text:
Handbook of Genetic Counseling/Tamoxifen - Selective Estrogen Response Modifiers (SERMS)

Tamoxifen - Selective Estrogen Response Modifiers (SERMS)

Risk Reduction Agents for Breast Cancer

Why Estrogen is Important

 * Estrogen is a sex steroid hormone important for many physiologic processes
 * Affects growth, differentiation, and function of reproductive system
 * Maintains bone density and protects against osteoporosis
 * Thought to be cardioprotective, largely through its effects on blood lipids
 * Regulates reproductive behavior by effects in the brain
 * Estrogen effects are mediated through their binding to nuclear proteins called estrogen receptors (ER)
 * Binding activates receptor dimerization which activates or represses transcription depending on other tissue specific co-factors
 * ER-mediated transcription is stimulated through at least 2 transactivation domains called AF-1 and AF-2 (AF-1 is hormone-independent, whereas AF-2 is hormone-dependent)
 * There are two types of estrogen receptors: ER-alpha and ER-beta
 * The exact role of ER-beta in breast cancer is unknown
 * The role of ER-alpha is well defined
 * Maximum transcriptional activation requires both AF-1 and AF-2
 * Prolonged stimulation of breast ductal epithelium by estrogen can contribute to the development and progression of breast cancer
 * The role of hormone therapy in the treatment of metastatic breast cancer was first demonstrated in 1895 by Dr. George Beatson in Glasgow, Scotland
 * He performed a bilateral oophorectomy in a 33 year old woman with advanced cancer who lived 4 years before dying of recurrent disease
 * Approximately 50%-70% of women benefit from hormonal therapy if their tumors are positive for both ER and PR (progesterone)
 * Only 11% benefit if their tumors are negative for both types

What is a Selective Estrogen Response Modifier (SERM)?

 * SERMS have estrogen agonist effects in some tissues and antagonist effects in others
 * SERMS bind competitively to the ERs; AF-2 is not activated, but AF-1 remains active and receptor dimerization and nuclear localization occur
 * SERMS can initiate transcription in the presence of certain accessory proteins and result in the expression of some estrogen-responsive genes
 * The effect depends on the tissue and the gene
 * Ideally, we want an anti-estrogen effect in the breast and endometrium and estrogenic effects on lipid profiles, the CNS, skeletal, vagina and cardiovascular systems.
 * It is the anti-estrogenic effects in the CNS and vagina that cause menopausal side effects
 * Three categories of SERMS
 * Triphenylethylene derivatives like tamoxifen
 * Other nonsteroidal compounds like raloxifene
 * Steroidal compounds that have more complete antiestrogenic activity

Tamoxifen (Nolvadex; AstraZeneca Pharmaceuticals)

 * History and Background
 * Synthesized in the 1960s
 * The first chemotherapy to be approved for the prevention of any cancer
 * Approved by the FDA in 1977 for treatment of advanced breast cancer
 * Has demonstrated efficacy in the treatment of both premenopausal and postmenopausal patients with metastatic breast cancer as well as adjuvant treatment in post-menopausal patients following mastectomy, axillary dissection, and breast irradiation
 * Indicated as preventative treatment to reduce the incidence of breast cancer in high-risk patients and to reduce the risk of contralateral breast cancer
 * Most effective in patients who are ER+, PR+, and postmenopausal
 * Approved dose is 20mg daily for 5 years
 * Taking tamoxifen for longer than 5 years is not thought to be more effective than 5 years of therapy
 * Also used to treat men who have breast cancer
 * Approved in 1998, for reducing incidence of breast cancer in high-risk women
 * Approximately 1/3 of ER+ cancers are resistant to Tamoxifen
 * The Estrogen Effects of Tamoxifen
 * Anti-estrogen effect in breast, CNS, and vagina mucosa
 * Positive estrogen effect in liver (reducing cholesterol), bone, and endometrium
 * Acquired tamoxifen resistance is a cause of treatment failure in breast cancer
 * The mechanism of acquired tamoxifen resistance is not well defined
 * Mouse studies showed that tamoxifen-resistant tumors remained estrogen dependent in vivo but the resistance was associated with the ability of tamoxifen to stimulate tumor growth
 * Altered metabolism of tamoxifen was also seen in the tumor
 * Preclinical Studies
 * Decreased the incidence of mammary tumors in rodents, but increased the risk of liver tumors. There has been no increase in liver cancer in humans.
 * Clinical Trials: 3 randomized trials of tamoxifen as a chemopreventive agent
 * National Surgical Adjuvant Bowel and Breast Project (NSABP): Breast Cancer Prevention Trial (BCPT)
 * A landmark trial that was stopped early by the independent safety monitoring committee due to promising results
 * A trial of Tamoxifen (20mg daily for 5 years) versus placebo in 13,388 healthy women at risk for developing invasive breast cancer
 * A randomized, prospective, double-blind study that began June 1st 1992
 * Enrollment ended September 30, 1997
 * Study was terminated and results disclosed March 24, 1998
 * Eligibility criteria
 * Age 60 or older
 * Or age 35-59 with a 5-year predicted risk of developing breast cancer using the Gail model of 1.66%
 * Or over 35 years with a diagnosis of lobular carcinoma in situ
 * Results:
 * With a median follow-up of 54.6 months, tamoxifen decreased the overall risk of developing invasive breast cancer by 49% and non-invasive breast cancer by 50%
 * Breakdown of risk reduction:
 * 44% in women aged 49 years or younger
 * 51% in women 50-59 years
 * 55% in women 60 years or older
 * 56% in women with a history of LCIS
 * 86% in women with atypical hyperplasia
 * The reduction of breast cancer was limited to the reduction of ER+ breast cancer. No difference was seen in the occurrence of ER- tumors
 * The occurrence of ER+ tumors was decreased by 69%
 * 96% of participants were Caucasian
 * There was no difference in mortality between the tamoxifen-treated and placebo groups in the trial
 * A meta-analysis of 30,000 women in 55 trials with ER+ or unknown tumor status showed a mortality reduction of 26% during 5 years of follow up
 * Royal Marsden Tamoxifen Breast Cancer Prevention Study
 * From 1986 to 1996, 2494 women were randomized to tamoxifen (20mg daily) or placebo for 8 years
 * Eligibility:
 * Age between 30 and 70 with at least one first-degree relative under age 50 with breast cancer
 * Or one first-degree relative with bilateral breast cancer
 * Or one affected first-degree relative of any age plus another affected first- or second-degree relative
 * Or a benign breast biopsy and a first-degree relative with breast cancer
 * Use of hormone replacement therapy was allowed
 * 41% of women in the study received HRT which is a potential confounding factor
 * Results
 * At 70 months follow up, no difference in the incidence of breast cancer was seen
 * Italian Randomized Trial of Breast Cancer Prevention in Hysterectomized Women
 * In 1992, this trial of tamoxifen (20mg daily for 5 years) versus placebo began
 * Ended in 1997 with 5408 women with low to normal risk of breast cancer
 * The goal was to recruit 20,000 women
 * Half of the women recruited had already had an oophorectomy, which is known to reduce the risk of breast cancer, so only 3986 were available for evaluation
 * Eligibility: Healthy women age 35-70 who had a hysterectomy
 * Results: At median of 46 months follow up, there was no difference in the number of breast cancer cases in treatment versus control arms.
 * How do we explain the discrepancy of the 3 trials?
 * The studies are dissimilar in design, population enrolled, and eligibility criteria
 * The two European trials together, had fewer than half the number of breast cancer cases of the NSABP
 * The Italian trial had a high dropout rate
 * Royal Marsden study likely had large number of mutation carriers based on eligibility criteria
 * BCPT was largest and did not allow HRT: the influence of HRT on the potential effect of tamoxifen chemoprevention is unclear
 * There could be differences in compliance
 * Benefits of Tamoxifen
 * Fewer bony fractures due to slower bone loss
 * Lower blood cholesterol
 * Risks of Tamoxifen
 * Side effects similar to the onset of menopause
 * Hot flashes, vaginal discharge, dryness or itching, and irregular menses
 * Headaches, fatigue, nausea and/or vomiting, and skin rash
 * Serious side effects
 * Endometrial cancer (Risk ratio = 2.53 in Tamoxifen group in NSABP trial)
 * No endometrial cancer deaths occurred in the NSABP trial
 * All endometrial cancers were Stage I
 * Deep Vein Thrombosis (1.6x higher in NSABP trial)
 * Pulmonary embolism (3x higher in NSABP trial)
 * Stroke
 * Cataract development
 * Most serious adverse events have occurred in women over age 50

Other SERMS

 * Raloxifene (Evista; Eli Lilly and Co)
 * Background
 * A nonsteroidal compound; a benzothiophene derivative
 * Binds to ER with an affinity equal to that of estradiol
 * Unlike Tamoxifen, does not stimulate uterine tissue
 * There is a raloxifene response element that was identified in the promoter region of certain genes which could contribute to some of its functional differences
 * Has estrogenic effects on bone, lipid metabolism, and blood clotting
 * The MORE (Multiple Outcomes of Raloxifene Evaluation) Study
 * Study Design
 * 7704 postmenopausal women with osteoporosis were followed for a median of 40 months
 * Women taking estrogen or who had a history of breast cancer were excluded
 * Randomized, double-blind study of raloxifene (60mg or 120mg per day) versus placebo
 * Results
 * The primary endpoint was that raloxifene reduced the risk of osteoporosis progressing as seen by the preservation of bone mineral density, the reduction of bone turnover, and the decreased incidence of vertebral fractures
 * Approved in the US in 1997 for the prevention of osteoporosis
 * Raloxifene also decreased the incidence of invasive breast cancers by 76% among postmenopausal women with osteoporosis during 3 years of treatment
 * The risk reduction was similar for both doses of raloxifene and was confined to ER+ tumors
 * 13 cases of breast cancer were confirmed among the 5129 women assigned to raloxifene versus 27 among the 2576 women assigned to the placebo (RR=0.24)
 * Raloxifene decreased the risk of ER+ breast cancer by 90%
 * Raloxifene increased the risk of venous thromboembolic disease (RR=3.1), but did not increase the risk of endometrial cancer.
 * Study of Tamoxifen and Raloxifene (STAR) trial
 * Large, multi-institutional, randomized, double-blind study for breast cancer prevention in postmenopausal women which began in June 1999
 * Will randomize 22,000 postmenopausal women at increased risk for developing breast cancer to tamoxifen (20mg daily) or raloxifene (60mg daily) for 5 years
 * Women must be postmenopausal and at least 35 years old
 * Increased risk is defined as LCIS treated by local excision only or at least a 1.66% projected 5-year probability of developing invasive breast cancer
 * Designed to see if raloxifene is more or less effective than tamoxifen in reducing the chance of developing breast cancer in women at increased risk of developing the disease
 * STAR trial information
 * NCI (800) 422-6237 or cancertrials.nci.nih.gov
 * NSABP www.nsabp.pitt.edu
 * Anticipated time of final analysis is 2006
 * NCI pilot trial is being done to evaluate the safety of 2 years of raloxifene therapy in high-risk premenopausal women.
 * Toremifene (Fareston: Schering Corp)
 * Very similar to tamoxifen; also a triphenylethylene; differs by only a single chlorine atom
 * First synthesized in 1981; first clinical trials done in 1982
 * Trials have been done to compare tamoxifen and toremifene
 * Response rates are similar
 * Median times to progression and overall survival were not significantly different
 * Some studies have found a slightly higher incidence of undesirable effects in the tamoxifen treatment group, but these differences are not statistically significant
 * There is no clinical data to imply that it causes endometrial carcinoma, although it may unmask pre-existing endometrial tumors
 * Approved for use as first-line therapy for postmenopausal women with ER+ advanced breast cancer in 1997 in the U.S.

Chemoprevention for BRCA1/2 Mutation Carriers

 * Will Tamoxifen be as effective in mutation carriers as it is in other women who are at increased risk of breast cancer?
 * The risk of BRCA1 tumors appears to be associated with estrogen related risk factors and oophorectomy reduces risk of hereditary breast cancer suggesting tamoxifen may be effective
 * From 10 studies, 83% of BRCA1 breast tumors have been found to be ER-, whereas 76% of BRCA2 breast tumors were ER+
 * If chemoprevention is needed for at least 10 years to produce and effect, new chemoprevention agents will need to be developed for women in their 30s, as the breast cancer risk curves are steepest between 40 and 50 years of age.
 * Mary-Claire King's report of the NSABP trial (2001)
 * The main outcome measure was to compare the incidence of breast cancer among BRCA1/2 mutation carriers who were receiving tamoxifen versus placebo
 * Design and Method
 * Peripheral white blood cells were stored from study participants in the NSABP trial in anticipation of the identification of BRCA1/2
 * Genomic analysis of BRCA1/2 was done for 288 breast cancer cases
 * 19 carriers were identified
 * 5/8 BRCA1 mutation carriers had taken tamoxifen
 * RR=1.67; 95% confidence interval, 0.32-10.7
 * 3/11 BRCA2 mutation carriers had taken tamoxifen
 * RR=0.38; 95% confidence interval, 0.06-1.56
 * The power to detect a moderate protective effect was low
 * The results were not statistically significant
 * Tamoxifen reduced the risk of breast cancer in BRCA2 mutation carriers by 62%, but did not reduce the risk of breast cancer in BRCA1 mutation carriers
 * Must consider that tamoxifen use began at age 35 or older
 * It is not known if tamoxifen use at a younger age would reduce breast cancer incidence in BRCA1 mutation carriers.
 * King concludes that for women who have not yet developed breast cancer, genotype at BRCA1 and BRCA2 has a major impact on the expected effect of tamoxifen in reducing incidence of primary breast cancer
 * Steven Narod's case-control study (2000)
 * Results contrast with the results of the NSABP trial, but sample size is much greater
 * The aim of the study was to see if tamoxifen protects against contralateral breast cancer in BRCA1/2 mutation carriers since it is known to do so in the general population
 * Study Design
 * Compared 209 women with bilateral breast cancer and BRCA1/2 mutations (cases) and 384 women with unilateral breast cancer and BRCA1/2 mutations (controls) in a matched case-control study.
 * Results
 * Tamoxifen use was reported by 10.5% of the 209 bilateral cases and 21.1% of the 384 unilateral controls
 * Tamoxifen protected against contralateral breast cancer for carriers of BRCA1 and BRCA2 mutations
 * In women who used tamoxifen for 2-4 years, the risk of contralateral breast cancer was reduced by 75%

The Future of Chemoprevention

 * To develop hormonally active agents with more favorable toxicity profiles
 * Currently SERMS, aromatase inhibitors, and novel hormonal contraceptive regimens are being researched
 * Anti-estrogen drugs called ERDs are estrogen receptor down-regulators and act by decreasing the number of active estrogen receptors on a cell or by decreasing their level of responsiveness to estrogen
 * On April 25th 2002, the FDA approved an ERD called Faslodex (fulvestrant) for postmenopausal women with advanced ER+ disease for whom tamoxifen is no longer effective
 * Given as a monthly intramuscular injection
 * Side effects:
 * Nausea, vomiting, constipation, diarrhea, headache, and hot flashes
 * Aromatase inhibitors
 * They lower the amount of estrogen being produced by the body, rather than block estrogen's ability to "turn on" cancer cells
 * In post-menopausal women, androgen is converted to estrogen by aromatase
 * Aromatase inhibitors block this conversion and are often used by women who have already tried other anti-estrogen therapies
 * Examples
 * Arimidex (anastrozole)
 * Femara (letrozole)
 * Aromasin (exemestane)
 * To develop agents for the prevention of ER- breast cancer
 * Approximately 1/3 of invasive cancers are ER-
 * Women under 50 years old are more than twice as likely to have an ER- tumor as women over 50
 * Do the majority of pre-cancerous mammary epithelial cells progress from an estrogen-dependent phenotype to an estrogen-independent phenotype later in the carcinogenesis process? Or does it arise de novo?
 * To define the precise molecular changes that characterize the progression of a normal breast epithelial cell through premalignancy and malignancy
 * Then can search for agents to reverse these changes or prevent malignant transformation from occurring
 * To develop biological markers of breast cancer risk and progression
 * Biomarkers could be used to refine short-term risk assessments
 * Could be used to predict response to specific classes of preventive agents


text:
Talk:Bioeconomics

What does any of this have to do with 'bioeconomics'? It's an introductory economics example applied using fish as an example. If I were to talk about burritos instead, would it be burritonomics? We shouldn't be making up new words.

Re:

We're not making up new words. The term 'bioeconomics' has been using for more than half decades.

I agree. We need a comprehensive introduction to bioeconomics, not a series of mathematics examples.

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

title: Talk:Bioeconomics


text:
Handbook of Genetic Counseling/Tay-Sachs Disease

Tay–Sachs Disease

Contracting

 * Establish rapport with small talk
 * 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 Tay–Sachs for those members present
 * Discuss topics to be covered during the appointment
 * Ask if anyone has any questions

What is Tay–Sachs Disease (TSD)?

 * Also called Hexosaminidase A deficiency
 * A genetic disorder that commonly affects the Ashkenazi Jewish population
 * Hexosaminidase A is a lysosomal enzyme that is required to catalyze one step in the catabolism of gangliosides.
 * The lack of hexosaminidase A results in the faulty metabolism of sphingolipids
 * A specific sphingolipid, GM2 ganglioside accumulates in the cells, especially nerve and brain cells
 * Death usually occurs before age 4 in the infantile type of disease
 * Juvenile, chronic, and adult onset forms of the disorder also exist
 * No specific therapy is currently available.

Genetic Etiology

 * Inherited in an autosomal recessive fashion
 * The chromosomal locus of HEXA is 15q23-q24
 * Mutations in the HEXA gene are associated with the Tay–Sachs phenotype

Molecular Genetics

 * The HEXA gene is ~35 kb, has 14 exons and both 5' and 3' UTRs
 * The normal gene product is Beta-hexosaminidase alpha chain
 * The gene encodes the alpha chain of the heterodimeric protein, beta-hexosaminidase A (HEX A)
 * The protein has a single alpha chain and a single beta chain; both HEX A and HEX B show GM2 ganglioside cleaving activity, but that of HEX A is 8x greater than HEX B
 * The gene for HEX B is located on chromosome 5; this subunit is responsible for most of the catalytic activity
 * More than 90 HEXA mutations have been identified
 * The majority are associated with the infantile phenotype
 * 2 null mutations result in 90-95% of the cases of infantile Tay–Sachs disease in the Ashkenazi Jewish population.
 * The abnormal gene product: mutations result in many effects ranging from processing or subunit assembly to defective catalytic activity

Incidence and Carrier Frequency

 * 1:3600 Ashkenazi Jewish live births.
 * The carrier rate is 1:25-30 Ashkenazi Jewish persons
 * The carrier rate for the French-Canadian population is 1:50
 * Among non-Jews, the disease incidence is about 100 times less common and the carrier rate is 1:250-1:300.
 * As the result of extensive genetic counseling of carriers identified through screening programs and the monitoring of at risk pregnancies, the incidence of TSD has been reduced by greater than 90%.

Risk Assessment

 * If both parents are carriers, the risk of occurrence is 25% with each pregnancy
 * If either or both parents are carriers, the risk to have a carrier child is 50% for each pregnancy
 * When both parents are carriers, unaffected children have a 67% risk of being carriers.

Age of Onset and Life Span

 * Onset at age 3-6 months
 * Death before the age of 4

Clinical Features

 * Hexosaminidase A deficiency is characterized by:
 * Progressive weakness and loss of motor skills beginning between 3-6 months
 * Decreased attentiveness
 * Increased startle response
 * A cherry red spot of the fovea centralis of the macula of the retina can be seen in >90% of cases
 * Hyperreflexia with sustained ankle clonus
 * These signs are followed by:
 * Progressive neurodegeneration
 * Seizures
 * Blindness, typically by the end of the 8th month of life
 * Spasticity of the limbs
 * An increase in head circumference often reaches 3 standard deviations above normal due to an enlargement of the brain NOT hydrocephalus
 * Progressive inability to swallow
 * Breathing difficulties
 * Juvenile, chronic and adult-onset forms have later onset, slower progression, and more variable neurologic findings

Testing

 * Diagnostic (Biochemical)
 * The diagnosis of TSD relies upon the absence or near absence of HEX A in the serum or WBC of a symptomatic individual in the presence of normal or elevated activity of HEX B isoenzyme
 * If the HEX A activity is undetectable= homozygote, affected
 * Carrier (Biochemical)
 * In population screening, assay of HEX A activity in serum or leukocytes using synthetic substrates provides a simple, inexpensive and accurate method for heterozygote identification
 * Serum is used for males and women who are not pregnant and not using oral contraceptives
 * Leukocytes are used for testing pregnant women, women using oral contraceptives and any individual whose serum activity level was in the inconclusive range.
 * If the HEX A activity is ~1/2 the normal level=heterozygote, carrier
 * Molecular Genetic Testing:
 * Used to identify specific disease-causing alleles in affected individuals and to distinguish pseudodeficiency alleles from disease-causing alleles in individuals with apparent deficiency of HEX A activity identified through screening programs
 * Mutation analysis is available for the 6 most common mutations at most clinical laboratories
 * Comprised of three null alleles (non expressing) +TATC1278, +1IVC12, +1IVS9, which in the homozygous state or in compound heterozygosity are associated with TSD
 * The G269S allele, which is associated with the adult onset form of TSD in the homozygous state or in compound heterozygosity with a null allele
 * And two pseudodeficiency alleles R247W and R249W, which are not associated with the neurological disease, but are associated with reduced degradation of synthetic substrate when HEX A activity is determined
 * Pseudodeficiency alleles reduce HEX A activity toward synthetic substrates, but not toward the natural substrate GM2 ganglioside
 * Since all assays use artificial substrate, a potential problem arises when distinguishing between a true deficient allele and a pseudodeficient allele.
 * Problem avoided by using a DNA-based test on any individual who had abnormal activity to identify the disease causing mutation
 * Prenatal
 * Available when:
 * HEX A enzyme assay has shown both parents to be carriers for TSD and molecular genetics has ruled out the possibility of pseudodeficient alleles in either parent
 * If one parent is known to be a heterozygote and the other parent has inconclusive enzymatic activity and no disease-causing mutation can be found
 * And if the mother is a known carrier and the father's status is unknown or he is unavailable for testing
 * Testing can be performed by assay of the HEX A activity in fetal cells obtained by CVS or amniocentesis
 * If the mutation has been identified in both parents, then mutational analysis of the HEXA gene in fetal DNA (extracted from fetal cells removed by CVS or amniocentesis) can be done.

Management and Treatment

 * Treatment for TSD is primarily supportive
 * Provide adequate nutrition and hydration
 * Manage infectious disease
 * Protect the airway
 * Control seizures with anticonvulsant medications, alter dose based on severity and type of seizure
 * As the patient becomes more disabled, good bowel management is important
 * Older patients with the adult-onset form may need antidepressants or antipsychotic therapy
 * Enzyme and gene therapy:
 * Attempts have been unsuccessful
 * Infusions and bone marrow transplantation have had no benefit
 * CNS enzyme replacement are in the experimental stage at this time

Differential Diagnosis

 * Activator deficient TSD
 * The enzymatic activity of both HEX A and HEX B is normal
 * GM2 ganglioside accumulation occurs due to a deficit of the intralysosomal glycoprotein "GM2 activator" that is required for the degradation of GM2 ganglioside.
 * The phenotype is identical to TSD
 * The cherry red spot of the fovea centralis of the macula of the retina is seen during the first year of life in patients with Gaucher disease, GM1 gangliosidosis, galactosialidosis, Niemann-Pick type A, and Sandhoff disease
 * Neurologic regression during the first 6 months of life is seen in many disorders including: Krabbe disease, Canavan disease, Alexander disease, infantile Gaucher disease, and both infantile and late infantile forms of neuronal ceroid-lipofuscinosis.
 * Sandoff disease presents with the same neurological findings as TSD, although it is rarely seen in Jewish infants.
 * For the adult form- SMA3, Friedreich ataxia, ALS and other lysosomal storage diseases should be considered

Psychosocial Issues

 * Impending death
 * Devastating disease
 * Contemplation of pregnancy termination
 * Guilt

Prevention

 * Heterozygote detection
 * Population-based screens for Ashkenazi Jews
 * Therapeutic termination

Support Groups

 * National Tay–Sachs and Allied Diseases Association, Inc
 * 2001 Beacon Street, Suite 204
 * Brighton, MA 02135
 * Phone: 1-800-906-8723
 * Email: NTSAD-boston@worldnet.att.net
 * www.ntsad.org

 * National Foundation for Jewish Genetic Diseases
 * 250 Park Ave, Suite 1000
 * New York, NY 10177
 * Phone: 212-371-1030
 * Email: NFJGD@aol.com
 * www.nfjgd.org

Web References

 * www.geneclinics.org


text:
Handbook of Genetic Counseling/Treacher Collins

Treacher Collins

Contracting

 * Greet and welcome family
 * What are your questions and concerns for genetics?
 * Overview Agenda
 * Medical/Developmental/Family Hx updates
 * Discuss genetic contributions to Treacher Collins
 * Personnel from other specialties will be in to talk with you
 * Questions

Intake

 * Basic Info
 * Age (yr & month)
 * Race/sex
 * Reason for referral
 * Medical History
 * Since your last visit, have you had any:
 * Surgeries?
 * Illnesses?
 * Hospitalizations?
 * Health concerns?
 * New medications?
 * Treatment History
 * What have you been doing/I see you have been doing ____________
 * How has this been working?
 * Developmental History
 * School_________________ Grade____________
 * Services: PT_________OT__________ Speech___________
 * Any special education classes?
 * Early Intervention?
 * Any private evaluations?
 * How would you say __ is functioning developmentally?
 * On tract?
 * What areas are lacking?
 * Activities
 * What does ___ enjoy doing?
 * Does he get to interact with peers?
 * Family History Update
 * New births?
 * New medical problems (psychological or medical)
 * Impressions: (discuss diagnosis, thoughts)
 * Psychosocial Assessment
 * What are things like at home?
 * Who lives at home?
 * Are you thinking of having more children?
 * How are you (parents) dealing with this diagnosis?
 * What resources have you found helpful?
 * Would you like more resources?
 * Do you (parents) find time for yourselves?
 * Who lives in the area to help you?
 * Who takes care of ___ when you need a break?
 * How are your financial resources?
 * Are you having any trouble paying for medical care?
 * What do you need that you don't have?
 * What services do you need that aren't covered by your insurance?

Treacher Collins Syndrome

 * Mode of Inheritance: Autosomal Dominant
 * Chromosome Location: 5q32-q33.1
 * Molecular genetics:
 * Defective gene: treacle
 * Over 50% of case thought to be due to de novo mutations
 * Variable Expression
 * Incidence
 * Clinical Features
 * Abnormal external ears to almost complete absence of an ear
 * Hearing loss
 * Very small jaw (micrognathia)
 * Extra large mouth
 * Defect in the lower eyelid (coloboma)
 * Scalp hair extends onto cheeks
 * Cleft palate
 * Diagnosis
 * The child usually will show normal intelligence
 * Diagnosis usually made on features including:
 * Abnormal eye shape (palpebral fissure, slant)
 * A flat or hypoplastic malar region (cheekbones)
 * Facial clefts
 * Small jaw (micrognathia or hypoplastic mandible)
 * Low-set ears
 * Ear malformation (unusual shape to the ears)
 * Abnormal ear canal
 * Conductive hearing loss
 * Defects in the eye (coloboma that extends into the lower lid)
 * Decreased eyelashes on the lower eyelid
 * Management & Treatment
 * Screening for hearing loss
 * Intervention to allow better scholastic performance
 * Plastic surgery for small chin, cleft palate, and other defects
 * Complications
 * Feeding difficulty
 * Speaking difficulty
 * Communication problems
 * Vision problems
 * Cosmetic appearance can cause other people to think the problem is worse than it is
 * Prognosis
 * Children with Treacher-Collins grow to become normally functioning adults of normal intelligence.
 * Careful attention to any hearing problems helps ensure better performance in school.

Testing

 * DNA Diagnostic Lab
 * Johns Hopkins Hospital
 * CMSC 1004
 * 600 N. Wolfe St.
 * Baltimore, MD 21287
 * Contact: Barbara Karczeski, MS
 * email: bkarczes@jhmi.edu
 * phone: (410) 955-0483
 * fax: (410) 955-0484

Genes & Chromosomes

 * CellsàChromosomesàGenes
 * Chromosome location: 5
 * AD inheritance
 * 50% chance of passing gene one
 * 40-50% of mutations are "de novo"

Resources

 * Treacher Collins Foundation
 * P.O. Box 683
 * Norwich, Vermont 05055
 * 1-800-823-2055
 * www.treachercollinsfnd.org

 * Treacher Collins Family Support Group (UK)
 * http://www.treachercollins.net

 * Treacher Collins Connection
 * http://www.tcconnection.org/

Conclusions

 * Review session/diagnosis
 * Answer additional questions
 * Give resource info & contact info


text:
Talk:ZK/How-Tos

Contributors

2006/03/10 Juan Jose Buendia Mardones for adding JBoss Installation How-to.

2006/03/16 Thomas Muller for adding Hibernate Session Handling How-to.

2006/03/16 Thomas Muller for adding Eclipse WTP How-to.

2006/04/10 Anonymous for adding Jetty Installation How-to.

2006/04/10 Dmitri for adding Spring How-to.

2006/04/10 Dmitri for adding OC4J Installation How-to.

2006/04/10 Daniel Eyassu for adding BEA WebLogic Installation How-to.

title: Talk:ZK/How-Tos


text:
General Chemistry/Thermodynamics/Entropy

Entropy is the measure of disorder in a system.

An Example
First, let's examine a non-chemistry example. Say you have one card from a deck of playing cards. It can have one of 52 possible values. Now you pick up four more cards. If the deck were shuffled randomly, the odds of you holding, say, a "straight flush" are 0.00154%. The odds of having a "high card", which is essentially a "nothing" hand, is 50.12%. In the case of a straight flush, the cards you are holding are highly organized. They must be in a specific, exact pattern (like 10 9 8 7 6 of the same suit). To have a high card, no two cards must have the same rank and the cards cannot be in order.

There is a very low probability of having a straight flush because the cards are in a very orderly state. There is a large probability of having "nothing" because the cards are in a random, disorderly state. In our card-playing system, straight flushes have low entropy because they are so orderly. "Nothing" hands have high entropy because they are disorderly and random. Furthermore, it takes minimal effort to toss all the cards in the air and randomize their order. Increasing the entropy of the system comes naturally. On the other hand, sorting the cards in order takes time and effort. It does not happen randomly. Decreasing the entropy of the system is unnatural and takes effort, or energy.

In Chemistry
The entropy of a chemical system is a measure of its disorder or chaos. More precisely, it is a measure of the dispersion of energy. A solid has low entropy (low chaos, orderly) because the molecules are locked into a rigid structure. Their energy is not dispersed freely. A gas has high entropy (high chaos, disorderly) because the molecules are free to move about randomly. The energy of the system is dispersed over a large area with unlimited possibilities of the location of each molecule.

As temperature decreases, so does entropy. Theoretically, at absolute zero (0 K, or -273 °C), the entropy of the system would be zero. This is because the solid would be perfectly crystallized so that its energy is not dispersed at all.

As you will soon learn, the Second Law of Thermodynamics tells us that the entropy of the universe always increases. Think about it. If you have built a house of cards, the entropy of the system is low. A house of cards is very orderly, with each card having a very specific location. The house of cards will undoubtedly collapse. The resulting pile of cards is very disorderly. The cards can be in any position and still be a random pile of cards. The entropy has increased spontaneously. Houses of cards will spontaneously collapse, but they never spontaneously build themselves up. This is because high entropy is natural and low entropy is unnatural.

Entropy Changes
When analyzing the entropy change of a chemical reaction, you would need specific numbers. As a guideline, you can estimate the entropy change based on some basic rules:

If you do happen to know the absolute entropy of substances in a reaction (by looking it up in a chart), you can calculate the change in entropy. Entropy is symbolized with $$S$$. The change in entropy is $$\Delta S$$. As with enthalpy, the degree symbol ($$\Delta S^o$$) represents STP. The change in entropy is the absolute entropy of the products minus the absolute entropy of the reactants.


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Talk:Operations Strategy/JIT

why isn't there more information?

title: Talk:Operations Strategy/JIT


text:
Student Congress Debate/Speech Structure

 * Introduction (15-30 sec.)
 * Attention Ladies and gentlemen, the motion that's for discussion today is '.......'
 * Purpose ("I stand in affirmation/negation on the bill/resolution...")
 * Preview ("for the following reasons")
 * Body (2 Minutes)
 * Clash!
 * State issues on the floor
 * State points in conflict
 * Prove your point with evidence including the source and date of publication, add the credentials of the source
 * Logic - explain why this evidence reinforces your point and your side
 * Tell the assembly the impact of your point and how it should affect their vote
 * Present a Challenge to the Opposition.
 * Conclusion (30 sec.)
 * Summarize key points of clash.
 * Summarize key points.
 * Come full circle.
 * Open yourself to questions. ("I now yield my time to the chair.")

Sample Speech
[Attention grabber]

Fellow senators, I [rise to the affirmative/stand in negation] of this [bill/resolution] [because of/for] the following [two/three] contentions:

First shall be that, [contention #1]

Second shall be that, [contention #2]

[First, let me talk about/I will start off by saying that] [contention #1]. [reason, citations] Also, I [rise to the affirmative/stand in negation] of this legislature because [reason, citations]. Finally, this [can/cannot] work because [reason, citations].

[Second, let me talk about/I will continue by saying that] [contention #2]. [reason, citations] Also, I [rise to the affirmative/stand in negation] of this legislature because [reason, citations]. Finally, this [can/cannot] work because [reason, citations]

So, in conclusion I urge your [affirmation/negation] of this [bill/resolution] because [summarize contention #1], [summarize contention #2], and because [summarize contention #3] because, as stated, [restate contentions #1, #2, and #3].

I now yield my time to the chair.


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Geometry/Hyperbolic and Elliptic Geometry

There are precisely three different classes of three-dimensional constant-curvature geometry: Euclidean, hyperbolic and elliptic geometry. The three geometries are all built on the same first four axioms, but each has a unique version of the fifth axiom, also known as the parallel postulate. The 1868 Essay on an Interpretation of Non-Euclidean Geometry by Eugenio Beltrami (1835 - 1900) proved the logical consistency of the two Non-Euclidean geometries, hyperbolic and elliptic.

The Parallel Postulate
The parallel postulate is as follows for the corresponding geometries.

Euclidean geometry: Playfair's version: "Given a line l and a point P not on l, there exists a unique line m through P that is parallel to l." Euclid's version: "Suppose that a line l meets two other lines m and n so that the sum of the interior angles on one side of l is less than 180°. Then m and n intersect in a point on that side of l." These two versions are equivalent; though Playfair's may be easier to conceive, Euclid's is often useful for proofs.

Hyperbolic geometry: Given an arbitrary infinite line l and any point P not on l, there exist two or more distinct lines which pass through P and are parallel to l.

Elliptic geometry: Given an arbitrary infinite line l and any point P not on l, there does not exist a line which passes through P and is parallel to l.

Hyperbolic Geometry
Hyperbolic geometry is also known as saddle geometry or Lobachevskian geometry. It differs in many ways to Euclidean geometry, often leading to quite counter-intuitive results. Some of these remarkable consequences of this geometry's unique fifth postulate include:

1. The sum of the three interior angles in a triangle is strictly less than 180°. Moreover, the angle sums of two distinct triangles are not necessarily the same.

2. Two triangles with the same interior angles have the same area.

Models of Hyperbolic Space
The following are four of the most common models used to describe hyperbolic space.

1. The Poincaré Disc Model. Also known as the conformal disc model. In it, the hyperbolic plane is represented by the interior of a circle, and lines are represented by arcs of circles that are orthogonal to the boundary circle and by diameters of the boundary circle.

2. The Klein Model. Also known as the Beltrami-Klein model or projective disc model. In it, the hyperbolic plane is represented by the interior of a circle, and lines are represented by chords of the circle. This model gives a misleading visual representation of the magnitude of angles.

3. The Poincaré Half-Plane Model. The hyperbolic plane is represented by one-half of the Euclidean plane, as defined by a given Euclidean line l, where l is not considered part of the hyperbolic space. Lines are represented by half-circles orthogonal to l or rays perpendicular to l.

4. The Hyperboloid Model. The hyperbolic plane is represented on one of the sheets of a 2-sheeted hyperboloid. This model is used in modern physics to represent velocity space.

Defining Parallel
Based on this geometry's definition of the fifth axiom, what does parallel mean? The following definitions are made for this geometry. If a line l and a line m do not intersect in the hyperbolic plane, but intersect at the plane's boundary of infinity, then l and m are said to be parallel. If a line p and a line q neither intersect in the hyperbolic plane nor at the boundary at infinity, then p and q are said to be ultraparallel.

The Ultraparallel Theorem
For any two lines m and n in the hyperbolic plane such that m and n are ultraparallel, there exists a unique line l that is perpendicular to both m and n.

Elliptic Geometry
Elliptic geometry may be first considered as rotation geometry in 3D space: every rotation has both an axis (say specified by a unit vector r) and a turn, generally ranging from 0 degrees to 180 degrees. A turn in the interval (180, 360) may be interpreted as being about the opposite axis −r with turn taken as the complement in 360.

William Rowan Hamilton practiced celestial geometry as an astronomer. He invented 4D quaternion geometry which has a 3D sphere of versors that represent the sides of spherical triangles. The versor algebra has products corresponding to composed rotations. Elliptic geometry looks at this product as a spherical triangle: a side of the triangle is a versor, and quaternion multiplication relates two sides to the third as follows:

To get a versor, start with the formula of Euler $$\exp(i \theta) = \cos \theta + i \sin \theta$$

that uses an "imaginary unit" i with i2 = − 1. Now imagine an unit sphere $$S^2 \subset \real^3$$ of such units. Call a generic point on this sphere r so r2 = −1. For three points i, j, k at right angles to eachother, the unit vector may be written $$r = xi + yj + zk .$$ Hamilton's convention has i, j, and k anticommute, so ij = −ji, etcetera. To this space of imaginaries, Hamilton adjoined  a real number axis to form a real quaternion $$q = w + xi + yj + zk.$$ For a given r, its versors lie on a circle through 1 and −1. As r ranges over S2 these circles form the three-sphere. The elliptic geometry of rotations in 3-space has this hypersphere of versors as points. To obtain the distance between versors v and w, first find the versor $$v^{-1}w ,$$ then use its turn for the distance.

The connection between rotations and versor operators is shown in Associative Composition Algebra/Quaternions.


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Fluid Mechanics/Dimensional Analysis

Dimensional analysis is a mathematical technique used to predict physical parameters that influence the flow in fluid mechanics, heat transfer in thermodynamics, and so forth. The analysis involves the fundamental units of dimensions MLT: mass, length, and time. It is helpful in experimental work because it provides a guide to factors that significantly affect the studied phenomena.

Dimensional analysis is commonly used to determine the relationships between several variables, i.e. to find the force as a function of other variables when an exact functional relationship is unknown. Based on understanding of the problem, we assume a certain functional form.

Units/Dimensions
The defined units are based on the modern MLT system: mass, length, time. All other quantities can be expressed in terms of these basic units.

For example, Force /area×veilocity gradient MLT^-2/L^2×T^-1
 * velocity||m/s||= L/T
 * acceleration||m/s²||= L/T²
 * force||kgm/s²||= ML/T²
 * }
 * force||kgm/s²||= ML/T²
 * }
 * }

Where L/T, L/T², ML/T², etc. are referred to as the derived units.

Another system for dimensionless analysis is the FLT system, the force, length, time system. In this case, mass ≡ F/a, which makes the units of mass as FT²/L, since acceleration has units of L/T².

Rayleigh Method
An elementary method for finding a functional relationship with respect to a parameter in interest is the Rayleigh Method, and will be illustrated with an example, using the MLT system.

Say that we are interested in the drag, D, which is a force on a ship. What exactly is the drag a function of? These variables need to be chosen correctly, though selection of such variables depends largely on one's experience in the topic. It is known that drag depends on

This means that D = f(l,ρ,μV,g) where f is some function.

With the Rayleigh Method, we assume that D=ClaρbμcVdge, where C is a dimensionless constant, and a,b,c,d, and e are exponents, whose values are not yet known.

Note that the dimensions of the left side, force, must equal those on the right side. Here, we use only the three independent dimensions for the variables on the right side: M, L, and T.

Step 1: Setting up the equation
Write the equation in terms of dimensions only, i.e. replace the quantities with their respective units. The equation then becomes

 * $$\frac{ML}{T^2}=(L)^a\displaystyle\left(\frac{M}{L^3}\right)^b\displaystyle\left(\frac{M}{LT}\right)^c\displaystyle\left(\frac{L}{T}\right)^d\displaystyle\left(\frac{L}{T^2}\right)^e$$

On the left side, we have M¹L¹T-2, which is equal to the dimensions on the right side. Therefore, the exponents of the right side must be such that the units are M¹L¹T-2

Step 2: Solving for the exponents
Equate the exponents to each other in terms of their respective fundamental units:

 * M: 1 = b + c                since M¹ = MbMc
 * L: 1 = a - 3b - c + d + e   since L¹ = LaL-3bL-cLdLe
 * T: -2 = -c - d - 2e         since T-2 = T-cT-dT-2e

It is seen that there are three equations, but 5 unknown variables. This means that a complete solution cannot be obtained. Thus, we choose to solve a, b, and d in terms of c and e. These choices are based on experience. Therefore,

Solving (i), (ii), and (iii) simultaneously, we obtain

 * a = 2 - c + e

Substituting the exponents back into the original equation, we obtain

 * D = Cl2+e-cρ1-cμcV2-c-2ege

Collecting like exponents together,
 * $$D=C\displaystyle\left(\frac{V^2}{lg}\right)^{-e}\displaystyle\left(\frac{Vl\rho}{\mu}\right)^{-c}{\rho}l^2V^2$$

Which means

 * D = Cl2lel-cρρ-cμcV2V-cV-2ege

For the different exponents,

 * Terms with exponent of 1:    Cρ
 * Terms with exponent of 2:    l2V2
 * Terms with exponent of e:    leV-2ege = $$\displaystyle\left(\frac{lg}{V^2}\right)^e = \displaystyle\left(\frac{V^2}{lg}\right)^{-e}$$ (iv)
 * Terms with exponent of c:    l-cρ-cμcV-c = $$\displaystyle\left(\frac{l{\rho}V}{\mu}\right)^{-c}$$ (v)

The right sides of (iv) and (v) are known as the dimensionless groups.

Step 3: Determining the dimensionless groups
Note that e and c are unknown. Consider the following cases:

 * If e = 1    then (iv) becomes $$\displaystyle\left(\frac{lg}{V^2}\right)$$
 * If e = -1   then (iv) becomes $$\displaystyle\left(\frac{V^2}{lg}\right)$$
 * If c = 1    then (v) becomes $$\displaystyle\left(\frac{\mu}{l{\rho}V}\right)$$
 * If c = -1   then (v) becomes $$\displaystyle\left(\frac{l{\rho}V}{\mu}\right) = \displaystyle\left(\frac{lV}{\nu}\right)$$

 * Where ν is the kinematic viscosity of the fluid.

And so on for different exponents. It turns out that:

 * $${Reynolds\ Number}\equiv\frac{Vl}{\nu}=N_{R}=Re$$
 * $${Froude\ Number}\equiv\displaystyle\left(\frac{V^2}{lg}\right)^{\frac{1}{2}}=\frac{V}{\sqrt{lg}}=N_{F}=Fr$$

Where NR or Re and NF or Fr are the usual notations for the Reynolds and Froude Numbers respectively. Such dimensionless groups keep reoccurring throughout Fluid Mechanics and other fields.

Choosing exponents of -1 for c and -½ for e, which result in the Reynolds and Froude Numbers respectively, we obtain

 * D = g(Fr, Re)ρl2V2
 * Where g(Fr, Re) is a dimensionless function

This can also be written as

 * $$\frac{D}{{\rho}l^2V^2}=g(Fr,Re)$$

Which is a dimensionless quantity, and a function of only 2 variables instead of 5. This dimensionless quantity turns out to be the drag coefficient, CD.

 * $$C_D\equiv\frac{D}{{\rho}l^2V^2}$$

The Buckingham π Theorem/Method
This method will be illustrated by the same example as that for Rayleigh Method, the drag on a ship.

Say that we have n number of quantities (e.g. 6 quantities, which are D,l,ρ,μ,V, and g) and m number of dimensions (e.g. 3 dimensions, which are M, L, and T). These quantities can be reduced to (n - m) independent dimensionless groups, such as Re and Fr.

Say that

 * A1 = f(A2, A3, A4, ..., An)

where Ax are quantities such as drag, length, and so forth, as mentioned under the n number of quantities, and f implies the functional relationship between A1 and the other quantities.

Then re-arranging, we obtain

 * 0 = f(A2, A3, A4, ..., An) - A1 = f(A1, A2, A3, A4, ... , An)

Which can be further reduced, using the Buckingham π Theorem, to obtain

 * 0 = f(π1, π2, ..., πn-m)

Forming π Groups
For each π group, take m of the quantities, Ax, known as m repeating variables, and one of the other remaining variables. Note that experience dictates which quantities make the best repeating variables.

The π groups, in general form, would then be

 * π1 = A1x1A2y1A3z1A4
 * π2 = A1x2A2y2A3z2A5
 * ⋮
 * πn-m = A1xn-mA2yn-mA3zn-mAn

which are all dimensionless quantities.

Step 1: Setup π groups
For the MLT System, m = 3, so choose A1, A2, and A3 as the repeating variables.

Using the Buckingham π Theorem on the Drag Equation:

 * f(D, l, ρ, μ, V, g) = 0

Where m = 3, n = 6, so there will be n - m = 3 π groups.

We will select ρ, V, and l as the repeating variables (RV), leaving the remaining quantities as D, μ, and g. Note that if the analysis does not work out, we could always go back and repeat using new RVs. Thus,

 * π1 = ρx1Vy1lz1D
 * π2 = ρx2Vy2lz2μ
 * π3 = ρx3Vy3lz3g

Which are all dimensionless quantities, i.e. having units of M0L0T0

Step 2: Determine π groups
For the first π group,

 * π1  $$M^0L^0T^0=\displaystyle\left(\frac{M}{L^3}\right)^{x_1}\displaystyle\left(\frac{L}{T}\right)^{y_1}(L)^{z_1}\displaystyle\left(\frac{ML}{T^2}\right)$$

Expanding and collecting like units, we can solve for the exponents:

 * For M:    0 = x1 + 1               ⇒ x1 = -1
 * For T:    0 = -y1 - 2              ⇒ y1 = -2
 * For L:    0 = -3x1 + y1 + z1 + 1   ⇒ z1 = 3(-1) - (-2) - 1 = -2

Therefore, we find that the exponents x1, y1, and z1 are -1, -2, and -2 respectively. This means that the first dimensionless π group, π1, is

 * π1 = ρ-1V-2l-2D = $$\frac{D}{{\rho}V^2l^2}$$

For the second π group,

 * π2  $$M^0L^0T^0=\displaystyle\left(\frac{M}{L^3}\right)^{x_2}\displaystyle\left(\frac{L}{T}\right)^{y_2}(L)^{z_2}\displaystyle\left(\frac{M}{LT}\right)$$

Solving for the exponents,

 * For M:    x2 + 1 = 0               ⇒ x2 = -1
 * For T:    -y2 - 1 = 0              ⇒ y2 = -1
 * For L:    -3x2 + y2 + z2 - 1 = 0   ⇒ z2 = 1 - (-1) + 3(-1) = -1

Thus,

 * $$\pi_2=\rho^{-1}V^{-1}l^{-1}\mu=\frac{\mu}{{\rho}Vl}=\frac{\nu}{Vl}$$

However, we will now invert π2 so that

 * $$\pi_2=\frac{Vl}{\nu}=Reynolds\ Number$$

It is permissible to exponentiate any π group, e.g. π−1, π½, π2, etc., to form a new group, as this does not alter the functional form.

For the third π group,

 * π3  $$M^0L^0T^0=\displaystyle\left(\frac{M}{L^3}\right)^{x_3}\displaystyle\left(\frac{L}{T}\right)^{y_3}(L)^{z_3}\displaystyle\left(\frac{L}{T^2}\right)$$

Solving for the exponents,

 * For M:    x3 = 0                   ⇒ x3 = 0
 * For T:    -y3 - 2 = 0              ⇒ y3 = -2
 * For L:    -3x3 + y3 + z3 + 1 = 0   ⇒ z3 = -1 - (-2) = 1

Thus,

 * $$\pi_3=\rho^0V^{-2}lg=\frac{lg}{V^2}$$

Raising it to the power of -½,

 * $$\sqrt{\frac{1}{\pi_3}}=\frac{V}{\sqrt{lg}}=Froude\ Number$$

Thus, the three π groups can be written together as

 * $$f\displaystyle\left(\frac{D}{{\rho}l^2V^2},Re,Fr\right) = 0$$

Finally,

 * $$\frac{D}{{\rho}l^2V^2}=f(Re,Fr)$$

Note that this is the same result as obtained with the Rayleigh Method, but with the Buckingham π Method, we did not have to assume a functional dependence.

Common π Groups
Using the Buckingham π Theorem, we will now examine the π groups which appear most frequently in fluid dynamics. Most fluid flow situations depend on the following quantities:

There are 10 quantities, n = 10, and 3 dimensions, m = 3, so this gives n - m = 7 π groups. Choosing V, ρ, and l as the repeating variables, performing the Buckingham π analysis, and using different exponents for some π groups, we obtain the following π groups, which are common in the study of Fluid Mechanics:

$$\pi_1=\frac{{\Delta}p}{{\rho}V^2}=\text{Pressure Coefficient}=C_P$$

$$\pi_2=\frac{V}{\sqrt{gl}}=\text{Froude Number}=Fr$$

$$\pi_3=\frac{Vl\rho}{\mu}=\text{Reynolds Number}=Re$$

$$\pi_4=\frac{V^2l\rho}{\sigma}=\text{Weber Number}=We$$

$$\pi_5=\frac{V}{\sqrt{\frac{K}{\rho}}}=\text{Mach Number}=Ma$$

$$\pi_6=\frac{l}{D}=\text{Length:Diameter Ratio}$$

$$\pi_7=\frac{\epsilon}{D}=\text{Relative Roughness}$$

title: Fluid Mechanics/Dimensional Analysis


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Fluid Mechanics/Control Volume Analysis

Control Volume Analysis
A fluid dynamic system can be analyzed using a control volume, which is an imaginary surface enclosing a volume of interest. The control volume can be fixed or moving, and it can be rigid or deformable. Thus, we will have to write the most general case of the laws of mechanics to deal with control volumes.

Conservation of Mass
The first equation we can write is the conservation of mass over time. Consider a system where mass flow is given by dm/dt, where m is the mass of the system. The term on the left denotes the rate of change of the mass of the system. The first term on the right describes the amount of flow across the control surface. The second term on the right refer to the condition within the control volume. We have,

$$ \dot m = \int_{CS} \rho \left(   \mathbf{V}\cdot\mathbf{n}  \right) dA +\frac{d}{dt}\int_{CV}\rho dV $$

However, by definition of a system the mass of which is a constant; thus the left-hand side of the above equation equals to zero and it could be rewritten as:

$$ \int_{CS} \rho \left(   \mathbf{V}\cdot\mathbf{n}  \right) dA =-\frac{d}{dt}\int_{CV}\rho dV $$

For steady flow, the time derivative of the quantity is zero, we have

$$ \int_{CS} \rho \left(   \mathbf{V}\cdot\mathbf{n}  \right) dA =0 $$

And for incompressible flow, we have

$$ \int_{CS} \left(   \mathbf{V}\cdot\mathbf{n}  \right) dA = 0 $$

If we consider flow through a tube, we have, for steady flow,

$$ \rho_1A_1V_1 = \rho_2A_2V_2 $$

and for incompressible steady flow, A1V1 = A2V2.

Conservation of Momentum
Law of conservation of momentum as applied to a control volume states that

$$ \sum F = \frac{d}{dt} \left(   \int_{CV} \!\mathbf{V} \mathbf{\rho} \,dV  \right) + \int_{CS} \mathbf{V}\mathbf{\rho} \left(   \mathbf{V}\cdot\mathbf{n}

\right)dA $$

where V is the velocity vector and n is the unit vector normal to the control surface at that point.

The sum of the forces represents the sum of forces that act on the entirety of the fluid volume (body forces) and the forces that act only upon the bounding surface of a fluid (surface forces). Body forces include the gravitational force.

Conservation of Energy
The law of Conservation of Energy in fluid mechanics is a specific application of the First Law of Thermodynamics.

$$ \frac{d\mathbf{Q}}{dt} + \frac{d\mathbf{W}}{dt} = \frac{d}{dt} \left(   \int_{CV} e\mathbf{\rho} \,dV  \right) + \int_{CS} e\mathbf{\rho} \left(   \mathbf{V}\cdot\mathbf{n}  \right)dA $$

where e is the energy per unit mass.

Bernoulli's Equation
Bernoulli's equation considers frictionless flow along a streamline.

For steady, incompressible flow along a streamline, we have

$$ \frac{p}{\rho} + \frac{V^2}{2} + gz = constant $$

We see that Bernoulli's equation is just the law of conservation of energy without the heat transfer and work.

It may seem that Bernoulli's equation can only be applied in a very limited set of situations, as it requires ideal conditions. However, since the equation applies to streamlines, we can consider a streamline near the area of interest where it is satisfied, and it might still give good results, i.e., you don't need a control volume for the actual analysis (although one is used in the derivation of the equation).

Energy in terms of Head
Bernoulli's equation can be recast as

$$ \frac{p}{\rho g} + \frac{V^2}{2g} + z = constant $$

This constant can be called head of the water, and is a representation of the amount of work that can be extracted from it. For example, for water in a dam, at the inlet of the penstock, the pressure is high, but the velocity is low, while at the outlet, the pressure is low (atmospheric) while the velocity is high. The value of head calculated above remains constant (ignoring frictional losses).

Mechanical Energy Balance Equation
Yet another variation of the Bernoulli's equation is the mechanical energy balance equation. The mechanical energy balance equation is useful when needing to consider things such as work or losses due to friction, or if there are differences between the outlet and inlet (such as pressure, velocity, and height).

$$ \frac{\Delta p}{\rho} + \frac{\Delta (V^2)}{2} + g\Delta z + f = -w $$

Equation of Continuity

 * A differential mass balance relating density change to velocity.

\frac{\partial\rho}{\partial t} + \nabla\cdot \left(   \rho \mathbf{V}  \right) = 0 $$

 * For incompressible fluids the equation of continuity reduces to:

\rho \left(   \nabla \cdot     \mathbf{V}  \right) = 0 $$

 * since

\frac{\partial\rho}{\partial t} = 0 $$
 * for all incompressible fluids

Euler's Equation

 * applies conservation of momentum to inviscid, incompressible flow.

\rho \mathbf{g} - \nabla p = \rho\frac{d\mathbf{V}}{dt} $$

Stokes' Equation

 * applies conservation of momentum in creeping flow limit (low Reynold's Number)

\nabla p = \mu \nabla^2 \mathbf{V} $$

title: Fluid Mechanics/Control Volume Analysis


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Fluid Mechanics/Kinematics

Fluid Kinematics
In this section fluid motion will be described without concern with the actual forces necessary to produce the motion. The principles of conservation of mass and conservation of momentum permit some patterns of fluid motion, and exclude others. Many important real-world situations can be analyzed using this approach, without considering friction.

I.The Velocity Field
Fluids tend to flow easily, which results in a net motion of molecules from one point in space to another point as a function of time. Using the continuum hypothesis, fluids are broken down into fluid particles, which are composed of numerous fluid molecules. These particles interact with one another and with their surroundings. Thus the motion of a fluid, using a Eulerian model (continuum hypothesis), can be described in terms of the acceleration or velocity of fluid particles and not in terms of molecular motion.

The continuum assumption allows for any fluid property (density,pressure, velocity, acceleration, ...) to be described as a function of fluid location. The representation of fluid parameters in terms of spacial coordinates is called a field representation.

Ex:      T = T(x,y,z,t)

Eularian & Lagrangian Flow
Eulerian analysis uses the field concept, derived from the continuum assumption.

Lagrangian analysis involves following individual fluid particles as they move about, and determining how fluid properties vary as a function of time.

(-See below)

Steady vs Unsteady Flow
When the flowing particle velocity, temperature and pressure do not change with respect to time is called steady flow. It should be noted that the conditions are different at different points, but at a particular point it is constant.

Streamlines, Streaklines, Pathlines
If in a flow field a curve is drawn in such a way that the tangent to the curve at any point represents the velocity to that point. Such imaginary curve in the flow field is known is stream line. the curve along which a particle moves in a flow field for a given period of time is known as path line. the curve drawn by the particles in a flow field that passes through the same point for a given period of time is known as streak line for a steady flow stream line, path line and streak line will be the same.

II.Acceleration Field
The acceleration of a particle is the time rate of change of its velocity. Using the an Eulerian description for velocity, the velocity field V = V(x,y,z,t) and taking deriving it with respect to time, we obtain the acceleration field.

Now, consider a fluid particle A, moving along its pathline with velocity VA

VA = VA(rA,t) = VA[xA(t), yA(t), zA(t), t]

Differentiate to obtain the acceleration: (chain rule)

(1) $$ \vec{a} $$= dV/dt + dV/dx dx/dt + dv/dy dy/dt + dv/dz dz/dt

Note: these are partial derivatives, since velocity is a function with several variables. Changing the partial velocity components u = dx/dt, v = dy/dt, w = dz/dt in EQ. 1 we obtain:

$$ \vec{a} = {D\vec{V} \over Dt} = {\partial \vec{V} \over \partial t }+u{\partial \vec{V} \over \partial x}+v{\partial \vec{V} \over \partial y}+w{\partial \vec{V} \over \partial z } $$

Material Derivative
The material derivative is sometimes referred to as the substantial derivative, ...

Unsteady and Convective Effects
The material derivative, as seen above, contains two types of terms. Those involving the time derivative d/dt and those involving spatial derivatives d/dx, ..., ... . The time derivative portion is denoted as the local derivative, and represents the effects of unsteady flow. The local derivative occurs during unsteady flow, and becomes zero for steady flow.

The portion of the material derivative represented by the spatial derivatives is called the convective derivative. It accounts for the variation in fluid property, be it velocity or temperature for example, due to the motion of a fluid particle in space where its values are different.

III. Reynolds Transport Theorem
$$ \frac{D}{Dt} \int_{V(t)} \mathcal{F}(\vec{x},t) dV = \int_{V(t)} \frac{\partial \mathcal{F}}{\partial t} dV + \int_{S(t)} \mathcal{F} \vec{u} \cdot \hat{n} dS $$

Fluid Mechanics as a Subset of the Continuum Mechanics
Rate of continuity= AV

Frames of Reference in Fluid Mechanics
There are two different frames of reference that are commonly used in the analysis of fluid mechanics problems: Fixed (Eulerian) reference frames and Material (Lagrangian) reference frames.

 * In fixed reference frames fluid motion is defined with respect to a coordinate system that does not vary with time or fluid motion.
 * In material reference frames fluid motion is defined with respect to a coordinate system that follows the motion of the fluid so that the same volume of fluid remains enclosed throughout the analysis. The Reynold's Transport Theorem (to be defined later) is used to solve fluid mechanics problems when the frame of reference is Lagrangian.

title: Fluid Mechanics/Kinematics


text:
Talk:GCSE Science/Coursework marking system

Great page, whoever wrote it - really helpful. Thanks.


text:
Talk:FHSST Biology/Contents/How to use this textbook

Light related reading

 * http://www.usatoday.com/tech/science/discoveries/2005-12-04-nature-engineers_x.htm


text:
User:Akako~enwikibooks

Greetings. I am primarily a wikipedia user, and thus will not update this page often. My wikipedia user page will be more frequently looked at, so you may wish to leave me a note there instead of my wikibooks talk page.

title: User:Akako~enwikibooks


text:
User talk:Akako~enwikibooks

Greetings. I am primarily a wikipedia user, and thus will not update this page often. My wikipedia user page will be more frequently looked at, so you may wish to leave me a note there instead of here.

Your account will be renamed
Hello,

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Unfortunately, your account clashes with another account also called Akako. To make sure that both of you can use all Wikimedia projects in future, we have reserved the name Akako~enwikibooks that only you will have. If you like it, you don't have to do anything. If you do not like it, you can pick out a different name.

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Yours, Keegan Peterzell Community Liaison, Wikimedia Foundation 22:55, 17 March 2015 (UTC)

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title: User talk:Akako~enwikibooks


text:
Talk:Ada Programming/Error handling

DbC
With all due respect, the treatment of Design by Contract is sloppy, to put in mildly, and somewhat bragging about Ada's type system. In fact, DbC is formally specified, see ECMA 367, 8.9. It is integrated into Eiffel's vocabulary, and checked both at runtime and at compile time, covering a lot more than Ada can now hope to achieve. (See for example the discussion of introducing pragma Precondition and pragma Postcondition in the AI database.)

Ada's expressiveness is not the same in this regard, so I think it isn't the best thing to establish and instrumentalize a fuzzy notion of precisely defined concepts of DbC. (Except perhaps for anti-Ada trolls.) It is appropriate to make a reference to DbC, though.

It is true that the SPARK language and Eiffel have some common "mechanics". You can specify pre/post-conditions, you can have check-correctness and loop correctness, at the Ada subprogram/Eiffel feature level, for example. Of course, exception correctness is not needed in SPARK, but it would be needed in Ada, were DbC introduced to Ada.

But where is the class consistency in Ada, provided by class invariants in Eiffel? Initialising an object of a tagged type must establish the class invariant INVC, every call of a primitive operation must then reestablish INVC. This is of course integrated with the pre/postconditions of subprograms. How do you express this in the Ada language. I think it is fair to say that class correctness/package correctness is not available in Ada. What about package-scope operations not bound to the tagged type, yet affecting object components?

Inheritance in DbC means that contracts are inherited in a similarly consistent way that must follow formal rules. Failing that, the compiler will not accept the program text. (Roughly, oring of the preconditions, and anding of the postconditions, etc). I think talking about the pros of Ada's type system is not the same as talking about DbC, a formally specified, integrated part of a standardised language.

Last but not least, the notion of DbC includes a proof obligation. This thing is present in SPARK, but not in Ada.

Yeah, I should write an example package demonstrating DbC in Ada to match ECMA 367, 8.9 (plus visibility (= export status) and inheritance). Then we could demonstrate how Ada's type sytem and DbC can synergetically produce programs with less bugs than usual.

Wait, isn't this what SPARK is about? :-)

gb 15:08, 10 December 2005 (UTC)

CKWG: This definitly needs rewording. I don't know much about DbC, so I won't do it. 19. November 2013

It`s a Wiki
Well this is Wiki - you can allways improve the text and I would welcome that.

But note that this module originates from Computer programming/Error handling. Computer programming/Error handling is about error handling in generall - without any particular language in mind. The aim is more about telling people that errors need to be handled - and preferly in the language - then pushing DoC. More for "anti error handling trolls" then "anti Ada trolls". Yes they exitst. Programmers who belive that they can do it better then any sofisticated programming lanuguage.

Ada Programming/Error handling are only examples on how your can archive an particular technique in Ada. Have you seen the other page? Have you noticed how they share text and where they are different?

 * seen them, and I disagree with what is said about DbC, and optimization for example.

Sad that there is no Eiffel or Spark book on Wikibooks. It would really be interesting have to have Eiffel Programming/Error handling or SPARK Programming/Error handling as better example of DoC.

And have you read Design by contract? Every time I look at it there are more DbC implementations.

--Krischik T 18:08, 10 December 2005 (UTC)

 * I disagree. There is an increasing number of "me too"s, yes. How do they integrate inheritance and contracts? Where are the loop invariants? Can you write check-correct programs? Are they exception-correct? That is to say, how can you specify that the postcondition is going to be true in case of a handled exception, using these wannabe DbC systems?

 * I never said I find them any good ;-) - as far as I see it only "D" and "SPARK" realy deverve to be called a DoC language. And even there I might be wrong. It seams that you know a lot about the subject - more then me for that matter. So could you write up an article about DbC? Wikibooks is still missing one. The appropiate place for a chapter would be Computer_Programming/Design by Contract or (Not using a trademark) Computer_Programming/Programming by Contract with a link to that chapter at Computer_Programming and/or Computer_Programming. Of corse you can allways start a new book as well if you have enough material. --Krischik T 07:34, 12 December 2005 (UTC)

 * I have now added Computer_Programming/Design by Contract. (Programming by contract reminds me too much of employer/employee) The page isn't very well connected yet, I'll try to inject some links in the proper places

 * And the page has moved to Computer programming/Design by Contract, joining the other pages.

 * Writing a function in a Hoare triple is not DbC yet.

 * o.K. I'll have a try rewriting some of the remarks.

 * I tried, but where is the text??? After clicking the edit link (which takes me Computer_Programming/Error_handling/5), editing, previewing, and saving, the old text comes back. What am I doing wrong? The new text is still there when I do it again:

 * Nothing, the page cache has fooled you. You can either wait until the cache expires or click here http://en.wikibooks.org/w/index.php?title=Computer_programming/Error_handling&action=purge to purge the cache.

In Design by Contract (DbC) functions must be called with the correct parameters. This is the caller's part of the contract. If the types of actual arguments match the types of formal arguments, and if the actual arguments have values that make the function's preconditions True, then the subprogram gets a chance to fulfill its postcondition. Otherwise an error condition occours. Now you might wonder how that is going to work. Lets look at the example first:

 * gb 22:12, 10 December 2005 (UTC)

 * gb 21:37, 10 December 2005 (UTC)

Programming by Contract
Just read http://www.aechmea.de/html/german/Information01_e.htm. Since Eiffel has hogged the term "Design by Contract" they use the term "Programming by Contract" - Alltrue I hate it when companys hogg general terms for trademak it might be better to use the non protected term.

--Krischik T 18:37, 10 December 2005 (UTC)

 * In the case of Eiffel, they have created the thing. There was little O-O correctness theory of practical use before Eiffel AFAIK. Now everyone is trying to follow suit. If we, too, start using well defined terms in a sloppy manner, are we still doing it the Ada way? DbC is too valuable to be equated to just some checking in my view.

 * gb 21:51, 10 December 2005 (UTC)

Please make any Programming by Contract book generic (language agnostic)
Most programmers do not have the luxury of choosing the language they use. For several years I have been programming almost exclusively in VB6, next year I wil have to return to C++ for a while. Neither include direct support for PbC but that doesn't mean that programmers who are forced to use them can't benefit from the ideas. If PbC is introduced through the medium of a specific language, whether it is Eiffel, SPARK, or ADA busy programmers who use other languages will simply not be encouraged to apply the lessons of PbC even though quite a lot of them can be applied even in the absence of compiler support. So please separate the concepts of PbC from the language specific implementation. By the way I think that Programming by Contract is a better name than Design by Contract, especially if Betrand Meyer and co. have registered the latter as a trademark. --kwhitefoot 11:13, 12 December 2005 (UTC)

 * I have tried to follow your advice in Computer_Programming/Design by Contract. Since DbC is well thought out and integrated (criticism of arguably minor issues notwithstanding), I have stuck to DbC, in fairly general terms. Some pre/postcondition additions seem to miss quite a bit of DbC, however laudible they are. Comments etc. most welcome. gb 04:27, 15 December 2005 (UTC)

Error handling should be described as correctly as possible
I think that we should get this page correct, or else there is a risk of looking a little foolish.

However, before crossing out half of the text and adding another new half (which might not be good enough either), I'd like to discuss this.

Example:

Add the following function to Error_Handling_5 and observe that the compiler does indeed NOT help you to fullfill your contractual obligation. You'd think that calling Square_Root is all right, because all parameters are >= 0, but the compiler cannot tell this! Add this function, and see the compiler be happy:

function "**"(X: Float; E: Integer) return Float is  begin return -1.0; end "**";

Then run the program and notice Constraint_Error. Hence, as DbC requires, it is the programmer who MUST pay attention to calling a function with proper arguments. The Ada compiler cannot in general help you, even though it does some (sub)type checking.

Even if this example seems silly, absent SPARK it should prove that there is no a way for an Ada compiler to replace proper obedience to preconditions with type based magic.

So at the very least, the presentation requires rewording, and maybe a different theoretical model.

gb 07:01, 15 December 2005 (UTC)

True
A propper error handling chapter is indeed very important. There are to many false claims floating about - mostly from C programmers which allways thing they don't need support from the compiler. And if that means that DbC is not Ada then we need to say so - correctness of Computer_programming/Error_handling is more important then showing of Ada as a jack of all trades.

However In DcB or Strong-Typing I believe it is important to stess that runtime checks can be minimized. In languages without automated runtime checks you often have either to many checks (paranoid programmers adding checks anywhere) or to little checks (lazy programmers adding checks only when the problem happened at least once.

 * Could someone in the know please instruct how to edit the text and the examples after the first paragraphs of a section? There is a load of misinformation not just about DbC, but also about the pre/post of Sqrt, sorry, and I'd like to correct this. However, each time I try to edit, I get the first paragraph of the section and nothing else. What should I read/do? gb 20:08, 26 December 2005 (UTC)

 * This page is made up using transclusion, that is, including the text of other pages in it, as if they were templates. When you are hitting the edit link, you are using the one of a section that is inside of one of those pages. For editing the text after that fragments, you have to use the edit tab of this page. You will see in the wiki source where are other pages transcluded (using ), and then you can choose if you want to edit the text of this page, or the text of one of the transcluded pages. Hope this helps. ManuelGR 20:45, 26 December 2005 (UTC)

 * It has helped me, thanks. gb 23:44, 26 December 2005 (UTC)

title: Talk:Ada Programming/Error handling


text:
Talk:Synchronous and asynchronous communication methods

Suggested merge into Communication Theory
This would be a poor fit in the Communication Theory textbook: that text is made up of intellectual biographies of communication theorists, while this module contains only a brief definition of terminology. Perhaps we need a "Dictionary of Communication". Vault 16:08, 10 December 2005 (UTC)
 * That book however, would benefit from a listing of important terminology. If the Communication Theory book doesnt have room for this, then perhaps it should be expanded. We really don't need two books on the theory behind intra-personal communications. -- 00:31, 12 December 2005 (UTC)
 * This version of the module appears to have been an early draft. Its current incarntion makes much more sense. Delete/redirect. Vault 01:27, 12 December 2005 (UTC)
 * Fair enough, i didnt realize it was moved. I'll delete this one soon. -- 02:47, 12 December 2005 (UTC)


text:
Communication Theory/Introduction

Communication is deeply rooted in human behaviors and societies. It is difficult to think of social or behavioral events from which communication is absent. Indeed, communication applies to shared behaviors and properties of any collection of things, whether they are human or not.

We may turn to etymology for clues: "communication" (from the Latin "communicare") literally means "to put in common", "to share". The term originally meant sharing of tangible things; food, land, goods, and property. Today, it is often applied to knowledge and information processed by living things or computers.

We might say that communication consists of transmitting information. In fact, many scholars of communication take this as a working definition, and use Lasswell's maxim ("who says what to whom") as a means of circumscribing the field of communication. Others stress the importance of clearly characterizing the historical, economic and social context. The field of communication theory can benefit from a conceptualization of communication that is widely shared.

Communication Theory attempts to document types of communication, and to optimize communications for the benefit of all.

Indeed, a theory is some form of explanation of a class of observed phenomena. Karl Popper colorfully described theory as "the net which we throw out in order to catch the world--to rationalize, explain, and dominate it." The idea of a theory lies at the heart of any scholarly process, and while those in the social sciences tend to adopt the tests of a good theory from the natural sciences, many who study communication adhere to an idea of communication theory that is akin to that found in other academic fields.

This book approaches communication theory from a biographical perspective, in an attempt to show theory development within a social context. Many of these theorists would not actually consider themselves "communication" researchers. The field of communication study is remarkably inclusionary, and integrates theoretical perspectives originally developed in a range of other disciplines.

Theories and Models

Many suggest that there is no such thing as a successful body of communication theory, but that we have been relatively more successful in generating models of communication. A model, according to a seminal 1952 article by Karl Deutsch ("On Communication Models in the Social Sciences"), is "a structure of symbols and operating rules which is supposed to match a set of relevant points in an existing structure or process." In other words, it is a simplified representation or template of a process that can be used to help understand the nature of communication in a social setting. Such models are necessarily not one-to-one maps of the real world, but they are successful only insofar as they accurately represent the most important elements of the real world, and the dynamics of their relationship to one another.

Deutsch suggests that a model should provide four functions. It should organize a complex system (while being as general as possible), and should provide an heuristic function. Both these functions are similar to those listed above for theories. He goes on to suggest that models should be as original as possible, that they should not be obvious enough that they fail to shed light on the existing system. They should also provide some form of measurement of the system that will work analogously within the model and within the actual system being observed.

Models are tools of inquiry in a way that theories may not be. By representing the system being observed, they provide a way of working through the problems of a "real world" system in a more abstract manner. As such, they lend themselves to the eventual construction of theory, though it may be that theory of the sort found in the natural sciences is something that cannot be achieved in the social sciences. Unfortunately, while models provide the "what" and the "how," they are not as suited to explaining "why," and therefore are rarely as satisfying as strong theory.

title: Communication Theory/Introduction


text:
Talk:Communication Theory/Introduction

This page started with material copied from some of Halavais's now-excised sections in the Communication theory article. Vault 17:44, 10 December 2005 (UTC)

title: Talk:Communication Theory/Introduction


text:
User:MateoP~enwikibooks

Currently preparing a class in: Interventionism in Latin America During the Cold War: US and USSR

title: User:MateoP~enwikibooks


text:
User talk:MateoP~enwikibooks

Use this to reach me
Just leave a comment and sign. --MateoP 18:24, 10 December 2005 (UTC)

UK Constitution
Have you considered voting for UK Constitution and Government again this month, as it has been renominated. It relly is a very good book.Dolive35 15:58, 19 February 2006 (UTC)

Your account will be renamed
Hello,

The developer team at Wikimedia is making some changes to how accounts work, as part of our on-going efforts to provide new and better tools for our users like cross-wiki notifications. These changes will mean you have the same account name everywhere. This will let us give you new features that will help you edit and discuss better, and allow more flexible user permissions for tools. One of the side-effects of this is that user accounts will now have to be unique across all 900 Wikimedia wikis. See the announcement for more information.

Unfortunately, your account clashes with another account also called MateoP. To make sure that both of you can use all Wikimedia projects in future, we have reserved the name MateoP~enwikibooks that only you will have. If you like it, you don't have to do anything. If you do not like it, you can pick out a different name.

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Template:Social sciences bookshelf

 Social Science  A NTHROPOLOGY  - Anthropology - Introduction to Paleoanthropology - Linguistics - C OMMUNICATION  - Communication Theory - P OLITICAL SCIENCE  International Relations American Government Australian Government UK Constitution and Government United States Government - P SYCHOLOGY  - Introduction to Psychology - Social Psychology - Parapsychology - S OCIOLOGY  - Sociology - Introduction to Sociology (edit template) All Social Science books...

title: Template:Social sciences bookshelf


text:
User:Rogerd

is a US based editor.

I spent most of my wiki time on Engish Wikipedia. If you want to reach me, the best way is to leave a message there.

title: User:Rogerd


text:
Handbook of Genetic Counseling/Trisomy 13

Trisomy 13

Contracting

 * Introduce myself to Mrs. Doe. Remind her that we met 2 days ago.
 * How has Lil' John been doing? What are your concerns? How are you and your husband feeling about everything? empathy
 * Remember that Lil' John was referred to us to see if there might be something in his genetic makeup that could explain why he was born with some of the problems he has.

Give Results

 * I know it things are really crazy the day we met. Do you remember that we asked to take some of Lil' John's blood to look at his chromosomes?
 * We talked a little about how chromosomes hold all our genetic information and are inherited from our parents, so we're supposed to have 2 copies of each one.
 * We got Lil' John's test results back today. Unfortunately, they showed something different from what we would normally expect to see.
 * Lil' John has 3 copies of chromosome #13. This means that he has a condition called Trisomy 13.
 * silence
 * "I'm so sorry to give you this news"
 * respond to her reactions
 * use empathy

What is Trisomy 13?

 * Trisomy 13 is why Lil' John was born with his medical problems. Since our chromosomes have all the instructions that make our bodies develop and grow, when there is the wrong number (too many), our bodies are affected and don't develop correctly.
 * This is why Lil' John is so small, why he has a cleft lip & cleft palate, why he has a heart defect, and why he has extra fingers and holds his hands the way he does. This also means that Lil' John's brain didn't develop properly and he has profound mental retardation (why his head is so small).

What does this mean?

 * I'm very sorry to tell you that Trisomy 13 is considered to be a lethal condition. 50% die in the first week, 95% die by 6 months. Males have a poorer prognosis.
 * frequent causes of death: apnea, cardiopulmonary arrest, congenital heart disease, pneumonia
 * shocked
 * devastated

How did this happen?

 * When Lil' John was created, either the sperm or egg that made him had an extra copy of this chromosome in it, so he has three copies. (this is rare)
 * This is not anyone's fault. There is nothing you did to cause it & nothing you could have done to prevent it from happening.

What do we do now?

 * These children are usually not recommended for major medical intervention.
 * Try to keep the child comfortable - provide food (g-tube) and supportive care.
 * Decisions regarding prolonging life (ventilators), continued hospitalization, taking him home with support from Hospice Care (Starshine), residential home placement (St. Joseph's Home) - there are people who can help you take care of him.
 * No decisions must be made today. We'll support what you decide.
 * How are you feeling about everything? (overwhelmed, sad, angry)
 * empathy
 * normalize

Support Group Info.

 * SOFT - Support Organization for Trisomy 18 & 13
 * fellow parent

Follow-Up

 * Any other questions or things you would like to discuss?
 * I would like to give you a call later to see how you, Lil' John, and your family are doing. Can meet with your husband later too.
 * Here is my card - feel free to call me anytime if you have questions.
 * I'll write you a letter that summarizes everything we talked about today, so you don't have to remember it all.

Psychosocial Issues

 * How will you tell your husband? How will he react?
 * Who else will you tell - friends and family?
 * What kind of support do you have?
 * Infertility - tried to conceive for 8 years . . . how has this affected your marriage?
 * ART - 3 rounds of IVF and ICSI
 * AMA - age 43
 * declined prenatal testing because of miscarriage risk - how does that make you feel? would you have done anything differently?
 * interested in future children?
 * recurrence risk 0.5% - 1% (at 43, age related risk of CA is 3.23%)
 * how will this affect your marriage?
 * how have you and your husband dealt with difficult situations in the past?
 * Listen
 * ask more about her responses - why?


text:
Modern History/Independence in the Americas

Spain already had difficulty controlling its vast territories in the Americas when the ../French Revolution/ aligned Spain with France, causing problems in the colonies. Eventually there were declarations of independence on the American continents.

Independence of Haiti
Haiti had experienced the Haitian Revolution in the 1790s. Haiti was a self-governing colony of France. Napoleon sent a force to attack Haiti in 1802 or 1803 (FIXME exact year?), with the intention of restoring slavery and resuming direct control of the colony. As a result, the indigenous forces overran the invading French force. The indigenous leader, Jean-Jacques Dessalines, declared independence of Haiti on January 1, 1804.

Parts of Haiti opposed the rule of Dessalines. Someone assassinated him in 1806 and Haiti split into two governments.

British invasion of South America
(to do: What weapons were involved? [w])
 * Why did the British decide to attack South America? [C]
 * Which South American cities were the targets of British action? [C]
 * Who resisted the attack? [P]
 * How was Spain involved in resisting this attack? [G]

The British invasions of the Río de la Plata (Spanish: Invasiones Inglesas al Río de la Plata) were an unsuccessful series British attempts of military controlling the Spanish colonies located around the Río de la Plata basin in South America, between 1806 and 1807, as part of the global impact of the Napoleonic Wars. Spain was an ally of Napoleon at the time and, along with its South American colonies, cooperated in a trade boycott against the forces opposing Napoleon. The resistance of the local people and its active participation in the defence with no support from the Spanish Kingdom are seen as the penultimate step toward their independence.

In 1806, a British force of 1,000 to 2,000 men attacked Buenos Aires, the capital of the Viceroyalty of the River Plate. In 1807, a second invasion with at least 10,000 men targeted Montevideo and Buenos Aires. The northern port of Montevideo fell and became a British base. A large force approached Buenos Aires with the intent of capture.

At this point, Spain seemed to weak to defend its colony. However, the people of Buenos Aires decided not to welcome the British forces. The local population engaged the British in urban combat. (FIXME find a good description of the battle, and discover whether Spain sent any force)