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A-level Economics/AQA/Markets and Market failure

"Markets and Market Failure" is the first of 3 units which must be completed in order to attain an AS level and the first of 6 for a full A-level accredited by AQA.

What is Economics?
Economics is the study of the social relations of production and distribution and how different societies cope with the basic economic problem of scarcity. It is also the study of human behavior as it makes rational decisions to satisfy its needs.

and also, "Economics is a social science that studies human behaviour as a relationship between ends and scarce means that have alternative uses" (Robbins)

Scarcity
Scarcity is based on the premise that human beings have unlimited wants and needs and that the resources which can be used to fulfill these wants and needs are limited (or finite). This means that choices have to be made about what, how and for whom to produce goods or services. Given the fundamental problem of resource scarcity in the face of infinite human wants, economic agents must make choices between competing alternatives. If resources were not scarce, there would be no need to choose between competing alternatives. Economics for this reason is also referred to as the science of constrained choice. Scarcity is why efficiency is so important to economists as inefficient use of resources reduces the amount of wants which can be satisfied.

Factors of Production
Economic resources can be divided into four different categories; LAND, LABOUR and CAPITAL and ENTERPRISE. These are referred to as the factors of production, each of which has a factor payment.

Factor payments are payments made to scarce resources, or generated by the factors of production, in return for productive services. The factors of production are also known as resource inputs to the productive process.

Land

 * Land consists of all naturally occurring resources, i.e. agricultural land, mineral deposits. The resource land includes anything growing on land such as forestry or agricultural produce, or mineral subsoil assets lying beneath the surface. The factor land thus generates many different types of raw materials used in the production process.
 * The factor payment for land is RENT.

Labour

 * Labour is a measure of the work carried out by human beings
 * Supply of labour is initially determined by the total population but then more directly by the labour force (those who are of working age and who participate in the Labour force).
 * The skills and training of the labour force affects the overall PRODUCTIVITY.
 * The factor payment for labour is WAGES

Capital

 * Is the physical and non-human inputs used in production. This can can include factory buildings and other equipment such as vehicles, plant and machinery or tools used in the production process.
 * The factor payment for capital is INTEREST. Interest is a simplification which embeds the assumption that typically many firms use a mixture of equity and debt to fund to acquisition of capital. Interest is payable on debt used for capital acquisition or expansion.

Enterprise

 * Enterprise is the role of entrepreneur within the economy. The entrepreneurial ability of management organises the other three factors into a cohesive production process which results in the output of goods or services.Enterprise represents the skill of management.
 * The entrepreneur is the risk taker who combines the other factors of production to create a good or service for which there is demand.
 * There are several factors which can affect the level of entrepreneurship within an economy
 * Start-up costs - high start-up costs will discourage entrepreneurship as it reduces the level of profit which can be attained. High start-up costs also discourage entrepreneurship because the total loss is great if the business fails.
 * Level of profits - the higher the level of profit available the more incentive for the entrepreneur, this can be altered by wages levels and availability of labour, availability and cost of land, level of tax on profit
 * Support - Financial support, such as loans. Knowledge support, advice on things such as marketing or accounts can encourage entrepreneurs.
 * Factor payment for enterprise is PROFITS. Profit is also the return to the firm and its owners after all other factor payments have been made. Dividends represent a distribution of profits.

Markets
A market is anywhere where buyers and sellers meet for purpose of exchange, such as: eBay, a market etc. Within a market prices are determined by the market mechanism.

Demand
Demand is the amount of goods and services buyers are willing and able to purchase at a given price over a given period of time, Demand can be represented graphically in a demand curve or in a table known as a demand schedule. The main determinants of demand are; the price of the good, the price of substitute goods, the price of complimentary goods, levels of income. The price of a good and the quantity demanded usually have an inverse relationship; if one increase the other decreases.

Demand Schedule
Demand schedules are tables which show the price of a good and the quantity demanded.

Demand Curve
A demand curve is the graphical representation of a demand schedule, in which quantity demanded is plotted on the X axis and price on the Y axis. The curve on a demand curve slopes downwards left to right, the only exception being status goods in which the demand curve slopes upwards from left to right.

Movement Along a Demand Curve
Movement along a demand curve occurs when the only variable to change is the price. For goods (except status goods) an increase in price causes a contraction of demand and a decrease causing an expansion of demand. In this example the original price of the good was at P1 and the quantity demanded was at Q1. An increase in price to a level of P2 has caused a contraction of demand to a level of Q2.

Shifts in Demand Curves
A shift in a demand curve occurs when a variable other than price changes. For instance a change of income, a change in fashions or trends, a change in the price of a complimentary or substitute good, a successful/unsuccessful advertising campaign.

Price Elasticities of Demand
The extent to which the quantity demanded responds to a change in price.

Price elasticity of Demand = $${percent\ change\ in\ quantity\ demanded\ x \over percent\ change\ in\ price\ x}$$ Which can be worked out by; Price elasticity of Demand = $$ {{ change\ in\ quantity\ demanded\ of\ good\ x\ \over original\ quantity\ demanded\ of\ good\ x} \over { change\ in\ price\ of\ good\ x \over original\ price\ of\ good\ x}}$$

Types of Price Elasticity of Demand
Perfectly Inelastic Demand P.E.D = 0 Any change in price will have no change in demand and whatever the price is the demand will remain equal. If this were to occur firms would set as high a price as possible to make maximum profit. Inelastic Demand 0 < P.E.D < 1 This means that any change in price will have a less than proportional change in demand. Unitary Demand P.E.D = 1 Any change in price has an exactly proportional change in demand, i.e. 10% reduction in demand would cause a 10% reduction in price. Elastic Demand 1 < P.E.D < ≈ Any change in price will cause a greater than proportional change in demand. Perfectly Elastic Demand P.E.D = ≈ Any change in price will have an absolute change in demand as buyers will only buy at one price and no other.

Supply
The quantity of goods and services a firm is willing and able to sell at a given price over a given period of time.

Supply Schedule
As with demand schedules supply schedules are tables which displays the amount of goods and services supplied at what price.

Supply Curve
A supply curve is the graphical representation of a supply schedule, in which quantity supplied is plotted on the X axis and price on the Y axis. The curve of a supply curve slopes upwards right to left, the only exception being status goods in which the demand curve slopes downwards from right to left.

Equilibrium
Equilibrium is the point in a market at which supply and demand intersect, thus giving the equilibrium price and quantity. In the example below the equilibrium price is P1 and the equilibrium quantity is Q1. Were the price or the quantity supplied to change then the market would be in a state of disequilibrium. A price above P1 would mean there would be an excess of supplies, and a price below P1 would mean there is excess demand.

Elasticities
Elasticities measure the change on one variable in proportion to another.

Income elasticity of demand
Income elasticity of demand is a measure of the responsiveness of the demand for a good or service to a change in income. If an increase in income lead to an increase in demand, then the income elasticity of that good or service would be said to be positive. If a change in income lead to no change in demand then that good would be said to have an income elasticity of demand of zero. A rise in income leading to a decrease in demand would mean that the good or service is said to have a negative income elasticity of demand.

The following formula is used to calculate a good or service's income elasticity of demand: Income elasticity of Demand = $$ percentage\ change\ in\ quantity\ demanded\ of\ good\ x \over percentage\ change\ in\ income $$

Cross elasticity of demand
Cross elasticity of demand measures the responsiveness of the demand of one good to a change in the price of another good. This allows, for instance, how a rise in the price of natural gas affects the demand of electricity. In addition to this, by calculating the cross elasticity of demand, it is possible to identify the relationship between two goods or services. If the cross elasticity of demand for two goods is positive, then it can be summarised that the two goods are substitute goods, as would be the case for the example of natural gas and electricity. If the cross elasticity of demand for two goods is negative, then the two goods are complimentary goods, such as fish and chips. The following formula is used to calculate the cross elasticity of demand: Cross elasticity of Demand = $$ percentage\ change\ in\ quantity\ demanded\ of\ good\ x \over percentage\ change\ in\ price\ of\ good\ y $$

Price elasticity of supply
Price elasticity of supply is a measure of the responsiveness in quantity supplied to a change in price. The following formula is used to calculate price elasticity of supply: Price elasticity of Supply = $$ percentage\ change\ in\ quantity\ supplied\ of\ good\ x \over percentage\ change\ in\ price\ of\ good\ x $$

Factors Affecting Elasticity of Supply
1. Stock low stock-supply inelastic large stock-supply elastic

2. Time short period-inelastic long period-elastic

3. Availability of substitutes easily replicable capital and labour-elastic

4. Spare capacity less-inelastic more-elastic

Monopoly and The Allocation of Resources
An absolute monopoly is a market structure in which only one firm supplies a good or service. In addition to this there are, within the UK, legal monopolies, which are firms with a market share greater than 25%. In the long run, monopolies are created and prosper due to the erection of barriers to entry.

'Legal Barriers' The law can be used to create monopolies. This can be achieved in a number of ways. The use of copyrights or patents are examples of a legal barriers to entry. As one firm controls the production of goods for which they have a patent or copyright they can become monopolies. A further example would be the granting of a permit by the government to a firm, such as, the numerous train companies which are monopolies for their respective lines, allowing only them to run trains. Professional licensing is also promoted by existing firms in an effort to keep out additional firms. The licensing laws are often set up in ways that favor existing firms, but are difficult for new firms to meet.

'Resource Barriers' If a firm is able to control some or all of the resources necessary to produce a good, it can then become a monopoly. For instance, an oil company which controls all the oil fields has monopoly power over the production of oil. De Beers, the diamond company, controls over 95% of the Earth's diamond reserves, allowing only a certain number of diamonds to be mined a year, keeping the price high.

'Unfair Competition' Firms may undertake acts of unfair competition to maintain their monopoly status or to become monopolies. If a large firm is in competition with another then it could, as an example, lower its prices to a level which would drive a competitor out of business, safe in the knowledge that the loses associated can be sustained for a short amount of time due to the large reserves of the firm. Having driven the competing firm out of the market the monopoly is then free to revert back to the previous price charged.

'Natural Cost Advantages' Due to economies of scale (in which a larger firm can make a product at a lower per-unit cost than smaller firms due to the larger scale of its production capacities) and economies of scope (in which a single large firm can use the same input resource in multiple production processes, resulting in the production of multiple goods for lower per-unit costs than two smaller firms would experience), it is possible that a market with a single large firm is the most cost-efficient means of producing a good or service.


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A-level Mathematics/OCR/C2/Logarithms and Exponentials

Operations With Exponential Function
An exponential function is a function where a constant base (b) is raised to a variable.

Multiplication
Firstly, $$b^x \times b^{2x}$$ is $$b^{\left(x + 2x\right)}\,$$ which is $$b^{3x}\,$$. So when you multiply a base by the same base you add the variables. To clarify, here is an example with numbers:

Division
Secondly $$\frac{b^{2x}}{b^y}$$ is $$b^{\left( 2x - y \right)}\,$$. So when a base is divided by the same base you subtract the variables.

Here is an example with numbers: $$\frac{2^4}{2^2}=\frac{16}{4}=4=2^2$$.

Base raised to two powers
Thirdly $$\left(b^{2x}\right)^{3x}$$ is $$b^{\left(2x\right) \times \left(3x\right)}$$ which is $$b^{6x^2}$$. So when a base with a variable is raised to a variable you multiply the variables. Here is another example with numbers: (when x = 1) $$\left(2^2\right)^3=4^3=64=2^6$$.

Multiple bases
Fourthly when $$a^2 \times b^2 = ab \times ab$$ it is the same as $$\left(ab\right)^2\,$$. Here is an example with numbers: $$2^2 \times 3^2 = 36 = 6^2$$. There is a similar situation with division: $$\left(\frac{a}{b}\right)^2 = \frac{a}{b} \times \frac{a}{b} = \frac{a^2}{b^2}$$. So when you multiply or divide two different bases raised to the same variable you can multiply or divide them first and then raise them to the variable.

Fractional exponents
The last case is when x is presented as a fraction, you can make a square root function, for example $$b^\frac{1}{x}$$ becomes $$\pm \sqrt[x] b$$. However it is customary to only use the positive root and so $$b^\frac{1}{x}$$ is defined as $$\sqrt[x] b$$. Another similar case is when the fraction has a constant (designated as c) other than 1 in the numerator, for example $$b^ \frac {3}{x} = \left( \sqrt[x] b \right)^3$$ so $$b^ \frac {c}{x} = \left( \sqrt[x] b \right)^c$$.

The Laws of Exponents
The rules that have been suggested above are known as the laws of exponents and can be written as:

 * 1) $$b^xb^y = b^{x+y}\,$$
 * 2) $$\frac{b^x}{b^y} = b^{x-y}$$
 * 3) $$\left(b^x\right)^y = b^{xy}$$
 * 4) $$a^n b^n = \left(ab\right)^n\,$$
 * 5) $$\left(\frac{a}{b}\right)^n = \frac{a^n}{b^n}$$
 * 6) $$b^{-n}=\frac{1}{b^n}$$
 * 7) $$b^ \frac {c}{x} = \left( \sqrt[x] b \right)^c$$ where c is a constant
 * 8) $$b^1=b\,$$
 * 9) $$b^0=1\,$$

Solving exponential equations
In order to solve an exponential equation you need to make sure that all the bases are the same. Then you can remove the base and solve for the variable. Here is an example:

Solve for x. $$2^{\left(x-1\right)} = 16\,$$

Now we convert 16 to a base 2 raised to a number.

$$2^{\left(x-1\right)} = 2^4\,$$

Now we can remove the base. So we have:

$$x-1 = 4\,$$

Finally solve for x.

$$x = 5\,$$

Graphing an Exponential Function
When you graph an exponential function you use the same methods as with a regular function. There is a graph below that you can look at.

Logarithmic Functions
In mathematics you can find the inverse of an exponential function by switching x and y around: $$y = b^x\,$$ becomes $$x = b^y\,$$. The problem arises on how to find the value of y. The logarithmic function solved this problem. All conversions of logarithmic function into an exponential function follow the same pattern: $$x = b^y\,$$ becomes $$y = \log_b x\,$$. If a log is given without a written b then b=10. Also with logarithmic functions, b > 0 and $$b \ne 1$$. There are 2 cases where the log is equal to x: $$\log_bb^X = X\,$$ and $$b^{\log_bX} = X\,$$.

Laws of Logarithmic Functions
When X and Y are positive.

 * $$\log_bXY = \log_bX + \log_bY\,$$
 * $$\log_b \frac{X}{Y} = \log_bX - \log_bY\,$$
 * $$\log_b X^k = k \log_bX\,$$

Change of Base
When x and b are positive real numbers and are not equal to 1. Then you can write $$\log_a x\,$$ as $$\frac { \log_b x}{ \log_b a}$$. This works for the natural log as well. here is an example:

$$\log_2 8 = \frac { \log 8}{ \log 2} = \frac {.9}{.3} = 3\,$$ now check $$2^3 = 8\,$$

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


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Blender 3D: Noob to Pro/Advanced Tutorials/Python Scripting/Import scripts

Importing objects into Blender is not that different from exporting. However, there are a few additional things to take care of. Firstly, all references to "export" in the header should be changed to "import". Secondly, instead of simply writing out data that Blender provides to us, we are responsible for giving data to Blender and ensuring that it is properly formatted. Although Blender is flexible, allowing us to ignore things like vertex indices, we do need to be careful that we do things in a sensible order.

Additionally, there is a bit of housekeeping to deal with. We should be in edit mode while modifying the mesh data. We also need to link up our newly created data to the scene, after it has been properly constructed, so that Blender can see it and maintain it. This makes it visible to the user, as well as ensuring that it gets saved along with the scene.

Importing a Mesh
Here is a simple script that can import an OBJ file created by the export script. import Blender def import_obj(path): Blender.Window.WaitCursor(1) name = path.split('\\')[-1].split('/')[-1] mesh = Blender.NMesh.New( name ) # create a new mesh # parse the file file = open(path, 'r') for line in file: words = line.split if len(words) == 0 or words[0].startswith('#'): pass elif words[0] == 'v': x, y, z = float(words[1]), float(words[2]), float(words[3]) mesh.verts.append(Blender.NMesh.Vert(x, y, z)) elif words[0] == 'f': faceVertList = [] for faceIdx in words[1:]: faceVert = mesh.verts[int(faceIdx)-1] faceVertList.append(faceVert) newFace = Blender.NMesh.Face(faceVertList) mesh.addFace(newFace) # link the mesh to a new object ob = Blender.Object.New('Mesh', name) # Mesh must be spelled just this--it is a specific type ob.link(mesh) # tell the object to use the mesh we just made scn = Blender.Scene.GetCurrent for o in scn.getChildren: o.sel = 0 scn.link(ob) # link the object to the current scene ob.sel= 1 ob.Layers = scn.Layers Blender.Window.WaitCursor(0) Blender.Window.RedrawAll

Blender.Window.FileSelector(import_obj, 'Import') This will load an OBJ file into Blender, creating a new mesh object. Let's take a look at the more interesting portions. Blender.Window.WaitCursor(1) Turn on the wait cursor so the user knows the computer is importing. name = path.split('\\')[-1].split('/')[-1] mesh = Blender.NMesh.New( name ) # create a new mesh Here, we create a new mesh datablock. The name is made from the path only with the filename. ob = Blender.Object.New('Mesh', name) ob.link(mesh) Next, we create a new object and link it to the mesh. This instantiates the mesh. scn = Blender.Scene.GetCurrent scn.link(ob) # link the object to the current scene ob.sel= 1 ob.Layers = scn.Layers

Finally, we attach the new object to the current scene, making it accessible to the user and ensuring that it will be saved along with the scene. We also select the new object so that the user can easily modify it after import. Copying the scenes layers ensures that the object will occupy the scenes current view layers. Blender.Window.WaitCursor(0) Blender.Window.RedrawAll Now the finishing touches. We turn off the wait cursor. We also redraw the 3D window to ensure that the new object is initially visible. If we didn't do this, the object might not appear until the user changes the viewpoint or forces a redraw in some other way.


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A-level Physics/Forces, Fields and Energy/Electric fields

Like gravitational fields, electric fields are a field of force that act from a distance, where the force here is exerted by a charged object on another charged object.Uniform electrical fields goes from positive to negative and the radial electrical fields are the electrical fields that are exerted on a point charge. You may already be familiar with the fact that opposite charges attract, and that like charges repel. Here, we will look at ways to calculate field strengths and the magnitude of forces exerted, in a very similar manner to gravitational fields.

Representing electric fields
Electric field lines are drawn always pointing from positive to negative, like the flow of current. Just like magnetic and gravitational fields, the separation of the lines tell us the relative strength.

Radial fields
Radial fields are drawn from a centre point. The field is stronger nearer the surface of the object, and weakens as you move further away. For a positive charge, the arrows point outwards, and for a negative charge, the arrows point inwards.

Uniform fields

Uniform electric fields can be of two types depending on the behavior of the source of the electric field.

Static uniform electric field

In a static uniform electric field, the intensity or the strength of the electric field at each point is independent of time and the position of the point with respect to the source of the electric field. In other words, the electric field intensity is constant for all points. The electric field lines are represented by parallel lines. The source consists of charges that are at rest. A static uniform electric field can be established at points very close to a charged sheet. For example, a parallel plate capacitor offers a static uniform electric field in the dielectric medium present in between its plates. The field curves outwards slightly on the edges of the plates, and it is important that you draw it like that. These are conservative fields.

Moving uniform electric field

In a moving uniform electric field, the intensity or the strength of the electric field at each point is dependent on the time elapsed but is independent of the position of the point with respect to the source of the electric field. In other words, the electric field intensity varies with time alone. The electric field lines are represented by parallel lines. The source consists of charges that are moving. A moving uniform electric field can be established at points very close to a still charging sheet. For example, a parallel plate capacitor offers a moving uniform electric field in the dielectric medium present in between its plates, while its being charged. The field curves outwards slightly on the edges of the plates, and it is important that you draw it like that. These are non-conservative fields.

Coulomb's law
Coulomb's law is very similar to Newton's law of gravitation, except instead of relating the force between two masses together, it relates the force between two charges, $$Q_1$$ and $$Q_2$$. Since the two charges are point charges which have radial fields, they follow the inverse square law.

Therefore, the relationship can be expressed as:

 * $$F \propto \frac {Q_1 Q_2}{r^2}$$.

Or, in words:

Any two point charges exert a force on each other that is proportional to the product of their charges and inversely proportional to the square of the distance between them.

Just like Newton's law, we need to introduce a constant of proportionality to make it into an equation, which in this case is k:

 * $$F = k \frac {Q_1 Q_2}{r^2}$$.

Where $$k= \frac {1}{4 \pi \epsilon_0} \approx 8.99 \times 10^9$$.

Permittivity of free space
$$\epsilon_0$$ is known as the permittivity of free space, and is roughly $$8.85 \times 10^{-12}$$. It is often useful to just remember that $$k \approx 8.99 \times 10^9$$ in free space, however you do also need to know $$k= \frac {1}{4 \pi \epsilon_0}$$, as you may be given the permittivity of different mediums.

Signs of charges
Note that for each charge, you must keep the signs intact in the equation. If you were to have two positive, or two negative charges in the equation, the result would be positive, but if you were to have one negative and one positive charge, the final answer would be negative. The sign of the answer tells us whether the force between the two charges is an attraction, or a repulsion, like charges will repel, and opposite charges will attract. This also explains the minus sign in Newton's law of gravitation, since the force between two masses is always an attraction.

Electric field strength
Just as gravitational field strength is the force exerted per unit mass, we could define the electric field strength in terms of charge:

The electric field strength at a point is the force per unit charge exerted on a positive charge placed at that point.

This is just like saying that the electric field strength is the force a charge of +1 coulomb experiences in that electric field. Therefore, we can find the electric field strength, E, by:

 * $$E = \frac{F}{Q}$$.

From this equation, you can see that the electric field strength is measured in $$N C^{-1}$$.

Field strength of a uniform field
You can make a uniform electric field by charging two plates. Increasing the voltage between them will increase the field strength, and moving the plates further apart will decrease the field strength. A simple equation for field strength can be made from these two points:

 * $$E= \frac{V}{d}$$

Where V is the voltage between the plates, and d is the distance between them.

Here you can see that the units of electric field strength is $$Vm^{-1}$$. $$NC^{-1}$$ is equivalent to $$Vm^{-1}$$.

Field strength of a radial field
Since the electric field strength could be said to be the force exerted on a charge of +1C, we can substitute 1 coulomb for $$Q_2$$ in Coulomb's law. We then get the equation:

 * $$E = \frac {kQ}{r^2}$$, or

 * $$E = \frac {Q}{4 \pi \epsilon_0 r^2}$$

This will tell us the field strength of a charge, Q, at a distance, r.

Force on particles
To calculate the force an electron experiences in a uniform field, we can combine $$E = \frac {F}{Q}$$ with $$E= -\frac {V}{d}$$ in the following steps:

 * $$\frac {F}{Q} = -\frac {V}{d}$$

 * $${F} = -\frac {QV}{d}$$

For an electron with a charge of -e, this becomes:

 * $${F} = \frac {eV}{d}$$, or $$eE$$

This is useful if you are asked to find the force on an electron in a uniform field, most often in a cathode ray tube

Comparison of electric and gravitational fields
As you may have already noticed, electric and gravitational fields are quite similar. You should be aware of the similarities and differences between them.

Similarities

 * For point charges or masses, the variation of force with distance follows the inverse square law.
 * Both exert a force from a distance, with no contact.
 * The field strength of both is defined in terms of force per unit of the property of the object that causes the force (i.e. mass and charge).

Differences

 * Gravitational fields can only produce forces of attraction, whereas electric fields can produce attraction and repulsion.
 * Objects can be shielded from an electric field, but there is no way to shield an object from a gravitational field.
 * Electric fields only act upon charged masses, however gravitational fields act upon all masses.


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User:David Osborn

Introduction
Hi, I'm David Osborn. I'm most active in the GameDev.net community under the alias dcosborn. I also frequent the CGTalk forums, particularly the WIP/Critique: Game Art Design forum, and the Elysiun's Blender Python & Plugins forum. My contributions are rather sparse at the moment, but I hope to do a lot of Blender scripting work in the near future.

Blender 3D: Noob to Pro book

 * Wrote the Import scripts chapter

title: User:David Osborn


text:
Talk:Java Programming/Compilation

capitalization
I my opinion commands like JAVAC or JAVA, and filenames or extensions like .CLASS should not be capitalized, as they are in reality lower case, as seen in case-sensitive operating systems like Linux.

 * I agree -- I've started this conversion; see Java Programming Environment --djb 03:57, 7 December 2005 (UTC)

compiler options
I was planning on expanding this, but I want to know whether it would be better to list all the options (except the -X) are just the most common ones. IMacWin95 00:09, 16 February 2006 (UTC)
 * Well, a there should be a full reference somewhere... but, Getting Started may be the wrong place for that, I think. I'm still not sure why this chapter is existing, in this section. Any explanations? --Yuuki Mayuki 15:50, 16 February 2006 (UTC)

Too much information
This page is near the start of the book, quite often where the beginners will start, I think this is throwing too much information at them.

Just a quick example program, and showing them how to compile and run it using the javac and java commands respectively, any mentions of additional methods of compilation in my opinion should be kept for later chapters or even the appendix.--Mattylaws (talk) 23:59, 7 March 2010 (UTC)

Extendable
The eclipse section refers to extendability. I have no idea what this is. -newb

Newbie Frustration...
As a newbie, this chapter has failed me. After downloading & installing the JDK as instructed, writing the "HelloWorld" program as described, I cannot figure out how from this page how to compile it... which kinda defeats the point of this chapter.

As mentioned already, newbies will start here & the first priority should be to enable them to get something real basic to work. I don't care about the frills if the darn thing doesn't go.

What is needed is a step by step account of how to get "HelloWorld" to compile. At least from that I may be able to figure out what is wrong at my end.

EDIT: Found what I needed here http://introcs.cs.princeton.edu/java/15inout/windows-cmd.html

First lesson done. I sometimes think I'm a glutton for punishment... cheers

title: Talk:Java Programming/Compilation


text:
Talk:OpenOffice.org

Writer Tutorial
I have started a writer Tutorial but it needs more attention.
 * 1) Klingoncowboy4 21:28, 4 December 2005 (UTC)

 * I'll get working on the OOo Writer Tutorial, make it pretty. Should have a nice one by the 6th of this month, and then I'll work on the others. -- ZekeDragon 04 February 2006 - 01:03PST

Updating to v. 2.0.2
I have made a couple of changes to this end, but not checked installation instructions, etc., etc...

In particular, the statement "Clicking next again allows you to choose a directory in which to install the software." is, AFAIK, no longer true. Windows users cannot choose their install directory - or can they?... Would prefer another's confirmation rather than to make this change myself, considering my uncertainty. UserX 02:41, 16 March 2006 (UTC)

Removing the Version section
I'm thinking about removing the version section, cause this is a section that would need updating every time there is a version up. I think a book should contains information that isn't too time-critical, book should essentially contain information that won't change frequently. What do you think? --The Kid 10:30, 27 October 2006 (UTC)
 * How about "For current version see" and give a link? Just a thought (nice work in the module BTW) -- Herby  talk thyme 10:35, 27 October 2006 (UTC)

Cost
I don't like the use of the word "none" for cost. While the software is free to obtain, there are other cost factors (for businesses) like training, conversion etc. which should be noted. Oberiko 21:53, 10 November 2006 (UTC)

 * True, but if you already know other Office Suite, converting to OpenOffice is easy, and needs little retraining, if any, since they will most likely only need a little readjustment. If you don't know any other Office Suite, learning Open Office is easy and training cost is as much as training someone with other Office Suite. Anyway, don't ask someone who's completely blank on any Office Suite to create a Document, Spreadsheet, etc on any Office Suite. It's much cheaper to hire another person to do that job or since learning Office Suite is easy if the employee is already familiar with computer you could cut the training cost by encouraging the employee to learn autodidactly at their own pace (nowadays though, most people have at least some degree of familiarity with computers).

Base
A tutorial about OOoBase is very important and necessary. Can anybody write a structure for the page ?. --82.159.136.215 05:53, 31 May 2007 (UTC)
 * begun--Darrelljon (talk) 15:38, 30 May 2009 (UTC)

Images
Hello all. I'm writing the hebrew wikibook of OpenOffice. Please note that Commons have now some relevant images in categories such as OpenOffice.org Writer. I would also appreciate if you upload your images there too, so all the wikis could enjoy them. Thanks! Mintz l 10:59, 20 September 2007 (UTC)

title: Talk:OpenOffice.org


text:
Handbook of Genetic Counseling/Fanconi Anemia

Fanconi Anemia

Overview

 * Inherited anemia leading to bone marrow failure (aplastic anemia) and myelodysplasia (5%) or acute myelogenous leukemia (10%) and physical abnormalities (60-75%), and increased risk for other solid cancers

Associated Cancers

 * Acute myelogenous leukemia
 * Older patients risk of head and neck, esophageal, gastrointestinal, and genital tract cancers
 * Usually develop after 13 years of age (average age is 23)
 * Difficult to treat due to sensitivity to DNA-damaging agents such a chemo and radiation
 * Patients who receive androgen treatment are at increased risk of liver tumors

Physical Characteristics/symptoms
(25-40% have no physical abnormalities)
 * Short stature (60%)
 * Extreme fatigue
 * Frequent infections
 * Nosebleeds or easy bruising
 * Low white cell, red cell, or platelet count (age of onset highly variable)
 * Myelodysplasia
 * Upper limb malformations: misshapen, missing or extra thumbs or an incompletely developed or missing radius (50%)
 * Other skeletal anomalies (30%) - short low hairline, spina bifida, scoliosis, sacrococcygeal sinus, vertebral anomalies
 * Renal malformations (25%) pelvic, horseshoe, hypoplastic, dysplastic kidney or abnormal artery or abnormal collecting system
 * Abnormal skin pigmentation (café-au-lait spots, hyperpigmentation, hypopigmentation (65%)
 * Microcephaly
 * Eyes (25%) - micropthalmia, strabismus, epicanthal folds, hypertelorism/hypotelorism, ptosis, slanting, cataracts, epiphora, nystagmus
 * Genitalia (40%) -
 * males: hypogenitalia, undescended, absent or atrophic testes, azospermia, delayed puberty. Few males have fathered children
 * females: hypogenitalia, bicornuate uterus, absence of uterus or vagina, ovarian atresia, delayed menarche, irregular menses, early menopause. Successful pregnancies have been reported
 * Ears (10%) - deafness usually conductive due to middle ear anomalies, abnormal pinna, stenosis or atreasia of external auditory meatus, lowest, large or small ears
 * Heart structural defects, cardiomyopathy
 * Lower limbs-toe syndactyly, pes planus, abnormal toes, congenital hip dislocation
 * Mental retardation or learning disabilities
 * Low birth weight
 * Gastrointestinal problems/malformations

Genetic Basis

 * Mutations in any one the eleven known genes cause FA
 * Autosomal recessive inheritance FANCA 66% (16q24.3), FANCC 9.5% (9q22.3), FANCD1/BRCA2 3.3% (13q12.3), FANCD2 3.3% (3p25.3), FANCE 2.5% (6p21.3), FANCF 2.0% (11p15), FANCG 8.7% (9p13), FANCJ/BRIP1 1.6% (17q22-q24), FANCL 0.4% (2p16.1) and FANCM 0.4% (14q21.3)
 * X-linked inheritance FANCB 0.8% (Xp22.3)
 * FANCA and FANCC mutations account for 76% of patients
 * FA pathway regulates DNA repair

Incidence

 * Found equally in males and females
 * All ethnic groups
 * 1 in 100,000 live births

Carrier frequency

 * Estimated between 1 in 600 and 1 in 100
 * gene clinics states 1 in 300 for general population in US, Europe and Japan
 * AJ frequency is 1 in 89

Diagnosis and testing

 * Chromosomal breakage studies in presence of diepoxybutane (DEB) or mitomycin C (MMC)
 * Only FA cells exhibit increased chromosomal breakage in response to DEB
 * Chromosomal breakage can be performed prenatally with cells from CVS or amnio
 * If mutations known, mutation analysis can be performed prenatally
 * Chromosome breakage tests don't detect carriers
 * Siblings should be tested since 25-40% of individuals with FA may have no physical abnormalities
 * Complementation studies and mutation analysis available for 6 of the genes on research basis
 * Fanconi Anemia mutation database found at www.rockefeller.edu/fanconi/mutate/
 * FA cell repository in Oregon (will do complementation analysis)
 * Carrier testing available once mutations identified

Mosaicism

 * Some cells revert to normal phenotype
 * Attributed to recombination or gene conversion
 * May cause false negative DEB test

Geneotype-Phenotype

 * Appear to be some correlations

Differential Diagnosis

 * Bloom syndrome, ataxia telangiectasia, and other chromosomal breakage syndromes are all ruled out by DEB chromosomal breakage test
 * NF1 shares café au lait spots
 * Thrombocytopenia with absent radii
 * VACTERL syndrome
 * Above are ruled out by DEB or MMC test

Leukemia

 * Malignancy where bone marrow produces excess quantities of immature white cells called blasts
 * These suppress the development of healthy blood cells
 * Results in infections and bleeding
 * AML is a particularly aggressive type usually found in older people

Management of FA
(focuses on surveillance of and treatment for physical abnormalities, bone marrow failure, and related cancers)
 * Baseline tests
 * Ultrasound of kidneys and urinary tract
 * Formal hearing test
 * Baseline developmental assessment
 * Referral to ophthalmologist, endocrinologist, and geneticist for initial screening and counseling
 * Follow by hematologist
 * HLA typing of patient, sibs, and parents: full blood typing and blood chemistries
 * Regular blood counts
 * Many recommend annual bone marrow aspirate or biopsy to evaluate morphology, cellularity, and cytogenetics
 * Androgens
 * Improve blood counts in ~50% of patients
 * stimulate production of RBC's, often platelets, sometimes WBC's
 * patients often eventually fail to respond to this treatment
 * Hematopoetic growth factors
 * G-CSF or GM-CSF stimulate production of WBC's in some patients
 * Improved platelet and red cell count in a few patients
 * Generally not recommended for patients with a clonal cytogenetic abnormality
 * Blood transfusions
 * Should be avoided or minimized if patient is a candidate for bone marrow transplantation
 * Family members should be avoided as blood donors to minimize chance of sensitization if considering bone marrow transplant
 * Bone marrow transplant
 * Only long-term cure for blood problems
 * Many associated risks
 * Gene therapy
 * Clinical trials for patients with mutations in A or C gene
 * Potentially correct the hematopoietic defect, but not reduce the risk of developing solid tumors in other tissues
 * Not done if considering bone marrow transplant

Resources

 * Fanconi Anemia Cell Repository
 * Department of Medical and Molecular Genetics
 * Oregon Health & Science University
 * 3181 SW Sam Jackson Park Rd, L103
 * Portland, OR 97201
 * Phone: 503-494-6888

 * Fanconi Anemia Research Fund, Inc (FARF)
 * 1801 Willamette Street, Suite 200
 * Eugene, OR 97401
 * Phone: 800-828-4891; 541-687-4658
 * Fax: 541-687-0548
 * Email: info@fanconi.org
 * www.fanconi.org

 * Fanconi Anemia Mutation Registry
 * www.rockefeller.edu/fanconi/mutate

 * Fanconi Anemia Comprehensive Care Program
 * University of Minnesota Medical Center, Fairview
 * 500 Harvard St., Minneapolis, MN 55455
 * 612-273-2800 (local),888-601-0787 (toll-free)
 * specifically for genetic counseling information call Heather Zierhut, MS 612-626-6743
 * http://www.fairviewbmt.org/index.asp

 * Cancer Fund of America
 * 2901 Breezewood Lane, Knoxville, TN 37921-1009
 * (423) 938-5281
 * Supplies and financial aid for low income
 * cancer patients

 * Fanconi Anemia Comprehensive Care Center
 * 3333 Burnet Avenue, MLC 2022, Cincinnati, Ohio 45229
 * 513-636-3218, Toll-free: 1-800-344-2462, extension 3218
 * http://www.cincinnatichildrens.org/svc/alpha/b/blood/programs/fanconi-anemia/default.htm

 * Fanconi Anemia: Signs, Symptoms, Long-Term Outlook
 * http://www.cincinnatichildrens.org/health/info/blood/diagnose/fanconi-anemia.htm

 * For more resources see Fanconi Anemia: A Handbook for Families and Their Physicians, 2000


text:
Handbook of Genetic Counseling/Fetal Alcohol Syndrome

Fetal Alcohol Syndrome

Contracting

 * Establish rapport with small talk-acknowledge prior contact (Jane)
 * Assess the understanding for the referral to genetics
 * Assess the concerns of the family and what they hope to learn today
 * Ascertain the level of understanding of FAS for those members present
 * Discuss topics to be covered during the appointment- review medical/family history, physical exam

Elicit Medical History
It is important to establish a thorough, detailed medical history as certain medications (such as warfarin or valproic acid) may be teratogenic to the fetus or embryo if taken during pregnancy, and this may result in an exacerbation of congenital abnormalities.

Elicit Family History and Pedigree
history of alcohol or other substance abuse history of living with an alcohol abuser low socioeconomic class previous children with FAS low self esteem unemployment or social transience loss of a child to a foster home (Welch-Carre, 2005).
 * Confirm family history taken by Jane- any updates?
 * Often FAS-affected children are taken away from their biological parents and put into a foster or adoptive home, and a complete and thorough history is therefore important.
 * For the maternal history, the genetic counsellor should note such things as: documented high blood-alcohol concentration
 * The genetic counsellor should ask what kind of alcohol was consumed, the amount of consumption, and the frequency (Welch-Carre, 2005).
 * The genetic counsellor needs to record the child’s history, such as milestones, growth deficits, or CNS abnormalities (Welch-Carre, 2005).

Psychosocial Assessment
history of alcohol or other substance abuse history of living with an alcohol abuser low socioeconomic class previous children with FAS low self esteem unemployment or social transience loss of a child to a foster home (Welch-Carre, 2005).
 * Often FAS-affected children are taken away from their biological parents and put into a foster or adoptive home, and a complete and thorough history is therefore important.
 * For the maternal history, the genetic counsellor should note such things as: documented high blood-alcohol concentration
 * The genetic counsellor should ask what kind of alcohol was consumed, the amount of consumption, and the frequency (Welch-Carre, 2005).
 * The genetic counsellor needs to record the child’s history, such as milestones, growth deficits, or CNS abnormalities (Welch-Carre, 2005).

Definition

 * Fetal alcohol syndrome is a disorder characterized by abnormalities in physical and mental development as a result of prenatal alcohol exposure.

Etiology

 * Fetal alcohol syndrome (FAS) is caused by ethanol and/or its by-products
 * Ethanol is a teratogen that can cross the placenta and interrupt development during any stage of pregnancy.
 * Currently, it is not known whether alcohol is a mutagen affecting the ova or sperm prior to conception
 * Alcohol is now recognized as the most common major teratogen to which a fetus is liable to be exposed
 * 2 alcoholic drinks consumed per day by pregnant women have been shown to result in smaller birth size, while 4-6 drinks consumed per day show additional clinical features; both of the above can result in fetal alcohol effect (FAE)
 * FAE is a condition characterized by some, but not all, of the birth defects associated with FAS.
 * Most of the children believed to have FAS have been born to alcoholic women whose intake of alcohol was 8-10 or more drinks per day (Smith's pg. 555).
 * Although FAS is usually associated with exposure to large amounts of alcohol, this is not always the case.
 * The U.S. Surgeon General's conclusion that zero exposure to alcohol equals zero risk remains the only defensible true statement.

Incidence

 * An accurate incidence rate of FAS has not been established
 * One study suggests approximately 1-3:1,000 live births (Management Of Genetic Syndromes pg.151).

Timing

 * Alcohol exposure during the first trimester is associated with facial dysmorphology
 * Exposure during the second half of pregnancy is associated with growth deficiency
 * The brain appears to be uniquely vulnerable to alcohol
 * Variations in abnormalities are due to dose, frequency, timing of exposure and genetic factors of the mother and fetus.
 * The brain appears to be most vulnerable during the first trimester but can be affected throughout gestation.

Clinical Features

 * Pre- and postnatal onset growth deficiency
 * Craniofacial anomalies
 * Mild to moderate microcephaly
 * Short palpebral fissures, ptosis, epicanthal folds
 * Maxillary hypoplasia
 * Short nose
 * Smooth philtrum with thin and smooth upper lip
 * Malformations of the inner ear
 * Skeletal anomalies
 * Joint anomalies, abnormal position and/or function
 * Scoliosis
 * Altered palmer crease patterns
 * Small distal phalanges
 * Small fifth fingernails
 * Clinodactyly of the 4th and 5th fingers
 * Cardiac Anomalies
 * Heart murmur (usually disappears by age 1)
 * VSD- most common heart defect in children with FAS
 * Genitourinary
 * Renal anomalies are reported to occur at an increased frequency
 * Renal hypoplasia or hydronephrosis
 * Occasional abnormalities
 * Cleft lip with or without cleft palate
 * Micrognathia
 * Short or webbed neck
 * 10-20% have cervical vertebral malformations
 * Tetralogy of Fallot
 * Hydrocephalus
 * Strawberry hemangiomata
 * Brain Dysfunction
 * Ethanol exposure leads to structural alterations of the brain resulting in cognitive and behavioral dysfunction
 * Most serious consequence of heavy prenatal alcohol exposure
 * Diminished brain cell number and intelligence
 * Heterotopias (faulty migration) of neurons
 * Measures of brain dysfunction:
 * MR (not present in many)
 * Microcephaly
 * Epilepsy or other hard neurological signs
 * Subtle problems such as clumsiness and difficulties with visual-motor integration
 * Sleep regulation difficulty
 * Clinical features of ADHD
 * Poor inter-social relationships
 * Intelligence
 * The average IQ for patients with FAS is 63, which is considered mild mental retardation. Some patients with FAS have higher intelligence; patients can have a wide range of IQ's, including normal.
 * Developmental delay
 * Fine motor dysfunction
 * Irritability in infancy
 * Irregular patterns of academic achievement:
 * Hyperactivity (ADHD)
 * Poor communication skills
 * Difficulty remembering instructions
 * Irritability
 * Disorganization

Diagnostic Criteria

 * Cardinal features for FAS were established in the late 1970's
 * The condition can be characterized by:
 * A specific facial appearance
 * Evidence of organic brain damage
 * Growth deficiency
 * Alcohol exposure during gestation
 * A problem with the above criteria is the precision of measurement of each component (How many facial characteristics need to be present? How small must the child be?)
 * Overcome this problem with the 4-digit diagnostic code
 * 4 key diagnostic features (see above) are evaluated on a 4 point scale
 * A score of 1 reflects complete absence of the FAS feature and 4 reflecting a strong classic presence of the FAS feature
 * A score of 4444 denotes the most severe form of FAS while 1111 denotes a complete absence of FAS.
 * Scores between 1111 and 4444 represent the broad spectrum of outcome and exposure combinations

Risk Assessment

 * Risk of recurrence varies and is dependent upon the woman's drinking status during future pregnancies.
 * Women who do not drink during pregnancy have a 0% risk of recurrence
 * Women who are chronic alcoholics are at an increased risk of having a child with FAS.
 * Children with FAS have an increased risk of being alcoholics in adulthood.

Differential Diagnosis

 * Glue and solvent sniffing (toluene exposure) throughout pregnancy can produce infants who look strikingly like children with FAS
 * Seizure medications such as phenobarbital, valproic acid, and hydantoin can result in facial anomalies and organic brain damage

Management and Treatment

 * Carefully monitor growth by plotting on a growth curve
 * Children with FAS can be born as a SGA infant
 * Or birth size can be normal and fall below the growth curve during the 1st 12-18 months of life
 * Psychological and psychiatric assessments including a developmental evaluation (medication can be prescribed as necessary)
 * Family therapy
 * Special education in a variety of categories
 * Routine ophthalmologic evaluations
 * Routine audiological evaluations
 * Cardiovascular clinical evaluation at time of diagnosis
 * Renal ultrasounds (if patient has had a UTI or enuresis after age 8)
 * Clinical evaluation for spinal curvature
 * Implementing coping strategies in the home/classroom
 * Maintain a structured environment
 * Establish routines
 * Give short and concise instructions
 * Respond consistently to the child's behavior
 * Acknowledge the child's successes EVERY DAY
 * Redirect unacceptable behavior
 * Be patient
 * REPEAT…REPEAT….REPEAT

Psychosocial Issues

 * Biological mothers are often alcohol abusers and have a variety of health problems of their own.
 * One study shows that 50% of these mothers are missing or dead within 5 years of the birth.
 * 50% of children with FAS are in foster or adoptive care
 * Generally the reasons for final separation from the biological parent(s) were abuse and neglect.
 * This movement from home to home compounded by abuse and neglect usually has a profound effect on the child and his/her behavior.

Support Groups

 * Fetal Alcohol Syndrome Family Support Group
 * C/O Cardinal Hill of Northern Kentucky
 * 212 Levassor Avenue
 * Covington, Kentucky 41014
 * (859) 491-1171


text: Wikibooks:Computing department

title: Wikibooks:Computing department


text:
Cookbook talk:Cuisine of Nepal

well, first we would need to discuss the variety of cultures in nepal and their particular specialties. do buddhists have different tastes than hindus?--69.171.35.198 23:57, 4 December 2005 (UTC)

Local differences need amplification.
The main article seems to be written from a tourist perspective that is ignorant of the various cultural practices.

Although Kathmandu is in the "Middle Hills" between the high Himalaya and north of a conspicuous range of southern foothills called the Mahabharat Range, its indigenous cuisine is atypical of that region for several reasons. The Royal Family and the Ranas who once governed Nepal have northern Indian affinities, so meat-rich dishes with Moghul influences are much more common around Kathmandu than elsewhere in the Middle Hills. Secondly, the Kathmandu Valley is home to the Newar nationality, whose blend of Buddhist and Hindu practices are somewhat ideosyncratic. Newars freely eat meat from water buffalo, however strict Hindus find this objectionable because buffalo are cousins to cattle, whose meat is taboo.

In other parts of the Middle Hills, upper caste Hindus eat meat only occasionally. Meals are usually "dal-bhat-tarkari" - spicy lentil soup poured over boiled rice and accompanied with curried vegetables. Since wheat is grown as a cool season crop, chapatis may partly replace boiled rice. Vegetables are abundant during the summer monsoon, then become scarce during the cool winter and hot, dry spring months.

Lower caste groups are freer to eat pork and chicken. Beef is strictly limited to untouchables who are allowed to scavenge the corpses of animals that have died of natural causes. Indigenous ethnic groups living at higher elevations than rice-growing Hindus grow subtropical and temperate fruits and vegetables. These groups may seasonally move substantial herds of sheep, goats and cattle between lowlands in the winter and subalpine pastures in summer. Their diets are richer in vegetables and animal protein and may include pork unless Hindus live nearby. Fields above 1,500 meters are often better suited to growing maize, millet or barley than rice, although rice is usually preferred for its greater palatability.

Outside cosmopolitan Kathmandu where so many dietary traditions overlap, Tibetan food with its emphasis on potatoes, cold-tolerant grains such as barley and millet, and yak or buffalo meat is mainly confined to the northern, higher regions.

South of the Mahabharat Range where the Middle Hills give way to lowlands a fully tropical climate supports a greater variety of fruits and vegatables. Cultural practices and cuisine have more in common with northern India. Among Hindus there is a greater range of castes, particularly castes below the highest "bahun" (brahman) and "chhetri" (Kshatriya) levels that are numerically predominant in the "Hills". 76.80.9.100 11:28, 22 April 2007 (UTC)

title: Cookbook talk:Cuisine of Nepal


text:
Handbook of Genetic Counseling/Fetal Hydantoin Syndrome

Fetal Hydantoin Syndrome

Etiology

 * Prenatal hydantoin (dilantin, phenytoin) exposure

History/Epidemiology

 * Phenytoin= anticonvulsant first introduced in1938.
 * Teratogenic effects were first recognized in 1964.
 * Numerous studies have demonstrated increased risk for congenital defects, both major and minor.
 * Study conducted from 1985-1992
 * 332 newborns exposed to phenytoin (hydantoin, dilantin) during the 1st trimester
 * A total of 15 (4.5%) had major birth defects, including:
 * Cardiovascular
 * Spina bifida
 * Hypospadias

Clinical Features

 * Craniofacies:
 * Broad nasal bridge, wide anterior fontanelle, low hairline, broad alveolar ridge, short neck, hypertelorism, microcephaly, cleft lip/palate, low set ears, epicanthal folds, ptosis, coloboma, coarse scalp hair.
 * Limbs:
 * Small or absent nails, hypoplasia of distal phalanges, altered palmar crease, digital thumb, dislocated hip
 * Growth:
 * Mild to moderate growth deficiency, usually prenatal in onset
 * Performance:
 * Occasional borderline to mild mental deficiency. Performance in childhood is usually better than that predicted in infancy
 * Cardiovascular (occasional abnormalities):
 * Aortic valvular stenosis, coarctation of aorta, PDA, septal defects
 * GI (occasional abnormalities):
 * Pyloric stenosis, duodenal atresia, anal atresia
 * Other (occasional):
 * Small nipples that are widely spaced, umbilical and inguinal hernia.

Risks

 * Risks of delivering a child with congenital defects is 2-3x greater for women taking dilantin than for the general population.
 * Increased risk could be caused by epilepsy, the drugs, or a combination of the two. It is thought that the drugs are the causative factor.
 * Risks of child having full syndrome is about 10% and the risk for having some of the effects of the disorder is an additional 33%
 * Some reports have shown that phenytoin is a transplacental carcinogen. Tumors were reported to occur after in utero exposure to phenytoin in a few cases.
 * Phenytoin may induce folic acid deficiency in the epileptic patient by impairing GI absorption or by increasing hepatic metabolism. Therefore, the risk for having a baby with a spinal abnormality is increased.
 * Some risk of early hemorrhagic disease of the newborn. Occurs during the 1st 24 hours after birth and can be fatal. Exact mechanism: unknown. Drug is thought to deplete already low levels of fetal vitamin K therefore suppressing the vitamin K-dependent coagulation factors II, VII, IX, and X. Proposed treatment regimen: taking oral vitamin K during last 2 months of pregnancy, C section if difficult labor or trauma is suspected, administering intravenous vitamin K to the newborn in the delivery room (this regimen hasn't been tested in clinical controlled trials, but are logical).
 * Risk of not taking phenytoin: pregnant patient can have seizures and can cause the baby to have fetal hypoxia.

Breast Feeding

 * Phenytoin is excreted into breast milk. Milk:plasma ratios range from 0.18 to 0.54.
 * Little risk to the infant if maternal levels are kept in the therapeutic range
 * Drowsiness and decreased sucking were observed in one infant, no other adverse effects have been reported.
 * The American Academy of Pediatrics considers phenytoin to be compatible with breast feeding.


text:
Handbook of Genetic Counseling/Fetal Dilantin-Keppra Syndrome

Fetal Dilantin/Keppra Syndrome

Contracting

 * Introductions and small talk
 * Acknowledge recent hospitalization
 * Confirm referring physician
 * Assess understanding of the reason for the referral to genetics
 * How much information has your OB given you about the possible effects of taking dilantin/ keppra while pregnant?
 * Despite the increased risk of problems, there is a greater than 90% chance that the baby will be just fine.
 * What concerns or questions do you have that you would like to discuss today?
 * Outline session agenda
 * Medical and family history questions
 * Some of the possible effects that anticonvulsants can have on the pregnancy.
 * Options available to you
 * Discussion of concerns and questions

Elicit Medical History

 * Pregnancy/neonatal history:
 * LMP: __________
 * EDC: __________
 * Today's gestational age: __________
 * Have you had an ultrasound?
 * Date of ultrasound: __________
 * Results of ultrasound: __________
 * How has the pregnancy been going so far?
 * Seizures last week….any others
 * What medications are you taking? Dilantin and Kepra
 * Amount and frequency of each. When did you start taking each?
 * When did you begin having seizures?
 * What type of seizures do you typically have?
 * Any complications other than the seizures? Infections, colds, exposures etc. (Review and confirm information from the intake form at Bethesda)

Elicit Family History
(3 generations)
 * Anyone with seizure disorders?
 * Anyone had: multiple SAB, SB, early deaths or babies that required surgery as infants?
 * Anyone born with: birth defects or mental retardation
 * Has anyone had early cancers (dx. <50) or chronic illnesses (heart disease, diabetes)

Discuss possible side effects of taking anticonvulsants during pregnancy

 * Stress importance of taking medicines- to keep you healthy and therefore the baby healthy
 * Although it's very important for you to take these medications, sometimes seizure medications can have some effects on a developing baby.
 * All pregnancies are at a 3-5% risk of birth defects and mental retardation
 * Women who take anticonvulsants are at a 2-3x increased risk for some specific problems.
 * This doesn't mean that the baby will be born with a problem, it just means that we know that based on your special circumstances, your pregnancy is at an increased risk.
 * Some of the things that we sometimes see in children who have been exposed to dilantin during pregnancy include:
 * Subtle changes in the face..such as the shape of the eyes and nose. These are usually such subtle features that you might not even recognize them
 * Sometimes we see changes in the length of the fingers (slightly shortened) and the size of the fingernails (tiny)
 * But sometimes children can be born with more apparent changes such as a cleft lip/palate or an open spine.
 * Occasionally we see kids who have some delays in development ranging from borderline normal intelligence to mild mental retardation.
 * There is a small risk of other birth defects dealing with the heart and intestinal tract.
 * Keppra: this anticonvulsant hasn't been well studied but we do know that anticonvulsants in general have been associated with an increased risk of birth defects.
 * Some children who have been exposed to anticonvulsants during pregnancy have several of these features and some have none. Just based on your history I can't tell you whether or not your baby will have some or none of these features, but we do have some options that we can offer you.

Options

 * Level II ultrasound- high resolution to look at the anatomy. ~16 weeks is a good time, but (20+ is ideal).
 * High resolution u/s
 * Done by an experienced technician
 * Better to see more of the developing organs in greater detail
 * Will be looking closely at the features of the baby….spine, heart, brain, shape of the head to make sure that these organs/tissues formed correctly.
 * U/S is good to make us suspicious of some birth defects but it can't tell us everything. We won't know if there is mental deficiency by u/s. Also, u/s is dependent upon cooperation of the baby. Sometimes we just can't get a great view and may not be able to see everything we are looking for.
 * However, a normal ultrasound would certainly be reassuring.

Psychosocial Assessment

 * Who is living in your home?
 * How are the childcare needs being met?
 * Plans for additional children?
 * Do you have any financial concerns?

Follow-up

 * Questions?
 * Registry for patients taking anticonvulsants…
 * Do you plan to breast feed the baby? Dilantin is compatible with breast feeding.


text:
Handbook of Genetic Counseling/Fetal Valproate Syndrome

Fetal Valproate Syndrome

Valproic Acid and Antiepileptic Drugs During Pregnancy
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Fact Sheet

 * valproate is chemical present in depakote (commonly used to treat seizures or bipolar)
 * Valproate can negatively affect fetal growth and development, but is still used during pregnancy because maternal seizures can be dangerous to both mom and baby
 * Valproate crosses the placenta and dose fetus is exposed to may be higher than maternal dose
 * Valproic acid was released in 1967 in Europe and in 1978 in the United States to treat epilepsy
 * Epilepsy affects approximately 1 % of the population, and an estimated 1.1 million women in the United States with epilepsy are in the childbearing age range
 * Approximately 11,500 epileptic women become pregnant each year, many of which use valproic acid
 * One in two hundred pregnant women is epileptic
 * By 1980, publications began linking malformed children to in utero exposure to valproic acid (greater than 500 mg/day)

Adverse Outcomes

 * While risks have not been established for all of the various outcomes there is data for many.
 * stillbirth rates 1.3 - 14 % (ref 3)
 * perinatal mortality 1.4 - 7.8 %. (ref 3)
 * Congenital anomalies in babies born to mothers with epilepsy is estimated to be 2-3X's higher than general population (ref 1 and 2)which would mean about 6-15% others estimate below 10% (ref 3)
 * Some studies report association with autism and speech and language difficulties
 * Learning difficulties and mental retardation in approximately 29% of those with fetal valproate syndrome (ref 1)
 * malformations most likely related to first trimester exposure in a dose dependent fashion
 * Some of these adverse outcomes are associated with early first trimester phenomena (congenital malformations), others such as developmental delay are more likely to be associated with an exposure of greater duration, or during the third trimester.
 * Causal relationship of cleft lip and palate with valproic acid has not been established, but it has been associated with most anticonvulsants (p. 1093v) HOWEVER, in the study below they found 3 cases of cleft palate rate of 4% or 40 X's that in general population. In contrast to various studies that report no association. (ref 1)
 * A total of 69 cases that were solely exposed to VPA with adequate phenotypic description were identified.
 * The clinical manifestations of FVS encompass a wide spectrum of abnormalities: consistent facial phenotype, multiple systemic and orthopedic involvement, central nervous system dysfunction, and altered physical growth.
 * Twelve percent of affected children died in infancy and 29% of surviving patients had developmental deficits/mental retardation.
 * 30% had minor skin anomalies most common were hemangiomas and nipple abnormalities
 * respiratory tract abnormalities seen in 16% of patients (tracheomalacia was most common and etiology is unknown, but frequently seen with TEF)

Characteristic Features

 * In humans, VPA has been associated with an increased frequency of congenital malformations
 * VPA use during gestation has been associated with an increase risk of spina bifida. Several human studies have suggested that use of VPA during pregnancy increases the risk of neural tube defects (NTD) 20-40X, to approximately 1-2%, as compared to the general population risk of 0.05% (comparable to that of a woman who has a previous child with a NTD)
 * midfacial hypoplasia (flat nasal bridge with a broad base)
 * distinctive facial appearance
 * deficient orbital ridge
 * inferior epicanthal folds
 * anteverted nostrils
 * shallow philtrum
 * thin upper lip with a thick lower lip
 * prominent forehead
 * long thin overlapping fingers and toes, and hyper-convex nails have also been described
 * congenital heart disease
 * decreased postnatal growth.
 * increased risk of radial limb reduction defects and hypospadias in male fetuses
 * However, it is important to point out that several of the mothers in the studies were on multiple medications and it is difficult to assign causal effect as a result
 * proposed mechanism of action is that valproic acid influences folate metabolism, thereby altering the closure of the spinal column resulting in spina bifida

Review of the Literature
(1978-2000) (ref 1)
 * A total of 69 cases that were solely exposed to VPA with adequate phenotypic description were identified.
 * The clinical manifestations of FVS encompass a wide spectrum of abnormalities: consistent facial phenotype, multiple systemic and orthopedic involvement, central nervous system dysfunction, and altered physical growth.
 * The facial appearance is characterized by a small broad nose, small ears, flat philtrum, a long upper lip with shallow philtrum, and micro/retrognathia.
 * In this review, 62% of the patients had musculoskeletal abnormalities, 30% had minor skin defects, 26% had cardiovascular abnormalities, 22% had genital abnormalities, and 16% had pulmonary abnormalities.
 * Less frequently encountered abnormalities included brain, eye, kidney, and hearing defects.
 * Neural tube defects were seen in 3% of the sample.
 * Twelve percent of affected children died in infancy and 29% of surviving patients had developmental deficits/mental retardation.
 * Although 15% of patients had growth retardation, an overgrowth pattern was seen in 9%.

Risk Assessment for Seizures and Schizophrenia

 * Risk of children having epilepsy based on moms history is about 4% (Practical Genetic Counseling 4th edition 1993)
 * Risk of Schizophrenia 3-5% (from same source as above risk)

Other Antiepleptic Drugs (AED)
(and effects during pregnancy) (Taken primarily from information contained in a website by ©1998 Dr. Mark Yerby, North Pacific Epilepsy Research. ) six clinical AED syndromes have been reported in the medical literature
 * Fetal Trimethadione Syndrome
 * Children exposed to this drug in utero were more likely to be short in stature, microcephalic, have V-shaped eyebrows, epicanthal folds, low set ears, anteriorally folded helices, and irregular teeth. Inguinal hernias, hypospadias, and simian creases were also frequently observed.
 * A retrospective study of trimethadiaone exposures in 53 pregnancies revealed fetal loss or major malformations in 87 % of the pregnancies (Feldman et al. 1977).
 * Follow-up studies have reported significant rates of mental retardation among the exposed infants (Goldman et al. 1986).
 * Trimethadione, introduced in the 1940's for the treatment of absence epilepsy, has been largely supplanted by less toxic-more effective compounds and is seldom used in the treatment of epilepsy.
 * Fetal Hydantoin Syndrome (FHS)
 * Among the many dysmorphic findings associated with this syndrome, hypoplasia and irregular ossification of the distal phalanges was originally believed to be the single most characteristic feature.
 * Of the five children described by Hanson and Smith, only one was exposed to phenytoin monotherapy. The infants displayed facial dysmorphism including: epicanthal folds, hypertelorism, broad flat nasal bridges, an upturned nasal tip, wide prominent lips, and in addition distal digital hypoplasia (DDH), intrauterine growth retardation and mental retardation.
 * Subsequently, Hanson et al. (1976), reported a prevalence of FHS of 11%, with an additional 30% of the in utero exposed children expressing some of the syndrome's features.
 * He also suggested that these children are at greater risk for the development of neural crest tumors, although subsequent prospective studies have failed to verify this initial observation.
 * A prospective study from the University of Helsinki, examined 121 infants of mothers with epilepsy, 82 exposed to phenytoin, found no cases of FHS.
 * Hypertelorism and distal digital hypoplasia were the only dysmorphic features associated with phenytoin exposure in this study (Gaily et al. 1988).
 * As with the Fetal Alcohol Syndrome, it is now common nomenclature to consider children presenting with a more limited pattern of anomalies secondary to in utero hydantoin exposure to be expressing Fetal Hydantoin Effects (FHE; Hanson, 1986).
 * Primidone Embryopathy
 * Affected children present with hirsute foreheads, thick nasal roots, anteverted nostrils, long philtrums, straight thin upper lips, and DDH. These children tend to be small for dates, have an increased risk for psychomotor retardation and heart defects (Rudd and Freedom 1979, Gustavson and Chen 1985).
 * A case report of a family in whom all 4 siblings had clinical features of the FHE demonstrates the complexity involved in evaluating affected children.
 * The first 2 children in this family were exposed to both phenytoin and primidone in utero. In an attempt to prevent dysmorphism in subsequent pregnancies, the phenytoin was discontinued.
 * Unfortunately, the third and fourth children had the same dysmorphic features as their elder siblings having been exposed to primidone monotherapy (Krauss et al. 1984).
 * phenobarbital
 * facial dysmorphism, pre- and post-natal growth deficiency, developmental delay, and minor anomalies
 * clinical features were similar to those seen with in utero exposure to both phenytoin and alcohol, hence the author felt that it should not be classified as a separate syndrome (Seip 1976).
 * He also noted that all three of these compounds can result in folate deficiency and hypothesized that such a deficiency could be the common mechanism for the dysmorphism seen with such in utero teratogen exposures.
 * valproic acid embryopathy (see above information)
 * Fetal Carbamazepine Syndrome
 * described by a single group of investigators (Jones et al. 1989)
 * Dysmorphic features include: up slanting palpebral fissures, epicanthal folds, short nose, long philtrum, DDH and microcephaly. Developmental delay was also found in 20 % of exposed children, although the authors used one standard deviation from the mean as the cut-off for abnormality, rather than the customary two standard deviations.
 * Applying the conventional definitions to their data, eliminates any increased risk for developmental delay in the carbamazepine exposed children.
 * Reduction in fetal head circumference has been reported in carbamazepine exposed children (Hiilesmaa et al. 1981). Although smaller than controls, the head sizes were still within the normal range and the differences between the IME and controls disappeared as the children matured.

Difficulty Determining Risks

 * clinicians are uncertain how much of the adverse outcome difficulty is secondary to AED, maternal seizures, or simply the genetics of having epilepsy
 * In one large study, The Teratogenicity of Anticonvulsant Drugs. N Engl J Med 2001; 344: 1 132-8 (April 12) showed that women with seizures who were not on AED's were not at an increased risk of having children with birth defects while those that were treated with AED's were at a significant increased risk (However, possible confounding because women not treated with meds are likely to have less severe seizure disorder)
 * Controversy remains regarding the causes of the increased risk of adverse outcomes of pregnancy. AED are suspected of contributing to an increase in the risk of congenital malformations and dysmorphic features. Yet increased generalized convulsive seizures are associated with premature labor and fetal death.
 * Facial dysmorphism can be difficult to quantify and is certainly not specific to any one anticonvulsant drug. Infants of epileptic mothers with similar dysmorphic features have been described in the pre-anticonvulsant era (Baptisti 1938, Philbert and Dam 1982).
 * The long-term outcome and significance of these anomalies remain unclear
 * In those few cases which have been followed into early childhood, the dysmorphic features tend to disappear as the child grows older in some, but not all instances (Janz 1982)


text:
Talk:The Unicyclopedia/BC wheel

Is there actually a difference between the Skate Mount and what I decided to call the "Free Mount"? I'm the only BC-er I've ever met so I don't have much terminology to go on. Mark Williamson 03:04, 5 December 2005 (UTC)

title: Talk:The Unicyclopedia/BC wheel


text:
Handbook of Genetic Counseling/FG Syndrome

FG Syndrome

Introduction and Contracting

 * Can you explain to me in your own words why you were referred to genetics?
 * What questions if any do you have for us today
 * What are your main concerns at this time
 * Outline the session and what will occur
 * Medical and developmental history
 * Family history (pedigree)
 * Dr. will physically examine him
 * We will explain any conclusions if any that we have reached and discuss what we think might be the explanation for the concerns and problems

Pedigree

 * Basic 3 generation pedigree unless specific findings come up and may need explore maternal side further due to X-linked pattern of FG syndrome
 * birth defects
 * pregnancy loss
 * poor muscle tone
 * chronic constipation
 * hearing loss
 * vision problems
 * kidney problems
 * problems with the digestive tract
 * other chronic health problems
 * mental retardation of learning difficulties
 * large head size
 * broad thumbs and toes
 * fingernails that grow over tips of fingers
 * behavioral problems

Overview of FG

 * X-linked recessive condition
 * First described 1974 by Drs. John M. Opitz and Elizabeth G. Kaveggia
 * Named after initials of first patients described
 * Multiple congenital anomaly/mental retardation syndrome
 * Characterized by MR, macrocephaly, congenital hypotonia, macrocephaly, facial dysmorphism and anomalies of the digestive tract
 * No features are pathognomonic

FG syndrome physical characteristics

 * prenatal oligohydrammios
 * High degree of variability of physical features
 * Hypotonia with joint hyperlaxity evolves into spasticity with joint contractures later in life
 * chronic constipation is a distinctive major finding in FG (usually resolves during mid-childhood)
 * hearing loss
 * vision problems
 * genital abnormalities (cryporchidism)
 * respiratory problems
 * congenital heart defects uncommon but include hypoplastic left heart, small VSD; VSD and mitral and aortic valve defect (Opitz, 1988)
 * agenesis of the corpus collosum
 * anteriorly positioned or imperforate anus
 * kidney problems
 * large head
 * broad thumbs and toes
 * characteristic fingerprint patterns
 * webbed fingers and toes
 * skeletal defects (occasionally including craniosynostosis and scoliosis)
 * sacral pit
 * tethered cord and Chiari I malformations
 * wide set eyes
 * broad nasal bridge
 * low set simple ears that are small, rounded, and protruding
 * thin upper lip and fuller lower lip
 * cowlicks and a widow's peak hairline

Developmental and behavioral features of FG syndrome

 * delayed acquisition of speech and motor skills
 * Individuals with FG Syndrome tend to be outgoing, talkative, and crave lots of attention
 * May be easily frustrated and are prone to temper tantrums
 * Hyperactivity and impulsiveness have been reported
 * Most function in mild to moderate range of MR other reports state it is usually severe MR
 * Some clinicians feel MR is universal finding in FG, but others feel there is a wide range of cognitive ability and some are in normal range
 * Often language skills are underdeveloped
 * "Autistic-like" behaviors have been discussed. This may be due to a common trait of the FG Syndrome--- sensory integrative dysfunction. However, they are not believed to be autistic
 * Frequent fascinations with mechanical objects and toys, tendency to self-absorption

Life expectancy

 * Death during infancy as high as 1/3 of patients due to bronchopulmonary problems and/or heart defects
 * "Once they survived infancy death is rare"

Genetics

 * presumably due to mutations on the X chromosome
 * presumed to cause disruption in the development of the fetus
 * X-linked recessive
 * Heterogeneous condition
 * mapped one gene (FGS1) to Xq13 (Briault et al.) in some families using linkage analysis
 * evidence for another gene locus (FGS2) at Xq28 or Xq11q12 based on fact these are breakpoints of an inversion that segregate with FG phenotype (Briault et al., 2000)
 * Dr. Opitz lists a potential third gene (FGS3) at Xp22.3 (Opitz, Sep, 2001)
 * 9 candidate genes excluded in three families (A Lossi, A Fatima, S Briault, C Moraine, C Schwartz, 2000)

Diagnosis

 * Clinical diagnosis
 * No molecular testing available (Opitz, 2001)
 * Diagnosis based on clustering of symptoms with no symptom being pathognomonic
 * Some believe it is not uncommon and may account for many cases of unexplained X-linked MR

Genetic Testing

 * Linkage analysis is possible in large families with multiple affected family members
 * Prenatal testing and carrier testing only possible through such linkage analysis described above

Differential Diagnosis

 * Fragile X syndrome
 * shares feature of protruding ears and X-linked MR as well as behaviors that are sometimes described by people as "autistic like"
 * ATR-X syndrome (X-linked alpha thalassemia, mental retardation)
 * have severe MR, congenital hypotonia, genital abmormalities and a small head
 * differs from FG because those with FG have macrocephaly, friendly personality and hyperactivity
 * Williams syndrome
 * shares personality and behavioral features with FG
 * different in that there is presence of "salient anxiety and internalizing symptoms in WS"
 * G/BBB syndrome (Opitz syndrome)
 * Considerable overlap in features of G/BBB and FG syndromes
 * Features that are shared with FG include: sensorineural dysfunction, behavioral problems, imperforate anus, hypoplasia or agenesis of the corpus callosum, kidney abnormalities, cryptorchidism, heart (cardiac) defects, and mental retardation.
 * One form of G/BBB syndrome is inherited in X-linked recessive fashion and is due to mutations in MID1 gene
 * Other symptoms of G/BBB include; dysphagia, cleft palate and or cleft lip (which are not usually seen in FG). Pulmonary agenesis or hypoplasia and tetralogy of Fallot have been seen only in the G/BBB syndrome so far.

Web info

 * http://www.gle.egsd.k12.co.us/opitz/opitznord.html -- (information about Opitz G/BBB syndrome)
 * Opitz JM, FG syndrome. Orphanet encyclopedia, September 2001: http://orphanet.infobiogen.fr/data/patho/GB/uk-FG.html
 * http://www.fg-syndrome.org (FG Syndrome Family Alliance web site)
 * This site seems to be biased towards the opinions of Dr. Opitz which are not shared by all medical professionals.


text:
Handbook of Genetic Counseling/FG Syndrome-2

FG syndrome

Introduction

 * Myself, GC, Doc
 * What are they expecting today? What concerns do they have?

Contracting

 * Medical Hx/Pregnancy Hx
 * Family Hx
 * Physical Exam
 * Suggestions for testing/diagnosis
 * Answer any questions

Medical History

 * Hearing test?
 * Developmental milestones
 * Behavior issues, when did they start? How severe? Examples?
 * Has he always been floppy?
 * Constipated?

Family Hx

 * Birth defects, MR, cancer at early age, genetic conditions

F-G syndrome

 * Other names: Opitz-Kaveggia syndrome
 * Definition: X-linked condition with the following characteristics
 * Characteristics
 * MR
 * Hypotonia from birth
 * Seizures
 * Large head
 * Cowlick of frontal hairline
 * Hypertelorism
 * Sensorineural deafness
 * Short stature
 * Imperforate anus
 * Constipation
 * Congenital heart defects
 * Broad first toes
 * Attention-seeking behaviors
 * Genetics
 * X-linked recessive
 * Diagnosis
 * clinical

Resources

 * FG syndrome Family Alliancee
 * www.geocities.com/HotSprings/Spa/3687/index.html

 * FAQ's about FG syndrome


text:
Handbook of Genetic Counseling/First Trimester Screening

First Trimester Screening

Overview

 * Screen low-risk population to identify those at higher risk to give birth to child with a chromosome abnormality
 * Normal result does not mean that there are no abnormalities
 * Abnormal result indicates that diagnostic testing by amniocentesis or CVS is warranted
 * Consists of ultrasound and blood test
 * Performed between 10th and 14th week of pregnancy

Procedure

 * Biochemical screening
 * Blood draw done by finger stick onto filter paper
 * May be taken between 8 weeks, 4 days and 13 weeks, 3 days
 * Measures levels of substances found in the blood of all pregnant women
 * FreeBeta Human chorionic gonadotropin (hCG) measurements
 * Glycoprotein derived from the placenta
 * Serum levels tend to be high in patients carrying a fetus affected with Down Syndrome (average = 1.9 MoM)
 * Serum levels significantly reduced in patients carrying a fetus affected with Trisomy 18 (average = 0.18 MoM)
 * Pregnancy Associated Plasma Protein A (PAPP-A)
 * Produced by trophoblast of placenta
 * Significantly reduced in blood of women carrying fetuses with Down Syndrome (average = 0.44 MoM)
 * Significantly reduced in blood of women carrying fetuses with Trisomy 18 (average = 0.32 MoM)
 * Ultrasonagraphic findings
 * Measure nuchal translucency (NT)
 * Amount of fluid that accumulates behind the neck of the baby
 * Echo-free space between skin and soft tissue overlying cervical spine
 * Present only during first trimester
 * About 30-86% of fetuses with increased nuchal translucency have chromosomal abnormality
 * Increased in fetuses with chromosome abnormalities, cardiac defects, and certain genetic syndromes
 * Greater than 3.5 mm is considered out of normal range
 * Increased NT is not diagnostic of chromosome abnormality
 * Lymphedema seen in NT may be result of fetal cardiac abnormalities
 * Usually resolves in second trimester
 * No consensus on how to measure nuchal translucency resulting in conflicting results about effectiveness
 * Measured transbdominally in 95% of cases and transvaginally in other 5%
 * Procedure takes between 15 and 30 minutes

Detection Rate

 * Biochemical screening without NT
 * Identifies greater than 60% of Down Syndrome
 * Identifies 90% of Trisomy 18
 * About 1 in 25 women with an increased risk based on screening will have baby with Down Syndrome
 * Biochemical screening with NT
 * Identifies about 90% of Down Syndrome
 * Identifies up to 97% of Trisomy 18
 * False positive rate is 5%
 * About 1 in 17 women with an increased risk based on screening will have baby with Down Syndrome
 * Cannot screen for open neural tube defects so AFP testing still recommended in 2nd trimester
 * Cannot identify all birth defects

Benefits and Limitations of Testing

 * Benefits
 * Helps reduce maternal anxiety at earlier gestational age
 * Allows patient to have CVS for diagnosis in 1st trimester
 * Allows for 1st trimester termination of affected fetus
 * Not an invasive procedure - no risk to mother or to fetus
 * Limitations
 * Currently not covered by insurance
 * Only screens for two out of possible thousands of genetic conditions
 * Screening will miss about 10% of Down Syndrome
 * Still requires invasive procedure for diagnosis
 * Not as sensitive if multiple pregnancies
 * Patient specific risks rely on accuracy of clinical information that is interpreted for results of test

Research Study at Magee-Womens Hospital

 * Eligibility criteria: women 18-45 between 10 and 14 weeks
 * To determine if first trimester screening is an effective method to detect Down Syndrome and other chromosome abnormalities
 * If risk higher than 1 in 270, can continue routine prenatal care, undergo CVS at 10-13 weeks, or have amniocentesis after 15 weeks
 * Women who choose to participate must provide information on pregnancy outcome
 * Responsible for all costs, including blood sample, ultrasound, and genetic counseling


text:
Handbook of Genetic Counseling/Fragile X Syndrome

'''NOTE: This has not been reviewed since 2002 and many new discoveries have been made in that time. This handbook needs a full review for errors.''' Cited text is new as of Jan. 7, 2022.

General Information about Fragile X syndrome

 * Most common form of genetically inherited mental impairment.
 * It is inherited in a non-standard X-linked fashion (gene clinics states it is X-linked dominant other sources refer to it as X-linked recessive)
 * FMR1 gene on X chromosome at Xq27.3 was sequenced in 1991
 * It makes the protein FMRP (fragile X mental retardation protein). There is evidence that FMRP plays a role in regulating protein synthesis.
 * The number of CGG repeats in the FMR1 gene determines whether someone is classified as normal, intermediate, premutation, or full mutation (fragile x syndrome) :
 * Normal 5–44 repeats is typical (gene is active and not methylated)
 * Intermediate 45–54 repeats: People with intermediate repeats do not have fragile x syndrome and are not at risk for having children with fragile x syndrome. They may have a slightly higher chance of having some symptoms related to other fragile X-associated disorders (fragile x-associated tremor/ataxia syndrome, fragile x-associated primary ovarian insufficiency) and may pass the slightly higher chance of having these disorders to their children.
 * Premutation 55–200 (gene is not usually methylated) males and females usually unaffected
 * Full mutation >200: People with a full mutation have fragile x syndrome (gene is usually fully methylated and therefore inactive)

Genotype-Phenotype Correlations
Premutation Full mutation
 * The phenotype of males with an FMR1 mutation is almost entirely dependent on the nature of the mutation; the phenotype of females with an FMR1 mutation is dependent on both the nature of the FMR1 mutation and random X-chromosome inactivation
 * Males and females who have a fragile X premutation have normal intellect and appearance.
 * There have been multiple reports of individuals with a premutation and typically subtle intellectual or behavioral symptoms.
 * Males who have a full fragile X mutation generally have moderate to severe intellectual disability (average IQ of 41) and may or may not have a distinctive appearance.
 * About 50% of females who have a full fragile X mutation have intellectual disability; however, they are usually less severely affected than males with a full mutation. (Some sources quote 1/3 or 33% they are usually older references)
 * Conversely, about 50% of females who are heterozygous for the full mutation are intellectually normal. This variability among females is believed to result from the distribution of X chromosome inactivation ratios in the brain. (Some sources quote 2/3 or 66%)

Repeat size mosaicism

 * Although some data suggest that individuals with mosaicism perform at a higher intellectual level than individuals with completely methylated full mutations, these individuals have mild to severe intellectual disability. (Average IQ 60)
 * Rarely, patients with methylation mosaicism or completely unmethylated full mutations and normal intellect have been reported
 * Mosaicism is present in about 15% to 20% of individuals with FMR1 mutations.
 * Presumably these individuals produce at least some FMR1 protein because the FMR1 gene is unmethylated.
 * The existence of these exceptional patients suggests that repeat expansion and methylation of the gene are not absolutely coupled.

Risks of expansion

 * Factors influencing likelihood of expansion include:
 * Gender -- expansion nearly always occurs in female meiosis
 * Women with the premutation may pass fragile X to their offspring due to genetic anticipation (when egg is made # of repeats increases and expansion occurs).
 * Males with the premutation will pass this premutation to their daughters without it expanding to a full mutation in the process. However, expansion can occur in her offspring and can therefore lead to affected grandchildren.
 * Size of repeat: the larger the repeat, the more likely it is to expand
 * Presence of AGG interruptions --Sequences of uninterrupted CGG repeats are at higher risk to be expanded-explains why alleles with same CGG copy number have different risks for instability

 * Taken from
 * Unlike classical X-linked dominant disorders where all females with a mutation are affected, only about 50% of females with a full mutation have intellectual disability. This variability in phenotype is likely to be related to variability in X chromosome inactivation, a phenomenon independent of FMR1 mutations.

Characteristics
Physical Characteristics:
 * Males are more likely to exhibit the characteristics of fragile X because they have only one X chromosome. However, females may also exhibit a few of these characteristics.
 * Physical features may be quite subtle and people with fragile X may be normal in appearance
 * See chart below for common physical features in males (From Fragile X Syndrome Diagnosis, Treatment, and Research)
 * Females share some of the same features

Cognitive Characteristics

 * Majority of boys (80%) and 50% of girls have mild to moderate intellectual disability (IQ below 70). Other girls may show signs of specific learning difficulties such as in math.
 * Common problems include delayed milestones (speech and language delays are common in males, but less common in females)

Behavioral Characteristics

 * Behavior ranges from socially engaging and friendly to autistic-like and occasionally aggressive.
 * They may display some or all of the behavioral characteristics in the chart on the side
 * Behaviors also include short attention span and they are often initially diagnosed as ADHD (often treated with adderall, or clonidine)
 * They may also have difficulty adjusting to change.
 * Obsessive compulsive behavior is quite common (preservative or repetitive behavior) this may improve with SSRI's
 * Psychosis may occur and is often precipitated by aging or severe stress

Medical Concerns

 * Table from Fragile X Syndrome Diagnosis, Treatment, Research

Treatment/Therapy/Prevention/Anticipatory guidance

 * Currently, there is no specific treatment for Fragile X. Therapy tends to focus on the behavioral and learning issues that are often associated with Fragile X Syndrome. These may include:
 * Behavioral techniques to manage hyperactivity and temper tantrums
 * Some boys don't sleep for long periods of time and meds can be given for this
 * Medicinal treatment for management of behavioral issues
 * Educational intervention (special classes, etc.)
 * Therapy including: speech therapy, occupational therapy, physical therapy, and sensory integration therapy (to manage sensitivity to sensory input)
 * Therapeutic calming techniques and a regular routine may also help with behavior problems.

Adults with fragile X

 * Hyperactivity tends to improve in adolescents and adults with fragile X
 * Anxiety, (particularly social anxiety) is present and more common in individuals who are not impulsive or hyperactive
 * Anxiety or uncertainty often leads to aggressive outbursts in new situations
 * Treatments for anxiety may help
 * Possibly up to 50% of adult males experience mitral valve prolapse
 * Mild aortic root dilation may also occur
 * Hypertension is relatively common, but may be the result of anxiety.

Testing
Two main DNA testing approaches:
 * PCR-- (size indicates approximate number of repeats present) It is very accurate in sizing normal and premutation alleles. The efficiency is inversely related to number of CGG repeats present Large permutations and mutations difficult to analyze and may fail to yield detectable product. It also does not give information about FMR1 methylation
 * Southern blot analysis - Doesn't allow precise sizing, but accurately detects alleles in all size ranges and estimates size. It also allows methylation status to be assayed.
 * Labs often do both
 * Research based testing available for other mutations in the FMR1 gene

Prenatal testing

 * Possible via both CVS and amniocentesis once genetic status of parents is confirmed.
 * Results from CVS testing must be interpreted with caution because the methylation status of the FMR1 gene is often not yet established in chorionic villi at the time of sampling.
 * CVS may lead to a situation in which follow-up amniocentesis is necessary to resolve an ambiguous result.

Preimplantation genetic diagnosis

 * Expensive and chance of no pregnancy
 * Chance of pregnancy best determined by a reproductive endocrinologist: A woman's age and fertility potential are great determinants of chance of pregnancy with IVF-PGD
 * Only performed at specific centers (needs verification)

Indications for Fragile X screening

 * Individuals of either sex with intellectual disability, developmental delay, or autism, especially if they have any physical or behavioral characteristics of FXS, a family history of FXS, or male/female relatives with an intellectual disability of unknown etiology
 * Any person who has a family member with a diagnosis of fragile X syndrome or a family history of intellectual disability
 * Fetuses of known carrier mothers
 * Patients with cytogenetic fragile X test result that is discordant with their phenotype. These include patients with strong clinical indication and who have had negative or ambiguous cyto test result, and patients with an atypical phenotype with positive cytogenetic test result
 * population screening not recommended at this time (needs verification)

Differential Diagnosis

 * MR, ADHD, autistic like features can be seen in Asperger, FAS, and autism
 * Coffin-Lowery shares features of prominent ears, coarse features
 * Lujan Fryns syndrome - marfanoid habitus and machroorchidism
 * Atkin syndrome - large ears, short stature, machroorchidism
 * Fragile X has been seen in conjunction with chromosomal aneuploidy syndromes

Resources

 * National Fragile X Foundation
 * 1861 International Drive, Suite 200 McLean, VA 22102
 * Phone: (800) 688-8765
 * Email: [mailto:contact@fragilex.com contact@fragilex.com]
 * Web: https://fragilex.org

 * FRAXA Research Foundation
 * Newsletter: FRAXA Research Foundation Newsletter. Subscription through FRAXA
 * 45 Pleasant St
 * Newburyport, MA 01950
 * Phone: 978-462-1866
 * Fax: 978-463-9985
 * Email: info@fraxa.org
 * www.FRAXA.org
 * www.yourgenesyourhealth.org/ygyh/ (site with great animation and simple to follow explanation showing everything step by step)

Web references

 * fragilex.org


text:
Financial Modelling in Microsoft Excel

Contents

 * Principles
 * /Specifying a model/
 * Designing a model
 * /Building for safety/
 * Testing a model
 * Analysing a model

title: Financial Modelling in Microsoft Excel


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Financial Modelling in Microsoft Excel/Overview

Financial models need to be: This needs clear layout, good documentation, data validation & results testing.
 * useful – they need to assist the user in solving the business problem
 * This needs good business analysis and design skills
 * accurate – they must do exactly what they say they do
 * This needs correct logic, accurate calculations & relevant results
 * flexible, so they can evolve throughout the analytical process and beyond
 * provable – the inputs, calculations and results can all be verified

A good guiding rule is to keep things as simple and as clear as possible, for example:
 * using common functions rather than complex or rarely used functions
 * keeping formulae short
 * not being "clever", which may just confuse other people
 * separating the spreadsheet into clearly marked sections

Code Complete, the classic book on programming by Steve McConnell, says that managing complexity is the major imperative.


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User talk:Etscrivner

Copyright problem with Image:Geom-ch6-triUpsideDown.png
--Derbeth talk 09:56, 5 December 2005 (UTC)

title: User talk:Etscrivner


text:
User talk:Dermotbalson

Copyright problem with Image:PaletteDialog.jpg
--Derbeth talk 09:57, 5 December 2005 (UTC)

Excel
I think that if you cut off all the taskbars and menus from the screenshot and leave only the spreadsheet, there would be no problem marking such screenshot as fair use software-screenshot. And if you really must show some menu bars or something, don't show the window title ("Excel" is registered trademark). Such screenshot should also be fair use IMO. --Derbeth talk 09:00, 16 December 2005 (UTC)

title: User talk:Dermotbalson


text:
User talk:212.62.19.185

You have been temporarily blocked from editing Wikibooks. You were warned several times that linking to commercial sites is not allowed. If you wish to make useful contributions, you are welcome to come back after the block expires.

title: User talk:212.62.19.185