogs > Layers to open the layers dialogue. This dialogue is useful when editing with layers.

Starting
Open up the layers dialogue, and add as many layers as you like to the image. Note that any image editing or filters will only apply to your currently selected layers.

Transparency
The Opacity slider controls the transparency or opaqueness of a specific layer. This will not affect the internal alpha channel of the layer.

Layer Mask
A layer mask is a grayscale layer that controls the local transparency of a layer. This is useful for non-destructively deleting part of a layer, or only making part of a layer visible.

Using a Layer Mask to selectively edit an image
A layer mask is a very useful tool if you only want to edit part of an image. First duplicate the layer that you want to edit. Then make your changes to the bottom layer. Now add a black layer mask to the unchanged layer. Then use the white paint brush on the layer mask, to restore parts of the original version. A black area in a layer mask will have zero opacity, while a white (RGB 255,255,255) area will be completely opaque.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: GIMP/Layers


text:
User:SausageSucker

SausageSucker has made invaluable contributions to Wikibooks. His amazing skills with the English language are amazing.

title: User:SausageSucker


text:
User talk:SausageSucker

SausageSucker is awesome! SausageSucker 03:17, 17 September 2006 (UTC)

Your change to the page US History/Contents/Civil War was determined to be unhelpful, and has been reverted. Please use the sandbox for any tests you want to do. Take a look at the welcome page if you would like to learn more about contributing. Thanks.--Az1568 06:27, 17 September 2006 (UTC)

title: User talk:SausageSucker


text:
User talk:24.98.138.10

Re:Your recent edits to MapleStory/Monsters. This page has been moved to StrategyWiki Please do not make any changes or additions to this page.--Az1568 06:40, 17 September 2006 (UTC)

title: User talk:24.98.138.10


text:
The Housework Manual

Table of contents

 * /Introduction/

Laundry

 * Bringing in the Dry Laundry
 * Separation and Washing

The Kitchen
This is the place where most of our food is prepared and it needs to be kept spotlessly clean, otherwise we will have many diseases affecting us.
 * Washing Dishes

title: The Housework Manual


text: Category:Book:The Housework Manual

title: Category:Book:The Housework Manual


text:
Talk:Horticulture/Slugs

Transwiki notes
Copied from Pest control of slugs 09:37, 17 September 2006 (UTC), history pasted here in anticipation of deletion (how-to article) -- SB_Johnny | talk 09:37, 17 September 2006 (UTC)

(cur) (last) 05:31, 17 September 2006 SB Johnny (Talk | contribs) (cur) (last) 05:30, 17 September 2006 SB Johnny (Talk | contribs) (rv silliness) (cur) (last) 22:58, 16 September 2006 Joao 100 (Talk | contribs) (→Irritants and repellents) (cur) (last) 22:57, 16 September 2006 Joao 100 (Talk | contribs) (→Irritants and repellents) (cur) (last) 04:19, 10 September 2006 Billlion (Talk | contribs) (→Directly applied psticides) (cur) (last) 04:18, 10 September 2006 Billlion (Talk | contribs) (→Baits, decoys and traps) (cur) (last) 04:16, 10 September 2006 Billlion (Talk | contribs) (→See also - mv new para) (cur) (last) 15:06, 9 September 2006 Anncjones (Talk | contribs) (→See also) (cur) (last) 14:04, 4 September 2006 Ke6isf (Talk | contribs) (Sentence fragment, but easy to correct.) (cur) (last) 04:11, 5 June 2006 Onceler (Talk | contribs) m (→Irritants and repellants - sp (oops)) (cur) (last) 04:00, 5 June 2006 Onceler (Talk | contribs) (copy edit (made categories/lists for ease of reference)) (cur) (last) 11:45, 3 June 2006 SB Johnny (Talk | contribs) (iron phosphate) (cur) (last) 13:20, 27 May 2006 Gurch (Talk | contribs) (copyedit, re-order paragaphs) (cur) (last) 19:59, 24 May 2006 Dumbo1 (Talk | contribs) (cur) (last) 03:30, 13 March 2006 Hooperbloob (Talk | contribs) (+cat) (cur) (last) 22:36, 2 March 2006 198.175.229.3 (Talk) (cur) (last) 15:28, 1 February 2006 Eskimbot (Talk | contribs) m (robot Adding: fr) (cur) (last) 15:21, 15 January 2006 24.41.16.184 (Talk) (cur) (last) 21:48, 14 December 2005 64.222.81.240 (Talk) (cur) (last) 07:30, 21 November 2005 Shaddack (Talk | contribs) (cat) (cur) (last) 10:15, 16 September 2005 Histrion (Talk | contribs) m (→External links - typo) (cur) (last) 11:25, 31 August 2005 24.71.223.140 (Talk) (cur) (last) 04:20, 11 August 2005 209.143.57.4 (Talk) (Diatomaceous_earth) (cur) (last) 15:09, 21 July 2005 Snek01 (Talk | contribs) m (:cs) (cur) (last) 13:57, 17 July 2005 Shantavira (Talk | contribs) (copy edit and depersonalise) (cur) (last) 12:13, 9 July 2005 195.171.200.235 (Talk) (cur) (last) 17:58, 27 May 2005 67.101.8.19 (Talk) (+some more methods) (cur) (last) 12:23, 8 May 2005 Oven Fresh (Talk | contribs) m (+cat) (cur) (last) 09:43, 18 January 2005 MPF (Talk | contribs) (copyedit & more details) (cur) (last) 16:27, 2 December 2004 Billlion (Talk | contribs) (cur) (last) 16:23, 2 December 2004 Billlion (Talk | contribs) (moved from slug) (Latest | Earliest) View (previous 50) (next 50) (20 | 50 | 100 | 250 | 500).

title: Talk:Horticulture/Slugs


text:
Talk:International Relations/Prologue

All of the links at te bottom o fthis page are dead. They are attached to academic search databses which do not allow hotlinking. I am not going to delete them, but someone should make an attempt to find the actual source articles and relink them if possible.

title: Talk:International Relations/Prologue


text:
Swedish/Lesson 7

rooms : rum
(the) livingroom: vardagsrum(met)

(the) kitchen : kök(et)

(the) bedroom : sovrum(met)

(the) bathroom : badrum(met)

(the) toilet : toalett(en)

(the) kids room : barnkammare(n)

(the) dining room : matsal(en)

(the) hall : hall(en)

(the) attic : vind(en)

(the) cellar : källare(en)

(the) sauna : bastu(n)

title: Swedish/Lesson 7


text:
User talk:Sleehw no Retsehcnam

Your user page
Stop this stupid jokes, ok? --Derbeth talk 10:40, 17 September 2006 (UTC)

title: User talk:Sleehw no Retsehcnam


text:
College Survival Guide/Acknowledgements

Those who critique, edit, revise, or improve upon this book is allowed to write their name or alias in this great document.

= The Creator =
 * Cyberman

= The Editors =

= The Revisors =

= The Reviewers =

= The Advisors =

title: College Survival Guide/Acknowledgements


text:
IB Chemistry/Medicines and Drugs

Definitions to Know
Agonist- Chemical substance that mimics the effects of a neurotransmitter being increased in the brain.

Alginates - Substances that float on the contents of the stomach to produce a neutralizing layer, preventing heartburn

Alkaloid - Nitrogen–containing compound of plant origin containing a heterocyclic ring and a tertiary amine group

Amphetamine - A sympathomimetic drug, which means it mimics the effect of stimulation on the sympathetic nervous system, that is chemically related to adrenaline and were used to treat narcolepsy during WWII and depression and obesity in the 50’s and 60’s

Antacids - simple bases, such as metal oxides, hydroxides, carbonates, or hydrogen carbonates, that combat indigestion by neutralizing the acid, preventing inflammation, relieving pain and discomfort, and allowing the mucus layer and stomach lining to mend; e.g. Al(OH)3, NaHCO3, CaCO3, milk of magnesia (a mixture of MgO and Mg(OH)2

antagonist - Chemical substances that blocks or decreases the reuptake of a certain neurotransmitter in the brain.

Antibacterials - Chemicals which prevent the growth and multiplication of bacteria; the first effective one was dye trypan red (sleeping sickness), then salvarsan (syphilis), then prontosil (strep), then penicillin

Antidepressants - A synthetic chemical drug used to increase the serotonin levels in the brain. Used to treat mood disorders, particular depression. The most common type of antidepressants used are selective serotonin reuptake inhibitors, also known as SSRIs. Although mood disorders are not the direct cause from low serotonin, studies have shown that low serotonin levels are related. A few well known SSRIs most commonly prescribed for patients with depression is Prozac (Fluoxetine), Zoloft (Sertraline), Paxil (Paroxetine), and Luvox (Fluvoxamine). Mild side affects do come along with antidepressants. They normally take about 6- 8 weeks to show effectiveness. Antidepressants are highly recommended to be under the supervision of a psychiatrist as well as therapy.

Anti–foaming agents - Agents used to prevent flatulence; most common is dimethicone

Aspirin - Ethanoate ester of salicylic acid; mild analgesic; anticoagulant, strokes and the recurrence of myocardiac infarction

Bacterium - A micro–organism that is made up of a complex mixture of proteins, sugars, and lipids and contains a single chromosome consisting of DNA in each cell

Breathalyzer - A test for alcohol in the breath the individual in question breathes into a tube containing potassium or sodium dichromate crystals of an orange color; if the crystals turn green, the dichromate has been reduced to Cr+3 by a sufficiently high level of alcohol, generally over the legal limit for driving; “Green does not mean go home; it means go directly to jail, do not pass Go, do not collect $200”; this test is not strong enough to be used in a court of law

Broad spectrum antibiotics - Antibacterials that are effective against a wide range of bacteria

Caffeine - The world’s most widely used stimulant; is present in coffee, tea, chocolate, cola drinks, and some painkillers and other medicines

Depressants - Drugs which depress the central nervous system by interfering with the transmission of nerve impulses in the nerve cells; some common depressants include alcohol, benzodiazepine (BZD), and Prozac

Designer drugs - Drugs created by modifying the structure of an amphetamine

Digestion - The breakdown of food into molecules that can be utilized by individual cells in the body

Ecstasy - A designer drug which relieves Parkinson’s disease but is frequently abused

Effective Dose - The dose required to bring about a noticeable affect in 50 percent of the population

Gastric juices - Mucous, pepsinogen, and hydrochloric acid

Heartburn - GORD, stomach acid refluxes up the oesophagus

Indigestion - Discomforted caused from excessive acid production; caused by overeating, alcohol, smoking, anxiety, and eating certain types of foods in some individuals

Lethal dose - The dose required to kill fifty percent of the animal population, known as the LD50

Mild analgesic - Reduces suffering from pain by decreasing the level of pain

Narrow spectrum antibiotics - Including some penicillins, antibacterials which are effective against only certain types of bacteria

Nicotine - The substance found in tobacco that is largely responsible for causing approximately 1/3 of the world’s population to be addicted to smoking

Pineal gland - A small lump of tissue at the base of the brain that produces melatonin

Risk–to–benefit ratio - The ratio balancing the risks of taking a drug, including side effects, with the benefits garnered from the drug

Side effects - Unwanted repercussions from taking a certain drug

Strong analgesic - Reduces suffering from pain by increasing one’s pain tolerance level; are available only by prescription; most important naturally occurring are morphine and codeine; heroin and Demerol are synthetically produced

Thalidomide - A tranquilizer released in 1958 that was said to cure morning sickness; unrevealed side effects of the drug, which were not revealed until 1961, caused many women who took this drug to give birth to malformed children (teratogenic)

Tolerance - Adaptation of the body to a certain drug; a person who develops tolerance for a drug requires larger and larger doses to achieve the original effect

Common Effects of Several Chemicals
Alcohol - Antiseptic, depressant-Alcoholism– psychological and physical dependence, violent behavior, family breakdowns, loss of consciousness at high doses, cirrhosis of the liver, liver cancer, dementia, delirium tremens (DT’s) after sudden discontinuation; lethal when taken with benzodiazepines, narcotics, barbiturates, and solvents and increases stomach bleeding when taken with aspirin

Amphetamines - Sympathomimetism, treats narcolepsy, depression, and obesity-Heart rate and breathing increase, tolerance, dependence, appetite down, possible depression, emotional instability

Antacids - Combat excess stomach acid, preventing inflammation, relieving pain and discomfort, allow the mucus layer and stomach lining to heal (or ulcer)-Diarrhea, constipation, possible bone damage, bloating and belching

Antidepressants - Nausea, insomnia, dizziness, sweating, headaches, decrease sex drive, fatigue, dry mouth, constipation and weight gain or loss.

Aspirin - Painkiller, can be taken for arthritis and rheumatism, prevents blood clotting, prevent strokes or the recurrence of heart attacks-Bleeding of the stomach, allergies to it can lead to bronchial asthma, Reye’s disease in children under 12 (rare), overdose can lead to acidosis

Caffeine - Stimulant, diuretic, catalyst in painkillers-Restlessness

Ecstasy - Relieves symptoms of Parkinson’s disease-Mental relaxation, increase sensitivity to stimuli, hallucinations, can be fatal after just a single dose. May damage cells in the brain used to release serotonin creating chemical imbalances which can cause many psychiatric disorders and perhaps, memory loss due to shortening of dentrites.

Morphine - Strong analgesic and painkiller-Constipation

Nicotine - Increases concentration and relieves tension-Addiction, increased heart rate and blood pressure, increased risk of heart disease and coronary thrombosis, withdrawal– craving for tobacco, nausea, weight gain, insomnia, irritability, depression

Opiates (Diethanoylmorphine or heroin) - Even more powerful painkiller than morphine and codeine-Short–term: euphoria, painkilling, nervous system depression, breath and heart rate down, high doses lead to coma/death; Long–term: constipation, loss of sex drive, disruption of menstrual cycle, risk of parenterally–distributed diseases, social problems

Paracetamol (Acetaminophen)- Mild analgesic, preferred over aspirin for children-Renal damage and vascular disorders (rare), overdose can lead to death, renal, hepatic, and cervical damage

Thalidomide - Combats morning sickness-Causes women to give birth to malformed children (teratogenic)

D1
D1.1 Effects of medicine and drugs on the Functioning of the Body

A medicine or drug is any chemical that

• Alters the physiological state (living systems), including consciousness, activity level or coordination • Alters incoming sensory sensations • Alters mood or emotions

Medicine and drugs are generally used to improve health, by helping the body in it's healing process. The mechanism of the drug action still isn't known completely, and the placebo effect can occur, where the body is fooled into healing itself.

D1.2 Stages of research, development, and testing of new pharmaceutical products

This process is very long, and very expensive. Usually, the drug or medicine is either isolated from an existing species, or created chemically. The medicine/drugs is then tested in trails to demonstrate the effectiveness.

Before human trials start, the drugs are tested on animals to determine the lethal dose and the effective dose. After determining these two doses, the therapeutic index can be calculated.

Therapeutic index = LD50/ED50

This compares the therapeutic effects to the toxic effects. For example, if the therapeutic index is 100 then the ration is 100:1, which means that increasing the dose a hundred fold for the effective dose would result in 50 percent death rate.

After the therapeutic index is established, the drug can then move to clinical trials with humans. Usually, this involves volunteers and patients, with half getting a placebo. This trial is observed to see if the drug is helpful and to find the possible side effects.

Drugs usually have unwanted side effects. Side effects change depending on the reason for taking the drug. The severity of the complaints in the trials will help determine if the risk-to-benefit ratio is acceptable. Even if the risk is high, if the drug helps with a life-threatening disease, then the side effects will be more acceptable. The tolerance is also determined.

If it passes the initial clinical trail, then more rigorous testing will occur, with widened use in a variety of clinical situations. If it passes all these trials, then it can be approved by a drug administration for over the counter use or through prescription only.

One case where the problem wasn't stopped was with the drug Thalidomide. The drug was a tranquilizer with the purpose of stopping morning sickness in pregnant women. Severe side effects occured, and it became known that the drug had problems which were shown in earlier clinical trials. The drug continued to be marketed, and was eventually withdrawn years later. The drug caused birth defects, with absent or deformed limbs.

D1.3

Other Important Facts to Know
Methods of Administering Drugs

1. Mouth (Oral)

2. Inhalation (tracheal)

3. Through the anus (rectal)

4. Injection (parenteral- Three Types: Intravenous, Subcutaneous, and Intramuscular)

5. Topically (creams, sprays, drops, etc.)

•	The [H+] of HCl in the stomach is between 0.03 and 0.003, and the pH 1.5–2.5

•	Legal limit for driving is a BAC of 80 mg alcohol per 100 cm3 blood

•	1 unit alcohol = ½ pint beer or lager, 1 glass of wine, 1 measure of spirits

Mechanism of Action of Antibiotics

1. Penicillins and cephalosporins prevent bacteria from making normal cell walls

2. Other antiobiotics act inside the bacteria interfering with the chemical activities essential to their life function

I'm really sorry, but I can't find my notes on Viruses. As soon as I locate them, I will put them in. Good luck! It's really not that hard of an exam if you know what you're doing.

Viruses:

- Lack a cell structure and are more difficult to treat in the body than bacteria

- Viruses consist only of DNA or RNA, and protein

- Antiviral drugs target specific viral infections by causing changes to the cell membrane which prevent the entry of viruses

- Antivirals can also alter the cell's DNA so it cannot be used by the virus or block enzyme activity to prevent viral multiplication

Specific Drugs to Know for Viruses:

- Oseltamivir (Tamiflu) and zanamivir (Relenza) are antivirals for flu that inhibit the enzyme neuraminidase, which allows new viral particles to escape from the host cell and cause infection. They must be taken immediately as symptoms appear or the viral infection will already have spread too far.

- Oseltamivir and zanamivir have similar structures, and act as competitive inhibitors with neuraminidase as their structures are similar to sialic acid, its normal substrate.

title: IB Chemistry/Medicines and Drugs


text:
User talk:Picus viridis

Welcome
Hello and welcome to Wikibooks!

Here are some tips to help you get started:
 * You can sign your name on Talk and vote pages using four tildes, like this: ~~~~.
 * Remember to conduct any editing experiments in the sandbox.
 * Check out our help page if you need additional help.
 * Eventually, you might want to read the Manual of Style and Policies and Guidelines.
 * Take a look at Naming policy
 * See list of templates which can save your time
 * Remember to maintain a Neutral point of view.
 * Explore, be bold in editing pages, and have fun!

You will find more resources in Community Portal. If you want to ask a question, visit the Study help desk, the Staff lounge, IRC channel or ask me personally on my talk page.

Good luck! --Derbeth talk 16:58, 17 September 2006 (UTC)

title: User talk:Picus viridis


text:
The Computer Revolution/Internet/Hackers

Hacking
What is Hacking?

Hacking means the act of breaching into a computer or network. Hacking can occur two ways, it can occur in person if the hacker has physical access to the computer or network or through the Internet which tends to be the most common way. It doesn't matter how the hacking occurs because it is still illegal. In the United States and various other countries the act of hacking is considered a criminal offense. Some of the illegal acts performed during hacking are stealing important data like credit card information, corrupt a computer system, and create and disperse spam. Hacking has become quite easier due to the growing wireless network popularity, which allows hackers to gain unauthorized access to a wireless network by simply being a couple a hundred feet from an unsecured wireless access point.

Hacking is not only a concern for the average computer user, but can be a threat to national security in the U.S. There are so many systems that are run for security purposes in the U.S with the use of Internet connection that a hacker could be able to get into a major government system. This has bought an increase risk in cyberterrorism. There are many things that could be affected by cyberterrorism that inculde: banks, airlines, stockmarkets, and big systems like the nation’s power grid. With the risk of cyberterrorism increasing the President has made it an important task to work on improving cybersecurity and assigning a task force just for this specific problem. Morley, Deborah and Parker, Charles. Understanding Computer: Today and Tomorrow 13th Edition. Course Technology: Boston, MA, 2011

The majority of hackers conduct broad-based, indiscriminate probes of any and all computers connected to the internet. Targeted attacks against large businesses or government entities are far less common, but garner a lot of attention. This is why it is important for any computer user to take security measures that lessens the ability of hackers to steal the resources of a system. The resources of a computer system include the files and sensitive data stored on the computer, AND the computer itself. Hijacked computers can be just as valuable as stolen data due to their raw computing power and internet connections. Any hijacked computer is a worthy addition to the hackers' arsenal of zombie computers and botnets. Hackers will use hijacked computers to send out spam and emails containing viruses and other malware, disseminate illicit materials or take part in hacking attacks in other computer networks. In summary, hackers may use hijacked systems to perform the following illegal actions.
 * •	To send unwanted spam.
 * •	To engage in click fraud (A type of Internet crime that occurs in pay-per-click online advertising when a person, automated script or computer program imitates a legitimate web user clicking on an ad, for the purpose of generating a charge per click).
 * •	To send malicious emails to your friends, family and clients. In this way hijacked systems function as a spreader of viruses, malware and spyware.
 * •	To install a key logger and capture every username and password typed; they can then use your computer to log into your financial accounts; conduct transactions and perpetrate electronic theft.
 * •	To mount a coordinated attack on select targets, such as banks or governmental institutions.
 * •	To sniff out other traffic on your network. Any networked computer can be used to "sniff" out and copy traffic on your network, such as the network traffic from credit card or other data processing servers.
 * •	To use your computer to send out data through the internet. In extreme cases, they can use it as a hub to exchange illicit, illegal or stolen materials, as a relay station to hide the true origin of certain content or as a message board for shady activities.

Computer Training & CCNA Networking Solutions. n.d. Web Site. 11 October 2012. .

Spam
What is Spam? Spam is the abuse of electronic messaging systems to send unsolicited, undesired bulk messages. While the most widely recognized form of spam is e-mail spam, the term is applied to similar abuses in other media.There are two main types of spam, and they have different effects on Internet users. Cancellable Usenet spam is a single message sent to 20 or more Usenet newsgroups. (Through long experience, Usenet users have found that any message posted to so many newsgroups is often not relevant to most or all of them.) Usenet spam is aimed at "lurkers", people who read newsgroups but rarely or never post and give their address away. Usenet spam robs users of the utility of the newsgroups by overwhelming them with a barrage of advertising or other irrelevant posts. Furthermore, Usenet spam subverts the ability of system administrators and owners to manage the topics they accept on their systems.Email spam targets individual users with direct mail messages. Email spam lists are often created by scanning Usenet postings, stealing Internet mailing lists, or searching the Web for addresses. Email spams typically cost users money out-of-pocket to receive. Many people - anyone with measured phone service - read or receive their mail while the meter is running, so to speak. Spam costs them additional money. On top of that, it costs money for ISPs and online services to transmit spam, and these costs are transmitted directly to subscribers.

E-mail spam is a subset of spam that involves sending nearly identical messages to thousands (or millions) of recipients by E-mail.

 * 1) Tips for Fighting Spam:
 * 2) Delete messages from people you do not recognize.
 * 3) Never Reply to a spam message
 * 4) Opt out of anything you don't want to receive
 * 5) Use spam filters
 * 6) Fight back by reporting spammers.

Spoof
when we are talking about spoofing in IT, we refer to counterfeit an identity. It is sometimes used for searching or malicious uses.

There are different types of spoofing. The well known type of spoofing is IP spoofing.However, there are others like ARP spoofing, DNS spoofing, WEB spoofing, and Email spoofing.

IP spoofing is a technique that is used by hackers to get an original IP address by creating IP packets. This consists in sending messages from untrusted source, but who receives the message thinks that it comes from trusted host.

http://www.webopedia.com/TERM/I/IP_spoofing.html

ARP spoofing is a hacking methodology to forge the content of an ARP table on an Ethernet (LAN) by creating or changing the ARP table. The LAN works with MAC addresses and the ARP protocol converts IP address to MAC address in order to establish communication between computers. If the wrong information is saved into the ARP table,it is because the computer believes that it is valid.

http://www.codeproject.com/internet/winarpspoof.asp

DNS spoofing is a forgery of the Domain Name Service to generate a request to Server.

http://www.iss.net/security_center/advice/Underground/Hacking/Methods/Technical/Spoofing/DNS/default.htm

WEB spoofing is when hackers can make an exact copy of the whole World Wide Web (Web page)with the objective to acquire and monitor information (e.g. passwords or account numbers) of that web page. In summary, web spoofing is a forgery of a web page where hackers can control and manipulate the whole private information.

http://www.cs.princeton.edu/sip/pub/spoofing.html

E-mail spoofing email spoofing method allows hackers sending emails from a fake email that they got from a personal or entity email. Spammers use this technique because they want to send messages to thousands and thousands users. Those emails seem to have been originated from a source that does not exist and those emails are called "junk or spam" emails.

http://www.hbpsystems.co.uk/blog/email-spamming,-spoofing-and-how-to-prevent-it/

Phishing & Pharming
Phishing (pron. "fishing") and Pharming (pron. "farming") have nothing to do with activities related to fish species or cultivating agricultural lands, although there is a distinctive play on the terminology and concepts associated with farming and fishing.

Hackers involved in phishing and pharming are undertaking illegal activities for the purpose of getting personal/confidential information from computer users (i.e., personal, financial or password data). Phishers "bait their hooks," "cast their net" and "fish" for information in the hope of "luring" and ultimately "catching" identity victims "hook, line and sinker" into a trap that leads the user into divulging their financial and/or password information. Likewise, pharmers are "harvesting" personal information, but generally operate on a less obvious level than phishers and, as a result, pharming has been referred to as "phishing without a lure" (http://www.cyveillance.com/web/online_risks/phishing.htm  Retrieved Sept 19, 2006).

Pharming is a type of phishing and phishing is a short form for "password harvesting fishing." In both cases, computer users are targeted. In pharming, they are directed or redirected to bogus or impostor web pages. Phishers, however, operate on a smaller scale than pharmers and rely on e-mail as their solicitation method. So, phishers tend to "... approach their targets one by one," but pharmers, involve many victims at a time and therefore "... threatens to reel in entire schools of victims" (http://www.wired.com/news/infostructure/0,1377,66853,00.html Retrieved Sept 28, 2006). Pharming combines such threats as viruses and spyware plus such things as domain spoofing and DNS (Domain Name System) poisoning or domain hijacks to redirect users (http://www.theregister.co.uk/2005/01/31/pharming/  Retrieved Sept 19, 2006). The more highly targeted version of phishing is called "spear-fishing" which utilizes e-mails to target users in a specific company by appearing to originate from within -- oftentimes from HR or the IT department or someone known to the user (http://www.businessweek.com/magazine/content/05_28/c3942014_mz003.htm#ZZZDLBOMKAE  Retrieved Sept 19, 2006 &  http://www.wordspy.com/words/spear-phishing.asp  Retrieved Sept 19, 2006). Added to this mix is "puddle phishing" which targets smaller companies and targets -- often customers of smaller financial institutions (http://www.wordspy.com/words/puddlephishing.asp  Retrieved Sept 19, 2006).

Phishing, brand spoofing and carding are one and the same. Phishing, a variant of "fishing," is "Web lingo" coined by hackers. The use of "ph" in place of the letter "f" appears to be a favorite among hackers. Their first substitution of letters appears to have been adopted in the late 1960s when they referred to themselves as "phone phreaks" or telephone system hackers (http://www.wordspy.com/words/phishing.asp Retrieved Sept 19, 2006). Today's variant on this is "phone phishing" -- also called pretext calling -- which appears to be more damaging to victims than activities of the "phone phreaks" in the pre-computerized world and is less detectable than Internet phishing because the victim is not directly involved and, in fact, is completely unaware someone is gaining access to their personal data via customer service representatives (http://www.wordspy.com/words/phonephishing.asp  Retrieved Sept 19, 2006).

Scamming practices definitely pre-date the computer and so too does phishing, but the advent of new technology and increasing use of this technology for more business transactions has led to a "wide potential profit zone" for the more computer-savvy cyber-criminals of today (http://www.wired.com/news/infostructure/0,1377,66853,00.html  Retrieved Sept 19, 2006). Deceptive phishing scams for the purpose of identity theft, although illegal, can be very lucrative, so who says crime does not pay today? It certainly can be costly for the targeted party(ies) subjected to huge financial and identity rip-offs, often in need of costly legal assistance (http://www.computerworld.com/securitytopics/security/story/0,10801,89096,00.html  Retrieved Sept 19, 2006 &  http://www.csoonline.com/read/100105/pharm.html  Retrieved Sept 19, 2006).

Computer scams have added to personal and business costs (i.e., in time, effort, money and legal challenges), has led to the creation of a vast number of IT related security jobs and resulted in numerous security businesses -- in surveillance, computer security and anti-phishing software development. It maybe difficult to protect oneself from some forms of pharming and phishing, but there are some basic steps which will help avoid the more obvious traps. One can get advice and tips from various on-line sites such as http://www.businessweek.com/technology/content/may2004/tc20040524_8133_tc024.htm (Retrieved Sept 19, 2006). In addition, there have been many social (e.g., user training), legal and technical responses (e.g, anti-phishing software) developed and adopted in an effort to protect users, including the use of spam filters and verification tools (http://en.wikipedia.org/wiki/Phishing Retrieved Sept 19, 2006).

The best defense advice is 'Beware, Be Alert and Be Informed.'

Adware
Definition: "Any software application in which advertising banners are displayed while the program is running is called Adware. And any software that sends data back to a third party - WITHOUT ASKING the user - is Spyware"(http://www.adware.info/).

Have you ever noticed when you are on a particular website of your interest and all of a sudden an advertisement pops up and disrupts your page, not to mention wastes your time? This is Adware. Companies will offer you free software, while advertising on your computer. (https://www.microsoft.com/windowsxp/using/security/expert/honeycutt_spyware.mspx)What a great way for companies to maximize their advertising demographic.

Tips to stop from being an adware victim

Don't be a "yes or no" clicker - When popups come onto your screen (which annoy you and slow you down) take the extra 10 seconds to read it. That way you aren't downloading anything you do not want. This could be adware and could create a bigger problem. It is tempting to get frustrating and click something to make the box disappear. Take your time.

Caution - When offered a free download or program - In this material world today where anything and everything comes with a dollar sign attached, it is understandable that we jump at the chance to take anything that is free. In the world of software downloading, this free software gift may often come with built in adware and will download onto your computer creating constant advertising and popups without you even knowing you actually created the problem. Companies make their money off of this free advertising. (https://www.microsoft.com/windowsxp/using/security/expert/honeycutt_spyware.mspx)

Webjack
What is webjacking? Webjacking is when hackers take web-pages that you frequent and then take you to other websites which could be pornography or websites that are used to scam people.

(http://www.wordspy.com/words/Webjack.asp)

How hackers webjack your computer Hackers will go into your computer and place a trojan, on your computer or server in order to redirect you to websites or steal your files. Another way in which hackers try to webjack your computer is by sending you an email, which looks like the exact site to which you are registered with for example your bank. This email will ask you to update your personal information, example names, addresses, credit card or bank information.

(http://www.onrec.com/content2/news.asp?ID=12167)

Once again these hackers get into your computer by using pop-ups. Webjacking is a form of criminal activity and can be very dangerous to users. These jackers can copy your webpage domain. A user will type in the correct address to the site they are trying to go to but instead of going to the actual site, they will be redirected to a fraudulent site which is an exact replica of the site they were trying to go to. For example if you were trying to go to your bank website to transfer money onto your credit card. You enter all of your personal information onto that site thinking you are on your bank website, but you are actually on a criminal site giving your bank information and access to your accounts to a hacker.

Webjacking affects customers, businesses and most of all scams many innocent people. Once a business website has been webjacked, the actual business will loose online contact with their customers, which will cause the business to loose many of its customers. But webjacking also affects innocent customers to loose their money.

(http://www.minnesotatechnology.org/publications/magazine/2002/Fall/Webjacked.asp)

If you receive any emails from your bank institution or any other businesses, do not give any of your personal information out. Always call your bank to find out if the email is legitimate.

Webjacking is a new territory for the law, if you find yourself a victim of webjacking there are several steps you should take:

- Contact the legitimate organization whose website has been webjacked. Although they may not be able to compensate you, they need to be aware in order to stop the hacker. - Contact the Uniform Dispute Resolution Policy (UDRP). - Contact the authorities and court systems. You may be able to seek damages based on several laws like Privacy.

http://www.minnesotatechnology.org/publications/magazine/2002/Fall/Webjacked.asp

DoS
DoS stands for Denial of Service, and it is a malicious tactic used mainly for demonstrative or abusive purposes. It works by exhausting a server's resources needed to respond to requests for data. This is usually done in the form of sending data requests from false computer addresses, so when the server tries to respond with data, it gets lost and stalls momentarily before disconnecting. When these requests are coordinated in large numbers they can be detrimental to a server's ability to function. When multiple computers are coordinated into a botnet, the attack is no longer called a DoS attack, rather it is referred to as a DDoS, a Distributed Denial of Service attack.

Hacking Groups and Cyber Attacks
According to "Global News", LulzSec is short for Lulz Security. “Lulz” is a variation of the Internet slang “lol” which means “laugh out loud.” Lulz can also be understood as “laughs,” or “amusement.” The group is thought to have formed in May 2011, and were most active in May and June 2011.

Allegedly, LulzSec is an elite organization of hackers that is linked to the online “hacktivist” group Anonymous, as well as the offshoot groups “Internet Feds” and “AntiSec.” LulzSec is most interested in the theft of confidential information, defacing websites, and cyber attacks. They attack businesses, governments and cyber-security firms worldwide, including: Visa, MasterCard and PayPal, government computers in Tunisia, Algeria, Yemen and Zimbabwe, Fox Broadcasting Co. and Tribune Co., Sony Pictures, Public Broadcasting Service (PBS) and the U.S. Senate

Another "hacking group","Anonymous" is described below. According to Wikipedia, a flag conveying symbolism associated with Anonymous. The imagery of the "suit without a head" represents leaderless organization and anonymity.[1] Individuals appearing in public as Anonymous, wearing the Guy Fawkes masks popularized by the comic book and film V for Vendetta.

According to Wikipedia, Anonymous (used as a mass noun) is an Internet meme that originated in 2003 on the imageboard "4chan", representing the concept of many online and offline community users simultaneously existing as an anarchic, digitized global brain.[2] It is also generally considered to be a blanket term for members of certain Internet subcultures, a way to refer to the actions of people in an environment where their actual identities are not known.[3] In its early form, the concept has been adopted by a decentralized online community acting anonymously in a coordinated manner, usually toward a loosely self-agreed goal, and primarily focused on entertainment. Beginning with 2008, the Anonymous collective has become increasingly associated with collaborative, international hacktivism, undertaking protests and other actions, often in retaliation against anti-digital piracy campaigns by motion picture and recording industry trade associations.[4][5] Actions credited to "Anonymous" are undertaken by unidentified individuals who apply the Anonymous label to themselves as attribution.[6]

According to Wikipedia, many websites are strongly associated with Anonymous. This includes notable imageboards such as 4chan, their associated wikis, Encyclopædia Dramatica, and a number of forums.[7] After a series of controversial, widely-publicized protests and distributed denial of service (DDoS) attacks by Anonymous in 2008, incidents linked to its cadre members have increased.[8] In consideration of its capabilities, Anonymous has been posited by CNN to be one of the three major successors to WikiLeaks.[9]


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"A mind all logic is like a knife all blade. It makes the hand bleed that uses it. -Tagore''"

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'I am currently a senior at Plano Senior High School and have two Beagles. My friends are my blessings, and I would gladly take a bullet for them. For the most part I am Buddhist. I have aspirations to be a male model, no...really. I plan on marrying Jessica Alba, and naming my children Spartacus, and Che Guevera respectively. I am Indian, but I consider myself human above all. I am into photography, art, music, economics, psychology, and philosophy. My computer is an extension of myself. I am currently in love, and it is great. Leonardo Da Vinci is my hero, no matter how overrated you think he is. I want to settle down in either Baltimore, LA, or Tokyo. How now brown cow.'

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Category:Merge templates

Merge templates should be placed at the top of the page that is to be merged.

An exception to this is the Copied template which should to at the top of the talk ("discussion") page.

title: Category:Merge templates


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User:24.71.223.148

Sorry, it is not really possible for an Admin to edit the history. The best I could imagine would be to delete and recreate the article. Perhaps a developer could fix this. You might want to file a feature request in the Bugzilla for the MediaWiki software.

title: User:24.71.223.148


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User talk:24.23.136.125

This message is regarding the page MapleStory/Monsters. Please stop removing content from Wikibooks. It is considered vandalism. If you want to experiment, please use the sandbox. Thank you. --Az1568 20:11, 17 September 2006 (UTC)

title: User talk:24.23.136.125