<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Nocturia and explain in detail? [/INST] Nocturia is defined by the International Continence Society (ICS) as “the complaint that the individual has to wake at night one or more times for voiding (i.e. to urinate).” The term is derived from Latin nox, night, and Greek [τα] ούρα, urine. Causes are varied and can be difficult to discern. Although not every patient needs treatment, most people seek treatment for severe nocturia, waking up to void more than 2–3 times per night.

Prevalence
Studies show that 5–15% of people who are 20–50 years old, 20–30% of people who are 50–70 years old, and 10–50% of people 70+ years old, urinate at least twice a night. Nocturia becomes more common with age. More than 50 percent of men and women over the age of 60 have been measured to have nocturia in many communities. Even more over the age of 80 are shown to experience symptoms of nocturia nightly. Nocturia symptoms also often worsen with age. Although nocturia rates are about the same for both genders, data shows that there is a higher prevalence in younger women than younger men and older men than older women.

Impact
Research suggests that more than 60% of people are negatively affected by nocturia. The resulting insomnia and sleep deprivation can cause exhaustion, changes in mood, sleepiness, impaired productivity, fatigue, increased risk of accidents, and cognitive dysfunction.  25% of falls that older individuals experience happen during the night, of which 25% occur while waking up to void.A quality of life test for people who experience nocturia was published in 2004. The pilot study was conducted only on men.

Diagnosis
Nocturia diagnosis requires knowing the patients nocturnal urine volume (NUV). The ICS defines NUV as “the total volume of urine passed between the time the individual goes to bed with the intention of sleeping and the time of waking with the intention of rising.” Thus, NUV excludes the last void before going to bed, but includes the first morning void if the urge to urinate woke the patient. The amount of sleep a patient gets, and the amount they intend to get, are also considered in a diagnosis.As with any patient, a detailed history of the problem is required to establish what is normal for that patient. The principal diagnostic tool for nocturia is the voiding bladder diary. Based on information recorded in the diary, a physician can classify the patient as having global polyuria, nocturnal polyuria, or bladder storage problems. A voiding bladder diary should record:
number of voids
timing of voids
volume voided
volume and time of fluid intakePatients should include the first morning void in the NUV. However, the first morning void is not included with the number of nightly voids.

Causes
Polyuria
Polyuria is excessive or an abnormally large production or passage of urine. Increased production and passage of urine may also be termed diuresis. Polyuria is usually viewed as a symptom or sign of another disorder (not a disease by itself), but it can be classed as a disorder, at least when its underlying causes are not clear.

Global polyuria
Global polyuria is the continuous overproduction of urine that is not only limited to sleep hours. Global polyuria occurs in response to increased fluid intake and is defined as urine outputs of greater than 40 mL/kg/24 hours. The common causes of global polyuria are primary thirst disorders such as diabetes mellitus and diabetes insipidus (DI). Urination imbalance may lead to polydipsia or excessive thirst to prevent circulatory collapse. Central diabetes insipidus is caused by low levels of Vasopressin (also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin). ADH is produced in the hypothalamus and stored in and released from the posterior pituitary gland. ADH increases water absorption in the collecting duct systems of kidney nephrons, subsequently decreasing urine production. ADH regulate hydration levels in the body. that helps regulates water levels. In nephrogenic DI, the kidneys do not respond properly to the normal amount of ADH.Diagnosis of DI can be made by an overnight water deprivation test. This test requires the patient to eliminate fluid intake for a fixed period of time, usually around 8–12 hours. If the first morning void is not highly concentrated, the patient is diagnosed with DI. Central DI usually can be treated with a synthetic replacement of ADH, called desmopressin. Desmopressin is taken to control thirst and frequent urination.  Although there is no substitute for nephrogenic DI, it may be treated with careful regulation of fluid intake.

Nocturnal polyuria
Nocturnal polyuria is defined as an increase in urine production during the night but with a proportional decrease in daytime urine production that results in a normal 24-hour urine volume. With the 24-hour urine production within normal limits, nocturnal polyuria can be translated to having a nocturnal polyuria index (NPi) greater than 35% of the normal 24-hour urine volume. NPi is calculated simply by dividing NUV by the 24-hour urine volume.  Similar to the inability of control urination, a disruption of arginine vasopressin (ADH) levels has been proposed for nocturia. Compared with the normal patients, nocturia patients have a nocturnal decrease in ADH level.Other causes of nocturnal polyuria include diseases such as

congestive heart failure
nephritic syndrome
liver failure
lifestyle patterns such as excessive nighttime drinking
sleep apnea increasing obstructive airway resistance. Obstructive sleep apnea sufferers have shown to have increases in renal sodium and water excretion that are mediated by elevated plasma atrial natriuretic hormone (ANH) levels. ANH is released by cardiac muscle cells in response to high blood volume. When activated, ANH releases water, subsequently increasing urine production.

Bladder storage
Normal human bladder storage capacity varies from person to person and is considered 400 – 600 mL. A bladder storage disorder is any factor that increases the frequency of small volume voids. These factors are usually related to lower urinary tract symptoms that affect the capacity of the bladder. Some patients with nocturia have neither global nor nocturnal polyuria according to the above criteria. Such patients most likely have a bladder storage disorder that impacts their nighttime voiding or a sleep disorder. Nocturnal bladder capacity (NBC) is defined as the largest voided volume during the sleep period.Decreased NBC can be traced to a decreased maximum voided volume or decreased bladder storage. Decreased NBC can be related to other disorders such as:

benign prostatic hyperplasia (BPH), also known as prostate enlargement
neurogenic bladder dysfunction
learned voiding dysfunction
anxiety disorders
urinary tract infection
certain pharmacological agents.

Mixed cause
A significant number of nocturia cases occur from a combination of causes. Mixed nocturia is more common than many realise and is a combination of nocturnal polyuria and decreased nocturnal bladder capacity. In a study of 194 nocturia patients:
7% were determined to solely have nocturnal polyuria
57% solely had decreased NBC
36% had a mixed cause of the twoMultifactor caused nocturia is often unrelated to an underlying urological condition. Mixed nocturia is diagnosed through the maintenance and analysis of bladder diaries of the patient. Assessment of cause contributions are done through formulas.

Management
Lifestyle changes
Although there is no cure for nocturia, many actions can manage the symptoms.

Prohibiting caffeine and alcohol intake. Both are diuretic.
Beverage consumption regulation. In regard to nocturia, this specifically means avoiding consuming fluids for three or more hours before bedtime so giving the bladder less fluid to store overnight </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anemia and explain in detail? [/INST] Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Symptoms of anemia depend on how quickly hemoglobin decreases. Additional symptoms may occur depending on the underlying cause. Preoperative anemia can increase the risk of needing a blood transfusion following surgery. Anemia can be temporary or long term and can range from mild to severe.Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown. Causes of bleeding include trauma and gastrointestinal bleeding. Causes of decreased production include iron deficiency, vitamin B12 deficiency, thalassemia and a number of bone marrow tumors. Causes of increased breakdown include genetic disorders such as sickle cell anemia, infections such as malaria, and certain autoimmune diseases. Anemia can also be classified based on the size of the red blood cells and amount of hemoglobin in each cell. If the cells are small, it is called microcytic anemia; if they are large, it is called macrocytic anemia; and if they are normal sized, it is called normocytic anemia. The diagnosis of anemia in men is based on a hemoglobin of less than 130 to 140 g/L (13 to 14 g/dL); in women, it is less than 120 to 130 g/L (12 to 13 g/dL). Further testing is then required to determine the cause.A large number of patients diagnosed with anemia of chronic disease present with no active inflammation or dietary issues. These include many with reduced limb loading, such as spinal cord injured patients, astronauts, elderly people with limited mobility, bed-bound and experimental bed-rest subjects.Certain groups of individuals, such as pregnant women, benefit from the use of iron pills for prevention. Dietary supplementation, without determining the specific cause, is not recommended. The use of blood transfusions is typically based on a persons signs and symptoms. Symptoms of anemia depend on how quickly hemoglobin decreases. In those without symptoms, they are not recommended unless hemoglobin levels are less than 60 to 80 g/L (6 to 8 g/dL). These recommendations may also apply to some people with acute bleeding. Erythropoiesis-stimulating agents are only recommended in those with severe anemia.Anemia is the most common blood disorder, affecting about a third of the global population. Iron-deficiency anemia affects nearly 1 billion people. In 2013, anemia due to iron deficiency resulted in about 183,000 deaths – down from 213,000 deaths in 1990. This condition is most prevalent in children with also an above average prevalence in elderly and women of reproductive age (especially during pregnancy). The name is derived from Ancient Greek: ἀναιμία anaimia, meaning "lack of blood", from ἀν- an-, "not" and αἷμα haima, "blood".Anemia is one of the six WHO global nutrition targets for 2025 and for diet-related global targets endorsed by World Health Assembly in 2012 and 2013. Efforts to reach global targets contribute to reaching Sustainable Development Goals (SDGs), with anemia as one of the targets in SDG 2 for achieving zero world hunger.

Signs and symptoms
Anemia is considered to be the most common blood disorder. A person with anemia may not have any symptoms depending on the underlying cause, and no symptoms may be noticed, as the anemia is initially mild, and then the symptoms become worse as the anemia worsens. A patient with anemia may report feeling tired, weak, decreased ability to concentrate, and sometimes shortness of breath on exertion.Symptoms of anemia can come on quickly or slowly. Early on there may be few or no symptoms. If the anemia continues slowly (chronic), the body may adapt and compensate for this change. In this case, no symptoms may appear until the anemia becomes more severe. Symptoms can include feeling tired, weak, dizziness, headaches, lack of physical exertion, shortness of breath, difficulty concentrating, irregular or rapid heartbeat, cold hands and feet, cold intolerance, pale or yellow skin, poor appetite, easy bruising and bleeding, and muscle weakness. Anemia that develops quickly, often, has more severe symptoms, including, feeling faint, chest pain, sweating, increased thirst, and confusion. There may be also additional symptoms depending on the underlying cause.In more severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The person may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure.On examination, the signs exhibited may include pallor (pale skin, mucosa, conjunctiva and nail beds), but this is not a reliable sign. A blue coloration of the sclera may be noticed in some cases of iron-deficiency anemia. There may be signs of specific causes of anemia, e.g. koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells – in hemolytic anemia), nerve cell damage (vitamin B12 deficiency), bone deformities (found in thalassemia major) or leg ulcers (seen in sickle-cell disease). In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement).  There may be signs of heart failure.
Pica, the consumption of non-food items such as ice, paper, wax, grass, hair or dirt, may be a symptom of iron deficiency; although it occurs often in those who have normal levels of hemoglobin .
Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. Restless legs syndrome is more common in people with iron-deficiency anemia than in the general population.

Causes
The causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemia), blood loss and fluid overload (hypervolemia). Several of these may interplay to cause anemia. The most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn, most commonly by iron deficiency.

Impaired production
Disturbance of proliferation and differentiation of stem cells
Pure red cell aplasia
Aplastic anemia affects all kinds of blood cells. Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities.
Anemia of kidney failure due to insufficient production of the hormone erythropoietin
Anemia of endocrine disease
Disturbance of proliferation and maturation of erythroblasts
Pernicious anemia is a form of megaloblastic anemia due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12. Lack of dietary B12 causes non-pernicious megaloblastic anemia.
Anemia of folate deficiency, as with vitamin B12, causes megaloblastic anemia
Anemia of prematurity, by diminished erythropoietin response to declining hematocrit levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age.
Iron deficiency anemia, resulting in deficient heme synthesis
Thalassemias, causing deficient globin synthesis
Congenital dyserythropoietic anemias, causing ineffective erythropoiesis
Anemia of kidney failure (also causing stem cell dysfunction)
Other mechanisms of impaired RBC production
Myelophthisic anemia or myelophthisis is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors, fibrosis, or granulomas.
Myelodysplastic syndrome
anemia of chronic inflammation
Leukoerythroblastic anemia is caused by space-occupying lesions in the bone marrow that prevent normal production of blood cells.

Increased destruction
Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These types generally feature jaundice, and elevated levels of lactate dehydrogenase.
Intrinsic (intracorpuscular) abnormalities cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic disorders.Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen.
Hereditary elliptocytosis is another defect in membrane skeleton proteins.
Abetalipoproteinemia, causing defects in membrane lipids
Enzyme deficiencies
Pyruvate kinase and hexokinase deficiencies, causing defect glycolysis
Glucose-6-phosphate dehydrogenase deficiency and glutathione synthetase deficiency, causing increased oxidative stress
Hemoglobinopathies
Sickle cell anemia
Hemoglobinopathies causing unstable hemoglobins
Paroxysmal nocturnal hemoglobinuria
Extrinsic (extracorpuscular) abnormalities
Antibody-mediated
Warm autoimmune hemolytic anemia is caused by autoimmune attack against red blood cells, primarily by IgG. It is the most common of the autoimmune hemolytic diseases. It can be idiopathic, that is, without any known cause, drug-associated or secondary to another disease such as systemic lupus erythematosus, or a malignancy, such as chronic lymphocytic leukemia.
Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic or result from an underlying condition.
Rh disease, one of the causes of hemolytic disease of the newborn
Transfusion reaction to blood transfusions
Mechanical trauma to red blood cells
Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and disseminated intravascular coagulation
Infections, including malaria
Heart surgery
Haemodialysis
Parasitic
Trypanosoma congolense alters the surfaces of RBCs of its host and this may explain T. c. induced anemia

Blood loss
Anemia of prematurity, from frequent blood sampling for laboratory testing, combined with insufficient RBC production
Trauma or surgery, causing acute blood loss
Gastrointestinal tract lesions, causing either acute bleeds (e.g. variceal lesions, peptic ulcers) or chronic blood loss (e.g. angiodysplasia)
Gynecologic disturbances, also generally causing chronic blood loss
From menstruation, mostly among young women or older women who have fibroids
Many type of cancers, including colorectal cancer and cancer of the urinary bladder, may cause acute or chronic blood loss, especially at advanced stages
Infection by intestinal nematodes feeding on blood, such as hookworms and the whipworm Trichuris trichiura
Iatrogenic anemia, blood loss from repeated blood draws and medical procedures.The roots of the words anemia and ischemia both refer to the basic idea of "lack of blood", but anemia and ischemia are not the same thing in modern medical terminology. The word anemia used alone implies widespread effects from blood that either is too scarce (e.g., blood loss) or is dysfunctional in its oxygen-supplying ability (due to whatever type of hemoglobin or erythrocyte problem). In contrast, the word ischemia refers solely to the lack of blood (poor perfusion). Thus ischemia in a body part can cause localized anemic effects within those tissues.

Fluid overload
Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia:
General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space.
From the 6th week of pregnancy, hormonal changes cause an increase in the mothers blood volume due to an increase in plasma.

Intestinal inflammation
Certain gastrointestinal disorders can cause anemia. The mechanisms involved are multifactorial and not limited to malabsorption but mainly related to chronic intestinal inflammation, which causes dysregulation of hepcidin that leads to decreased access of iron to the circulation.
Helicobacter pylori infection.
Gluten-related disorders: untreated celiac disease and non-celiac gluten sensitivity. Anemia can be the only manifestation of celiac disease, in absence of gastrointestinal or any other symptoms.
Inflammatory bowel disease.

Diagnosis
Definitions
There are a number of definitions of anemia; reviews provide comparison and contrast of them. A strict but broad definition is an absolute decrease in red blood cell mass, however, a broader definition is a lowered ability of the blood to carry oxygen. An operational definition is a decrease in whole-blood hemoglobin concentration of more than 2 standard deviations below the mean of an age- and sex-matched reference range.It is difficult to directly measure RBC mass, so the hematocrit (amount of RBCs) or the hemoglobin (Hb) in the blood are often used instead to indirectly estimate the value. Hematocrit; however, is concentration dependent and is therefore not completely accurate. For example, during pregnancy a womans RBC mass is normal but because of an increase in blood volume the hemoglobin and hematocrit are diluted and thus decreased. Another example would be bleeding where the RBC mass would decrease but the concentrations of hemoglobin and hematocrit initially remains normal until fluids shift from other areas of the body to the intravascular space.The anemia is also classified by severity into mild (110 g/L to normal), moderate (80 g/L to 110 g/L), and severe anemia (less than 80 g/L) in adults. Different values are used in pregnancy and children.

Testing
Anemia is typically diagnosed on a complete blood count. Apart from reporting the number of red blood cells and the hemoglobin level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using a microscope can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.
A blood test will provide counts of white blood cells, red blood cells and platelets. If anemia appears, further tests may determine what type it is, and whether it has a serious cause. although of that, it is possible to refer to the genetic history and physical diagnosis. These tests may include:

complete blood count (CBC); a CBC is used to count the number of blood cells in a sample of the blood. For anemia, it will likely to be interested in the levels of the red blood cells contained in blood (hematocrit), hemoglobin,  mean corpuscular volume.
determine the size and shape of red blood cells; some of red blood cells might also be examined for unusual size, shape and color.
serum ferritin; This protein helps store iron in the body, a low levels of ferritin usually indicates a low levels of stored iron.
serum vitamin B12; low levels usually develop an anemia, vitamin B12 is needed to make red blood cells, which carry oxygen to all parts of human body.
blood tests to detect rare causes; such as an immune attack on red blood cells, red blood cell fragility, and defects of enzymes, hemoglobin, and clotting.
a bone marrow sample; when the cause is unclear, a bone marrow test is performed, most often, when some blood cell defect is suspected.Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A reticulocyte count is a quantitative measure of the bone marrows production of new red blood cells.  The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response.
If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of erythropoiesis can help assess whether the bone marrow will be able to compensate for the loss and at what rate.
When the cause is not obvious, clinicians use other tests, such as: ESR, serum iron, transferrin, RBC folate level, hemoglobin electrophoresis, renal function tests (e.g. serum creatinine) although the tests will depend on the clinical hypothesis that is being investigated.
When the diagnosis remains difficult, a bone marrow examination allows direct examination of the precursors to red cells, although is rarely used as is painful, invasive and is hence reserved for cases where severe pathology needs to be determined or excluded.

Red blood cell size
In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency. In clinical workup, the MCV will be one of the first pieces of information available, so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.
Limitations of MCV include cases where the underlying cause is due to a combination of factors – such as iron deficiency (a cause of microcytosis) and vitamin B12 deficiency (a cause of macrocytosis) where the net result can be normocytic cells.

Production vs. destruction or loss
The "kinetic" approach to anemia yields arguably the most clinically relevant classification of anemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte (precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear with signs of hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding, such as guaiac-positive stool, radiographic findings, or frank bleeding.
The following is a simplified schematic of this approach:
* For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause.** Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.
Here is a schematic representation of how to consider anemia with MCV as the starting point:

Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow.

Microcytic
Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:

Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.

Iron deficiency anemia is due to insufficient dietary intake or absorption of iron to meet the bodys needs. Infants, toddlers, and pregnant women have higher than average needs. Increased iron intake is also needed to offset blood losses due to digestive tract issues, frequent blood donations, or heavy menstrual periods.  Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 12% of all women of childbearing age have iron deficiency, compared with only 2% of adult men. The incidence is as high as 20% among African American and Mexican American women. Studies have shown iron deficiency without anemia causes poor school performance and lower IQ in teenage girls, although this may be due to socioeconomic factors.  Iron deficiency is the most prevalent deficiency state on a worldwide basis.  It is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips (angular stomatitis).
In the United States, the most common cause of iron deficiency is bleeding or blood loss, usually from the gastrointestinal tract. Fecal occult blood testing, upper endoscopy and lower endoscopy should be performed to identify bleeding lesions. In older men and women, the chances are higher that bleeding from the gastrointestinal tract could be due to colon polyps or colorectal cancer.
Worldwide, the most common cause of iron deficiency anemia is parasitic infestation (hookworms, amebiasis, schistosomiasis and whipworms).The Mentzer index (mean cell volume divided by the RBC count) predicts whether microcytic anemia may be due to iron deficiency or thalassemia, although it requires confirmation.

Macrocytic
Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid, or both. Deficiency in folate or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.
Pernicious anemia is caused by a lack of intrinsic factor, which is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune condition targeting the parietal cells (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B12.
Macrocytic anemia can also be caused by the removal of the functional portion of the stomach, such as during gastric bypass surgery, leading to reduced vitamin B12/folate absorption. Therefore, one must always be aware of anemia following this procedure.
Hypothyroidism
Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of liver disease can also cause macrocytosis.
Drugs such as methotrexate, zidovudine, and other substances may inhibit DNA replication such as heavy metalsMacrocytic anemia can be further divided into "megaloblastic anemia" or "nonmegaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (six to 10 lobes). The nonmegaloblastic macrocytic anemias have different etiologies (i.e. unimpaired DNA globin synthesis,) which occur, for example, in alcoholism.
In addition to the nonspecific symptoms of anemia, specific features of vitamin B12 deficiency include peripheral neuropathy and subacute combined degeneration of the cord with resulting balance difficulties from posterior column spinal cord pathology. Other features may include a smooth, red tongue and glossitis.
The treatment for vitamin B12-deficient anemia was first devised by William Murphy, who bled dogs to make them anemic, and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease. George Minot and George Whipple then set about to isolate the curative substance chemically and ultimately were able to isolate the vitamin B12 from the liver. All three shared the 1934 Nobel Prize in Medicine.

Normocytic
Normocytic anemia occurs when the overall hemoglobin levels are decreased, but the red blood cell size (mean corpuscular volume) remains normal. Causes include:

Dimorphic
A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patients RBCs would be larger and paler than the donors RBCs. A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in common nutritional anemia.

Heinz body anemia
Heinz bodies form in the cytoplasm of RBCs and appear as small dark dots under the microscope. In animals, Heinz body anemia has many causes. It may be drug-induced, for example in cats and dogs by acetaminophen (paracetamol), or may be caused by eating various plants or other substances:

In cats and dogs after eating either raw or cooked plants from the genus Allium, for example, onions or garlic.
In dogs after ingestion of zinc, for example, after eating U.S. pennies minted after 1982.
In horses which eat dry or wilted red maple leaves.

Hyperanemia
Hyperanemia is a severe form of anemia, in which the hematocrit is below 10%.

Refractory anemia
Refractory anemia, an anemia which does not respond to treatment, is often seen secondary to myelodysplastic syndromes. Iron deficiency anemia may also be refractory as a manifestation of gastrointestinal problems which disrupt iron absorption or cause occult bleeding.

Transfusion dependent
Transfusion dependent anemia is a form of anemia where ongoing blood transfusion are required. Most people with myelodysplastic syndrome develop this state at some point in time. Beta thalassemia may also result in transfusion dependence. Concerns from repeated blood transfusions include iron overload. This iron overload may require chelation therapy.

Treatment
Treatment for anemia depends on cause and severity. Vitamin supplements given orally (folic acid or vitamin B12) or intramuscularly (vitamin B12) will replace specific deficiencies.

Oral iron
Nutritional iron deficiency is common in developing nations. An estimated two-thirds of children and of women of childbearing age in most developing nations are estimated to have iron deficiency without anemia; one-third of them have iron deficiency with anemia. Iron deficiency due to inadequate dietary iron intake is rare in men and postmenopausal women. The diagnosis of iron deficiency mandates a search for potential sources of blood loss, such as gastrointestinal bleeding from ulcers or colon cancer.Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with ferrous sulfate, ferrous fumarate, or ferrous gluconate.  Daily iron supplements have been shown to be effective in reducing anemia in women of childbearing age.  When taking iron supplements, stomach upset or darkening of the feces are commonly experienced.  The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed.  Vitamin C aids in the bodys ability to absorb iron, so taking oral iron supplements with orange juice is of benefit.In the anemia of chronic kidney disease, recombinant erythropoietin or epoetin alfa is recommended to stimulate RBC production, and if iron deficiency and inflammation are also present, concurrent parenteral iron is also recommended.

Injectable iron
In cases where oral iron has either proven ineffective, would be too slow (for example, pre-operatively), or where absorption is impeded (for example in cases of inflammation), parenteral iron preparations can be used. Parenteral iron can improve iron stores rapidly and is also effective for treating people with postpartum haemorrhage, inflammatory bowel disease, and chronic heart failure. The body can absorb up to 6 mg iron daily from the gastrointestinal tract. In many cases, the patient has a deficit of over 1,000 mg of iron which would require several months to replace. This can be given concurrently with erythropoietin to ensure sufficient iron for increased rates of erythropoiesis.

Blood transfusions
Blood transfusions in those without symptoms is not recommended until the hemoglobin is below 60 to 80 g/L (6 to 8 g/dL). In those with coronary artery disease who are not actively bleeding transfusions are only recommended when the hemoglobin is below 70 to 80g/L (7 to 8 g/dL). Transfusing earlier does not improve survival. Transfusions otherwise should only be undertaken in cases of cardiovascular instability.A 2012 review concluded that when considering blood transfusions for anaemia in people with advanced cancer who have fatigue and breathlessness (not related to cancer treatment or haemorrhage), consideration should be given to whether there are alternative strategies can be tried before a blood transfusion.

Vitamin B12 intramuscular injections
In many cases, vitamin B12 is used by intramuscular injection in severe cases or cases of malabsorption of dietary-B12. Pernicious anemia caused by loss of intrinsic factor cannot be prevented. If there are other, reversible causes of low vitamin B12 levels, the cause must be treated.Vitamin B12 deficiency anemia is usually easily treated by providing the necessary level of vitamin B12 supplementation. The injections are quick-acting, and symptoms usually go away within one to two weeks. As the condition improves, doses are reduced to weeks and then can be given monthly. Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms. Treatment should begin rapidly for severe neurological symptoms, as some changes can become permanent. In some individuals lifelong treatment may be needed.

Erythropoiesis-stimulating agents
The objective for the administration of an erythropoiesis-stimulating agent (ESA) is to maintain hemoglobin at the lowest level that both minimizes transfusions and meets the individual persons needs. They should not be used for mild or moderate anemia. They are not recommended in people with chronic kidney disease unless hemoglobin levels are less than 10 g/dL or they have symptoms of anemia. Their use should be along with parenteral iron. The 2020 Cochrane Anaesthesia Review Group review of Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non‐cardiac surgery  demonstrated that patients were much less likely to require red cell transfusion and in those transfused, the volumes were unchanged (mean difference -0.09, 95% CI -0.23 to 0.05). Pre-op Hb concentration was increased in those receiving high dose EPO, but not low dose.

Hyperbaric oxygen
Treatment of exceptional blood loss (anemia) is recognized as an indication for hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical Society. The use of HBO is indicated when oxygen delivery to tissue is not sufficient in patients who cannot be given blood transfusions for medical or religious reasons </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Adenovirus infection and explain in detail? [/INST] Adenovirus infection is a contagious viral disease, caused by Adenoviruses, commonly resulting in a respiratory tract infection. Typical symptoms range from those of a common cold, such as nasal congestion, coryza and cough, to difficulty breathing as in pneumonia. Other general symptoms include fever, fatigue, muscle aches, headache, abdominal pain and swollen neck glands. Onset is usually two to fourteen days after exposure to the virus. A mild eye infection may occur on its own, combined with a sore throat and fever, or as a more severe adenoviral keratoconjunctivitis with a painful red eye, intolerance to light and discharge. Very young children may just have an earache. Adenovirus infection can present as a gastroenteritis with vomiting, diarrhoea and abdominal pain, with or without respiratory symptoms. However, some people have no symptoms.Adenovirus infection in humans are generally caused by Adenoviruses types B, C, E and F. Spread occurs mainly when an infected person is in close contact with another person. This may occur by either fecal–oral route, airborne transmission or small droplets containing the virus. Less commonly, the virus may spread via contaminated surfaces. Other respiratory complications include acute bronchitis, bronchiolitis and acute respiratory distress syndrome. It may cause myocarditis, meningoencephalitis or hepatitis in people with weak immune systems.Diagnosis is by signs and symptoms, and a laboratory test is not usually required. In some circumstances, a PCR test on blood or respiratory secretions may detect adenovirus DNA. Other conditions that appear similar include whooping cough, influenza, parainfluenza, and respiratory syncytial virus. Adenovirus gastroenteritis appears similar to diarrhoeal diseases caused by other infections. Infection by adenovirus may be prevented by washing hands, avoiding touching own eyes, mouth and nose with unwashed hands, and avoiding being near sick people. A live vaccine to protect against types 4 and 7 adenoviruses has been used successfully in some military personnel. Management is generally symptomatic and supportive. Most adenovirus infections get better without any treatment. Medicines to ease pain and reduce fever can be bought over the counter.Adenovirus infections affect all ages. They occur sporadically throughout the year, and outbreaks can occur particularly in winter and spring, when they may spread more quickly in closed populations such as in hospitals, nurseries, long-term care facilities, schools, and swimming pools. Severe disease is rare in people who are otherwise healthy. Adenovirus infection accounts for up to 10% of respiratory infections in children. Most cases are mild and by the age of 10-years, most children have had at least one adenovirus infection. 75% of conjunctivitis cases are due to adenovirus infection. In 2016, the Global Burden of Disease Study estimated that globally, around 75 million episodes of diarrhea among children under the age of five-years, were attributable to adenovirus infection. The first adenoviral strains were isolated in 1953 by Rowe et al.

Signs and symptoms
Symptoms are variable, ranging from mild symptoms to severe illness. They depend on the type of adenovirus, where it enters into the body, and on the age and well-being of the person. Recognised patterns of clinical features include respiratory, eye, gastrointestinal, genitourinary and central nervous system. There is also a widespread type that occurs in immunocompromised people. Typical symptoms are of a mild cold or resembling the flu; fever, nasal congestion, coryza, cough, and pinky-red eyes. Infants may also have symptoms of an ear infection. Onset is usually two to fourteen days after exposure to the virus. There may be tiredness, chills, muscle aches, or headache. However, some people have no symptoms. Generally, a day or two after developing a sore throat with large tonsils, glands can be felt in the neck. Illness is more likely to be severe in people with weakened immune systems, particularly children who have had a hematopoietic stem cell transplantation. Sometimes there is a skin rash.

Respiratory tract
Preschool children with adenovirus colds tend to present with a nasal congestion, runny nose and abdominal pain. There may be a harsh barking cough. It is frequently associated with a fever and a sore throat. Up to one in five infants with bronchiolitis will have adenovirus infection, which can be severe. Bronchiolitis obliterans is uncommon, but can occur if adenovirus causes pneumonia with prolonged fever, and can result in difficulty breathing. It presents with a hyperinflated chest, expiratory wheeze and low oxygen. Severe pneumonia is most common in very young children age three-to-18 months and presents with sudden illness, ongoing cough, high fever, shortness of breath and a fast rate of breathing. There are frequently wheezes and crackles on breathing in and out.

Eyes
Adenovirus eye infection may present as a pinky-red eye. Six to nine-days following exposure to adenovirus, one or both eyes, typically in children, may be affected in association with fever, pharyngitis and lymphadenopathy (pharyngoconjunctival fever (PCF)). The onset is usually sudden, and there is often rhinitis. Adenovirus infection can also cause adenoviral keratoconjunctivitis.  Typically one eye is affected after an incubation period of up to a week. The eye becomes itchy, painful, burning and reddish and lymphadenopathy may be felt by the ear nearest the affected eye. The symptoms may last around 10-days to three-weeks. It may be is associated with blurred vision, photophobia and swelling of the conjunctiva. A sore throat and nasal congestion may or may not be present. This tends to occur in epidemics, affecting predominantly adults. In very young children, it may be associated with high fever, sore throat, otitis media, diarrhoea, and vomiting.

Gastrointestinal tract
Adenovirus infection can cause a gastroenteritis when it may present with diarrhoea, vomiting and abdominal pain, with or without respiratory or general symptoms. Children under the age of one-year appear particularly vulnerable. However, it usually resolves within three-days. It appears similar to diarrhoea diseases caused by other infections.

Other organs
Uncommonly the bladder may be affected, presenting with a sudden onset of burning on passing urine and increased frequency of passing urine, followed by seeing blood in the urine a day or two later. Meningism may occur in adenovirus associated meningoencephalitis, which may occur in people with weakened immune systems such as with AIDS or lymphoma. Adenovirus infection may result in symptoms of myocarditis, dilated cardiomyopathy, and pericarditis. Other signs and symptoms depend on other complications such as dark urine, itching and jaundice in hepatitis, generally in people who have a weakened immune system. Adenovirus is a rare cause of urethritis in men, when it may present with burning on passing urine associated with red eyes and feeling unwell.

Cause and mechanism
Adenovirus infection in humans are generally caused by Adenoviruses types B, C, E and F.Although epidemiologic characteristics of the adenoviruses vary by type, all are transmitted by direct contact, fecal-oral transmission, and occasionally waterborne transmission. Some types are capable of establishing persistent asymptomatic infections in tonsils, adenoids, and intestines of infected hosts, and shedding can occur for months or years. Some adenoviruses (e.g., serotypes 1, 2, 5, and 6) have been shown to be endemic in parts of the world where they have been studied, and infection is usually acquired during childhood. Other types cause sporadic infection and occasional outbreaks; for example, epidemic keratoconjunctivitis is associated with adenovirus serotypes 8, 19, and 37. Epidemics of febrile disease with conjunctivitis are associated with waterborne transmission of some adenovirus types, often centering on inadequately chlorinated swimming pools and small lakes. ARD is most often associated with adenovirus types 4 and 7 in the United States. Enteric adenoviruses 40 and 41 cause gastroenteritis, usually in children. For some adenovirus serotypes, the clinical spectrum of disease associated with infection varies depending on the site of infection; for example, infection with adenovirus 7 acquired by inhalation is associated with severe lower respiratory tract disease, whereas oral transmission of the virus typically causes no or mild disease. Outbreaks of adenovirus-associated respiratory disease have been more common in the late winter, spring, and early summer; however, adenovirus infections can occur throughout the year.Several adenoviruses, including Ad5, Ad9, Ad31, Ad36, Ad37, and SMAM1, have at least some evidence of causation of obesity in animals, adipogenesis in cells, and/or association with human obesity.

Diagnosis
Diagnosis is by signs and symptoms, and a laboratory test is not usually required. In some circumstances such as severe disease, when a diagnosis needs to be confirmed, a PCR test on blood or respiratory secretions may detect adenovirus DNA. Adenovirus can be isolated by growing in cell cultures in a laboratory. Other conditions that appear similar include whooping cough, influenza, parainfluenza, and respiratory syncytial virus. Since adenovirus can be excreted for prolonged periods, the presence of virus does not necessarily mean it is associated with disease.

Prevention
Infection by adenovirus may be prevented by washing hands, avoiding touching own eyes, mouth and nose before washing hands and avoiding being near sick people. Strict attention to good infection-control practices is effective for stopping transmission in hospitals of adenovirus-associated disease, such as epidemic keratoconjunctivitis. Maintaining adequate levels of chlorination is necessary for preventing swimming pool-associated outbreaks of adenovirus conjunctivitis. A live adenovirus vaccine to protect against types 4 and 7 adenoviruses has been used in some military personnel. Rates of adenovirus disease fell among military recruits following the introduction a live oral vaccine against types 4 and 7. Stocks of the vaccine ran out in 1999 and rates of disease increased until 2011 when the vaccine was re-introduced.

Treatment
Treatment is generally symptomatic and supportive. Medicines to ease pain and reduce fever can be bought over the counter. For adenoviral conjunctivitis, a cold compress and lubricants may provide some relief of discomfort. Steroid eye drops may be required if the cornea is involved. Most adenovirus infections get better without any treatment.

Prognosis
After recovery from adenovirus infection, the virus can be carried for weeks or months.Adenovirus can cause severe necrotizing pneumonia in which all or part of a lung has increased translucency radiographically, which is called Swyer-James Syndrome. Severe adenovirus pneumonia also may result in bronchiolitis obliterans, a subacute inflammatory process in which the small airways are replaced by scar tissue, resulting in a reduction in lung volume and lung compliance.

Epidemiology
Adenovirus infections occur sporadically throughout the year, and outbreaks can occur particularly in winter and spring. Epidemics may spread more quickly in closed populations such as in hospitals, nurseries, long-term care facilities, boarding schools, orphanages and swimming pools. Severe disease is rare in people who are usually healthy. Around 10% of respiratory infections in children are caused by adenoviruses </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Braxton Hicks contractions and explain in detail? [/INST] Braxton Hicks contractions, also known as practice contractions or false labor, are sporadic uterine contractions that may start around six weeks into a pregnancy. However, they are usually felt in the second or third trimester of pregnancy.

Associated conditions
Braxton Hicks contractions are often confused for labor. Braxton Hicks contractions allow the pregnant womans body to prepare for labor. However, the presence of Braxton Hicks contractions does not mean a woman is in labor or even that labor is about to commence. Another common cause of pain in pregnancy is round ligament pain.
Table 1 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Time and explain in detail? [/INST] Time is the continued sequence of existence and events that occurs in an apparently irreversible succession from the past, through the present, into the future. It is a component quantity of various measurements used to sequence events, to compare the duration of events or the intervals between them, and to quantify rates of change of quantities in material reality or in the conscious experience. Time is often referred to as a fourth dimension, along with three spatial dimensions.Time has long been an important subject of study in religion, philosophy, and science, but defining it in a manner applicable to all fields without circularity has consistently eluded scholars.
Nevertheless, diverse fields such as business, industry, sports, the sciences, and the performing arts all incorporate some notion of time into their respective measuring systems.Time in physics is operationally defined as "what a clock reads".The physical nature of time is addressed by general relativity with respect to events in spacetime. Examples of events are the collision of two particles, the explosion of a supernova, or the arrival of a rocket ship. Every event can be assigned four numbers representing its time and position (the events coordinates). However, the numerical values are different for different observers. In general relativity, the question of what time it is now only has meaning relative to a particular observer. Distance and time are intimately related, and the time required for light to travel a specific distance is the same for all observers, as first publicly demonstrated by Michelson and Morley. General relativity does not address the nature of time for extremely small intervals where quantum mechanics holds. At this time, there is no generally accepted theory of quantum general relativity.Time is one of the seven fundamental physical quantities in both the International System of Units (SI) and International System of Quantities. The SI base unit of time is the second, which is defined by measuring the electronic transition frequency of caesium atoms. Time is used to define other quantities, such as velocity, so defining time in terms of such quantities would result in circularity of definition. An operational definition of time, wherein one says that observing a certain number of repetitions of one or another standard cyclical event (such as the passage of a free-swinging pendulum) constitutes one standard unit such as the second, is highly useful in the conduct of both advanced experiments and everyday affairs of life. To describe observations of an event, a location (position in space) and time are typically noted.
The operational definition of time does not address what the fundamental nature of it is. It does not address why events can happen forward and backward in space, whereas events only happen in the forward progress of time. Investigations into the relationship between space and time led physicists to define the spacetime continuum. General relativity is the primary framework for understanding how spacetime works. Through advances in both theoretical and experimental investigations of spacetime, it has been shown that time can be distorted and dilated, particularly at the edges of black holes.
Temporal measurement has occupied scientists and technologists and was a prime motivation in navigation and astronomy. Periodic events and periodic motion have long served as standards for units of time. Examples include the apparent motion of the sun across the sky, the phases of the moon, and the swing of a pendulum. Time is also of significant social importance, having economic value ("time is money") as well as personal value, due to an awareness of the limited time in each day and in human life spans.
There are many systems for determining what time it is, including the Global Positioning System, other satellite systems, Coordinated Universal Time and mean solar time. In general, the numbers obtained from different time systems differ from one another.

Measurement
Generally speaking, methods of temporal measurement, or chronometry, take two distinct forms: the calendar, a mathematical tool for organising intervals of time,
and the clock, a physical mechanism that counts the passage of time. In day-to-day life, the clock is consulted for periods less than a day, whereas the calendar is consulted for periods longer than a day. Increasingly, personal electronic devices display both calendars and clocks simultaneously. The number (as on a clock dial or calendar) that marks the occurrence of a specified event as to hour or date is obtained by counting from a fiducial epoch – a central reference point.

History of the calendar
Artifacts from the Paleolithic suggest that the moon was used to reckon time as early as 6,000 years ago. Lunar calendars were among the first to appear, with years of either 12 or 13 lunar months (either 354 or 384 days). Without intercalation to add days or months to some years, seasons quickly drift in a calendar based solely on twelve lunar months. Lunisolar calendars have a thirteenth month added to some years to make up for the difference between a full year (now known to be about 365.24 days) and a year of just twelve lunar months. The numbers twelve and thirteen came to feature prominently in many cultures, at least partly due to this relationship of months to years. Other early forms of calendars originated in Mesoamerica, particularly in ancient Mayan civilization. These calendars were religiously and astronomically based, with 18 months in a year and 20 days in a month, plus five epagomenal days at the end of the year.The reforms of Julius Caesar in 45 BC put the Roman world on a solar calendar. This Julian calendar was faulty in that its intercalation still allowed the astronomical solstices and equinoxes to advance against it by about 11 minutes per year. Pope Gregory XIII introduced a correction in 1582; the Gregorian calendar was only slowly adopted by different nations over a period of centuries, but it is now by far the most commonly used calendar around the world.
During the French Revolution, a new clock and calendar were invented in an attempt to de-Christianize time and create a more rational system in order to replace the Gregorian calendar. The French Republican Calendars days consisted of ten hours of a hundred minutes of a hundred seconds, which marked a deviation from the base 12 (duodecimal) system used in many other devices by many cultures. The system was abolished in 1806.

History of other devices
A large variety of devices have been invented to measure time. The study of these devices is called horology.An Egyptian device that dates to c. 1500 BC, similar in shape to a bent T-square, measured the passage of time from the shadow cast by its crossbar on a nonlinear rule. The T was oriented eastward in the mornings. At noon, the device was turned around so that it could cast its shadow in the evening direction.A sundial uses a gnomon to cast a shadow on a set of markings calibrated to the hour. The position of the shadow marks the hour in local time. The idea to separate the day into smaller parts is credited to Egyptians because of their sundials, which operated on a duodecimal system. The importance of the number 12 is due to the number of lunar cycles in a year and the number of stars used to count the passage of night.The most precise timekeeping device of the ancient world was the water clock, or clepsydra, one of which was found in the tomb of Egyptian pharaoh Amenhotep I. They could be used to measure the hours even at night but required manual upkeep to replenish the flow of water. The ancient Greeks and the people from Chaldea (southeastern Mesopotamia) regularly maintained timekeeping records as an essential part of their astronomical observations. Arab inventors and engineers, in particular, made improvements on the use of water clocks up to the Middle Ages. In the 11th century, Chinese inventors and engineers invented the first mechanical clocks driven by an escapement mechanism.

The hourglass uses the flow of sand to measure the flow of time. They were used in navigation. Ferdinand Magellan used 18 glasses on each ship for his circumnavigation of the globe (1522).Incense sticks and candles were, and are, commonly used to measure time in temples and churches across the globe. Waterclocks, and later, mechanical clocks, were used to mark the events of the abbeys and monasteries of the Middle Ages. Richard of Wallingford (1292–1336), abbot of St. Albans abbey, famously built a mechanical clock as an astronomical orrery about 1330.Great advances in accurate time-keeping were made by Galileo Galilei and especially Christiaan Huygens with the invention of pendulum-driven clocks along with the invention of the minute hand by Jost Burgi.The English word clock probably comes from the Middle Dutch word klocke which, in turn, derives from the medieval Latin word clocca, which ultimately derives from Celtic and is cognate with French, Latin, and German words that mean bell. The passage of the hours at sea was marked by bells and denoted the time (see ships bell). The hours were marked by bells in abbeys as well as at sea.

Clocks can range from watches to more exotic varieties such as the Clock of the Long Now. They can be driven by a variety of means, including gravity, springs, and various forms of electrical power, and regulated by a variety of means such as a pendulum.
Alarm clocks first appeared in ancient Greece around 250 BC with a water clock that would set off a whistle. This idea was later mechanized by Levi Hutchins and Seth E. Thomas.A chronometer is a portable timekeeper that meets certain precision standards. Initially, the term was used to refer to the marine chronometer, a timepiece used to determine longitude by means of celestial navigation, a precision firstly achieved by John Harrison. More recently, the term has also been applied to the chronometer watch, a watch that meets precision standards set by the Swiss agency COSC.
The most accurate timekeeping devices are atomic clocks, which are accurate to seconds in many millions of years, and are used to calibrate other clocks and timekeeping instruments.
Atomic clocks use the frequency of electronic transitions in certain atoms to measure the second. One of the atoms used is caesium, most modern atomic clocks probe caesium with microwaves to determine the frequency of these electron vibrations. Since 1967, the International System of Measurements bases its unit of time, the second, on the properties of caesium atoms. SI defines the second as 9,192,631,770 cycles of the radiation that corresponds to the transition between two electron spin energy levels of the ground state of the 133Cs atom.
Today, the Global Positioning System in coordination with the Network Time Protocol can be used to synchronize timekeeping systems across the globe.
In medieval philosophical writings, the atom was a unit of time referred to as the smallest possible division of time. The earliest known occurrence in English is in Byrhtferths Enchiridion (a science text) of 1010–1012, where it was defined as 1/564 of a momentum (11⁄2 minutes), and thus equal to 15/94 of a second. It was used in the computus, the process of calculating the date of Easter.
As of May 2010, the smallest time interval uncertainty in direct measurements is on the order of 12 attoseconds (1.2 × 10−17 seconds), about 3.7 × 1026 Planck times.

Units
The second (s) is the SI base unit. A minute (min) is 60 seconds in length, and an hour is 60 minutes or 3600 seconds in length. A day is usually 24 hours or 86,400 seconds in length; however, the duration of a calendar day can vary due to Daylight saving time and Leap seconds.

Definitions and standards
A time standard is a specification for measuring time: assigning a number or calendar date to an instant (point in time), quantifying the duration of a time interval, and establishing a chronology (ordering of events). In modern times, several time specifications have been officially recognized as standards, where formerly they were matters of custom and practice. The invention in 1955 of the caesium atomic clock has led to the replacement of older and purely astronomical time standards such as sidereal time and ephemeris time, for most practical purposes, by newer time standards based wholly or partly on atomic time using the SI second.
International Atomic Time (TAI) is the primary international time standard from which other time standards are calculated. Universal Time (UT1) is mean solar time at 0° longitude, computed from astronomical observations. It varies from TAI because of the irregularities in Earths rotation. Coordinated Universal Time (UTC) is an atomic time scale designed to approximate Universal Time. UTC differs from TAI by an integral number of seconds. UTC is kept within 0.9 second of UT1 by the introduction of one-second steps to UTC, the "leap second". The Global Positioning System broadcasts a very precise time signal based on UTC time.
The surface of the Earth is split up into a number of time zones. Standard time or civil time in a time zone deviates a fixed, round amount, usually a whole number of hours, from some form of Universal Time, usually UTC. Most time zones are exactly one hour apart, and by convention compute their local time as an offset from UTC. For example, time zones at sea are based on UTC. In many locations (but not at sea) these offsets vary twice yearly due to daylight saving time transitions.
Some other time standards are used mainly for scientific work. Terrestrial Time is a theoretical ideal scale realized by TAI. Geocentric Coordinate Time and Barycentric Coordinate Time are scales defined as coordinate times in the context of the general theory of relativity. Barycentric Dynamical Time is an older relativistic scale that is still in use.

Philosophy
Religion
Linear and cyclical
Ancient cultures such as Incan, Mayan, Hopi, and other Native American Tribes – plus the Babylonians, ancient Greeks, Hinduism, Buddhism, Jainism, and others – have a concept of a wheel of time: they regard time as cyclical and quantic, consisting of repeating ages that happen to every being of the Universe between birth and extinction.In general, the Islamic and Judeo-Christian world-view regards time as linear
and directional,
beginning with the act of creation by God. The traditional Christian view sees time ending, teleologically,
with the eschatological end of the present order of things, the "end time".
In the Old Testament book Ecclesiastes, traditionally ascribed to Solomon (970–928 BC), time (as the Hebrew word עידן, זמן iddan (age, as in "Ice age") zĕman(time) is often translated) was traditionally regarded as a medium for the passage of predestined events. (Another word, زمان" זמן" zamān, meant time fit for an event, and is used as the modern Arabic, Persian, and Hebrew equivalent to the English word "time".)

Time in Greek mythology
The Greek language denotes two distinct principles, Chronos and Kairos. The former refers to numeric, or chronological, time. The latter, literally "the right or opportune moment", relates specifically to metaphysical or Divine time. In theology, Kairos is qualitative, as opposed to quantitative.In Greek mythology, Chronos (ancient Greek: Χρόνος) is identified as the Personification of Time. His name in Greek means "time" and is alternatively spelled Chronus (Latin spelling) or Khronos. Chronos is usually portrayed as an old, wise man with a long, gray beard, such as "Father Time". Some English words whose etymological root is khronos/chronos include chronology, chronometer, chronic, anachronism, synchronise, and chronicle.

Time in Kabbalah
According to Kabbalists, "time" is a paradox and an illusion. Both the future and the past are recognised to be combined and simultaneously present.

In Western philosophy
Two contrasting viewpoints on time divide prominent philosophers. One view is that time is part of the fundamental structure of the universe – a dimension independent of events, in which events occur in sequence. Isaac Newton subscribed to this realist view, and hence it is sometimes referred to as Newtonian time.
The opposing view is that time does not refer to any kind of "container" that events and objects "move through", nor to any entity that "flows", but that it is instead part of a fundamental intellectual structure (together with space and number) within which humans sequence and compare events. This second view, in the tradition of Gottfried Leibniz and Immanuel Kant, holds that time is neither an event nor a thing, and thus is not itself measurable nor can it be travelled.
Furthermore, it may be that there is a subjective component to time, but whether or not time itself is "felt", as a sensation, or is a judgment, is a matter of debate.In Philosophy, time was questioned throughout the centuries; what time is and if it is real or not. Ancient Greek philosophers asked if time was linear or cyclical and if time was endless or finite. These philosophers had different ways of explaining time; for instance, ancient Indian philosophers had something called the Wheel of Time. It is believed that there was repeating ages over the lifespan of the universe. This led to beliefs like cycles of rebirth and reincarnation. The Greek philosophers believe that the universe was infinite, and was an illusion to humans. Plato believed that time was made by the Creator at the same instant as the heavens. He also says that time is a period of motion of the heavenly bodies. Aristotle believed that time correlated to movement, that time did not exist on its own but was relative to motion of objects. he also believed that time was related to the motion of celestial bodies; the reason that humans can tell time was because of orbital periods and therefore there was a duration on time.The Vedas, the earliest texts on Indian philosophy and Hindu philosophy dating back to the late 2nd millennium BC, describe ancient Hindu cosmology, in which the universe goes through repeated cycles of creation, destruction and rebirth, with each cycle lasting 4,320 million years.Ancient Greek philosophers, including Parmenides and Heraclitus, wrote essays on the nature of time.Plato, in the Timaeus, identified time with the period of motion of the heavenly bodies. Aristotle, in Book IV of his Physica defined time as number of movement in respect of the before and after.In Book 11 of his Confessions, St. Augustine of Hippo ruminates on the nature of time, asking, "What then is time? If no one asks me, I know: if I wish to explain it to one that asketh, I know not." He begins to define time by what it is not rather than what it is,
an approach similar to that taken in other negative definitions. However, Augustine ends up calling time a "distention" of the mind (Confessions 11.26) by which we simultaneously grasp the past in memory, the present by attention, and the future by expectation.
Isaac Newton believed in absolute space and absolute time; Leibniz believed that time and space are relational.
The differences between Leibnizs and Newtons interpretations came to a head in the famous Leibniz–Clarke correspondence.
Philosophers in the 17th and 18th century questioned if time was real and absolute, or if it was an intellectual concept that humans use to understand and sequence events. These questions lead to realism vs anti-realism; the realists believed that time is a fundamental part of the universe, and be perceived by events happening in a sequence, in a dimension. Isaac Newton said that we are merely occupying time, he also says that humans can only understand relative time. Relative time is a measurement of objects in motion. The anti-realists believed that time is merely a convenient intellectual concept for humans to understand events. This means that time was useless unless there were objects that it could interact with, this was called relational time. René Descartes, John Locke, and David Hume said that ones mind needs to acknowledge time, in order to understand what time is. Immanuel Kant believed that we can not know what something is unless we experience it first hand.

Immanuel Kant, in the Critique of Pure Reason, described time as an a priori intuition that allows us (together with the other a priori intuition, space) to comprehend sense experience.
With Kant, neither space nor time are conceived as substances, but rather both are elements of a systematic mental framework that necessarily structures the experiences of any rational agent, or observing subject. Kant thought of time as a fundamental part of an abstract conceptual framework, together with space and number, within which we sequence events, quantify their duration, and compare the motions of objects. In this view, time does not refer to any kind of entity that "flows," that objects "move through," or that is a "container" for events. Spatial measurements are used to quantify the extent of and distances between objects, and temporal measurements are used to quantify the durations of and between events. Time was designated by Kant as the purest possible schema of a pure concept or category.
Henri Bergson believed that time was neither a real homogeneous medium nor a mental construct, but possesses what he referred to as Duration. Duration, in Bergsons view, was creativity and memory as an essential component of reality.According to Martin Heidegger we do not exist inside time, we are time. Hence, the relationship to the past is a present awareness of having been, which allows the past to exist in the present. The relationship to the future is the state of anticipating a potential possibility, task, or engagement. It is related to the human propensity for caring and being concerned, which causes "being ahead of oneself" when thinking of a pending occurrence. Therefore, this concern for a potential occurrence also allows the future to exist in the present. The present becomes an experience, which is qualitative instead of quantitative. Heidegger seems to think this is the way that a linear relationship with time, or temporal existence, is broken or transcended.
We are not stuck in sequential time. We are able to remember the past and project into the future – we have a kind of random access to our representation of temporal existence; we can, in our thoughts, step out of (ecstasis) sequential time.Modern era philosophers asked: is time real or unreal, is time happening all at once or a duration, is time tensed or tenseless, and is there a future to be? There is a theory called the tenseless or B-theory; this theory says that any tensed terminology can be replaced with tenseless terminology. For example, "we will win the game" can be replaced with "we do win the game", taking out the future tense. On the other hand, there is a theory called the tense or A-theory; this theory says that our language has tense verbs for a reason and that the future can not be determined. There is also something called imaginary time, this was from Stephen Hawking, he says that space and imaginary time are finite but have no boundaries. Imaginary time is not real or unreal, it is something that is hard to visualize. Philosophers can agree that physical time exists outside of the human mind and is objective, and psychological time is mind-dependent and subjective.

Unreality
In 5th century BC Greece, Antiphon the Sophist, in a fragment preserved from his chief work On Truth, held that: "Time is not a reality (hypostasis), but a concept (noêma) or a measure (metron)." Parmenides went further, maintaining that time, motion, and change were illusions, leading to the paradoxes of his follower Zeno. Time as an illusion is also a common theme in Buddhist thought.J. M. E. McTaggarts 1908 The Unreality of Time argues that, since every event has the characteristic of being both present and not present (i.e., future or past), that time is a self-contradictory idea (see also The flow of time).
These arguments often center on what it means for something to be unreal. Modern physicists generally believe that time is as real as space – though others, such as Julian Barbour in his book The End of Time, argue that quantum equations of the universe take their true form when expressed in the timeless realm containing every possible now or momentary configuration of the universe, called "platonia" by Barbour.A modern philosophical theory called presentism views the past and the future as human-mind interpretations of movement instead of real parts of time (or "dimensions") which coexist with the present. This theory rejects the existence of all direct interaction with the past or the future, holding only the present as tangible. This is one of the philosophical arguments against time travel. This contrasts with eternalism (all time: present, past and future, is real) and the growing block theory (the present and the past are real, but the future is not).

Physical definition
Until Einsteins reinterpretation of the physical concepts associated with time and space in 1907, time was considered to be the same everywhere in the universe, with all observers measuring the same time interval for any event.
Non-relativistic classical mechanics is based on this Newtonian idea of time.
Einstein, in his special theory of relativity,
postulated the constancy and finiteness of the speed of light for all observers. He showed that this postulate, together with a reasonable definition for what it means for two events to be simultaneous, requires that distances appear compressed and time intervals appear lengthened for events associated with objects in motion relative to an inertial observer.
The theory of special relativity finds a convenient formulation in Minkowski spacetime, a mathematical structure that combines three dimensions of space with a single dimension of time. In this formalism, distances in space can be measured by how long light takes to travel that distance, e.g., a light-year is a measure of distance, and a meter is now defined in terms of how far light travels in a certain amount of time. Two events in Minkowski spacetime are separated by an invariant interval, which can be either space-like, light-like, or time-like. Events that have a time-like separation cannot be simultaneous in any frame of reference, there must be a temporal component (and possibly a spatial one) to their separation. Events that have a space-like separation will be simultaneous in some frame of reference, and there is no frame of reference in which they do not have a spatial separation. Different observers may calculate different distances and different time intervals between two events, but the invariant interval between the events is independent of the observer (and his or her velocity).

Classical mechanics
In non-relativistic classical mechanics, Newtons concept of "relative, apparent, and common time" can be used in the formulation of a prescription for the synchronization of clocks. Events seen by two different observers in motion relative to each other produce a mathematical concept of time that works sufficiently well for describing the everyday phenomena of most peoples experience. In the late nineteenth century, physicists encountered problems with the classical understanding of time, in connection with the behavior of electricity and magnetism. Einstein resolved these problems by invoking a method of synchronizing clocks using the constant, finite speed of light as the maximum signal velocity. This led directly to the conclusion that observers in motion relative to one another measure different elapsed times for the same event.

Spacetime
Time has historically been closely related with space, the two together merging into spacetime in Einsteins special relativity and general relativity. According to these theories, the concept of time depends on the spatial reference frame of the observer, and the human perception, as well as the measurement by instruments such as clocks, are different for observers in relative motion. For example, if a spaceship carrying a clock flies through space at (very nearly) the speed of light, its crew does not notice a change in the speed of time on board their vessel because everything traveling at the same speed slows down at the same rate (including the clock, the crews thought processes, and the functions of their bodies). However, to a stationary observer watching the spaceship fly by, the spaceship appears flattened in the direction it is traveling and the clock on board the spaceship appears to move very slowly.
On the other hand, the crew on board the spaceship also perceives the observer as slowed down and flattened along the spaceships direction of travel, because both are moving at very nearly the speed of light relative to each other. Because the outside universe appears flattened to the spaceship, the crew perceives themselves as quickly traveling between regions of space that (to the stationary observer) are many light years apart. This is reconciled by the fact that the crews perception of time is different from the stationary observers; what seems like seconds to the crew might be hundreds of years to the stationary observer. In either case, however, causality remains unchanged: the past is the set of events that can send light signals to an entity and the future is the set of events to which an entity can send light signals.

Dilation
Einstein showed in his thought experiments that people travelling at different speeds, while agreeing on cause and effect, measure different time separations between events, and can even observe different chronological orderings between non-causally related events. Though these effects are typically minute in the human experience, the effect becomes much more pronounced for objects moving at speeds approaching the speed of light. Subatomic particles exist for a well-known average fraction of a second in a lab relatively at rest, but when travelling close to the speed of light they are measured to travel farther and exist for much longer than when at rest. According to the special theory of relativity, in the high-speed particles frame of reference, it exists, on the average, for a standard amount of time known as its mean lifetime, and the distance it travels in that time is zero, because its velocity is zero. Relative to a frame of reference at rest, time seems to "slow down" for the particle. Relative to the high-speed particle, distances seem to shorten. Einstein showed how both temporal and spatial dimensions can be altered (or "warped") by high-speed motion.
Einstein (The Meaning of Relativity): "Two events taking place at the points A and B of a system K are simultaneous if they appear at the same instant when observed from the middle point, M, of the interval AB. Time is then defined as the ensemble of the indications of similar clocks, at rest relative to K, which register the same simultaneously."
Einstein wrote in his book, Relativity, that simultaneity is also relative, i.e., two events that appear simultaneous to an observer in a particular inertial reference frame need not be judged as simultaneous by a second observer in a different inertial frame of reference.

Relativistic versus Newtonian
The animations visualise the different treatments of time in the Newtonian and the relativistic descriptions. At the heart of these differences are the Galilean and Lorentz transformations applicable in the Newtonian and relativistic theories, respectively.
In the figures, the vertical direction indicates time. The horizontal direction indicates distance (only one spatial dimension is taken into account), and the thick dashed curve is the spacetime trajectory ("world line") of the observer. The small dots indicate specific (past and future) events in spacetime.
The slope of the world line (deviation from being vertical) gives the relative velocity to the observer. Note how in both pictures the view of spacetime changes when the observer accelerates.
In the Newtonian description these changes are such that time is absolute: the movements of the observer do not influence whether an event occurs in the now (i.e., whether an event passes the horizontal line through the observer).
However, in the relativistic description the observability of events is absolute: the movements of the observer do not influence whether an event passes the "light cone" of the observer. Notice that with the change from a Newtonian to a relativistic description, the concept of absolute time is no longer applicable: events move up and down in the figure depending on the acceleration of the observer.

Arrow
Time appears to have a direction – the past lies behind, fixed and immutable, while the future lies ahead and is not necessarily fixed. Yet for the most part, the laws of physics do not specify an arrow of time, and allow any process to proceed both forward and in reverse. This is generally a consequence of time being modelled by a parameter in the system being analysed, where there is no "proper time": the direction of the arrow of time is sometimes arbitrary. Examples of this include the cosmological arrow of time, which points away from the Big Bang, CPT symmetry, and the radiative arrow of time, caused by light only travelling forwards in time (see light cone). In particle physics, the violation of CP symmetry implies that there should be a small counterbalancing time asymmetry to preserve CPT symmetry as stated above. The standard description of measurement in quantum mechanics is also time asymmetric (see Measurement in quantum mechanics). The second law of thermodynamics states that entropy must increase over time (see Entropy). This can be in either direction – Brian Greene theorizes that, according to the equations, the change in entropy occurs symmetrically whether going forward or backward in time. So entropy tends to increase in either direction, and our current low-entropy universe is a statistical aberration, in a similar manner as tossing a coin often enough that eventually heads will result ten times in a row. However, this theory is not supported empirically in local experiment.

Quantization
Time quantization is a hypothetical concept. In the modern established physical theories (the Standard Model of Particles and Interactions and General Relativity) time is not quantized.
Planck time (~ 5.4 × 10−44 seconds) is the unit of time in the system of natural units known as Planck units. Current established physical theories are believed to fail at this time scale, and many physicists expect that the Planck time might be the smallest unit of time that could ever be measured, even in principle. Tentative physical theories that describe this time scale exist; see for instance loop quantum gravity.

Travel
Time travel is the concept of moving backwards or forwards to different points in time, in a manner analogous to moving through space, and different from the normal "flow" of time to an earthbound observer. In this view, all points in time (including future times) "persist" in some way. Time travel has been a plot device in fiction since the 19th century. Travelling backwards or forwards in time has never been verified as a process, and doing so presents many theoretical problems and contradictive logic which to date have not been overcome. Any technological device, whether fictional or hypothetical, that is used to achieve time travel is known as a time machine.
A central problem with time travel to the past is the violation of causality; should an effect precede its cause, it would give rise to the possibility of a temporal paradox. Some interpretations of time travel resolve this by accepting the possibility of travel between branch points, parallel realities, or universes.
Another solution to the problem of causality-based temporal paradoxes is that such paradoxes cannot arise simply because they have not arisen. As illustrated in numerous works of fiction, free will either ceases to exist in the past or the outcomes of such decisions are predetermined. As such, it would not be possible to enact the grandfather paradox because it is a historical fact that ones grandfather was not killed before his child (ones parent) was conceived. This view does not simply hold that history is an unchangeable constant, but that any change made by a hypothetical future time traveller would already have happened in his or her past, resulting in the reality that the traveller moves from. More elaboration on this view can be found in the Novikov self-consistency principle.

Perception
The specious present refers to the time duration wherein ones perceptions are considered to be in the present. The experienced present is said to be specious in that, unlike the objective present, it is an interval and not a durationless instant. The term specious present was first introduced by the psychologist E.R. Clay, and later developed by William James.

Biopsychology
The brains judgment of time is known to be a highly distributed system, including at least the cerebral cortex, cerebellum and basal ganglia as its components. One particular component, the suprachiasmatic nuclei, is responsible for the circadian (or daily) rhythm, while other cell clusters appear capable of shorter-range (ultradian) timekeeping.
Psychoactive drugs can impair the judgment of time. Stimulants can lead both humans and rats to overestimate time intervals, while depressants can have the opposite effect. The level of activity in the brain of neurotransmitters such as dopamine and norepinephrine may be the reason for this. Such chemicals will either excite or inhibit the firing of neurons in the brain, with a greater firing rate allowing the brain to register the occurrence of more events within a given interval (speed up time) and a decreased firing rate reducing the brains capacity to distinguish events occurring within a given interval (slow down time).Mental chronometry is the use of response time in perceptual-motor tasks to infer the content, duration, and temporal sequencing of cognitive operations.

Early childhood education
Childrens expanding cognitive abilities allow them to understand time more clearly. Two- and three-year-olds understanding of time is mainly limited to "now and not now". Five- and six-year-olds can grasp the ideas of past, present, and future. Seven- to ten-year-olds can use clocks and calendars.

Alterations
In addition to psychoactive drugs, judgments of time can be altered by temporal illusions (like the kappa effect), age, and hypnosis. The sense of time is impaired in some people with neurological diseases such as Parkinsons disease and attention deficit disorder.
Psychologists assert that time seems to go faster with age, but the literature on this age-related perception of time remains controversial. Those who support this notion argue that young people, having more excitatory neurotransmitters, are able to cope with faster external events.

Spatial conceptualization
Although time is regarded as an abstract concept, there is increasing evidence that time is conceptualized in the mind in terms of space. That is, instead of thinking about time in a general, abstract way, humans think about time in a spatial way and mentally organize it as such. Using space to think about time allows humans to mentally organize temporal events in a specific way.
This spatial representation of time is often represented in the mind as a Mental Time Line (MTL). Using space to think about time allows humans to mentally organize temporal order. These origins are shaped by many environmental factors––for example, literacy appears to play a large role in the different types of MTLs, as reading/writing direction provides an everyday temporal orientation that differs from culture to culture. In western cultures, the MTL may unfold rightward (with the past on the left and the future on the right) since people read and write from left to right. Western calendars also continue this trend by placing the past on the left with the future progressing toward the right. Conversely, Arabic, Farsi, Urdu and Israeli-Hebrew speakers read from right to left, and their MTLs unfold leftward (past on the right with future on the left), and evidence suggests these speakers organize time events in their minds like this as well.This linguistic evidence that abstract concepts are based in spatial concepts also reveals that the way humans mentally organize time events varies across cultures––that is, a certain specific mental organization system is not universal. So, although Western cultures typically associate past events with the left and future events with the right according to a certain MTL, this kind of horizontal, egocentric MTL is not the spatial organization of all cultures. Although most developed nations use an egocentric spatial system, there is recent evidence that some cultures use an allocentric spatialization, often based on environmental features.A recent study of the indigenous Yupno people of Papua New Guinea focused on the directional gestures used when individuals used time-related words. When speaking of the past (such as "last year" or "past times"), individuals gestured downhill, where the river of the valley flowed into the ocean. When speaking of the future, they gestured uphill, toward the source of the river. This was common regardless of which direction the person faced, revealing that the Yupno people may use an allocentric MTL, in which time flows uphill.A similar study of the Pormpuraawans, an aboriginal group in Australia, revealed a similar distinction in which when asked to organize photos of a man aging "in order," individuals consistently placed the youngest photos to the east and the oldest photos to the west, regardless of which direction they faced. This directly clashed with an American group that consistently organized the photos from left to right. Therefore, this group also appears to have an allocentric MTL, but based on the cardinal directions instead of geographical features.The wide array of distinctions in the way different groups think about time leads to the broader question that different groups may also think about other abstract concepts in different ways as well, such as causality and number.

Use
In sociology and anthropology, time discipline is the general name given to social and economic rules, conventions, customs, and expectations governing the measurement of time, the social currency and awareness of time measurements, and peoples expectations concerning the observance of these customs by others. Arlie Russell Hochschild and Norbert Elias have written on the use of time from a sociological perspective.
The use of time is an important issue in understanding human behavior, education, and travel behavior. Time-use research is a developing field of study. The question concerns how time is allocated across a number of activities (such as time spent at home, at work, shopping, etc.). Time use changes with technology, as the television or the Internet created new opportunities to use time in different ways. However, some aspects of time use are relatively stable over long periods of time, such as the amount of time spent traveling to work, which despite major changes in transport, has been observed to be about 20–30 minutes one-way for a large number of cities over a long period.
Time management is the organization of tasks or events by first estimating how much time a task requires and when it must be completed, and adjusting events that would interfere with its completion so it is done in the appropriate amount of time. Calendars and day planners are common examples of time management tools.

Sequence of events
A sequence of events, or series of events, is a sequence of items, facts, events, actions, changes, or procedural steps, arranged in time order (chronological order), often with causality relationships among the items.
Because of causality, cause precedes effect, or cause and effect may appear together in a single item, but effect never precedes cause. A sequence of events can be presented in text, tables, charts, or timelines. The description of the items or events may include a timestamp </s>