2% other solutes (electrolytes, nitrogens, nutrients, and regulatory substances)
What is the function of albumin?
Maintain osmotic pressure and act as a carrier protein
What is the function of gamma globulin?
Humoral immunity and antibodies
Synthesized by plasma cells
What are the functions of alpha and beta globulins?
maintain osmotic pressure and act as carrier proteins
synthesized in the liver
What is the function of fibrinogin?
How are blood stains typically prepared?
Blood or bone marrow smear allowed to dry; stained with Reis stain
What organelles are present in an RBC?
no nucleus; only plasma membrane, cytoskeleton, hemoglobin, and glycolytic enzymes; no other organelles
Characteristic donut shape
7.5 um in diameter
4-6 million RBCs per microliter of blood
What is anemia and what causes it?
pathologic conditioin characterized by low blood concentration of hemoglobin
Caused by decreases in number of erythrocytes, amount of hemoglobin, or function of hemoglobin
What is the hematocrit?
Volume of RBCs per unit of volume blood; the percent total volume occupied by RBCs
normal is 38-48%
Females typically a little lower than males
What is the mean corpuscular hemoglobin concentration (MCHC)?
the ratio of hemoglobin to hematocrit
normal is 32-36%
What creates the characteristic donut (biconcave) shape of the erythrocyte?
membrane proteins and interactions between them (glycophorin, actin, tropomyosin, adducts)
What are spherocytosis and ellipocytosis?
Result of defects in the proteins ankyrin and spectrin; the RBCs can't move through the capillaries as well; body recognizes them as bad and demolishes them; leads to anemia
ellipocytosis (football shaped)
What do sickle cell anemia and thalassemia have in common?
Both have defects in hemoglobin (the oxygne carrying structure)
How does diabetes lead to elevated hemoglobin A1C levels?
excess glucose interacts with amino acids to form reactive intermediates that eract with circulating proteins to form advanced glycated end products (AGE) which slow conductioni speed and can lead to endothelial leakage and thicker BM
also AGE leads to non-enzymatic glycation of hemoglobin; glycohemoglobin (HbA1C)
Why is glycohemoglobin a measurement of average blood sugar over the past 2-3 months?
erythrocytes are freely permeable to glucose, which binds the N-terminal of valine irreversibly
120 days is average lifespan of erythrocyte
What are leukocytes?
Another name for WBCs; function to defend body against foreign material and infectious disease
What are neutrophils?
10-15 um; most abundant WBC in circulation
Function: migrate to site of infection to phagocytize bacteria
Histologically: multi-lobed nucleus with densely clumped chromatin; strand of nuclear material connects the lobes
What are the 3 types of cytoplasmic granules in neutrophils?
Specific (Small and numerous; contain phospholipases; target bacteria)
Azurophilic (large and less numberous; lysosomes)
Tertiary (Phosphatases, metalloproteinases)
What are the 3 types of neutrophils?
Band neutrophils (U-shaped nucleus; immature neutrophil; gives idea of proliferation)
Barr body (only in females)
What are eosinophils?
12-15 um; less abundant in circulation than neutrophils
Function: might into connective tissue; first line of defense against parasites
Histologically: bilobed nucleus; large cytoplasmic granules
What are basophils?
12-15 um; least abundant WBC in circulation
Function: migrate into connective tissue and play a role in hypersensitivity reactions
Histologically: key feature is large, intensely staining granules; nuclues is not very evident but biolobed if you can see it)
What are lymphocytes?
8-10 um; smallest nucleating cell in circulation
Histologically: roughly same size as RBC; large nucelus with pale cytoplasm surrounding; no granules
Differentiate to T-cells (recognize antigens), B-cells (antibody protection), and NK cells (kills virus-infected cells and timor cells)
T-cells, B-cells, and NK cells are examples of what type of WBC?
What are monocytes?
Function: migrate from circulation where they differentiate to macrophages and are involved in bacterial phagocytosis, antigen presentation, and removal of cellular debris (garbage collector)
Histologically: no granules; largest nucleating cell in circulationg; nucleus is abnormally shaped; chromatin stains in rope-like pattern
What are platelets and where do they come from?
Thrombocytes; 2-3 um
Function: adhere to endothelium to promote vessel repair, blood clotting, and vasoconstriction
Cellular fragments of megakerocytes
What is diapedesis?
Occurs at post-capillary venules in response to a seignal
Includes capture and rolling (upregulation of selectins that WBCs loosely associate with), firm adhesion (cell adhesion molecules; CAMs; integrins), spreading, diapedesis (histamines functionally reduce cell-cell interactions between endothelial cells), and attraction to site of infection by cytokines
What is hematopoeisis?
The process of producing mature RBCs
Site of this shifts through development: yolk sac, spleen/liver, bone marrow by late teens
Includes myeloid series and erythroid series
How can you tell if a cell is in the myeloid series?
the nucleus is oddly shaped
These stem cells produce neutrophils, eosinophils, and basophils
How can you tell if a cell is in the erythroid series?
Nucleus is round
Produces RBCs when it looses its nucleus and other organelles
Which structure is more likely to be single-stranded: RNA or DNA?
RNA though it can form higher order structures
Also, RNA has additional 2' hydroxyl which reduces its stability
What is the function of tRNA?
adaptor between AA and mRNA sequence
What is the function of mRNA?
contains protein coding sequence from gene; it is made from transcription
What is the function of rRNA?
structural and catalytic componenet of ribosomse; shows that RNA can also catalyze reactions, not only proteins
What is the function of snRNA?
What is the function of miRNA?
inhibits translation and degrades mRNA
Most simply, what is transcription?
Highly regulated (Primarily at initiation steps)
First step in genotype-->phenotype
Why did we spend so much time examining transcription in E.coli?
Because the general principles of bacterial transcription apply to eukaryotes as well
RNA polymerization begins with what common molecule?
ATP or GTP
In which direction is RNA synthesized?
5'-->3', just like DNA replication
Which of the following does not require a primer: transcription or replication?
Transcription does not
What is the TSS?
Transcriptional start site
RNA polymerase begins transcribing from this point
What is the promoter region?
Sequence info that directs transcription
Usually in the 5' (or upstream) direction of the TSS
Found in essentially all genes
Necessary for recruitment of general transcription factors
How do enhancers/silencers alter transcription?
In one of 2 ways: post-initiation events (eukaryotes only) and recruitment of transcription factors and RNA polymerase to core promoter
Can be near of far, upstream or downstream
Combination of various elemtns makes the regulation complex
What is teh core promoter in prokaryotes?
-10 box and -35 box
Consistent distance from start site
Contact points for RNA polymerase proteins
Region between -10 box and TSS is unwound
What are 2 enhancers found in prokaryotes?
UP element and FIS site (much farther upstream than UP)
Conserved; something specific always binds to these
What 5 subunits make up RNA polymerase?
beta (catalytic subunit)
beta' (clamps DNA during transcription)
Sigma (interacts with -10 and -35 boxes; targets polymerase to promoter; initiation factor; open complex is more stable than a closed complex in the sigma cycle)
and 2 alpha subunits
When transcription begins, what happens to the sigma subunit?
it dissociates from the holoenzyme RNA polymerase so that it polymerase can go somewhere; critical for promoter clearance and elongation
What are the 2 components of the alpha subunit of RNA polymerase?
alpha CTD: the c-terminus; interacts with enhancers and silencers
alpha NTD: N-terminus; binds to core promoter
With transcription, what is the difference between the holoenzyme and the core polymerase?
Core polymerase is the holoenzyme minus the sigma subunit (elongation)
What is the general rule of thumb reagardinf rate of transcription?
The more contacts you have between the DNA and the holoenzyme, the more translation you'll have
What are the different transcriptional states of genes?
Repression: foot on the brake; some translation because you can never completely stop it
De-repression: foot on the brake, proceeds slowly
Activation: hit the gas and go
Constitutive expression: cruise control; for the general housekeeping genes; always on, but can be regulated
What is the best way to regulate transcription?
Regulate the recruitment of RNA polymerase to the promoter by: chaning promoter strength (depends on 10/35 elements), additional Poly RNA to DNA contacts (includes UP element with sigma)
Proteins that bind to enhancers/silencers affect RNA pol recruitment too
Post-recruitment regulation is also important
What are the transcriptional states of lac operon in E. coli?
Repression: when no lactose is present; lac repressor binds specific DNA sequence in operator and prevents RNA pol from binding promoter
De-repression: lactose is there, but not the only sugar present; allactose (intermediate metabolite of lactose breakdown) binds lac repressor can causes conformational change so that it can't bind DNA anymore
Activation: lactose is only sugar presentp; cAMP binds CAP which interacts with sequence upstream of promoter; increases recruitment of RNA pol to promoter
With regards to transcription, what is allosterism?
The idea that binding of small molecules away from the active site alters function
What are the different kinds of RNA polyemrase in eukaryotes and whihc is most common?
I (transcribes gene for rRNA)
II (transcribes gene for mRNA and miRNA; sensitive to alpha amanitin which shuts off transcription completely; most common)
III (trancribes genes for tRNA, 5s rRNA, and snRNA)
Mitochondrial (transcribes genes for mitochondrial genome)
What are the core promoter elements of transcription in eukaryotes?
TATA, Inr (initiator), and DPE; function similarly to 10/35 box in bacteria
Which type of regulatory element in eukaryotes affects the transcriptional baseline?
Proximal promoter elements
How do distal regualtory elements in eukaryotes aleter transcription?
Recruitment of trancription factors to core promoter
Altering chromatin structure
Intronic regulatory elements (exclusively on the introns)
Can be used upstream of downstream (1-50kbp distance)
What are locus control regions?
Regulatory elemnts that govern transcription of a group of genes at a single chromosomal locus; can be thousands to millions of bps
What are the steps of transcription by RNAPII in eukaryotes?
loosen chromatin structure
Binding of general transcriptioin factors toc ore promorter
Binding of RNA pol II to DNA
Phosphorylation of RNAPII, promoter clearance, and product elongation
What are HDACs and what are they involved in?
acetylate lysines of chromatin structure to loosen it (along with HATs)
Inhibitors of HDACs are currently being tested as cancer treatments because they stop transcription
What are the general transcription factors that bind to the core promoter in eukaryotes?
TFIIA, B, D, E and H
TFIID binds the core promoter (TATA box) and all others are just involved in the assembly and recognition of core promoter
What makes up the pre-initiation complex in eukaryotic transcription?
Mediator complex (guides RNAPII to TFII)
RNAPII (huge 12 subunit complex)
What is the rate limiting step of transcription in eukaryotes?
formation of the pre-initiation complex
Which part of the TFII complex is responsible for phosphorylating RNAPII?
TFIIH and a second kinase, Ptef-B phosphorylate RNAPII on its c-terminus
Once this happens, RANPII leaves TFIIs and Med and moves down strand; now called the initiation complex
To have productive elongation (>50 bps), Ptef-B must add some more phosphates to RNAPII
How does the positive regulatory element affect transcription in eukaryotes?
enhances in 2 ways: binds to HAT to increase loosening of chromatin and helps to recruit TFII and Med proteins to promoter
How does the chromatin remodeling complex (CRC) affect transcription in eukaryotes?
enhances transcription by peeling DNA from nucleosome
How do transcriptional repressor proteins work in eukaryotes?
block the binding of general transcription factors and
recruit HDAC enzymes that deacetylate the nucleosomes; this results in compact, inaccessible chromatin
What are the 4 tasks of adolescents?
Independence from parents
Being like their peers
Accepting body image
Establishing sexual, vocational and moral identities
What are the 3 stages of adolescence?
Early adolescence (10-13)
Middle adolescence (14-16)
Late adolescence (16-2....)
What are the typically characteristics of early adolescence?
Onset of puberty, concern with body, desire to be separate from family, peer importance, and concrete thinking
The following characteristics are indicative of which phase of adolescence: completion of puberty, peers set standards, some desire to be separate from family, increased independence and some abstract thinking?
The following characteristics are indicative of which stage of adolescence: complete physical maturation, secure body image and gender role, emancipation from parents, nearly complete cognitive development, creation of life goals?
What are the stages of puberty in a typical girl?
thelarche (with asymmetrical breast development)
pubarche (6 mo later)
menarche (2 years later)
In a typical boy, what is the first stage of puberty?
testicular enlargment (98% of the time)
Who is more likely to enter pubtery first, males or females?
Females (completed in 4 years)
Males start later but complete in approximately 3 years
What does the pneumonic device HEADSS tell you to ask about in the adolescent interview?
Education (insight to learning disabilities)
Activities (counsel on exercising)
Drugs (ask if their friends do it)
Sex (what to expect and do friends have sex?)
What can you legally refuse to tell a parent about their adolescent?
Everything except whether the teen has thoughts of harming themself or others or if you suspect abuse (mandated reporter)
Definition: Healthy behavior
One that helps prevent illness and promotes health
Unhealthy behaviors play at least some role in each of the 12 leading causes of death; most common contributers to mortality are alcohol, tobacco, firearms, motor vehicle, diet, activity, and sexual behavior
Nationally, health habits tend to cluster in geographic regions
Defnition: Fundamental attribution error
When making attributions about actions or behavior, people tend to over-emphasize dispositional factors and under-emphasize situational factors
This is a possible reason for the persistence of bad health behaviors despite the knowledge that they're bad
What are the 3 most prominent influencers of an individual's universal behaviors?
Psychopathology (engage in different behaviors if you're depressed, bipolar, etc.)
SES (important to distinguish between situational and generational poverty here)
What must be known to alter or intervene with an unhealthy behavior?
Why they engage in behavior and what would motivate them to change
In terms of behavior and psychology, what is a construct?
variable or factor that influences whether a behavior will be changed
Includes habits, intent/willingness to act, cues, social influence, emotions, and environment
The following order defines which psychological model of behavioral modification:
individual-->interpersonal-->community-->institutions-->structures, policies and systems?
What are the three levels at which behaviors can be modified?
Individual (medications and counseling)
Situational (family, social groups, job, etc.)
Environmental (taxation, laws, ad campaigns, etc.)
What is the health belief model?
Individual's beliefs about their health and what will improve their health
Influenced by self-efficacy (confidence that specific task can be completed), perceived susceptibility, severity, benefits, and barriers
Not really a very good predictor of behavior changes
What are the essential characteristics of a stage theory?
Small number of distinct stages
Similar barriers facing all people in same stage
Different barriers facing people in different stages
Precontemplation, contemplation, preparation, action, and mainenance best describe which model of behavioral change?
Transtheoretical Model (TTM)
What does the social learning theory say about behaviors?
Behaviors are learned throguh modeling or the observation of oterh engaged in said behavior
You are also more likely to imitate the behaviors of those you have the most contact with
massive, wide-spread pre-mature cell death
Generally in response to injury; always considered pathological
Caused by leaking of lysosome enzymes into the cytoplasm and their consequent digestioin of the cell
Definition: Reversible cell injury
characterized by reduced oxidative phosphorylation of the cell and consequent depletion of energy stores; also causes cellular swelling because of changes in ion concentrations (Na+)
What are 2 types of cell death?
Necrosis and Apoptosis
programmed cell death of a single cell
Can be caused by cell injury or be part of a normal process
Hypoxia and free radical, physical agents, chemical agents/drugs, infectious organisms, immunologic reactions, genetics derangements, and nutritional imbalances can all cause what?
At which point does a reversible cell injury become irreversible and lead to cell death?
Not possible to pinpoint the time, they are on a continuum
What are the 3 types of radicals associated with hypoxia and consequent cell injury?
Superoxide anion (O2.) formed by cytochrome p450; can be removed by superoxide dismutase
Hydrogen peroxide (H2O2) removed by catalase or glutatione peroxidase
Hydroxyl radical (.OH) which initiates lipid peroxidation (ruins membranes) and DNA damage
Defects in volume regulation, increased permeability to Na+, cellular (hydropic) and mitochondrial swelling, plasma membrane blebs, dissociation of ribosomes, and aggregation of nucleolus are all characteristic of what?
Reversible cell death
Under a light microscope, how can you tell necrosis and apoptosis apart?
Can not be differentiated under a microscope
In necrosis, there is a dramatic change in the concentration of which intracellular ion?
Calcium; leads to calcification and formation of dense bodies that cause mitochondrial damage; also increases oxidative stress and lipid peroxidation which causes CytC to leak out of mitochondria and signal cell to die
What happens as a direct result of membrane defects in necrosis?
cells aggregate, coagulate, and change color (makes it easy to identify cell death location)
What is the morphology of a cell undergoing necrosis?
Eosinophilia (due to binding of eosin to denatured cytoplasm proteins)
Pyknosis (DNA condenses into solid chunks)
Karyohexis (DNAases and RNAases break up nucleus)
Karyolysis (DNAases chop up DNA into finer pieces)
What are the 5 types of necrosis?
Liquifactive necrosis (includes abscess formation and coagulative necrosis of the brain)
Definition: Coagulative necrosis
Typical in hypoxic or ischemic injury (blood supply has been completely cut off)
Myocardial infarction (cells block arteries; soft atherosclerotic plaques are most dangerous) and gangrene are 2 most common examples
What is the earliest histological sign of myocardial infarction?
Hemorrhage followed by entrace of neutrophils (turns tissue yellow)
Definition: Liquifactive necrosis
occurs when rate of cell destruction exceeds rate of repair
Abscess formation (tissue dissolves away and area filled with puss) and Coagulative necrosis of the brain (liquifies tissue; glial cells are responsible for healing because there are no fibroblasts) are the only 2 times this really occurs
Would you treat an abscess with antibiotics? Why or why not?
No because abscess is avascular and pH is to low for efficient functioning of antibiotic
Definition: Fat necrosis
occurs exclusively in adipose tissue
Only way to get it is pancreatitis (lipids released by fatty acids become saponified to form calcium soaps; look like amorphous blue areas on H and E stain) or trauma
Definition: Caseous necrosis
found in associated with mycobacteria (TB is most common); due to the presence of mycolic acids in their cell membranes; TB does not kill tissue, it's the dramatization of the body's immune response that does it; first and most importantly, you must rule out TB!
Definition: Fibrinoid necrosis
Indication of sever damage to blood vessel walls; damage triggers thrombosis and clotting cascade; caused by malignant hypertension
List the primary initiation site, recognition factor, and secodnary inititation site of transcription
1 site: core promoter (10/35 in prokaryotes, TATA in eukaryotes)
Recog. Factor: TFIID (and complex)
2 site: downstream of TFII
List the primary initiation site, recognition factor, and secondary initiation site of DNA replication
1 site: Origin of replication (ori)
Recognition factor: ORC
2 site: DNA polymerase/ pol alpha adjacent to ORC binding site
List the primary initiation site, recognition factor, and secodnary initiation site of the poly-adenylation of RNA
1 site: Poly A signal (AAUAA)
Recognition factor: Cleavage factors
2 site: ~30 nucleotides downsream of AAUAA
List the primary initiation site, recognition factor, and secondary initiation site of splicing
1 site: differs based on what the cell needs
Recognition factors: snRNPs
2 site: "branch-point" adenosine in splicing
List the primary initiation site, recognition factors, and secondary intitiation site of translation
1 site: 7-methyl guanosine cap of mRNA
Recognition factors: eIF4F complex (Composed of 3 subunits, eIFA, eIFG, and eIFE)
2 site: AUG start codon (Kozak/shine-dalgarno sequence)
What does UTR stand for?
Untranslated regions; sequences in mRNA that are not translated; often cotnain conserved sequences that affect mRNA stability
5' UTR is between 7-methyl cap and AUG start codon
3' UTR is after UAG stop codon (often contains sequences that enhance or inhibit translation)
Definition: Cap binding complex
eIF4F protein complex; in eukaryotes only
In translation, this is an adaptor between the 7-methyl guanosine cap and ribosome; recruits small subunit of ribosome to mRNA; ensures taht only mRNAs are translated
Consists of 3 subunits; eIFA, eIFG, eIFE
What do 4E binding proteins do? (4E-BPs)
Inhibit translation by binding eIF4F complex so it won't bind cap of mRNA
If these are phosphorylated (as in diabetes), it won't bind the complex and translation is uninhibited
eIF4F is expressed at higher levels in cancerous cells because not properly regulated
How do ribosomes involved in translation differ in prokaryotes and eukaryotes?
Prokaryotes: 50S subunit and 30S subunit form 70S ribosome
Eukaryotes: 60S subunit and 40S subunit form an 80S ribosome
What are the p site and the a site of a ribosomal subunit?
The p site (peptidyl tRNA site) is on the larger subunit of the ribosome and is where the chain lengthens and grows
The a site is where tRNAs bring in the next AA in the sequence
AA chain shifts from p site to a site, new AA is added, tRNA leaves, ribosome translocates to next codon, and the elongated chain shifts back to p site
What does the term polysomes indicate?
There are multiple ribosomes on a single mRNA; these dissociate and are translocated in the direction of translation (5'-->3' N-terminus-->C-terminus)
What is a polysome fraction?
A subpopulation of highly translated mRNAs in the cell
Can control protein synthesis by moving mRNAs in or out of polysome fraction (conceptual movement)
How do tRNAs "know" which AA to bring to the chain next?
Specific for 3 letter codon
What is the basic structure of tRNA?
anti-codon region that base pairs with the codon
Arms of t are base paired together to stabilize structure
acceptor stem (part attached to AA) has nucleotides base paired in a double helix and a part that is signle-stranded
An ester bond links the AA to the molecule; AA needs to be protected by proteins until it's loaded onto the growing chain
What does an aminoacyl tRNA synthetase do?
each AA has specific tRNA synthetases, but all isoacceptor tRNAs for an AA use the same synthetase; each synthetase binds AA, ATP (AMP attaches and 2 Pis go away, eventually loose AMP) and tRNA
What is the function if eIF2 in translation?
Eukaryotic initiation factor 2
escorts met-tRNA to ribosome
once start codon is recognized, eIF2 leaves and large ribosomal subunit combine with the small one
What is the function of eIF1 and eIF3 in translation?
bridges small subunit to cap complex
It's a linake for recruitment activity; interacts with cap binding complex to bring ribosome to mRNA
What is the sequence of events in translation in eukaryotes?
Small ribo subunit recruited to mRNA and bridged with eIF1 and eIF3
Small ribo scans along mRNA looking for start codon
Recognition of start codon (release of initiation factors, eIF1 and eIF3)
Termination (UAG; release factor binds to a site and causes teh release of everything)
What is the Kozak sequence?
The sequence in eukaryotes to which the 16S rRNA base pairs with; the more similar the sequence is to this, the stronger and better the binding will be; normally occurs at first AUG codon after the cap
What is the Shine-Delgarno sequence?
The defined start sequence in prokaryotes; can occur at internal AUG codons
What catalyzes the formation of a peptide bond between AA and the newly synthesized chain in translation?
Peptidyl transferase; energy required for peptide bond is from ATP used in tRNA charging
What is the function of EF2 (elongation factor 2) in translation?
Translocates the ribosome; it's a GTPase that binds GTP, hydrolyzes it, and phuses tRNA along when p site is empty
Servesa s a timer/switch
What is the function of EF1 (elongation factor 1) in translation?
escorts the next AA-tRNA to the vacant a site
Forming a peptide bond and subsequent translocation of the ribosome requires how many ATP/GTPs?
1 ATP (tRNA charging) and 1 GTP (translocation by EF2)
What does the release factor (RF) do in translation?
causes the termination of translation at a stop codon and the release of all subunits
ribo subunits are recycled
How does PERK regulate translation?
PERK kinase phosphorylates eIF2 so that it cannot participate in initiation
need to shut down translation when the ER is stressed and proteins are misfolded and begin accumulating; shut down translation so that these can be fixed
What is the defect in Wolcott-Rahison syndrome?
mutation in PERK gene so that the protein has reduced or no kinase activity; can't shut off translation
cells that can't shut off undergo apoptosis; leads to neonatal diabetes, epiphyseal dysplasia, osteoporosis, growth retardation
What is the primary target of over 50% of all antibiotics?
Where are micro RNAs (miRNAs) most often found?
in the 3' UTR region; have a hairpin structure; 21-22 nucleotide non-coding RNAs; regulate gene expression through repression of translation and/or destabalization of RNA; represses translation by interferring with translocation
Transcribed in the nucleus, processed in the cytoplasm to become active; target RISC (RNA induced silencing complex); binds this and guides it to specific mRNA; deadenylates mRNA and essentially destroys it
What are the 3 levels of prevention?
Primary (avoidance of a disease; not smoking)
Secondary (detection of disease in early, more treatable stage)
Tertiary (management of disease to minimize discomfort)
When should you utilize a screening test?
When the patient will benefit from the use of it; depends on how early disease can be detected, sensitivity and specificity of test, rate of false positives, harm caused by screening, and amount of motrality/increased survival brought about by test
When can a disease be detected, and when is it most likely to be detected?
Preclinical phase: after biological onset of disease, but prior to manifestation of symptoms
Most likely to be detected during clinical phase: after the manifestation of symptoms, often too late
What are the 2 types of bias associated with screening?
Lead time bias (Identifying disease earlier in natural course does not increase survival time)
Length time bias (tendency of screening test to preferentially identify individuals who have a longer preclinical phase of disease)
What are the leading sites of cancer-related deaths in men and women?
Cases: men (prostrate, lung, colon) women (breast, lung, colon)
Deaths: men (lung, prostrate, colon) women (lung, breast, colon)
Many of the secondary killers cannot be prevented through behavioral modification which s why screening is so important
What does "validity of a test" mean?
The ability to distinguish between who has a disease and who does not
No test can have perfect specificity and sensitivity
ability of a test to identify those who HAVE disease (look at the oclumns)
Probability of testing positive given the presence of a the disease
to be perfect, no false negatives
ability of a test to identify those who do NOT have disease (second row of columns)
Probability of testing negative given the absence of a disease
to be perfect, no false positives
How are specificity and sensitivity related to prevalence?
They are independent of each other
S and S do not change
Defintion: predictive value
Posterior or post-test probability
given certain test result, what is the probability that you actually do or do not have the disease
deals with rows
Dependent on the prevalence of disease in a population; higher prevalence increases PPV and decreases NPV
Definition: Likelihood ratios
Similar to predictive value
Positive LR: Sensitivity/(1-Specificity)
Negative LR: (1-Sens/Spec)
Which type of white blood cell releases histamines and heparin?