Unit 2, Online Lab #1: Blood Pressure

I was having difficulty emailing and/or copying from the Virtual Lab website, so I decided to create my own graph using the Create a Graph website you recommended. I also typed the journal questions and answers directly into my blog instead of using their journal because of the same issues. I have included screen shots from the Virtual Lab website to show that my work was performed there.

JOURNAL ENTRIES (pre-lab):
Question 1: State a problem about the relationship of age and gender to blood pressure.
Answer 1: Although age and gender impact blood pressure, there are other factors that impact it as well. Genentics and overall health also play a role in determining blood pressure.
Question 2: Use your knowledge about the heart and the circulatory system to make a hypothesis about how the average blood pressure for a group of people would be affected by manipulating the age and gender of the group members.
Answer 2: As age increases, average blood pressure will increase (for both men and women). Men will have higher blood pressure than women.
Question 3: How will you use the investigation screen to test your hypothesis? What steps will you follow? What data will you record?
Answer 3: I will measure the blood pressure of a group of women and a group of men for each age group.

I will start with the youngest age group and measure a group of women. I will stay with the same age group and measure a group of men. I will move on to the next age group and repeat the process until I have gone through each age group. After the measurement is done for each age group/gender combination, I will record the measurements in the table.

After the measurements are complete for each group, I will also review the medical charts and note hereditary history and unhealthy habits that may impact blood pressure.

DATA TABLE AND GRAPH:
The data table is shown in the following two screen shots.

I graphed the data using the Create a Graph website. The first graph shown below is the one from that website. The second graph is a screen shot of the graph generated in the Virtual Lab website. I was not happy with this graph. It was difficult to see the entire graph in one screen shot and the axes were labeled incorrectly.


JOURNAL ENTRIES (post-lab):
Question 4: Analyze the result of your experiment. Explain any patterns you observed.
Answer 4:

• Over the age of 17 and on average, men have higher blood pressure compared to women of the same age group
• On average, females in the 18-24 age group have lower blood pressure compared to females in the 11-17 age group
• On average, females in the 25-34 age group have lower systolic blood pressure compared to females in the 11-17 age group. The average diastolic blood pressure of the same two age groups is the same.
• On average, the blood pressure of males increases as you move up from one age group to the next.
• Taking both systolic and diastolic blood pressure into account, the smallest change from one age group to the next is from the 18-24 age group to the 25-34 age group. This is true for men and women.
• The other contributing factors (weight, family history, salt in diet, exercise, and alcohol consumption) did not seem to have much of an impact on the blood pressure of those in the 25-34 age group. In other words, those in this age group could get away with being a few pounds overweight and/or eating a high salt diet without it negatively impacting their chances of having hypertension.
• The other contributing fators had a much greater impact for those over 35.
• Being overweight only did not necessarily mean one will have hypertension.
• When combined with one of the other factors, being overweight greatly increased the chances of having hypertension.
• There was not one of the other contributing factors was seen in every person with hypertension.

Question 5: Did the result of your experiment support your hypothesis? Why or why not? Based on your experiment what conclusion can you draw about the relationship of age and gender to group blood pressure averages?
Answer 5: The results of my experiment supported part of my hypothesis to a certain extent. I was correct that men would have higher blood pressure compared to women. I was partially correct when I said that as age increased, so would blood pressure. This was not true when comparing the average blood pressure of those in age group 11-17 to the average blood pressure of those in age group 18-24. Both the average systolic and diastolic blood pressure in the 18-24 year olds was lower than that of the 11-17 year olds. The conclusion that I draw is that in general, as you (male or female) get older, your blood pressure is going to increase. And men are going to have higher blood pressure compared to women of the same age.
Question 6: During the course of your experiment, did you obtain any blood pressure reading that were outside of the normal range for the group being tested? What did you notice on the medical charts for these individuals that might explain their high reading?
Answer 6: Yes, I did obtain blood pressure readings that were outside the normal ranges. I noticed that the high blood pressure could be explained by one of the other contributing factors. For example, most of those with high blood pressure were overweight, from just a few pounds up to almost 50 pounds overweight. I also noticed that most of those with high blood pressure also had one or more of the other contributing factors to blame for it. Some of them also had a diet high in salt, others did not exercise, while others consumed alcohol or had a family history of hypertension. There was only one person who was under weight that had high blood pressure. The only contributing factor that person was guilty of was eating a high salt diet. That person was also male.
Question 7: List risk factors associated with the hypertension. Based on your observation, which risk factor do you think is most closely associated with hypertension?
Answer 7: Risk factors associated with hypertension are as follows:

• Obesity
• Family history of hypertension
• High salt diet
• Lack of exercise
• Alcohol consumption

I think being overweight is most closely associated with hypertension.
Question 8: What effect might obesity have on blood pressure? Does obesity alone cause a person to be at risk for high blood pressure? What other factors, in combination with obesity, might increase a person's risk for high blood pressure?
Answer 8: Obesity has many negative health implications. But if you think about just the extra weight an obese person has to carry around....Their heart needs to pump enough blood to supply oxygen and nutrients to that extra weight. The additional blood flow required may increase blood pressure. All of the other factors (listed above) in combination with obesity might contribute to high blood pressure. A few other factors not listed are tobacco use and stress.

Compendium Review Unit 2 Major Topic: Oxygen/Microbes/Immunity

Oxygen...Microbes...Immunity

Table of Contents
I. Cardiovascular System: Heart and Blood Vessels
II. Cardiovascular System: Blood
III. Lymphatic System and Immunity
IV. AIDS Supplement
V. Sickle Cell Anemia

I. Cardiovascular System: Heart & Blood Vessels
A. Overview of the Cardiovascular System (heart & blood vessels)
1. Circulation performs exchanges
a. circulation of blood - to service cells
b. blood removes waste product from tissue fluid
c. blood delivers oxygen and nutrients to tissue fluid
d. lungs - exchange carbon dioxide for oxygen
e. kidneys - remove waste
f. intestines - where nutrients enter the blood
g. liver - removes poisons, takes up amino acids and returns proteins
2. Functions of the cardiovascular system
a. heart contracts -> blood pressure -> moves blood
b. blood vessels transport - heart, arteries, capillaries, veins, heart
c. capillaries exchange
d. blood flow regulated by heart and blood vessels
3. Lymphatic system
a. collects excess tissue fluid
Figure 5.1 from the text shows a general view of how the cardiovascular system works with the other systems of the body for the exchange of O2, CO2, waste, and nutrients.

B. The Types of Blood Vessels(artery, arteriole, capillary, venule, vein)
1. Arteries: from the heart (endothelium, smooth muscle & elastic tissue, connective tissue)
2. Capillaries: exchange (endothelium, basement membrane)
a. bypassed by arteriovenous shunt
3. Veins: to the heart (less smooth muscle, less connective tissue, thinner)
a. valves - in veins carrying blood against force of gravity
Figure 5.2 from the text shows an overview of the tissues and vessels that make up and surround a capillary bed.C. The Heart is a Double Pump
1. Passage of blood through the heart
a. O2 POOR blood -> sup vena cava and inf vena cava -> right atrium
b. right atrium -> tricuspid valve -> right ventricle
c. right ventricle -> pulmonary semilunar valve -> pulmonary trunk -> 2 pulmonary arteries -> lungs
d. pulmonary veins with O2 RICH blood -> left atrium
e. left atrium -> bicuspid valve -> left ventricle
f. left ventricle -> aortic semilunar valve -> aorta -> body proper
g. atria - thin walled, ventricles - thicker walled (pump blood farther)
2. Heartbeat is controlled
a. internal control of the heartbeat - SA node-atrium->AV node->AV bundle->Purkinje fibers-ventricles
b. external control of heartbeat - medulla oblongata, epinephrine and norepinephrine
3. Electrocardiogram is a record of the heartbeat (PQRST waves)
Figure 5.3 from the text illustrates the external anatomy of the heart. Figure 5.4 from the text illustrates a cross sectional view of the anatomy of the heart.
D. Features of the Cardiovascular System
1. Pulse rate equals heart rate (arterial walls pulse when left ventricle contracts
2. Blood flow is regulated
a. blood pressure moves blood in arteries
b. blood flow - slow in capillaries
c. blood flow in veins returns blood to heart (blood pressure low, velocity high=skeletal muscle pump, respiratory pump, valves)
d. blood pressure dependent on: volume of space involved, # of molecules in space, kinetic engergy of molecules
E. Two Cardiovascular Pathways
1. Pulmonary circuit: exchange of gases
a. CO2 given off and O2 taken into blood at pulmonary capillaries
2. Systemic circuit: exchanges with tissue fluid
a. tracing the path of blood (aorta, proper branch of aorta, region, returning vein, vena cava)
b. coronary circulation - supplies the heart
c. hepatic portal system - connects digestive tract to liver and liver to inf vena cava
Figure 5.10 from the text shows the flow of blood through the pulmonary and systemic circuits. Figure 5.11 from the text shows the systemic circuit and its major arteries and veins.F. Exchange at the Capillaries
1. Blood pressure and osmotic pressure control movement of fluid through capillary wall
2. Arterial end of cap. bed - blood pressure higher, water out
3. Capillary bed - pressures equal, solutes diffues (CO2, wastes in & O2, nutrients out)
4. Venule end of cap. bed - osmotic pressure higher, water in
5. Excess fluid collected by lymphatic capillaries
Figure 5.12 shows the exchanges that take place at the capillariesG. Cardiovascular Disorders
1. Disorders of the blood vessels
a. hypertension - high blood pressure (atherosclerosis, plaque, thrombus, embolus)
b. stroke, heart attack, aneurysm
c. dissolving blood clots (t-PA, aspirin)
d. treating clogged arteries (bypass surgery, stent, gene therapy)
2. Disorders of the heart
a. heart transplants (left ventricle assist device, total artificial heart)

Definitions from Chapter 5 can be found here.

II. Cardiovascular System: Blood
A. Blood: An Overview
1. Functions of the blood
a. transport - O2, nutrients, CO2, waste, hormones
b. defense - phagocytosis, antibodies, blood clotting
c. regulation - picks up & transports heat, regulates pH, maintains water-salt balance
2. Composition of blood
a. formed elements - red and white blood cells and platelets, produced in red bone marrow
b. plasma
i. water
ii. salts - buffer
iii. organic molecules - glucose, amino acids, urea, plasma proteins
Below is an image take from this website that shows all of the formed elements of blood.B. Red Blood Cells & Transport of Oxygen
1. How red blood cells carry oxygen
a. hemoglobin - globin=proteing containing 4 highly folded polypeptide chains, heme=iron-containing group in center of polypeptide chain
b. iron accepts O2 in lungs, lets go in tissues
c. 1 RBC (has no nucleus) = 280 million hemoglobin molecules, 1 hemoglobin=4 O2
d. RBCs - biconcave shape=greater surface area for diffusion, internal space=O2 transport
2. How red blood cells help transport carbon dioxide
a. 7% dissolved in plasma
b. 25% combines with terminal amino groups of globin molecules of hemoglobin
c. 68% transported as bicarbonate ion in plasma
e. RBCs - lack most organelles, produce ATP anaerobically, no consumption of O2 they carry
3. Red blood cells are produced in bone marrow
a. RBC stem cell divides -> new cells differentiate into mature RBCs
b. constant regeneration - RBCs only live 120 days
c. RBCs destroyed in liver and spleen by macrophages
d. globin -> amino acids, iron -> marrow, remaining heme portion degraded
e. erythropoietin - produced in kidneys, liver, other tissue - stimulates RBC production in stem cells of bone marrow
f. blood doping
4. Disorders involving red blood cells
a. anemia - too few RBCs or low hemoglobin, due to low iron, vit B12, folic acid
b. hemolysis - rupturing of RBCs, sickle-cell disease
Figure 6.3 from the text shows the single file lines of RBCs moving through capillaries, a close up of RBCs, and the four highly folded polypeptide chains of a hemoglobin molecule.C. White Blood Cells & Defense Against Disease
1. Types of white blood cells
a. neutrophil (granular leukocyte) - 1st responders to bacterial infection
b. eosinophil (granular leukocyte) - increase in # during parasitic worm infection or allergic reaction
c. basophil (granular leukocyte) - release histamine during allergic reaction
d. mast cell (granular leukocyte - release histamine during allergic reaction
e. lymphocyte (agranular leukocyte) - T cells and B cells
f. monocyte (agranular leukocyte) - differentiate into macrophages & dendritic cells
2. Disorders involving white blood cells
a. severe combined immunodeficiency disease
b. leukemia
c. infectious mononucleosis
The image below taken from this website is of a white blood cell that is trapping bacterial cells.D. Platelets & Blood Clotting
1. Blood clotting
a. 12 clotting factors plus Ca2+
b. prothrombin activator+prothrombin+Ca2+->thrombin+fibrinogen+Ca2+->fibrin threads
2. Disorders related to blood clotting
a. thrombocytopenia - insufficient number of platelets
b. thromboembolism - dilodged thrombus obstructs blood vessel
c. hemophilia - inherited clotting disorder, deficiency of clotting factor
Figure 6.8 from the text shows the process of clotting, generalized.E. Blood Typing & Transfusions
1. ABO groups
a. type A blood - type A antigen (on surface of RBC) & anti-B antibodies (in plasma)
b. type B blood - type B antigen & anti-A antibodies
c. type AB blood - type A & type B antigens, no antibodies
e. type O blood - no antigens, anti-A & anti-B antibodies
2. Rh blood groups
a. indicates whether person has Rh factor on RBC
b. Rh- individuals do not have antibody to Rh factor, produce them if exposed
Figure 6.9 from the text illustrates the 4 ABO blood groups and associated antigens and antibodies.F. Homeostasis
Figure 6.13 is a great overview of the contribution that each of the body systems makes to the maintenance of homeostasis.

Definitions from Chapter 6 can be found here.

III. Lymphatic System & Immunity
A. Microbes, Pathogens, & You
1. Bacteria
a. single celled prokaryote, no nucleus
b. shapes=bacillus (rod), spirillum (curved), coccus (spherical)
c. anatomy=fimbriae, flagellum, capsule, cell wall, plasma membrane, piluls, plasmid, ribosome, nucleoid
d. examples of infections - strep throat, TB, botulism, food poisoning, gangrene 2. Viruses
a. bridge gap between living and nonliving
b. acellular
c. obligate parasites
d. outer capsid made of protein, inner core made of nucleic acid
e. adheres to a receptor on cell surface, injects nucleic acid
f. uses cells host's enzymes and ribosomes for replication
g. viral genetic material is DNA or RNA
h. examples of infections - colds, flu, measles, chicken pox, polio, rabies, AIDS
i. emerging viruses - transported to new location, change in vector, change in face
3. Prions
a. proteinaceous infectious particles
b. cause a group of degenerative diseases of the nervous system (CJD, mad cow, scrapie)
Figure 7.1 from the text shows the parts of a bacterium. Figure 7.4 from the text shows the parts of a virus.
B. The Lymphatic System
1. Lymphatic vessels
a. capillaries, vessels, ducts -> cardiovascular veins in shoulders
b. capillaries take up excess tissue fluid
c. thoracic duct and right lymphatic duct
d. vessels - have valves and movement of lymph dependent on muscle contraction
2. Lymphatic organs
a. red bone marrow (makes RBCs, WBCs), thymus gland(makes hormones,maturation of T cells) - both primary
b. lymph nodes (filter lymph), spleen (filters blood), lympatic nodules, Peyer's patches- secondary
C. Nonspecific Defenses
1. Barriers to entry 1st line of defense
a. skin and mucous membranes
b. chemical barriers - skin oil, persperation, tears, saliva, acidic - stomach, vagina
c. resident bacteria - normal flora
2. Inflammatory response 2nd line of defense
a. redness, heat, swelling, pain
b. WBCs rush in - neutrophils, cytokines, monocytes (macrophages), lymphocytes
d. protective proteins - complement proteins - interferons, membrane attack complex
Figure 7.9 from the text depicts the inflammatory response. Figure 7.10 from the text illustrates how protective proteins (complement system) work against a bacterium.D. Specific Defenses
1. How specific defenses work
a. respond to antigens
b. primarily responsible - lymphocytes (T cell & B cell)
c. antibody-mediated immunity - B lymphocytes contain antigen specific receptors
d. antigen fits to BCR, B cell undergoes clonal expansion
e. cloned B cells become plasma cells (produce & secrete antibody) membory cells (can fight same antigen later on)
f. structure of antibody - Y-shaped, 5 classes determined by Y structure, variable region form antigen-bodning site
g. cell-mediated immunity - T lymphocytes, TCR requires antigen-presenting cell (APC) which already phagocytized a pathogen & presents antigen to TCR on self protein
h. T cell compares antigen to self protein and activation occurs, clonal expansion
i. cytotoxic T cells (cause apoptosis in virus-infected or tumor cell) & helper T cells (regulate immunity by secreting cytokines) produced
Tables and images from the text have been uploaded for later reference here. Figure 7.12 from the text shows the structure of an antibody. E. Acquired Immunity
1. Active immunity
a. vaccines - non-virulent pathogen or it's product
b. vaccine exposure->initially no antibody->antibody increases->levels off->declines
c. booster - second exposure to increase - titer increase to greater level
2. Passive immunity
a. prepared antibodies or immune cells given to combat a disease
b. example - newborn infants (antibodies from mother thru placenta, breast milk)
c. monoclonal antibodies - detect pregnancy, ID infections, deliver toxic drugs to tumors
d. cytokines & immunity - interferons & interleukins being investigated to use as adjuncts for vaccines and for cancer treatment
Figure 7.17 from the text illustrates the production of monoclonal antibodies.F. Hypersensitivity Reactions
1. Allergies
a. immediate allergic response (caused by IgE antibodies) eg - anaphylactic shock
b. delayed allergic response (initiated by memory T cells) - eg - TB skin test, contact dermititis (poison ivy)
2. Tissue rejection
a. prevention - immunosuppressive durgs, xenotransplantation, lab organs
3. Disorders of the immune system
a. autoimmune diseases - myasthenia gravis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis

Definitions from Chapter 7 can be found here.

IV. AIDS Supplement
A. Origin of & Prevalence of HIV
1. AIDS caused by HIV which infects & destroys cells (helper T & macrophages) of immune systems
2. Originated in Africa
3. Prevalence of HIV
a. of the 38.6 million people infected with HIV, 24.5 million in Sub-Saharan Africa, 8.3 million in Asia, 2 million in North America, Wester and Central Europe,1.6 million in Latin America
B. Phases of an HIV Infection
1. Category A: Acute Phase
a. no apparent symptoms
b. highly infectious
c. CD4 T cell count - has never fallen below 500 cells per mm3 of blood
d. at first, antibodies low count so not detectable
e. after time, body starts producing CD4 T cells like crazy to overcome the destruction of them by HIV
2. Category B: Chronic Phase
a. CD4 count - 499 to 200 cells/mm3
b. symptoms related to poor immune system - yeast infections, cervical displasia, prolonged diarrhea, thick sores on tongue, shingles, fevers, fatigue, cough
c. HIV particles - # is increasing
3. Category C: AIDS
a. diagnosed with AIDS
b. CD4 count below 200
c. 1 or more - 25 AIDS defining illnesses (opportunistic infections)
d. death results from: Pneumocystis jiroveci pneumonia, Mycobacterium tuberculosis, toxoplasmic encephalitis, Kaposi's sarcoma, invasive cervical cancer
C. HIV Structure and Life Cycle
1. Structure
a. 2 single strands of RNA (retrovirus)
b. various proteins
c. envelope - contains embedded spikes - Gp120
d. protection: 3 protein coats (nucleocapsid, capsid, matrix)
e. matrix contains 3 enzymes: reverse transcriptase (catalyst for reverse transcription), integrase (catalyst for integration of viral DNA into DNA of host), protease (catalyst for breakdown of newly synthesized viral polypept. into viral proteins)
Taken from this website, the drawing below shows the structure of the HIV virus..2. HIV life cycle
a. attachment - HIV to plasma membrane of target cell
b. fusion - of HIV to plasm membrane
c. entry - uncoating of capsid and protein coats, RNA, viral proteins released
d. reverse transcription - reverse transcriptase - single stranded RNA -> DNA
e. integration - viral DNA and integrase into nucleus of host cell, host cell DNA spliced, and viral DNA integrated (HIV now called provirus)
f. biosynthesis and cleavage - production of more viral RNA, protease cleavs long viral polypeptide chains
g. assembly - of viral enzymes, capsid proteins, and RNA into viral particles
h. budding - virus gets envelope
3. Transmission and Prevention of HIV
a. transmitted through bodily fluids during sexual contact, needle-sharing, transfusions, birth or breast feeding
b. prevention - abstinence, sex with 1 uninfected partner, use of condom
4. HIV testing and treatment for HIV
a. tests for HIV antibody
b. treatment - available but not without concerns (drug-resistant viruses)
c. drug therapy -HAART - different drugs interfere with life cycle of HIV
d. vacccines - being studied
The image below, taken from this website, shows the life cycle of the HIV virus.V. Sickle Cell Anemia
A. Discovery and Biological Basis
1. Discovered by cardiologist James B. Herrick and his intern Ernest E. Irons
2. Patient's physical symptoms: pain in back, muslces of back, arms, dark urine, fever, weakness, dizziness, shortness of breath
3. Patient's blood test: nucleated and sickle shaped RBCs
4. Biology of RBCs
a. RBCs made up mostly of hemoglobin (Hb)
b. Hb made up of 4 protein subunit with iron atom at center of each
c. each iron atom has affinity for O2
d. Hbs most important characteristic: reversibly bind and release O2 equally
e. Hb binds O2 when oxygen pressure is high and releases it when its pressure is low
f. anemia - signifant decrease in amount of functional Hb
g. sickle cell anemia causes depletion
i. O2 carrying capactiy reduced b/c of molecular changes in sickeled cell
ii. peculiar shape and rigidity, stick together and clog small arteries
h. effects
i. short term: poor O2 delivery causes shortness of breath
ii. long term: oxygen deprivation leads to poor tissue development
iii. hemolysis & clogging of arteries and capillaries in lungs, kidneys, & liver causes system malfuction and death usually by 30
5. Genetic basis of sickle cell anemia
a. 2 forms: sickle cell anemia (more severe) and sickle cell disease (rarely show complications) discovered
b. sickle cell disease - threshold effect, where a quantitative change produces a qualitative change
6. Localization of the genetic defect
a. through experimentation, defect determined to be in Hb molecule
B. Molecular Biology of Sickle Cell Anemia
1. Electrophoresis helped determine details of sickle cell anemia
a. inherited in simple Mendelian fashion
b. incomplete dominance (those with sickle cell trait have half normal RBCs and half sickle cell RBCs)
c. 1st genetic disease localized to a defect in the structure of a specific protein molecule
2. Sickle cell and normal hemoglobin
a. two-dimensional paper chromatography used to determine the peptide fragment of Hb that was different between normal and sickle cell RBCs (Linus Pauling)
b. Vernon Ingram determined the two Hb molecules differ by 1 amino acid
3. Discovering the difference between normal and sickle-cell Hb
a. Hb made up of 2 alpha and 2 beta chain (4 total) polypeptide chains
b. sickle cell Hb has 2 normal alpha chains; mutation in #6 position of both beta chains
c. protrusion formed by substitued aa at #6 location in beta chains locks into complementary site on other beta chains, linking sickle cell Hb molecules
C. Biogeography and Ecology of Sickle Cell Anemia
1. Unique geographic distribution pattern
a. high frequency of sickle cell anemia in families of African descent
b. higher frequency of sickle cell trait in Africa compared to US
c. sickle cell disease in Africa not common - high infant mortality rate for homozygous recessive infants
2. The malarial connection
a. frequency distribution of malaria mapped out closely to that of sickle cell
b. hypothesized in 1954 by Anthony Allison that heterozygous individuals for sickle cell have an advantage in combating malaria over those with normal Hb
c. balanced poymorphism explains how mutant gene (though by itself does not have an advantage) is selected for in the presence of malaria
3. How does sickle cell help combat malaria?
a. asexual reproductive stage of the protozoan consume high amounts of oxygen, as sickle cell become depleted of oxygen, they sickle and are removed from the body by the spleen....along with the merozoites
4. Treatment and Political Aspects
a. continuing search for treatment
b. drug therapies - some success, most limit detrimental effects instead of curing
c. gene Therapy - goal - replace bad gene Hbs with good allele Hba
d. political aspects - less money raised for sickle cell disease compared to predominantly caucasian afflicting diseases (cistic fibrosis and muscular dystrophy)

REFERENCES:
Mader, Syliva S. Human Biology. New York, NY: McGraw-Hill (2008).

The section on sickle cell anemia (roman numeral five) is a summary of the information provided in this website.

Links provided throughout the summary take you to online sources.


IMPORTANT NOTE: Any time "text" or "the text" is referenced in the above summary, I am referring to the textbook Human Biology by Sylvia Mader (cited directly above).