Pathophysiology week 2

Seasonal allergic rhinitis is most involved in type II hypersensitivity reactions. True or False

False Seasonal allergic rhinitis is most involved in type I hypersensitivity reactions

A 5-year-old patient's parents report loss of appetite and fatigue in their child. The parents also state that the child refuses to walk as a result of pain. The child's most likely diagnosis is a. ALL (acute lymphoid leukemia) b. CLL (chronic lymphoid leukemia) c. AML (acute myeloid leukemia) d. CML (chronic myeloid leukemia)

a. ALL (acute lymphoid leukemia) ALL is primarily a disorder of children with an abrupt onset of bone pain, bruising, fever, and infection. Children may refuse to walk and experience fatigue, loss of appetite, and abdominal pain. In CML, AML, and CLL, children do not complain of pain with walking. Additionally, chronic leukemia is most commonly found in adults.

In general, the best prognosis for long-term disease-free survival occurs with a. All (acute lymphoid leukemia) b. CLL (chronic lymphoid leukemia) c. AML (acute myeloid leukemia) d. CML (chronic myeloid leukemia)

a. All (acute lymphoid leukemia) ALL is highly curable in the pediatric population with an 85% survival rate in children. The average age of patients with CLL is 65 to 70 years. Median survival rate is less than 8 years. Patients younger than age 60 have a 4-year survival rate of 30% to 40% in AML. CML does not respond well to chemotherapy and carries a long-term survival rate of 50% to 60%.

Hemophilia B is also known as Christmas disease. True or false

true

The anemia resulting from a deficiency of either vitamin B12 (cobalamin) or folate is caused by a disruption in DNA synthesis of the blast cells in the bone marrow that produces very large abnormal bone marrow cells called megaloblasts. true or false

true megablast

Which clinical finding is indicative of compartment syndrome? a. Peripheral edema b. Absent peripheral pulses c. Redness and swelling d. Atrophy of distal tissues

b. Absent peripheral pulses

Transfusion reactions involve RBC destruction caused by a. donor antigens b. recipient antibodies c. donor T-cells d. recipient T-cells

b. recipient antibodies The recipient of the blood transfusion has antibodies to the donor's red blood cell (RBC) antigens; the antibodies destroy large numbers of RBC. Donor antigens, donor T, and recipient T cells do not cause transfusion reactions

A child with a history of recent strep throat infection develops glomerulonephritis. This is most likely a type _____ hypersensitivity reaction. a. I b. II c. III d. IV

c. III

A low mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular volume (MCV) are characteristic of which type of anemia? a. Vitamin B12 deficiency b. Folate deficiency c. Iron deficiency d. Erythropoietin deficiency

c. Iron deficiency

Patients with immunodeficiency disorders are usually first identified because they a. run high fevers. b. have unusually high WBC counts. c. develop brain infections. d. develop recurrent infections

d. develop recurrent infections

A commonly ingested substance associated with prolongation of the bleeding time is a. acetaminophen. b. tobacco. c. caffeine. d. aspirin.

d. aspirin.

The final step in clot formation is a. conversion of prothrombin to thrombin b. platelet degranulation and adhesion c. conversion of fibrinogen to fibrin d. clot retraction

d. clot retraction Clot retraction, the final stage of clot formation, occurs when the components of the fibrin clot are compressed or contracted to form a firm clot. Platelets serve as a catalyst in accelerating the conversion of prothrombin to thrombin. Platelet degranulation is not involved in clot formation. The formation of a fibrin clot occurs when fibrinogen is converted to fibrin, usually at the site of an injury.

Venous obstruction leads to edema because it ________ pressure. a. increase capillary oncotic b. increase arterial blood c. decrease tissue d. increase capillary hydrostatic

d. increase capillary hydrostatic Increased fluid accumulation in the interstitial space also occurs when the lymphatic flow is impaired or when capillaries become more permeable and "leak" fluid. These pressure gradients lead to edema. Interstitial fluid colloid osmotic pressure increases play a role in edema. Arterial blood pressure does not lead to edema. Decreased tissue pressure does not lead to edema in venous obstruction

Venous obstruction leads to edema because it ________ pressure. a. increases capillary oncotic b. increases arterial blood c. decreases tissue d. increases capillary hydrostatic

d. increases capillary hydrostatic

What laboratory finding is usually found in aplastic anemia? a. leukocytes b. thrombocythemia c. neutrophilia d. pancytopenia

d. pancytopenia Aplastic anemia is a stem cell disorder affecting the bone marrow mass. It is usually caused by toxic, radiant, or immunologic injury to the bone marrow stem cells, which causes a decrease in red cells, white cells, and platelets, or pancytopenia. Thrombocythemia causes an increased number of platelets and is not found in aplastic anemia. Leukocytosis indicates a higher white blood count and is not found in aplastic anemia. The presence of neutrophils in laboratory findings does not indicate a diagnosis of aplastic anemia.

The megakaryocyte is a precursor to a. factor IX. b. white blood cells. c. red blood cells. d. platelets

d. platelets

The only known curative treatment for CML is allogeneic bone marrow transplantation from a suitable donor. True or False

True Allogeneic bone marrow transplantation from a suitable donor is the only curative treatment for CML.

The liver is responsible for the synthesis of coagulation factors, with the exception of part of factor VIII. True or false

True The liver is responsible for the synthesis of coagulation factors, with the exception of part of factor VIII.

What is the correct definition of complete remission (CR) of leukemia a. CR in the absence of leukemia cells in the blood b. CR is less than 5% blast in marrow and normal CBS values c. CR is absence of leukemia cells regardless of CBS values d. CR is less than 5% leukemia cells in the blood

a. CR in the absence of leukemia cells in the blood Complete remission (CR) is a return to normal hematopoiesis. The bone marrow must have less than 5% blasts and must be maintained for at least 4 weeks in order to achieve CR. CR is an absence of leukemic cells, in addition to normal red cell, platelet, and neutrophil counts. CR must include normal hematopoiesis as well as an absence of leukemic cells. CR must include less than 5% blasts in marrow in addition to no detectible neoplastic cells.

Which disorder is considered a primary immunodeficiency disease? a. HIV/ AIDS b. Malnutrition immunodeficiency c. Cancer immunodeficiency d. Radiation immunodeficiency

a. HIV/ AIDS HIV/AIDS is a primary immunodeficiency disease involving destruction of T helper cells. Malnutrition immunodeficiency is a secondary immunodeficiency disorder and leads to T-cell destruction and dysfunction. Cancer immunodeficiency is a secondary immunodeficiency disorder caused by the destruction of rapidly proliferating cells from chemotherapeutic agents. Radiation immunodeficiency is a secondary immunodeficiency disorder caused by the destruction of rapidly proliferating cells from the effects of radiation.

Which group of clinical findings describes the typical presentation of ALL (acute lymphoid leukemia)? a. Pain in long bones, infection, fever, bruising b. Vertebral fracture, hypercalcemia, bone pain c. Elevated WBC count found on routine examination, asymptomatic d. Painless enlarged cervical lymph node, fever, weight loss

a. Pain in long bones, infection, fever,

The relationship of blood flow (Q), resistance (R), and pressure (P) in a vessel can be expressed by which equation? a. Q=P/R b. Q=R/P c. R=PQ d. P=Q/R

a. Q = P/R The relationship between the variables of pressure and resistance is expressed by Ohm's law: Q = P/R. Q is the blood flow, P is the pressure difference, and R is the resistance. Ohm's law is Q = P/R. R = PQ is not the expression for the relationship between blood flow, resistance, and pressure. P = Q/R is not the correct expression reflecting Ohm's law.

The Philadelphia chromosome is a balanced chromosome translocation that forms a new gene called a. bcr-abl. b. Rb. c. p53. d. ARA-c.

a. bcr-abl.

Velocity of blood flow is measured in a. centimeter per second b. millimeters per minute c. yards per hour d. kilometers per minute

a. centimeter per second Velocity of blood flow is measured in centimeters per second. Millimeters per minute is the not the measurement of the velocity of blood flow. Yards per hour is not a measurement of velocity. The velocity of blood flow is not measured in kilometers per minute.

A laboratory test finding helpful in confirming the diagnosis of iron-deficiency anemia is a. elevated total iron-binding capacity. b. elevated MCHC and MCV c. elevated total and indirect bilirubin d. positive or indirect Coombs test

a. elevated total iron-binding capacity. In iron-deficiency anemia, the total iron-binding capacity is elevated. The red cell indices of MCHC and MCV are decreased in iron-deficiency anemia. Total and indirect bilirubin levels are not utilized in diagnosing iron-deficiency anemia. Coombs testing is not utilized in obtaining a diagnosis of iron-deficiency anemia.

Red blood cells obtain nearly all their energy from metabolism of a. glucose. b. fats. c. proteins. d. acetyl coenzyme A.

a. glucose.

A 3-year-old boy who exhibits prolonged bleeding after minor trauma and a prolonged aPTT, but a normal platelet count, is likely to be diagnosed with a. hemophilia b. liver dysfunction c. disseminated intravascular coagulation d. thrombocytopenia

a. hemophilia Hemophilia is rare, but it is the most common severe inherited coagulation disorder. Prolonged bleeding from a minor trauma is a characteristic manifestation. Liver disease is commonly manifested by a decreased platelet count and prolonged coagulation studies. DIC is more often seen in adults as the result of trauma or sepsis. A very low platelet count is often seen in thrombocytopenia.

The major cause of death from leukemic disease is a. infection b. malnutrition c. hypovolemic shock. d. kidney failure

a. infection

Most carbon dioxide is transported in the bloodstream as a. carboxyhemoglobin b. bicarbonate ion c. dissolved carbon dioxide d. carbonic acid

b. bicarbonate ion Approximately 90% of the CO2 in the arterial blood and 60% of the CO2 in the venous blood are transported as bicarbonate. Carbon dioxide is not transported as carboxyhemoglobin. Some of the remaining carbon dioxide binds with protein to form carbaminohemoglobin for CO2 transport, but dissolved carbon dioxide is not the primary means of bloodstream transportation. Carbonic acid is disassociated into hydrogen and bicarbonate ions for elimination by the lungs and kidneys.

Risk factors for atherosclerosis include a. female gender. b. hyperlipidemia. c. high-protein diet. d. low-fiber diet.

b. hyperlipidemia.

Which condition enhances lymphatic flow? a. increased tissue hydrostatic pressure b. increased interstitial fluid colloid osmotic pressure c. decreased capillary hydrostatic pressure d. increased capillary oncotic pressure

b. increased interstitial fluid colloid osmotic pressure Lymphatic flow is controlled by increasing interstitial fluid colloid osmotic pressure and by the stimulation of the contractile fibers (often called lymphatic pumps) as they are stretched. Increasing interstitial fluid colloid osmotic pressure enhances lymphatic flow. Lymphatic flow is not enhanced by decreased capillary hydrostatic pressure. Lymphatic flow is controlled by increases in osmotic pressure, not oncotic pressure.

Disseminated intravascular coagulation may be treated with heparin therapy to a. enhance fibrinolysis b. inhibit clotting factor consumption c. activate platelets d. enhance liver synthesis of clotting factor

b. inhibit clotting factor consumption Although controversial, heparin may be used to minimize further consumption of clotting factors. Fibrinolysis is not enhanced by the use of heparin. The use of heparin does not activate platelets. Heparin is not known to enhance liver synthesis of clotting factors.

Blood flow throughout the periphery is regulated by a. cardiac output b. the autonomic nervous system c. velocity d. hemodynamics

b. the autonomic nervous system Blood flow throughout the periphery is controlled by central mechanisms that are mediated by the autonomic nervous system, the venous and thoracic pumps, and intrinsic autoregulatory mechanisms. Cardiac output does not control peripheral blood flow. Velocity is the measure of distance traveled in a given interval. Hemodynamics is the principle that governs the quantity of blood passing by a given point at a certain period.

Peripheral edema is a result of a. arterial insufficiency. b. venous thrombosis. c. hypertension. d. atherosclerosis

b. venous thrombosis.

While in the hospital for management of acute lymphoid leukemia (ALL), a patient develops severe thrombocytopenia. The most appropriate action for this condition is a. anticoagulant therapy b. chemotherapy c. activity restriction d. isolation

c. activity restriction Thrombocytopenia can produce a life-threatening hemorrhage. Patients with this condition should be protected from trauma and placed on activity restriction to reduce the risk of bleeding. Anticoagulant therapy in a patient with thrombocytopenia could actually cause the patient more bleeding. Thrombocytopenia is a complication of leukemia and chemotherapy. Chemotherapy is not an appropriate treatment option for thrombocytopenia. Isolation is not effective in managing the risk of hemorrhage.

Excessive red cell lysis can be detected by measuring the serum a. hemoglobin. b. methemoglobin. c. bilirubin. d. erythropoieti

c. bilirubin.

Tissues are able to autoregulate their rate of blood flow by controlling a. perfusion pressure b. arterial blood pressure c. vascular resistance d. venous return to the heart

c. vascular resistance Systemic vascular resistance is used to determine the resistance of vessels, diseases, or drug therapies that affect vessels. Any condition that increases vascular resistance requires more work for the heart to overcome the resistance and eject blood volume. Blood moves from an area of higher pressure to an area of lower pressure. The arterial and arteriolar walls with their muscular media coats provide the high-pressure end of the gradient. Seeking a lower pressure, blood moves toward the venous system. The thinner, more pliable walls of the venous bed furnish the low-pressure portion of the pressure gradient.

Which condition is associated with an elevated reticulocyte count? a. renal disease b. aplastic anemia c. hypertension d. hemolytic anemia

d. hemolytic anemia Hemolytic anemia is associated with an increased number of circulating reticulocytes or reticulocytosis. Anemia of chronic renal failure is not associated with reticulocytosis. Rather, it occurs from failure of the renal endocrine function. Aplastic anemia is a stem cell disorder that is characterized by pancytopenia, a decrease in red cells, white cells, and platelets. Hypertension is not related to reticulocytosis.

An important mediator of a type I hypersensitivity reaction is a. Complement. b. antigen-antibody immune c. complexes. c. T cells. d. histamine.

d. histamine.

When a patient is struck in the eye by a baseball, the result is redness and swelling. This increase in blood flow to a localized area is called a. autoregulation b. edema c. hyperemia d. hypoxia

d. hyperemia Hyperemia is a local increase in blood flow. Autoregulation is the ability of blood vessels within organs to maintain a constant blood flow. Edema is the swelling that results from hyperemia. Hypoxia is an insufficient supply of oxygen.

An increase in hemoglobin affinity for oxygen occurs with a. hyperthermia b. shift to the right c. elevated PCO2 d. shift to the left

d. shift to the left An increase in oxygen affinity is known as a shift to the left on the dissociation curve. Hyperthermia does not have an effect on the hemoglobin affinity. Elevation in PCO2 is seen with changes in pH. A decrease in the oxygen affinity is associated with a shift to the right on the oxyhemoglobin dissociation curve.

Autologous stem cell transplantation is a procedure in which a. there is a high rejection rate. b. stem cells are transferred to the patient from an HLA-matched donor. c. stem cells are transferred to the patient from an identical twin. d. stem cells are harvested from the patient and then returned to the same patient.

d. stem cells are harvested from the patient and then returned to the same patient.

Which condition is associated with an elevated reticulocyte count? a. Renal disease b. Aplastic anemia c. Hypertension d.Hemolytic anemia

d.Hemolytic anemia

Which causes vasoconstriction? a. norepinephrine b. calcium channel blocker c. A-adrenergic antagonist d. acetylcholine

a. norepinephrine The release of norepinephrine results in arterial vasoconstriction via receptors located on the vascular smooth muscle walls. Calcium channel blockers produce vasodilation by interfering with calcium intake into the vascular smooth muscle cells. α-Adrenergic antagonists do not cause vasoconstriction. Acetylcholine does not have an effect on vasoconstriction.

When systemic vascular resistance is decreased, blood flow a. increase b. decrease. c. stays the same d. moves to the extremities

b. decrease When SVR is pathologically decreased, the blood is spread over a larger area and blood flow slows dramatically. Individual organs, such as the kidney and brain, may not obtain sufficient blood flow to meet metabolic needs. Blood flow decreases in response to decreases in vascular resistance. When SVR is pathologically decreased, the blood is spread over a larger area and blood flow slows dramatically. Individual organs, such as the kidney and brain, may not obtain sufficient blood flow to meet metabolic needs. Blood flow is not diverted to the extremities when systemic vascular resistance is decreased. However, the vital organs may not have sufficient blood flow to maintain metabolic needs.

Widespread activation of the clotting cascade secondary to massive trauma is called a. hemophilia B b. disseminated intravascular coagulation (DIC). c. Hageman disease d, idiopathic thrombocytopenia

b. disseminated intravascular coagulation (DIC). Widespread clotting in small vessels leads to consumption of the clotting factors and platelets, which in turn leads to bleeding. DIC is either acute or chronic and occurs secondary to malignancy, sepsis, snake bites, trauma, shock, burns, and many other factors. Hemophilia B results from factor deficiency or the abnormal function of factor IX. Massive trauma is unrelated to the development of Hageman disease. Immune thrombocytopenia, formerly called idiopathic thrombocytopenia purpura, is an acquired immune-mediated disorder.

Severe combined immunodeficiency (SCID) syndrome is an example of a(n) a. deficient immune response. b. excessive immune response c. primary immune response d. hypersensitivity reaction.

b. excessive immune response SCID syndrome is an example of a deficient immune response in which the immune response is ineffective because of disease-causing genotypes or secondary/acquired dysfunction. An excessive immune response includes disorders in which the immune system is overfunctioning or hyperfunctioning. HIV/AIDS is an example of a primary acquired immunodeficiency disorder. Hypersensitivity reactions are an excessive immune response.

The prothrombin time (PT) and INR (international normalized ratio) measure the integrity of a. platelet function b. extrinsic pathway c. intrinsic pathway d. fibrinolysis .

b. extrinsic pathway The PT and INR assess the extrinsic pathway of coagulation. Platelet function is measured through a CBC. The aPTT assesses the intrinsic pathway of coagulation. The D-dimer assay reflects fibrinolysis.

Red blood cells differ from other cell types in the body, because they a. contain cytoplasmic proteins b. have no cytoplasmic organelles c. have a longer life span d. contain glycolytic enzymes

b. have no cytoplasmic organelles Red blood cells have no cytoplasmic organelles, nucleus, mitochondria, or ribosomes. Therefore, RBCs cannot synthesize protein or carry out oxidative reactions. Red blood cells are not capable of synthesizing protein because of their lack of organelles. Red blood cells live for 80 to 120 days in the circulation and then die and are replaced. Red blood cells do not contain glycolytic enzymes.

Blood flow is slow through capillaries because capillaries a. are so far from the heart b. have the largest total cross-sectional area c. are so marrow d. have no smooth muscle

b. have the largest total cross-sectional area The increased cross-sectional area in the capillary bed results in a significant decrease in velocity compared to the arterial and venous networks. Blood flow through the capillaries is not affected by the distance to the heart. Capillaries do have a diameter that is very small, but they have spaces that permit constituents to pass in and out of the capillaries. In some tissues, one or two smooth muscle cells form a precapillary sphincter that controls flow through the vessel.

Pernicious anemia is caused by a lack of a. iron b. intrinsic factor c. folate d. erythropoietin

b. intrinsic factor The fundamental defect causing pernicious anemia is the lack of intrinsic factor. Without it, vitamin B12 cannot be absorbed. Iron deficiency does not lead to pernicious anemia. Rather, it is the most common cause of anemia and is the result of unavailability of iron for hemoglobin synthesis. Pernicious anemia and folate deficiency are similar in etiology. Both are caused by a disruption in DNA synthesis of blast cells in bone marrow. Erythropoietin is necessary for the production of red cells

What is necessary for red blood cell production? a. phosphate b. iron c. magnesium d. calcium

b. iron Immature red blood cells produce hemoglobin, which is composed of two pairs of polypeptide chains, the globins. Each globin has an attached heme molecule that contains iron. Dietary iron is transported through the plasma on the RBC membrane. Phosphates are not a necessary component of red blood cell production. Magnesium is not a part of the production of red blood cells. Calcium is not involved in red blood cell production.

The primary source of erythropoietin is provided by the a. bone marrow. b. kidney. c. lung. d. liver.

b. kidney

A primary effector cell of the type I hypersensitivity response is a. monocytes b. mast cells c. neutrophils d. cytotoxic cells

b. mast cells Mast cells are a primary effector cell of the type I hypersensitivity response. Monocytes, neutrophils, and cytotoxic cells are not primary effectors of the type I hypersensitivity response.

The most appropriate treatment for secondary polycythemia is a. volume expansion with saline b. measured to improve oxygenation c. phlebotomy d. chemotherapy[y

b. measured to improve oxygenation Secondary polycythemia is because of chronic hypoxemia with a resultant increase in erythropoietin production. The goal of treatment is aimed at measures to reduce hypoxemia and improve oxygenation by implementing oxygen therapy. IV fluids may be used to treat relative polycythemia, because it is related to dehydration. Phlebotomy or increases in laboratory studies do not have an effect on secondary polycythemia. Polycythemia is not treated with chemotherapeutic agents.

A 58-year-old woman is seen in the clinic for reports of severe back pain. Her chest x-ray demonstrates generalized bone demineralization and compression fracture. Blood studies demonstrate elevated calcium levels. The most likely diagnosis is leukemia. a. leukemia b. myeloma c. Hodgkin disease d. back trauma

b. myeloma A diagnosis of plasma cell myeloma is confirmed by the presence of hypercalcemia, which can contribute to the compression fracture. Patients with leukemia diagnoses do not exhibit bone demineralization or elevated calcium levels. Lymphadenopathy is a more common manifestation of Hodgkin disease. Compression fractures can be the result of back trauma, but not in the presence of the other radiographic and laboratory results.

Certain autoimmune diseases are associated with the presence of specific proteins on a person's cells. These proteins are called ________ proteins. a. complement b. antibody receptor c. HLA or MHC d. TCR or BCR

c. HLA or MHC

Renal insufficiency is a common complication of which disease? a. Chronic myeloid leukemia (CML) b. Chronic lymphoid leukemia (CLL) c. Myeloma d. Hodgkin disease

c. Myeloma

The most effective therapy for anemia associated with kidney failure is a. iron administration b. high-protein diet c. erythropoietin administration d. vitamin B12 and folate administration

c. erythropoietin administration Therapy in anemia of chronic renal failure consists of dialysis and erythropoietin administration. The use of erythropoietin stimulating agents is to increase hemoglobin values to ensure adequate oxygen-carrying capacity. Iron, folate, and vitamin B12 replacement are initiated if necessary. Iron administration is utilized in iron-deficiency anemia. A high-protein diet is not the treatment of choice in the patient with renal failure, and a high-protein diet may be contraindicated. Vitamin B12 and folate are prone to nutritional anemias and receive replacement to adequate levels if necessary. However, dialysis and erythropoietin are more effective.

The effects of histamine release include a. vasoconstriction b. bronchodilation c. increased vascular permeability d. decreased gut permeability

c. increased vascular permeability Histamine release leads to increased vascular permeability, which fosters fluid movement out of capillaries and into tissues leading to the edema common in type I hypersensitivity. Histamine leads to bronchoconstriction, increased gut permeability, and vasodilation (not vasoconstriction).

RhoGAM (an Rh antibody) would be appropriate in an Rh-_____ woman with an _____ Rh-_____ antibody titer carrying an Rh-_____ fetus. a. negative; positive; positive b. positive; negative; negative c. negative; negative; positive d. negative; negative; negative

c. negative; negative; positive

A patient is diagnosed with a tortuous blood vessel of the right hand that bleeds spontaneously. This patient presents with a. petechiae. b. purpura. c. telangiectasia. d. thrombocytosis

c. telangiectasia.

Activation of the extrinsic pathway of coagulation is initiated by a. platelet factors. b. collagen exposure. c. tissue thromboplastin. d. factor VI

c. tissue thromboplastin.

The movement of blood through the vascular system is opposed by the force of a. viscosity b. the vessel length c. the vessel radius d. resistance

d. resistance The movement of blood through the vascular system is opposed by the force of resistance. Three determinants of resistance are vessel length, vessel radius, and blood viscosity. Viscosity is the thickness of fluid and has an effect on resistance. The length of the vessel does have an effect on the resistance. Vessel radius has an effect on resistance.

The most common primary immune deficiency that affects only B cells is a. DiGeorge b. Bruton agammaglobulinemia c. Wiskott-Aldrich d. selective IgA

d. selective IgA The most common B-cell primary immunodeficiency disorder is selective IgA deficiency. This disorder affects 1:2000 persons. DiGeorge is a T-cell primary immune deficiency. Bruton agammaglobulinemia is not the most common primary immune deficiency affecting B cells; frequency of disease is 1:250,000 males. Females are carriers. Wiskott-Aldrich affects both T cells and B cells.