title: Toxoplasmosis

text: Swollen lymph nodes are commonly found in the neck or under the chin, followed by the armpits and the groin. Swelling may occur at different times after the initial infection, persist, and recur for various times independently of antiparasitic treatment. It is usually found at single sites in adults, but in children, multiple sites may be more common. Enlarged lymph nodes will resolve within 1–2 months in 60% of cases. However, a quarter of those affected take 2–4 months to return to normal, and 8% take 4–6 months. A substantial number (6%) do not return to normal until much later.


title: Toxoplasmosis

text: Due to the absence of obvious symptoms, hosts easily become infected with "T. gondii" and develop toxoplasmosis without knowing it. Although mild, flu-like symptoms occasionally occur during the first few weeks following exposure, infection with "T. gondii" produces no readily observable symptoms in healthy human adults. In most immunocompetent people, the infection enters a latent phase, during which only bradyzoites (in tissue cysts) are present; these tissue cysts and even lesions can occur in the retinas, alveolar lining of the lungs (where an acute infection may mimic a "Pneumocystis jirovecii" infection), heart, skeletal muscle, and the central nervous system (CNS), including the brain. Cysts form in the CNS (brain tissue) upon infection with "T. gondii" and persist for the lifetime of the host. Most infants who are infected while in the womb have no symptoms at birth, but may develop symptoms later in life.


title: Toxoplasmosis

text: Reviews of serological studies have estimated that 30–50% of the global population has been exposed to and may be chronically infected with latent toxoplasmosis, although infection rates differ significantly from country to country. This latent state of infection has recently been associated with numerous disease burdens, neural alterations, and subtle gender-dependent behavioral changes in immunocompetent humans, as well as an increased risk of motor vehicle collisions.


title: Toxoplasmosis

text: While rare, skin lesions may occur in the acquired form of the disease, including roseola and erythema multiforme-like eruptions, prurigo-like nodules, urticaria, and maculopapular lesions. Newborns may have punctate macules, ecchymoses, or "blueberry muffin" lesions.


title: Toxoplasmosis

text: Diagnosis of cutaneous toxoplasmosis is based on the tachyzoite form of "T. gondii" being found in the epidermis. It is found in all levels of the epidermis, is about 6 by 2 μm and bow-shaped, with the nucleus being one-third of its size. It can be identified by electron microscopy or by Giemsa staining tissue where the cytoplasm shows blue, the nucleus red.


title: Toxoplasmosis

text: In its lifecycle, "T. gondii" adopts several forms. Tachyzoites are responsible for acute infection; they divide rapidly and spread through the tissues of the body. Tachyzoites are also known as "tachyzoic merozoites", a descriptive term that conveys more precisely the parasitological nature of this stage. After proliferating, tachyzoites convert into bradyzoites, which are inside latent intracellular tissue cysts that form mainly in the muscles and brain. The formation of cysts is in part triggered by the pressure of the host immune system. The bradyzoites (also called "bradyzoic merozoites") are not responsive to antibiotics. Bradyzoites, once formed, can remain in the tissues for the lifespan of the host. In a healthy host, if some bradyzoites convert back into active tachyzoites, the immune system will quickly destroy them. However, in immunocompromised individuals, or in fetuses, which lack a developed immune system, the tachyzoites can run rampant and cause significant neurological damage.


title: Toxoplasmosis

text: The parasite's survival is dependent on a balance between host survival and parasite proliferation. "T. gondii" achieves this balance by manipulating the host's immune response, reducing the host's immune response, and enhancing the parasite's reproductive advantage. Once it infects a normal host cell, it resists damage caused by the host's immune system, and changes the host's immune processes.


title: Toxoplasmosis

text: As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host's mitochondria and endoplasmic reticulum.


title: Toxoplasmosis

text: When first invading the cell, the parasite releases ROP proteins from the bulb of the rhoptry organelle. These proteins translocate to the nucleus and the surface of the PV membrane where they can activate STAT pathways to modulate the expression of cytokines at the transcriptional level, bind and inactivate PV membrane destroying IRG proteins, among other possible effects. Additionally, certain strains of T. "gondii" can secrete a protein known as GRA15, activating the NF-κB pathway, which upregulates the pro-inflammatory cytokine IL-12 in the early immune response, possibly leading to the parasite's latent phase. The parasite's ability to secrete these proteins depends on its genotype and affects its virulence.


title: Toxoplasmosis

text: The parasite also influences an anti-apoptotic mechanism, allowing the infected host cells to persist and replicate. One method of apoptosis resistance is by disrupting pro-apoptosis effector proteins, such as BAX and BAK. To disrupt these proteins, "T. gondii" causes conformational changes to the proteins, which prevent the proteins from being transported to various cellular compartments where they initiate apoptosis events. "T. gondii" does not, however, cause downregulation of the pro-apoptosis effector proteins.


title: Toxoplasmosis

text: "T. gondii" also has the ability to initiate autophagy of the host's cells. This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang "et al" finds that infected cells lead to higher levels of autophagosomes in normal and infected cells. Their research reveals that "T. gondii" causes host cell autophagy using a calcium-dependent pathway. Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells.


title: Toxoplasmosis

text: The mechanisms above allow "T. gondii" to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of "T. gondii" per host cell cause a more severe effect. The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals.


title: Toxoplasmosis

text: Since the parasite can change the host's immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats. This includes, but is not limited to, the responses to infections by "Helicobacter felis", "Leishmania major", or other parasites, such as "Nippostrongylus brasiliensis".


title: Toxoplasmosis

text: Toxoplasmosis is generally transmitted through the mouth when "Toxoplasma gondii" oocysts or tissue cysts are accidentally eaten. Congenital transmittance from mother to fetus can also occur. Transmission may also occur during the solid organ transplant process or hematogenous stem cell transplants.


title: Toxoplasmosis

text: Cats excrete the pathogen in their feces for a number of weeks after contracting the disease, generally by eating an infected intermediate host that could include mammals (like rodents) or birds. Oocyst shedding usually starts from the third day after ingestion of infected intermediate hosts, and may continue for weeks. The oocysts are not infective when excreted. After about a day, the oocyst undergoes a process called sporulation and becomes potentially pathogenic. In addition to cats, birds and mammals including human beings are also intermediate hosts of the parasite and are involved in the transmission process. However the pathogenicity varies with the age and species involved in infection and the mode of transmission of "T. gondii".


title: Toxoplasmosis

text: Toxoplasmosis may also be transmitted through solid organ transplants. Toxoplasma-seronegative recipients who receive organs from recently infected Toxoplasma-seropositive donors are at risk. Organ recipients who have latent toxoplasmosis are at risk of the disease reactivating in their system due to the immunosuppression occurring during solid organ transplant. Recipients of hematogenous stem cell transplants may experience higher risk of infection due to longer periods of immunosuppression.


title: Toxoplasmosis

text: Heart and lung transplants provide the highest risk for toxoplasmosis infection due to the striated muscle making up the heart, which can contain cysts, and risks for other organs and tissues vary widely. Risk of transmission can be reduced by screening donors and recipients prior to the transplant procedure and providing treatment.


title: Toxoplasmosis

text: Congenital toxoplasmosis is a specific form of toxoplasmosis in which an unborn fetus is infected via the placenta. Congenital toxoplasmosis is associated with fetal death and miscarriage, and in infants, it is associated with hydrocephalus, cerebral calcifications and chorioretinitis, leading to encephalopathy and possibly blindness. A positive antibody titer indicates previous exposure and immunity, and largely ensures the unborn fetus' safety. A simple blood draw at the first prenatal doctor visit can determine whether or not a woman has had previous exposure and therefore whether or not she is at risk. If a woman receives her first exposure to "T. gondii" while pregnant, the fetus is at particular risk.


title: Toxoplasmosis

text: Not much evidence exists around the effect of education before pregnancy to prevent congenital toxoplasmosis. However educating parents before the baby is born has been suggested to be effective because it may improve food, personal and pet hygiene. More research is needed to find whether antenatal education can reduce congenital toxoplasmosis.


title: Toxoplasmosis

text: For pregnant women with negative antibody titers, indicating no previous exposure to "T. gondii", serology testing as frequent as monthly is advisable as treatment during pregnancy for those women exposed to "T. gondii" for the first time dramatically decreases the risk of passing the parasite to the fetus. Since a baby's immune system does not develop fully for the first year of life, and the resilient cysts that form throughout the body are very difficult to eradicate with antiprotozoans, an infection can be very serious in the young.


title: Toxoplasmosis

text: Despite these risks, pregnant women are not routinely screened for toxoplasmosis in most countries, for reasons of cost-effectiveness and the high number of false positives generated; Portugal, France, Austria, Uruguay, and Italy are notable exceptions, and some regional screening programmes operate in Germany, Switzerland and Belgium. As invasive prenatal testing incurs some risk to the fetus (18.5 pregnancy losses per toxoplasmosis case prevented), postnatal or neonatal screening is preferred. The exceptions are cases where fetal abnormalities are noted, and thus screening can be targeted.


title: Toxoplasmosis

text: Pregnant women should avoid handling raw meat, drinking raw milk (especially goat milk) and be advised to not eat raw or undercooked meat regardless of type. Because of the obvious relationship between "Toxoplasma" and cats it is also often advised to avoid exposure to cat feces, and refrain from gardening (cat feces are common in garden soil) or at least wear gloves when so engaged. Most cats are not actively shedding oocysts, since they get infected in the first six months of their life, when they shed oocysts for a short period of time (1–2 weeks.) However, these oocysts get buried in the soil, sporulate and remain infectious for periods ranging from several months to more than a year. Numerous studies have shown living in a household with a cat is not a significant risk factor for "T. gondii" infection, though living with several kittens has some significance.


title: Toxoplasmosis

text: In 2006, a Czech research team discovered women with high levels of toxoplasmosis antibodies were significantly more likely to give birth to baby boys than baby girls. In most populations, the birth rate is around 51% boys, but people infected with "T. gondii" had up to a 72% chance of a boy.


title: Toxoplasmosis

text: Diagnosis of toxoplasmosis in humans is made by biological, serological, histological, or molecular methods, or by some combination of the above. Toxoplasmosis can be difficult to distinguish from primary central nervous system lymphoma. It mimics several other infectious diseases so clinical signs are non-specific and are not sufficiently characteristic for a definite diagnosis. As a result, the possibility of an alternate diagnosis is supported by a failed trial of antimicrobial therapy (pyrimethamine, sulfadiazine, and folinic acid (USAN: leucovorin)), i.e., if the drugs produce no effect clinically and no improvement on repeat imaging.


title: Toxoplasmosis

text: "T. gondii" may also be detected in blood, amniotic fluid, or cerebrospinal fluid by using polymerase chain reaction. "T. gondii" may exist in a host as an inactive cyst that would likely evade detection.


title: Toxoplasmosis

text: Serological testing can detect "T. gondii" antibodies in blood serum, using methods including the Sabin–Feldman dye test (DT), the indirect hemagglutination assay, the indirect fluorescent antibody assay (IFA), the direct agglutination test, the latex agglutination test (LAT), the enzyme-linked immunosorbent assay (ELISA), and the immunosorbent agglutination assay test (IAAT).


title: Toxoplasmosis

text: The most commonly used tests to measure IgG antibody are the DT, the ELISA, the IFA, and the modified direct agglutination test. IgG antibodies usually appear within a week or two of infection, peak within one to two months, then decline at various rates. "Toxoplasma" IgG antibodies generally persist for life, and therefore may be present in the bloodstream as a result of either current or previous infection.


title: Toxoplasmosis

text: To some extent, acute toxoplasmosis infections can be differentiated from chronic infections using an IgG avidity test, which is a variation on the ELISA. In the first response to infection, toxoplasma-specific IgG has a low affinity for the toxoplasma antigen; in the following weeks and month, IgG affinity for the antigen increases. Based on the IgG avidity test, if the IgG in the infected individual has a high affinity, it means that the infection began three to five months before testing. This is particularly useful in congenital infection, where pregnancy status and gestational age at time of infection determines treatment.


title: Toxoplasmosis

text: In contrast to IgG, IgM antibodies can be used to detect acute infection but generally not chronic infection. The IgM antibodies appear sooner after infection than the IgG antibodies and disappear faster than IgG antibodies after recovery. In most cases, "T. gondii"-specific IgM antibodies can first be detected approximately a week after acquiring primary infection and decrease within one to six months; 25% of those infected are negative for "T. gondii"-specific IgM within seven months. However, IgM may be detectable months or years after infection, during the chronic phase, and false positives for acute infection are possible. The most commonly used tests for the measurement of IgM antibody are double-sandwich IgM-ELISA, the IFA test, and the immunosorbent agglutination assay (IgM-ISAGA). Commercial test kits often have low specificity, and the reported results are frequently misinterpreted.


title: Toxoplasmosis

text: In 2021, twenty commercial anti-"Toxoplasma" IgG assays were evaluated in a systematic review, in comparison with an accepted reference method. Most of them were enzyme-immunoassays, followed by agglutination tests, immunochromatographic tests, and a Western-Blot assay. The mean sensitivity of IgG assays ranged from 89.7% to 100% for standard titers and from 13.4% to 99.2% for low IgG titers. A few studies pointed out the ability of some methods, especially WB to detect IgG early after primary infection. The specificity of IgG assays was generally high, ranging from 91.3% to 100%; and higher than 99% for most EIA assays. The positive predictive value (PPV) was not a discriminant indicator among methods, whereas significant disparities (87.5%–100%) were reported among negative predictive values (NPV), a key-parameter assessing the ability to definitively rule out a "Toxoplasma" infection in patients at-risk for opportunistic infections.


title: Toxoplasmosis

text: Recommendations for the diagnosis of congenital toxoplasmosis include: prenatal diagnosis based on testing of amniotic fluid and ultrasound examinations; neonatal diagnosis based on molecular testing of placenta and cord blood and comparative mother-child serologic tests and a clinical examination at birth; and early childhood diagnosis based on neurologic and ophthalmologic examinations and a serologic survey during the first year of life. During pregnancy, serological testing is recommended at three week intervals.


title: Toxoplasmosis

text: Even though diagnosis of toxoplasmosis heavily relies on serological detection of specific anti-"Toxoplasma" immunoglobulin, serological testing has limitations. For example, it may fail to detect the active phase of "T. gondii" infection because the specific anti-"Toxoplasma" IgG or IgM may not be produced until after several weeks of infection. As a result, a pregnant woman might test negative during the active phase of "T. gondii" infection leading to undetected and therefore untreated congenital toxoplasmosis. Also, the test may not detect "T. gondii" infections in immunocompromised patients because the titers of specific anti-"Toxoplasma" IgG or IgM may not rise in this type of patient.


title: Toxoplasmosis

text: Many PCR-based techniques have been developed to diagnose toxoplasmosis using clinical specimens that include amniotic fluid, blood, cerebrospinal fluid, and tissue biopsy. The most sensitive PCR-based technique is nested PCR, followed by hybridization of PCR products. The major downside to these techniques is that they are time-consuming and do not provide quantitative data.


title: Toxoplasmosis

text: Real-time PCR is useful in pathogen detection, gene expression and regulation, and allelic discrimination. This PCR technique utilizes the 5' nuclease activity of "Taq" DNA polymerase to cleave a nonextendible, fluorescence-labeled hybridization probe during the extension phase of PCR. A second fluorescent dye, e.g., 6-carboxy-tetramethyl-rhodamine, quenches the fluorescence of the intact probe. The nuclease cleavage of the hybridization probe during the PCR releases the effect of quenching resulting in an increase of fluorescence proportional to the amount of PCR product, which can be monitored by a sequence detector.


title: Toxoplasmosis

text: Toxoplasmosis cannot be detected with immunostaining. Lymph nodes affected by "Toxoplasma" have characteristic changes, including poorly demarcated reactive germinal centers, clusters of monocytoid B cells, and scattered epithelioid histiocytes.


title: Toxoplasmosis

text: The classic triad of congenital toxoplasmosis includes: chorioretinitis, hydrocephalus, and intracranial arteriosclerosis. Other consequences include sensorineural deafness, seizures, and intellectual disability.


title: Toxoplasmosis

text: Congenital toxoplasmosis may also impact a child's hearing. Up to 30% of newborns have some degree of sensorineural hearing loss. The child's communication skills may also be affected. A study published in 2010 looked at 106 patients, all of whom received toxoplasmosis treatment prior to 2.5 months. Of this group, 26.4% presented with language disorders.


title: Toxoplasmosis

text: Treatment is recommended for people with serious health problems, such as people with HIV whose CD4 counts are under 200 cells/mm. Trimethoprim/sulfamethoxazole is the drug of choice to prevent toxoplasmosis, but not for treating active disease.


title: Toxoplasmosis

text: A 2012 study shows a promising new way to treat the active and latent form of this disease using two endochin-like quinolones.


title: Toxoplasmosis

text: If infected during pregnancy, spiramycin is recommended in the first and early second trimesters while pyrimethamine/sulfadiazine and leucovorin is recommended in the late second and third trimesters.


title: Toxoplasmosis

text: In people with latent toxoplasmosis, the cysts are immune to these treatments, as the antibiotics do not reach the bradyzoites in sufficient concentration.


title: Toxoplasmosis

text: When a pregnant woman is diagnosed with acute toxoplasmosis, amniocentesis can be used to determine whether the fetus has been infected or not. When a pregnant woman develops acute toxoplasmosis, the tachyzoites have approximately a 30% chance of entering the placental tissue, and from there entering and infecting the fetus. As gestational age at the time of infection increases, the chance of fetal infection also increases.


title: Toxoplasmosis

text: If the parasite has not yet reached the fetus, spiramycin can help to prevent placental transmission. If the fetus has been infected, the pregnant woman can be treated with pyrimethamine and sulfadiazine, with folinic acid, after the first trimester. They are treated after the first trimester because pyrimethamine has an antifolate effect, and lack of folic acid can interfere with fetal brain formation and cause thrombocytopaenia. Infection in earlier gestational stages correlates with poorer fetal and neonatal outcomes, particularly when the infection is untreated.


title: Toxoplasmosis

text: Newborns who undergo 12 months of postnatal anti-toxoplasmosis treatment have a low chance of sensorineural hearing loss. Information regarding treatment milestones for children with congenital toxoplasmosis have been created for this group.


title: Toxoplasmosis

text: "T. gondii" infections occur throughout the world, although infection rates differ significantly by country. For women of childbearing age, a survey of 99 studies within 44 countries found the areas of highest prevalence are within Latin America (about 50–80%), parts of Eastern and Central Europe (about 20–60%), the Middle East (about 30–50%), parts of Southeast Asia (about 20–60%), and parts of Africa (about 20–55%).


title: Toxoplasmosis

text: In the United States, data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004 found 9.0% of US-born persons 12–49 years of age were seropositive for IgG antibodies against "T. gondii", down from 14.1% as measured in the NHANES 1988–1994. In the 1999–2004 survey, 7.7% of US-born and 28.1% of foreign-born women 15–44 years of age were "T. gondii" seropositive. A trend of decreasing seroprevalence has been observed by numerous studies in the United States and many European countries. Toxoplasma gondii is considered the second leading cause of foodborne-related deaths and the fourth leading cause of foodborne-related hospitalizations in the United States.


title: Toxoplasmosis

text: The protist responsible for toxoplasmosis is "T. gondii". There are three major types of T. gondii responsible for the patterns of toxoplasmosis throughout the world. There are types I, II, and III. These three types of "T. gondii" have differing effects on certain hosts, mainly mice and humans due to their variation in genotypes.


title: Toxoplasmosis

text: Because the parasite poses a particular threat to fetuses when it is contracted during pregnancy, much of the global epidemiological data regarding "T. gondii" comes from seropositivity tests in women of childbearing age. Seropositivity tests look for the presence of antibodies against "T. gondii" in blood, so while seropositivity guarantees one has been exposed to the parasite, it does not necessarily guarantee one is chronically infected.


title: Toxoplasmosis

text: "Toxoplasma gondii" was first described in 1908 by Nicolle and Manceaux in Tunisia, and independently by Splendore in Brazil. Splendore reported the protozoan in a rabbit, while Nicolle and Manceaux identified it in a North African rodent, the gundi (Ctenodactylus gundi). In 1909 Nicolle and Manceaux differentiated the protozoan from "Leishmania". Nicolle and Manceaux then named it "Toxoplasma gondii" after the curved shape of its infectious stage (Greek root "= bow).


title: Toxoplasmosis

text: The first recorded case of congenital toxoplasmosis was in 1923, but it was not identified as caused by "T. gondii". Janků (1923) described in detail the autopsy results of an 11-month-old boy who had presented to hospital with hydrocephalus. The boy had classic marks of toxoplasmosis including chorioretinitis (inflammation of the choroid and retina of the eye). Histology revealed a number of "sporocytes", though Janků did not identify these as "T. gondii".


title: Toxoplasmosis

text: It was not until 1937 that the first detailed scientific analysis of "T. gondii" took place using techniques previously developed for analyzing viruses. In 1937 Sabin and Olitsky analyzed "T. gondii" in laboratory monkeys and mice. Sabin and Olitsky showed that "T. gondii" was an obligate intracellular parasite and that mice fed "T. gondii"-contaminated tissue also contracted the infection. Thus Sabin and Olitsky demonstrated "T. gondii" as a pathogen transmissible between animals.


title: Toxoplasmosis

text: "T. gondii" was first described as a human pathogen in 1939 at Babies Hospital in New York City. Wolf, Cowen and Paige identified "T. gondii" infection in an infant girl delivered full-term by Caesarean section. The infant developed seizures and had chorioretinitis in both eyes at three days. The infant then developed encephalomyelitis and died at one month of age. Wolf, Cowen and Paige isolated "T. gondii" from brain tissue lesions. Intracranial injection of brain and spinal cord samples into mice, rabbits and rats produced encephalitis in the animals. Wolf, Cowen and Page reviewed additional cases and concluded that "T. gondii" produced recognizable symptoms and could be transmitted from mother to child.


title: Toxoplasmosis

text: The first adult case of toxoplasmosis was reported in 1940 with no neurological signs. Pinkerton and Weinman reported the presence of "Toxoplasma" in a 22-year-old man from Peru who died from a subsequent bacterial infection and fever.


title: Toxoplasmosis

text: In 1948, a serological dye test was created by Sabin and Feldman based on the ability of the patient's antibodies to alter staining of "Toxoplasma". The Sabin Feldman Dye Test is now the gold standard for identifying "Toxoplasma" infection.


title: Toxoplasmosis

text: Transmission of "Toxoplasma" by eating raw or undercooked meat was demonstrated by Desmonts et al. in 1965 Paris. Desmonts observed that the therapeutic consumption of raw beef or horse meat in a tuberculosis hospital was associated with a 50% per year increase in "Toxoplasma" antibodies. This means that more "T. gondii" was being transmitted through the raw meat.


title: Toxoplasmosis

text: In 1974, Desmonts and Couvreur showed that infection during the first two trimesters produces most harm to the fetus, that transmission depended on when mothers were infected during pregnancy, that mothers with antibodies before pregnancy did not transmit the infection to the fetus, and that spiramycin lowered the transmission to the fetus.


title: Toxoplasmosis

text: "Toxoplasma" gained more attention in the 1970s with the rise of immune-suppressant treatment given after organ or bone marrow transplants and the AIDS epidemic of the 1980s. Patients with lowered immune system function are much more susceptible to disease.


title: Toxoplasmosis

text: "Crazy cat-lady syndrome" is a term coined by news organizations to describe scientific findings that link the parasite "Toxoplasma gondii" to several mental disorders and behavioral problems. The suspected correlation between cat ownership in childhood and later development of schizophrenia suggested that further studies were needed to determine a risk factor for children; however, later studies showed that "T. gondii" was not a causative factor in later psychoses. Researchers also found that cat ownership does not strongly increase the risk of a "T. gondii" infection in pregnant women.


title: Toxoplasmosis

text: The term "crazy cat-lady syndrome" draws on both stereotype and popular cultural reference. It was originated as instances of the aforementioned afflictions were noted amongst the populace. A cat lady is a cultural stereotype of a woman who compulsively hoards and dotes upon cats. The biologist Jaroslav Flegr is a proponent of the theory that toxoplasmosis affects human behaviour.


title: Toxoplasmosis

text: Although "T. gondii" has the capability of infecting virtually all warm-blooded animals, susceptibility and rates of infection vary widely between different genera and species. Rates of infection in populations of the same species can also vary widely due to differences in location, diet, and other factors.


title: Toxoplasmosis

text: Although infection with "T. gondii" has been noted in several species of Asian primates, seroprevalence of "T. gondii" antibodies were found for the first time in toque macaques ("Macaca sinica") that are endemic to the island of Sri Lanka.


title: Toxoplasmosis

text: Australian marsupials are particularly susceptible to toxoplasmosis. Wallabies, koalas, wombats, pademelons and small dasyurids can be killed by it, with eastern barred bandicoots typically dying within about 3 weeks of infection.


title: Toxoplasmosis

text: It is estimated that 23% of wild swine worldwide are seropositive for "T. gondii". Seroprevalence varies across the globe with the highest seroprevalence in North America (32%) and Europe (26%) and the lowest in Asia (13%) and South America (5%). Geographical regions located at higher latitudes and regions that experience warmer, humid climates are associated with increased seroprevalence of "T. gondii" among wild boar. Wild boar infected with "T. gondii" pose a potential health risk for humans who consume their meat.


title: Toxoplasmosis

text: Among livestock, pigs, sheep and goats have the highest rates of chronic "T. gondii" infection. The prevalence of "T. gondii" in meat-producing animals varies widely both within and among countries, and rates of infection have been shown to be dramatically influenced by varying farming and management practices. For instance, animals kept outdoors or in free-ranging environments are more at risk of infection than animals raised indoors or in commercial confinement operations.


title: Toxoplasmosis

text: Worldwide, the percentage of pigs harboring viable parasites has been measured to be 3–71.43% and in the United States (via bioassay in mice or cats) to be as high as 92.7% and as low as 0%, depending on the farm or herd. Surveys of seroprevalence ("T. gondii" antibodies in blood) are more common, and such measurements are indicative of the high relative seroprevalence in pigs across the world. Neonatal piglets have been found to experience the entire range of severity, including progression to stillbirth. This was especially demonstrated in the foundational Thiptara et al. 2006, reporting a litter birth of three stillborns and six live in Thailand. This observation has been relevant not only to that country but to toxoplasmosis control in porciculture around the world.


title: Toxoplasmosis

text: Along with pigs, sheep and goats are among the most commonly infected livestock of epidemiological significance for human infection. Prevalence of viable "T. gondii" in sheep tissue has been measured (via bioassay) to be as high as 78% in the United States, and a 2011 survey of goats intended for consumption in the United States found a seroprevalence of 53.4%.


title: Toxoplasmosis

text: Due to a lack of exposure to the outdoors, chickens raised in large-scale indoor confinement operations are not commonly infected with "T. gondii". Free-ranging or backyard-raised chickens are much more commonly infected. A survey of free-ranging chickens in the United States found its prevalence to be 17–100%, depending on the farm. Because chicken meat is generally cooked thoroughly before consumption, poultry is not generally considered to be a significant risk factor for human "T. gondii" infection.


title: Toxoplasmosis

text: Although cattle and buffalo can be infected with "T. gondii", the parasite is generally eliminated or reduced to undetectable levels within a few weeks following exposure. Tissue cysts are rarely present in buffalo meat or beef, and meat from these animals is considered to be low-risk for harboring viable parasites.


title: Toxoplasmosis

text: Horses are considered resistant to chronic "T. gondii" infection. However, viable cells have been isolated from US horses slaughtered for export, and severe human toxoplasmosis in France has been epidemiologically linked to the consumption of horse meat.


title: Toxoplasmosis

text: In 1942, the first case of feline toxoplasmosis was diagnosed and reported in a domestic cat in Middletown, New York. The investigators isolated oocysts from feline feces and found that the oocysts could be infectious for up to 12 months in the environment.


title: Toxoplasmosis

text: The seroprevalence of "T. gondii" in domestic cats, worldwide has been estimated to be around 30–40% and exhibits significant geographical variation. In the United States, no official national estimate has been made, but local surveys have shown levels varying between 16% and 80%. A 2012 survey of 445 purebred pet cats and 45 shelter cats in Finland found an overall seroprevalence of 48.4%, while a 2010 survey of feral cats from Giza, Egypt found a seroprevalence rate of 97.4%. Another survey from Colombia recorded seroprevalence of 89.3%, whereas a Chinese (Guangdong) study found just a 2.1% prevalence.


title: Toxoplasmosis

text: "T. gondii" infection rates in domestic cats vary widely depending on the cats' diets and lifestyles. Feral cats that hunt for their food are more likely to be infected than domestic cats, and naturally also depends on the prevalence of "T. gondii"-infected prey such as birds and small mammals.


title: Toxoplasmosis

text: Most infected cats will shed oocysts only once in their lifetimes, for a period of about one to two weeks. This shedding can release millions of oocysts, each capable of spreading and surviving for months. An estimated 1% of cats at any given time are actively shedding oocysts.


title: Toxoplasmosis

text: It is difficult to control the cat population with the infected oocysts due to lack of an effective vaccine. This remains a challenge in most cases and the programs that are readily available are questionable in efficacy.


title: Toxoplasmosis

text: Infection with "T. gondii" has been shown to alter the behavior of mice and rats in ways thought to increase the rodents' chances of being preyed upon by cats. Infected rodents show a reduction in their innate aversion to cat odors; while uninfected mice and rats will generally avoid areas marked with cat urine or with cat body odor, this avoidance is reduced or eliminated in infected animals. Moreover, some evidence suggests this loss of aversion may be specific to feline odors: when given a choice between two predator odors (cat or mink), infected rodents show a significantly stronger preference to cat odors than do uninfected controls.


title: Toxoplasmosis

text: In rodents, "T. gondii"–induced behavioral changes occur through epigenetic remodeling in neurons associated with observed behaviors; for example, it modifies epigenetic methylation to induce hypomethylation of arginine vasopressin-related genes in the medial amygdala to greatly decrease predator aversion. Similar epigenetically induced behavioral changes have also been observed in mouse models of addiction, where changes in the expression of histone-modifying enzymes via gene knockout or enzyme inhibition in specific neurons produced alterations in drug-related behaviors. Widespread histone–lysine acetylation in cortical astrocytes appears to be another epigenetic mechanism employed by "T. gondii".


title: Toxoplasmosis

text: "T. gondii"-infected rodents show a number of behavioral changes beyond altered responses to cat odors. Rats infected with the parasite show increased levels of activity and decreased neophobic behavior. Similarly, infected mice show alterations in patterns of locomotion and exploratory behavior during experimental tests. These patterns include traveling greater distances, moving at higher speeds, accelerating for longer periods of time, and showing a decreased pause-time when placed in new arenas. Infected rodents have also been shown to have lower anxiety, using traditional models such as elevated plus mazes, open field arenas, and social interaction tests.


title: Toxoplasmosis

text: A University of California, Davis study of dead sea otters collected from 1998 to 2004 found toxoplasmosis was the cause of death for 13% of the animals. Proximity to freshwater outflows into the ocean was a major risk factor. Ingestion of oocysts from cat feces is considered to be the most likely ultimate source. Surface runoff containing wild cat feces and litter from domestic cats flushed down toilets are possible sources of oocysts. These same sources may have also introduced the toxoplasmosis infection to the endangered Hawaiian monk seal. Infection with the parasite has contributed to the death of at least four Hawaiian monk seals. A Hawaiian monk seal's infection with "T. gondii" was first noted in 2004. The parasite's spread threatens the recovery of this highly endangered pinniped. The parasites have been found in dolphins and whales. Researchers Black and Massie believe anchovies, which travel from estuaries into the open ocean, may be helping to spread the disease.


title: Toxoplasmosis

text: "Toxoplasma gondii" has been reported as the cause of death of a giant panda kept in a zoo in China, who died in 2014 of acute gastroenteritis and respiratory disease. Although seemingly anecdotal, this report emphasizes that all warm-blooded species are likely to be infected by "T. gondii", including endangered species such as the giant panda.


title: Toxoplasmosis

text: Chronic infection with "T. gondii" has traditionally been considered asymptomatic in people with normal immune function. Some evidence suggests latent infection may subtly influence a range of human behaviors and tendencies, and infection may alter the susceptibility to or intensity of a number of psychiatric or neurological disorders.


title: Toxoplasmosis

text: In most of the current studies where positive correlations have been found between "T. gondii" antibody titers and certain behavioral traits or neurological disorders, "T. gondii" seropositivity tests are conducted after the onset of the examined disease or behavioral trait; that is, it is often unclear whether infection with the parasite increases the chances of having a certain trait or disorder, or if having a certain trait or disorder increases the chances of becoming infected with the parasite. Groups of individuals with certain behavioral traits or neurological disorders may share certain behavioral tendencies that increase the likelihood of exposure to and infection with "T. gondii"; as a result, it is difficult to confirm causal relationships between "T. gondii" infections and associated neurological disorders or behavioral traits.


title: Toxoplasmosis

text: Some evidence links "T. gondii" to schizophrenia. Two 2012 meta-analyses found that the rates of antibodies to "T. gondii" in people with schizophrenia were 2.7 times higher than in controls. "T. gondii" antibody positivity was therefore considered an intermediate risk factor in relation to other known risk factors. Cautions noted include that the antibody tests do not detect toxoplasmosis directly, most people with schizophrenia do not have antibodies for toxoplasmosis, and publication bias might exist. While the majority of these studies tested people already diagnosed with schizophrenia for "T. gondii" antibodies, associations between "T. gondii" and schizophrenia have been found prior to the onset of schizophrenia symptoms. Sex differences in the age of schizophrenia onset may be explained in part by a second peak of "T. gondii" infection incidence during ages 25–30 in females only. Although a mechanism supporting the association between schizophrenia and "T. gondii" infection is unclear, studies have investigated a molecular basis of this correlation. Antipsychotic drugs used in schizophrenia appear to inhibit the replication of "T. gondii" tachyzoites in cell culture. Supposing a causal link exists between "T. gondii" and schizophrenia, studies have yet to determine why only some individuals with latent toxoplasmosis develop schizophrenia; some plausible explanations include differing genetic susceptibility, parasite strain differences, and differences in the route of the acquired "T. gondii" infection.


title: Toxoplasmosis

text: Correlations have also been found between antibody titers to "T. gondii" and OCD, as well as suicide among people with mood disorders including bipolar disorder. Positive antibody titers to "T. gondii" appear to be uncorrelated with major depression or dysthymia. Although there is a correlation between "T. gondii" and many psychological disorders, the underlying mechanism is unclear. A 2016 study of 236 persons with high levels of toxoplasmosis antibodies found that "there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment".


title: Toxoplasmosis

text: Latent "T. gondii" infection in humans has been associated with a higher risk of automobile accidents, potentially due to impaired psychomotor performance or enhanced risk-taking personality profiles.


title: Toxoplasmosis

text: Climate change has been reported to affect the occurrence, survival, distribution and transmission of "T. gondii". "T. gondii" has been identified in the Canadian arctic, a location that was once too cold for its survival. Higher temperatures increase the survival time of "T. gondii". More snowmelt and precipitation can increase the amount of "T. gondii" oocysts that are transported via river flow. Shifts in bird, rodent, and insect populations and migration patterns can impact the distribution of "T. gondii" due to their role as reservoir and vector. Urbanization and natural environmental degradation are also suggested to affect "T. gondii" transmission and increase risk of infection.


title: Cameron Winklevoss

text: Cameron Howard Winklevoss (born August 21, 1981) is an American cryptocurrency investor and Olympic rower, who (with his brother) founded Winklevoss Capital Management and Gemini cryptocurrency exchange. He competed in the men's pair rowing event at the 2008 Summer Olympics with his identical twin brother and rowing partner, Tyler Winklevoss. Winklevoss and his brother are known for co-founding HarvardConnection (later renamed ConnectU) along with Harvard classmate Divya Narendra. In 2004, the Winklevoss brothers sued Facebook founder Mark Zuckerberg, claiming he stole their ConnectU idea to create the popular social networking site Facebook. In addition to ConnectU, Winklevoss also co-founded the social media website Guest of a Guest with Rachelle Hruska. "Forbes" estimates that each twin has a cryptocurrency holding of $1.4 billion.


title: Cameron Winklevoss

text: Cameron Winklevoss was born in Southampton, New York, and raised in Greenwich, Connecticut. He is the son of Carol (née Leonard) and Howard Edward Winklevoss Jr.; Howard was an adjunct professor of actuarial science at the Wharton School of the University of Pennsylvania. At an early age, he (left-handed) and his identical "mirror-image" twin brother Tyler (right-handed) demonstrated a pattern of teamwork, building Lego together and playing musical instruments. At the age of 13, they taught themselves HTML and started a web-page company, which developed websites for businesses.


title: Cameron Winklevoss

text: Winklevoss went to the Greenwich Country Day School before attending the Brunswick School for high school. He showed a fondness for the classics in high school, studying Latin and Ancient Greek. During his junior year, he co-founded the crew program with Tyler.


title: Cameron Winklevoss

text: On June 14, 2002, Winklevoss's older sister, Amanda, died from unknown causes on the set of "Analyze That" in New York City.


title: Cameron Winklevoss

text: He enrolled at Harvard University in 2000 for his undergraduate studies where he majored in economics, earning an AB degree and graduating in 2004. At Harvard, he was a member of the men's varsity crew, the Porcellian Club and the Hasty Pudding Club.


title: Cameron Winklevoss

text: In 2009, Winklevoss entered the Saïd Business School at the University of Oxford where he obtained an MBA in 2010. While at Oxford he was an Oxford Blue, and rowed, in a losing effort, in the Blue Boat in the 156th Oxford-Cambridge Boat Race.


title: Cameron Winklevoss

text: In December 2002, Winklevoss, along with his brother Tyler Winklevoss and fellow Harvard classmate Divya Narendra, sought a better way to connect with fellow students at Harvard University and other universities. The three conceived of a social network for Harvard students named HarvardConnection; the concept ultimately expanded to other schools around the country. What made ConnectU different from other social media platforms was the need to have a specific domain that matched the 'club' you were getting into, like "harvard.edu." The idea was to make each school its own club, in which students could connect and be exclusive, similar to the infamous finals clubs at Harvard. In January 2003, they enlisted the help of fellow Harvard student, programmer and friend Sanjay Mavinkurve to begin building HarvardConnection. Mavinkurve commenced work on HarvardConnection but departed the project in spring 2003 when he graduated and went to work for Google.


title: Cameron Winklevoss

text: After the departure of Mavinkurve, the Winklevosses and Narendra approached Narendra's friend, Harvard student and programmer Victor Gao, to work on HarvardConnection. Gao, a senior in Mather House, opted not to become a partner in the venture, instead agreeing to be paid in a work for hire capacity. He was paid $400 for his work on the website code during the summer and fall of 2003, when he left the project.


title: Cameron Winklevoss

text: In 2004, ConnectU filed a lawsuit against Facebook alleging that creator Mark Zuckerberg had broken an oral contract with them. The suit alleged that Zuckerberg had copied their idea and illegally used source code intended for the website he was hired to create. Facebook countersued in regards to Social Butterfly, a project put out by The Winklevoss Chang Group, an alleged partnership between ConnectU and i2hub, another campus service. It named among the defendants ConnectU, Cameron Winklevoss, Tyler Winklevoss, Divya Narendra, Winston Williams, and Wayne Chang, founder of i2hub. A settlement agreement for both cases was reached in February 2008, reportedly valued at $65 million. However, in May 2010, it was reported that ConnectU is accusing Facebook of securities fraud on the value of the stock that was part of the settlement and wants to get the settlement undone. According to ConnectU's allegations, the value of the stock was worth $11 million instead of $45 million that Facebook presented at the time of settlement. This meant the settlement value, at the time, was $31 million, instead of the $65 million. On August 26, 2010, "The New York Times" reported that Facebook shares were trading at $76 per share in the secondary market, putting the total settlement value at close to $120 million. If the lawsuit to adjust the settlement to match the difference goes through, the value will quadruple to over $466 million. According to Steven M. Davidoff, "Facebook never represented its valuation in this negotiation, and so there is no prior statement that the company needs to correct." Additionally, Cameron has publicly announced that he fully supports Facebook.


title: Cameron Winklevoss

text: After defeat at the appellate court level, the Winklevoss twins decided to petition the Supreme Court of the United States to hear the case, but in June 2011 announced that they had changed their minds.


title: Cameron Winklevoss

text: One of ConnectU's law firms, Quinn Emanuel, inadvertently disclosed the confidential settlement amount in marketing material by printing "WON $65 million settlement against Facebook". Quinn Emanuel is seeking $13 million of the settlement. ConnectU fired Quinn Emanuel and sued the law firm for malpractice. On August 25, 2010, an arbitration panel ruled that Quinn Emanuel "earned its full contingency fee". It also found that Quinn Emanuel committed no malpractice.


title: Cameron Winklevoss

text: On December 21, 2009, i2hub founder Wayne Chang and The i2hub Organization launched a lawsuit against ConnectU and its founders, seeking 50% of the settlement. The complaint said, "The Winklevosses and Howard Winklevoss filed [a] patent application, U.S. Patent Application No. 20060212395, on or around March 15, 2005, but did not list Chang as a co-inventor." It also stated, "Through this litigation, Chang asserts his ownership interest in The Winklevoss Chang Group and ConnectU, including the settlement proceeds." Lee Gesmer of the firm Gesmer Updegrove posted the 33-page complaint online.


title: Cameron Winklevoss

text: On May 13, 2011, Judge Peter Lauriat ruled against the Winklevosses. Chang's case against them could proceed. The Winklevosses had argued that the court lacked jurisdiction because the settlement with Facebook has not been distributed and therefore Chang has not suffered any injury. Lauriat wrote, "The flaw in this argument is that defendants appear to conflate loss of the settlement proceed with loss of rights. Chang alleges that he has received nothing in return for the substantial benefits he provided to ConnectU, including the value of his work, as well as i2hub's users and goodwill." Lauriat also stated that although Chang's claims to the settlement are "too speculative to confer standing, his claims with respect to an ownership in ConnectU are not. They constitute an injury separate and distinct from his possible share of the settlement proceeds. The court concludes that Chang has pled sufficient facts to confer standing with respect to his claims against the Winklevoss defendants."


title: Cameron Winklevoss

text: In 2008 Cameron co-founded the online site Guest of a Guest, a blog that focuses on parties and nightlife in New York City, Los Angeles, the Hamptons and Washington, D.C., with Rachelle Hruska; she bought out his stake in 2012.


title: Cameron Winklevoss

text: Winklevoss began rowing at the age of 15, encouraged by family friends and the example of next-door neighbor Ethan Ayer who rowed at Harvard University and Cambridge University. Winklevoss began rowing at the Saugatuck Rowing Club on the Saugatuck River in 1997. Winklevoss' high school did not have a crew; in his junior year, he and his brother co-founded a crew program. In the summer of 1999, he made the United States Junior National Rowing Team, competing in the coxed pair event with his brother at the World Rowing Junior Championships in Plovdiv, Bulgaria.


title: Cameron Winklevoss

text: Winklevoss rowed at Harvard University for four years under coach Harry Parker, while completing his undergraduate studies. In 2004, he sat 6-seat in the "engine room" of the Harvard men's varsity heavyweight eight boat. The 2004 crew was nicknamed the "God Squad" because, according to his brother, some of them believed in God while the rest believed they "were" God. As a Harvard Crimson in 2004, he helped the "God Squad" win the Eastern Sprints, the Intercollegiate Rowing Association Championship, and the Harvard–Yale Regatta as part of an undefeated collegiate racing season.


title: Cameron Winklevoss

text: In the summer of 2004, Winklevoss and the God Squad traveled to Lucerne, Switzerland, to compete in the Lucerne Rowing World Cup. They defeated the 2004 British and French Olympic eight boats in the semi-final to earn a spot in the grand final, in which they placed 6th. The team then traveled to the Henley Royal Regatta where they competed in the Grand Challenge Cup. Winklevoss helped his team defeat the Cambridge University Blue Boat in the semi-final before they fell to the Dutch Olympic eight boat team (of the Hollandia Roeiclub) in the final by of a boat length. The Dutch team went on to win the Olympic silver medal at the Athens Olympic Games a month later.


title: Cameron Winklevoss

text: In 2007, Winklevoss was named to the United States Pan American Team and competed at the 2007 Pan American Games in Rio de Janeiro, Brazil. He won a silver medal in the men's coxless four event and a gold medal in the men's eight event on the Lagoa Rodrigo de Freitas.


title: Cameron Winklevoss

text: In 2008, Winklevoss was named to the United States Olympic Team and competed at the 2008 Olympic Games in Beijing, China. He rowed with his brother in the men's coxless pair event that took place at the Shunyi Olympic Rowing-Canoeing Park. The brothers were coached by Ted Nash. In their first heat, they failed to finish in the top three and did not qualify for the Semifinals. In the Repechage (a last chance to make the Semifinals), they took first, advancing them to the Semifinals. A strong finish in Semifinal 2 put them in the Final. They ended up finishing sixth out of the fourteen countries that had qualified for the Olympics.


title: Cameron Winklevoss

text: In 2009, Winklevoss won a bronze medal at the Rowing World Cup in Lucerne, Switzerland, in the men's coxless four event.


title: Cameron Winklevoss

text: In 2012, Winklevoss and his brother Tyler founded Winklevoss Capital Management, a firm which invests across multiple asset classes with an emphasis on providing seed funding and infrastructure to early-stage startups. The company is headquartered in New York's Flatiron District.


title: Cameron Winklevoss

text: Winklevoss and his brother were played by actor Armie Hammer in "The Social Network" (2010), a film directed by David Fincher about the founding of Facebook. Actor Josh Pence was the body double for Tyler with Hammer's face superimposed.


title: Cameron Winklevoss

text: The twins were depicted on the cartoon comedy show "The Simpsons" in the eleventh episode of Season 23 in the episode called "The D'oh-cial Network" which aired on January 15, 2012. The Winklevoss twins are seen rowing in the 2012 Olympic Games against Marge Simpson's sisters Patty and Selma. There is a reference made to the $65 million Facebook settlement.


title: Data

text: In the pursuit of knowledge, data (; ) is a collection of discrete values that convey information, describing quantity, quality, fact, statistics, other basic units of meaning, or simply sequences of symbols that may be further interpreted. A datum is an individual value in a collection of data. Data is usually organized into structures such as tables that provide additional context and meaning, and which may themselves be used as data in larger structures. Data may be used as variables in a computational process. Data may represent abstract ideas or concrete measurements.


title: Data

text: Data is commonly used in scientific research, economics, and in virtually every other form of human organizational activity. Examples of data sets include price indices (such as consumer price index), unemployment rates, literacy rates, and census data. In this context, data represents the raw facts and figures which can be used in such a manner in order to capture the useful information out of it.


title: Data

text: Data is collected using techniques such as measurement, observation, query, or analysis, and typically "represented" as numbers or characters which may be further processed. Field data are data that is collected in an uncontrolled in-situ environment. Experimental data is data that is generated in the course of a controlled scientific experiment. Data is analyzed using techniques such as calculation, reasoning, discussion, presentation, visualization, or other forms of post-analysis. Prior to analysis, raw data (or unprocessed data) is typically cleaned: Outliers are removed and obvious instrument or data entry errors are corrected.


title: Data

text: Data can be seen as the smallest units of factual information that can be used as a basis for calculation, reasoning, or discussion. Data can range from abstract ideas to concrete measurements, including but not limited to, statistics. Thematically connected data presented in some relevant context can be viewed as "information". Contextually connected pieces of information can then be described as "data insights" or "intelligence". The stock of insights and intelligence that accumulates over time resulting from the synthesis of data into information, can then be described as "knowledge". Data has been described as "the new oil of the digital economy". Data, as a general concept, refers to the fact that some existing information or knowledge is "represented" or "coded" in some form suitable for better usage or processing.


title: Data

text: Advances in computing technologies have led to the advent of big data, which usually refers to very large quantities of data, usually at the petabyte scale. Using traditional data analysis methods and computing, working with such large (and growing) datasets is difficult, even impossible. (Theoretically speaking, infinite data would yield infinite information, which would render extracting insights or intelligence impossible.) In response, the relatively new field of data science uses machine learning (and other artificial intelligence (AI)) methods that allow for efficient applications of analytic methods to big data.


title: Data

text: The Latin word "data" is the plural of 'datum', "(thing) given," neuter past participle of "dare" "to give".


title: Data

text: The first English use of the word "data" is from the 1640s. The word "data" was first used to mean "transmissible and storable computer information" in 1946. The expression "data processing" was first used in 1954.


title: Data

text: When "data" is used more generally as a synonym for "information", it is treated as a mass noun in singular form. This usage is common in everyday language and in technical and scientific fields such as software development and computer science. One example of this usage is the term "big data".


title: Data

text: When used more specifically to refer to the processing and analysis of sets of data, the term retains its plural form.


title: Data

text: This usage is common in natural sciences, life sciences, social sciences, software development and computer science, and grew in popularity in the 20th and 21st centuries. Some style guides do not recognize the different meanings of the term, and simply recommend the form that best suits the target audience of the guide. For example, APA style as of the 7th edition requires "data" to be treated as a plural form.


title: Data

text: Data, information, knowledge, and wisdom are closely related concepts, but each has its role concerning the other, and each term has its meaning. According to a common view, data is collected and analyzed; data only becomes information suitable for making decisions once it has been analyzed in some fashion. One can say that the extent to which a set of data is informative to someone depends on the extent to which it is unexpected by that person. The amount of information contained in a data stream may be characterized by its Shannon entropy.


title: Data

text: Knowledge is the awareness of its environment that some entity possesses, whereas data merely communicate that knowledge. For example, the entry in a database specifying the height of Mount Everest is a datum that communicates a precisely-measured value. This measurement may be included in a book along with other data on Mount Everest to describe the mountain in a manner useful for those who wish to decide on the best method to climb it. An awareness the characteristics represented by these data is knowledge.


title: Data

text: Data is often assumed to be the least abstract concept, information the next least, and knowledge the most abstract. In this view, data becomes information by interpretation; e.g., the height of Mount Everest is generally considered "data", a book on Mount Everest geological characteristics may be considered "information", and a climber's guidebook containing practical information on the best way to reach Mount Everest's peak may be considered "knowledge". "Information" bears a diversity of meanings that ranges from everyday usage to technical use. This view, however, has also been argued to reverse how data emerges from information, and information from knowledge. Generally speaking, the concept of information is closely related to notions of constraint, communication, control, data, form, instruction, knowledge, meaning, mental stimulus, pattern, perception, and representation. Beynon-Davies uses the concept of a sign to differentiate between data and information; data is a series of symbols, while information occurs when the symbols are used to refer to something.


title: Data

text: Before the development of computing devices and machines, people had to manually collect data and impose patterns on it. Since the development of computing devices and machines, these devices can also collect data. In the 2010s, computers are widely used in many fields to collect data and sort or process it, in disciplines ranging from marketing, analysis of social services usage by citizens to scientific research. These patterns in data are seen as information that can be used to enhance knowledge. These patterns may be interpreted as "truth" (though "truth" can be a subjective concept) and may be authorized as aesthetic and ethical criteria in some disciplines or cultures. Events that leave behind perceivable physical or virtual remains can be traced back through data. Marks are no longer considered data once the link between the mark and observation is broken.


title: Data

text: Mechanical computing devices are classified according to how they represent data. An analog computer represents a datum as a voltage, distance, position, or other physical quantity. A digital computer represents a piece of data as a sequence of symbols drawn from a fixed alphabet. The most common digital computers use a binary alphabet, that is, an alphabet of two characters typically denoted "0" and "1". More familiar representations, such as numbers or letters, are then constructed from the binary alphabet. Some special forms of data are distinguished. A computer program is a collection of data, which can be interpreted as instructions. Most computer languages make a distinction between programs and the other data on which programs operate, but in some languages, notably Lisp and similar languages, programs are essentially indistinguishable from other data. It is also useful to distinguish metadata, that is, a description of other data. A similar yet earlier term for metadata is "ancillary data." The prototypical example of metadata is the library catalog, which is a description of the contents of books.


title: Data

text: Whenever data needs to be registered, data exists in the form of a data document. Kinds of data documents include:


title: Data

text: Some of these data documents (data repositories, data studies, data sets, and software) are indexed in Data Citation Indexes, while data papers are indexed in traditional bibliographic databases, e.g., Science Citation Index.


title: Data

text: Gathering data can be accomplished through a primary source (the researcher is the first person to obtain the data) or a secondary source (the researcher obtains the data that has already been collected by other sources, such as data disseminated in a scientific journal). Data analysis methodologies vary and include data triangulation and data percolation. The latter offers an articulate method of collecting, classifying, and analyzing data using five possible angles of analysis (at least three) to maximize


title: Data

text: the research's objectivity and permit an understanding of the phenomena under investigation as complete as possible: qualitative and quantitative methods, literature reviews


title: Data

text: (including scholarly articles), interviews with experts, and computer simulation. The data is thereafter "percolated" using a series of pre-determined steps so as to extract


title: Data

text: An important field in computer science, technology, and library science is the longevity of data. Scientific research generates huge amounts of data, especially in genomics and astronomy, but also in the medical sciences, e.g. in medical imaging. In the past, scientific data has been published in papers and books, stored in libraries, but more recently practically all data is stored on hard drives or optical discs. However, in contrast to paper, these storage devices may become unreadable after a few decades. Scientific publishers and libraries have been struggling with this problem for a few decades, and there is still no satisfactory solution for the long-term storage of data over centuries or even for eternity.


title: Data

text: Data accessibility. Another problem is that much scientific data is never published or deposited in data repositories such as databases. In a recent survey, data was requested from 516 studies that were published between 2 and 22 years earlier, but less than 1 out of 5 of these studies were able or willing to provide the requested data. Overall, the likelihood of retrieving data dropped by 17% each year after publication. Similarly, a survey of 100 datasets in Dryad found that more than half lacked the details to reproduce the research results from these studies. This shows the dire situation of access to scientific data that is not published or does not have enough details to be reproduced.


title: Data

text: A solution to the problem of reproducibility is the attempt to require FAIR data, that is, data that is Findable, Accessible, Interoperable, and Reusable. Data that fulfills these requirements can be used in subsequent research and thus advances science and technology.


title: Data

text: Although data is also increasingly used in other fields, it has been suggested that the highly interpretive nature of them might be at odds with the ethos of data as "given". Peter Checkland introduced the term "capta" (from the Latin "capere", “to take”) to distinguish between an immense number of possible data and a sub-set of them, to which attention is oriented. Johanna Drucker has argued that since the humanities affirm knowledge production as "situated, partial, and constitutive," using "data" may introduce assumptions that are counterproductive, for example that phenomena are discrete or are observer-independent. The term "capta", which emphasizes the act of observation as constitutive, is offered as an alternative to "data" for visual representations in the humanities.


title: Better Call Saul (season 4)

text: The fourth season of the American television drama series "Better Call Saul" premiered on August 6, 2018, and concluded on October 8, 2018. The fourth season consists of 10 episodes and aired on Mondays at 9:00 pm (Eastern) in the United States on AMC. A spin-off prequel of "Breaking Bad", "Better Call Saul" was created by Vince Gilligan and Peter Gould, both of whom also worked on "Breaking Bad".


title: Better Call Saul (season 4)

text: The first and second seasons mainly took place in 2002, with season three advancing the storyline to 2003. The fourth season also takes place mainly in 2003, with the last four episodes taking place in 2004 after a time jump in the seventh episode. In season four, Jimmy and Kim struggle to cope with Chuck's death. Howard believes that he is responsible for Chuck's death, and suffers with depression and disengagement from work. Mike begins security inspections at Madrigal, disregarding the fact that his consulting contract was supposed to be only a paper transaction. Gus is suspicious of Nacho after Hector's stroke. Nacho becomes a mole for Gus inside the Salamanca organization. Gus hires an engineer and construction crew to begin construction of the meth "superlab" under the industrial laundry. Lalo Salamanca arrives to begin running the family's drug business.


title: Better Call Saul (season 4)

text: The fourth season of "Better Call Saul" received acclaim from critics and audiences, particularly for its pacing and character development, and six nominations for the 71st Primetime Emmy Awards, including Outstanding Drama Series.


title: Better Call Saul (season 4)

text: AMC renewed "Better Call Saul" for a 10-episode fourth season in June 2017. The fourth season premiered in August 2018, and aired on Mondays at 9:00pm (Eastern); the fourth season premiered later in the year than previous seasons, as both season 1 and 2 premiered in February 2015 and 2016, and season 3 premiered in April 2017. "Screen Rant" speculated that because the season was not confirmed until after the third season had finished airing, that the writers had a later start at writing, and the season did not begin filming until January 2018.


title: Better Call Saul (season 4)

text: "Better Call Saul" is set and filmed in Albuquerque, New Mexico, the same location as its predecessor. Filming for the fourth season of "Better Call Saul" began in January 2018. The first episode was directed by Minkie Spiro. On May 30, 2018, screenwriter Thomas Schnauz confirmed in a tweet that production of the fourth season had finished.


title: Better Call Saul (season 4)

text: In the first scene of the season, Jimmy is hiding his real identity under his Gene Takavic alias while working at a Cinnabon in a shopping mall in Omaha, Nebraska. The Cinnabon scenes in "Better Call Saul" are set in Omaha, but filmed at the Cottonwood Mall in Albuquerque, New Mexico.


title: Better Call Saul (season 4)

text: Mark Margolis, who plays drug kingpin Hector Salamanca, required brain surgery after suffering severe head injuries in an accidental fall during filming.


title: Better Call Saul (season 4)

text: The episode "Piñata" was directed by Andrew Stanton, who is better known for writing and directing several Pixar films, including "Finding Nemo" and "WALL-E". During a conversation with Mark Johnson and Melissa Bernstein, the show's executive producers, he was given the suggestion that he accept an opportunity to direct a "Better Call Saul" episode, which he jumped at, as he had already been a fan of both "Breaking Bad" and "Better Call Saul", and wanted the opportunity to work with the creators Vince Gilligan and Peter Gould.


title: Better Call Saul (season 4)

text: Returning main cast members are Bob Odenkirk as Jimmy McGill, Jonathan Banks as Mike Ehrmantraut, Rhea Seehorn as Kim Wexler, Patrick Fabian as Howard Hamlin, Michael Mando as Nacho Varga, and Giancarlo Esposito as Gus Fring. Michael McKean (Chuck McGill), who was credited as a main cast member in previous seasons, does not return as a series regular following Chuck's death in the third season finale. In a June 2017 interview following the third-season finale, McKean commented on the possibility of returning to the series, stating "I know they want to bring me in for some flashbacks this coming season." McKean made a guest appearance in a flashback sequence at the beginning of the sixth episode, "Piñata", and again in the season finale, "Winner".


title: Better Call Saul (season 4)

text: In May 2018, it was reported that Stefan Kapičić would have a recurring role in the fourth season. Kapičić stated, "I'm thrilled that I have a chance to become a part of "Better Call Saul" family. It is one of my favorite shows on TV and it's a dream come true be a part of the "Breaking Bad" universe." Lalo Salamanca, portrayed by Tony Dalton, is introduced in the eighth episode of the season. The character was first mentioned in the "Breaking Bad" episode "Better Call Saul".


title: Better Call Saul (season 4)

text: The episode "Something Beautiful" marks the first "Better Call Saul" appearance of Gale Boetticher, a supporting character from "Breaking Bad" played by David Costabile. Costabile had been in Albuquerque filming "Dig" while "Better Call Saul"s team was wrapping up production of the first season. He met with Gould, and they agreed to have Gale appear on "Better Call Saul". Costabile was able to work in filming for "Better Call Saul" between filming on "Billions", but had only about a week to memorize both his dialogue and the lyrics to Tom Lehrer's "The Elements" which he had to sing karaoke-style in his scenes. This short period contrasted with his past singing performances on "Breaking Bad", when he had more time to learn the lyrics.


title: Better Call Saul (season 4)

text: The death of Jimmy's brother Chuck serves as a catalyst for his further transformation into Saul Goodman, and Jimmy's entrance into the criminal world puts a strain on his relationship with Kim and his future as a lawyer. Chuck's death also deeply affects Kim and Howard. Mike becomes a contracted security consultant for Madrigal. Nacho's attempted murder of Hector Salamanca causes Hector's stroke and disability, and affects the operations of Don Eladio's drug cartel and Gus Fring's plot to take it over.


title: Better Call Saul (season 4)

text: Gilligan said in January 2018 that "Better Call Saul" "gets darker this season," and Odenkirk said that the fourth season would go to "another level."


title: Better Call Saul (season 4)

text: The fourth season, much like the previous three, received critical acclaim, particularly for its pacing and character development. On Metacritic, the season has a score of 87 out of 100 based on 16 critics. On Rotten Tomatoes, the season has a 99% approval rating with an average score of 8.9 out of 10 based on 185 reviews. The site's critical consensus states, "Well-crafted and compelling as ever, "Better Call Saul" deftly balances the show it was and the one it will inevitably become."


title: Better Call Saul (season 4)

text: Based on the first three episodes, Liz Shannon Miller of IndieWire gave the series a highly positive review with an "A" grade. She wrote that season four is "better, deeper, and more daring" and that it is "one of the most subtle and brilliant shows on TV." Spencer Kornhaber of "The Atlantic" said of the season premiere: "Old dynamics flip, long-gestating character studies pay off, and feelings geyser up in surprising places." Following the season finale, Judy Berman of "Time" wrote, "In showing us one individual's preordained moral downfall, "Better Call Saul" spent Season 4 demonstrating how a hypocritical criminal justice system can ensnare a whole class of people for life". Chris Evangelista of "/Film" wrote after the finale: ""Better Call Saul" remains one of the best shows on TV right now. Not only did Jimmy change this season, he changed those around him – and for the worst."


title: Better Call Saul (season 4)

text: Lalo Salamanca, portrayed by Tony Dalton, is introduced as a recurring character in this season, Alan Sepinwall of "Rolling Stone" said Dalton "makes a solid first impression in the role, so hopefully this will turn out to be more than filling in a blank most viewers had long since forgotten existed."


title: Better Call Saul (season 4)

text: In 2018, "Better Call Saul" was named one of the top 10 television programs of the year by the American Film Institute. The series won the award for Outstanding Achievement in Drama at the 35th TCA Awards.


title: Better Call Saul (season 4)

text: For the 71st Primetime Emmy Awards, the series received six nominations–for Outstanding Drama Series, Odenkirk for Outstanding Lead Actor in a Drama Series, Banks and Esposito each for Outstanding Supporting Actor in a Drama Series, McKean for Outstanding Guest Actor in a Drama Series, and Schnauz and Gould for Outstanding Writing for a Drama Series for the episode "Winner".


title: Better Call Saul (season 4)

text: The fourth season was released on Blu-ray and DVD in region 1 on May 7, 2019. The set contains all 10 episodes, plus audio commentaries for every episode and several behind-the-scenes featurettes.


title: Better Call Saul (season 4)

text: Outside the U.S. in certain international markets, season 4 was released on Netflix with episodes available the day after the episodes were broadcast on AMC.


title: Better Call Saul (season 4)

text: Similar to the series of fictional employee training videos used during season three, AMC posted ten mini-episodes of "Madrigal Electromotive Security Training" to YouTube and its social media accounts during the run of season four. The videos feature a mix of live-action footage of Banks portraying Mike in providing training to new security employees of Madrigal and animated segments. The series had been nominated for the Primetime Emmy Award for Outstanding Short Form Comedy or Drama Series, but the nomination was pulled by the Academy of Television Arts & Sciences after they discovered the episodes were too short for the category, stating "This decision is in no way a diminishment of the quality of Better Call Saul Employee Training or Mr. Banks' performance in it".


title: Over the Garden Wall

text: Over the Garden Wall is an American animated television miniseries created by Patrick McHale for Cartoon Network. The series centers on two half-brothers who travel across a mysterious forest to find their way home, encountering a variety of strange and fantastical things on their journey. The show is based on McHale's animated short film "Tome of the Unknown", which was produced as part of Cartoon Network Studios' shorts development program. Elijah Wood and Collin Dean voice the protagonists Wirt and Greg, and Melanie Lynskey voices Beatrice, a bluebird. The series' voice cast also includes Christopher Lloyd, Tim Curry, Bebe Neuwirth, Chris Isaak, Shirley Jones, Thomas Lennon, Jack Jones, Jerron Paxton, John Cleese and Samuel Ramey. The Blasting Company composed the soundtrack. "Over the Garden Wall" was broadcast throughout the week of November 3 to November 7, 2014.


title: Over the Garden Wall

text: The show was the first miniseries on the network. McHale first envisioned it in 2004 and pitched it to the network in 2006. After working on other Cartoon Network shows including "The Marvelous Misadventures of Flapjack" and "Adventure Time", the network expressed interest in McHale pitching a pilot. That pilot, "Tome of the Unknown", became the catalyst for "Over the Garden Wall". Production of the show began in March 2014 and was largely done in Burbank, California, but many of the show's storyboard artists worked from other U.S. cities, while the program's animation was outsourced to South Korean studio Digital eMation. The series' environment evokes 19th- and 20th-century Americana, while its digital backgrounds are designed to resemble brunaille paintings.


title: Over the Garden Wall

text: The series was well-received by television critics, who praised its atmosphere and characters. In 2015, the series won an Emmy Award for Outstanding Animated Program. A one-shot comic book adaptation penned by McHale has been produced, with four further issues commissioned. This was later expanded into an ongoing comic series that ran for 20 issues and continued in a series of graphic novels and comic book miniseries.


title: Over the Garden Wall

text: The series follows two half-brothers, Wirt and Greg (voiced by Elijah Wood and Collin Dean respectively), who become lost in a strange forest called the Unknown. To find their way home, the two must travel across the seemingly supernatural forest with the occasional help of the wandering, mysterious and elderly Woodsman (Christopher Lloyd) and Beatrice (Melanie Lynskey), an irritable bluebird who travels with the boys to find a woman called Adelaide, who can supposedly undo the curse on Beatrice and her family and show the half-brothers the way home.


title: Over the Garden Wall

text: Wirt, the older brother, is a worry-prone teenager who would rather keep to himself than have to make a decision. His passions including playing the clarinet and writing poetry, but he usually keeps these private out of fear of being mocked. On the other hand, Greg, the younger brother, is more naïve and carefree, much to Wirt's chagrin. Greg carries a frog (Jack Jones) that he found; Greg's attempts to give the frog a name are a running gag. Stalking the main cast is the Beast (Samuel Ramey), an ancient creature who leads lost souls astray until they lose their hope and willpower and turn into "Edelwood trees". Once they find Adelaide, Wirt discovers that she intends only to enslave the boys; outraged that Beatrice misled them, Wirt takes Greg and abandons her.


title: Over the Garden Wall

text: The penultimate episode reveals that Wirt and Greg are modern children who entered the Unknown after falling into a pond on Halloween. Wirt, attempting to take back an embarrassing poetry and clarinet tape he made for a girl he is infatuated with, had followed her to a ghost story party in a graveyard, where a police officer scared him and Greg into jumping over the cemetery's garden wall. On the other side of the wall, they landed on a train track. To save Greg from being hit by a train, Wirt pulled him into a nearby pond, knocking them both unconscious in the process and sending them to a Limbo-like realm between life and death.


title: Over the Garden Wall

text: In the final episode, Wirt saves Greg from being turned into an Edelwood tree by the Beast. At the end of the episode, Wirt and Greg wake up in a hospital back in their hometown. As the scene ends, Greg's frog, which swallowed a magic bell in the Unknown, begins to glow, suggesting that their experience in the Unknown may have been real. The series ends with a montage of how Wirt and Greg affected the inhabitants of the Unknown.


title: Over the Garden Wall

text: "Over the Garden Wall" was first envisioned in 2004 with a scarier and more adventure-based storyline. Before working as a storyboard artist on "The Marvelous Misadventures of Flapjack", artist Patrick McHale pitched the show in 2006, then known under the title "Tome of the Unknown". The series would follow two brothers—Walter and Gregory—who, after signing themselves into a Faustian deal with a devil named Old Scratch, journey across the Land of the In-Between to track down the pages of a book of forgotten stories.


title: Over the Garden Wall

text: McHale saw it as "a possible Halloween special", but had trouble adapting the premise with a larger story arc. After his work for "Flapjack", McHale moved on to co-develop "Adventure Time", where he served as creative director, and subsequently as a writer. The network later asked him if he had interest in developing a pilot, which led to him returning to "Tome of the Unknown", polishing it and pitching it again to the network. After creating a pilot episode, "", McHale and the network settled upon the miniseries format for the ensuing series, as McHale felt that it would lead to "something that felt higher quality than what we could do with a regular series". McHale abandoned the original idea centered around chapters of a mystical tome and the series' title became "Over the Garden Wall".


title: Over the Garden Wall

text: Production for "Over the Garden Wall" commenced in late 2013. McHale initially envisioned eighteen chapters in the series, but the episode count was brought to ten to accommodate budget and time constraints. Early drafts of episodes from the show's pitch bible included a skinless witch character and a villain who carves dice from the bones of kidnapped children, as well a running plot throughout four episodes in which Wirt and Gregory are transformed into animals (Gregory being a duck and Wirt being "either a bear or a dog ... Nobody can tell which").


title: Over the Garden Wall

text: The ten episodes marked the first miniseries on the Cartoon Network. The show features Wood and Dean (reprising their roles from the short), along with Lynskey as the main voice cast. McHale and his crew tried to maintain a balance between frightening imagery and "episodes that are just light and funny". For the music, McHale drew inspiration from "classic American, opera singing". Nick Cross served as art director and Nate Cash as supervising director; both worked with McHale alongside storyboard artists located in New York and Chicago. This distance proved difficult for McHale, who found it "particularly daunting considering the idiosyncratic nature of the production".


title: Over the Garden Wall

text: The series' art was inspired by a variety of sources, including the 1890s McLoughlin Brothers board game "Game of Frog Pond", illustrations by Gustave Doré for Cervantes's "Don Quixote", old illustrations for the Hans Christian Andersen story "The Tinderbox", the Cheshire Cat illustration by John Tenniel from "Alice's Adventures in Wonderland", and the "Dogville Comedies" short films. McHale referenced chromolithography, vintage Halloween postcards, magic lantern slides, and photographs of New England foliage to create the show's style.


title: Over the Garden Wall

text: McHale's original short, "Tome of the Unknown", was screened at the 2014 Santa Barbara International Film Festival, where McHale earned the Bruce Corwin Award for best animated short film. It also received an honorable mention at the 2013 Ottawa International Animation Festival.


title: Over the Garden Wall

text: At the 2014 San Diego Comic-Con International, a preview of the show was screened along with various panels for other shows on the network. Episode 2 was previewed at the 2014 New York Comic Con, which McHale and the main cast attended. The show made its premiere on November 3, 2014 on Cartoon Network, and ran over five consecutive nights. The entirety of it was published on iTunes preceding its broadcast.


title: Over the Garden Wall

text: The series aired on Cartoon Network in Australia from December 15 to 19, 2014 and on Cartoon Network in the United Kingdom and Ireland from April 6 to 10, 2015.


title: Over the Garden Wall

text: Various melodies and songs based on pre-1950s music are heard throughout the series. Elijah Wood, the voice actor for Wirt, has said that "if this show were a record, it would be played on a phonograph". Songs from the series include "Into the Unknown", its title song, composed by Patrick McHale and sung by Jack Jones; "A Courting Song", composed by the Petrojvic Blasting Company and performed by Frank Fairfield; and "Come Wayward Souls", sung by Samuel Ramey as the Beast.


title: Over the Garden Wall

text: The majority of the series' songs have been officially uploaded to YouTube. On the DVD release they can be heard, along with visuals and without dialogue, in a special feature known as the Composer's Cut. An extended version of the soundtrack, featuring 32 tracks and totaling around 44 minutes in length, was released in the form of a 180-gram vinyl record by Mondo in August 2016. The extended soundtrack debuted at the San Diego Comic-Con, with a limited 1,000 copies, featuring a cover designed by Sam Wolfe Connelly. The extended vinyl is also available as a webstore exclusive from Mondo.


title: Over the Garden Wall

text: In September 2015, Mondo released an audio cassette tape titled "For Sara", based on the cassette tape labelled with the same name seen in the series. The cassette features over twenty minutes of poetry spoken by Elijah Wood (in character as Wirt) and music performed by the Blasting Company. In September 2017, Mondo released the cassette a second time, with the subtitle "(Back-Up Master)".


title: Over the Garden Wall

text: "Over the Garden Wall" (with the short film "Tome of the Unknown") was released on DVD in Australia on July 8, 2015 by Cartoon Network and Madman Entertainment and by Cartoon Network and Warner Home Video on September 8, 2015, in the United States. The DVD features all ten episodes of the show, commentaries, the original pilot, alternate title cards, and deleted animatics. Other extras on the DVD include a "Composer's Cut," an option wherein a viewer can watch the show with only the visuals and the background music; and the mini-documentary "Behind Over the Garden Wall".


title: Over the Garden Wall

text: On April 6, 2016, Madman Entertainment released the miniseries on Blu-ray exclusively in Australia and New Zealand with the same bonus content as the DVD release. On March 2, 2020, Manga Entertainment released it in the UK on Blu-Ray and DVD.


title: Over the Garden Wall

text: "Over the Garden Wall" was critically acclaimed. On review aggregator Rotten Tomatoes, the series has an approval rating of 93% based on 15 reviews, with an average rating of 8.60/10. The website's critics consensus reads, ""Over the Garden Wall"'s modern sensibilities mix well with its fairy-tale setting, creating a whimsically witty series for viewers of all ages."


title: Over the Garden Wall

text: Preceding its premiere, Patrick Kevin Day of the "Los Angeles Times" called it "funny, creepy" and, from the premise, "not as simple as it sounds". In "TV Guide" and also before the premiere, Megan Walsh-Boyle felt that the show's fictional universe "sounds like a world worth getting lost in". Meredith Woerner of "io9" called a preview of the show "amazing", "weird, and cute and great", reflecting "all the things we love about this oddball animation renaissance we are currently living in". Conversely, Amid Amidi of "Cartoon Brew" judged from the same preview that the animation was lacking. While not discounting its storytelling, music, and production design, he felt that production skimped on animation; he was still looking forward to the series.


title: Over the Garden Wall

text: Robert Lloyd of the "Los Angeles Times" wrote that it was "a little too folksy and fairy story" at times, but that its "contemporary strangeness wins out", and concluded that "it is throughout something to behold". Lloyd later wrote that it evoked "a kind of artisanal quality", both in its design and setting, and though the writing felt "a little too intent on its own folksiness", it became more enjoyable throughout. In "The New York Times", Mike Hale also felt the writing was sometimes weak and the stories "perilously thin", but concluded that McHale developed an environment worth visiting.


title: Over the Garden Wall

text: Brian Moylan of "The Guardian" wrote that the visuals were "absolutely stunning", and that the stories contained "a certain darkness to it that is both mellow and twee at the same time, with a fair amount of anxiety creeping around the edges". Brian Lowry of "Variety" wrote that "Garden Wall" was "an admirable experiment", but not one to sustain "the five-night commitment", calling it "slightly mismatched" while praising a departure from "the more abrasive characteristic" of the network's primetime content. Kevin McDonough of the Illinois "Daily Journal" criticized some of the writing, but summed it up as "an ambitious cartoon" for both younger and older audiences. Jason Bree of the website Agents of Geek called the miniseries "the greatest thing Cartoon Network has ever produced". Kevin Johnson of "The A.V. Club" praised the series, giving it a grade of "A" and writing that "with such a perfect blend of mood, atmosphere, story, and characterization, "Over the Garden Wall"s 10-episode run will leave you wanting more, but like every great fairy tale, it's a story that knows when it's over."


title: Over the Garden Wall

text: A one-shot comic book adaptation of the show was announced in October 2014. Produced by KaBoom!, an imprint of Boom! Studios, the comic was released on November 5, 2014. The comic was supervised by McHale and was produced as an oversized special. The comic was illustrated by Jim Campbell, a writer/storyboard artist on the television series. A special variant cover, by McHale, was also released. The success of the standalone comic led to further issues being commissioned in May 2015 and began to be released in August 2015. According to McHale, the comic books would be similar to the one-shot comic, detailing the events that occurred in between certain episodes and would expand on the television miniseries. The success of the series of one-shots led to an ongoing series of comics, serving as both a sequel and prequel to the series, rather than telling adventures that happened between episodes. The stories are told parallel, with half the comic detailing Greg returning to mysterious dreamlands in his sleep. The other half chronicles the Woodsman's daughter, Anna, and how she became lost in the Unknown. After the ongoing series ended in November 2017, the "Over the Garden Wall" comics continued as a series of miniseries and original graphic novels.


title: Betty Broderick

text: Elisabeth Anne Broderick (née Bisceglia; born November 7, 1947) is an American woman who was convicted of murdering her ex-husband, Daniel T. Broderick III, and his second wife, Linda (née Kolkena) Broderick, on November 5, 1989. At a second trial that began on December 11, 1991, she was convicted of two counts of second-degree murder and later sentenced to 32-years-to-life in prison. The case received extensive media attention. Several books were written on the Broderick case, and a TV movie was televised in two parts. In 2020, an 8-episode miniseries was produced and aired about Broderick.


title: Betty Broderick

text: Betty Broderick was born Elisabeth Anne Bisceglia on November 7, 1947 and grew up in Bronxville, New York. She was the third of six children born to devout Roman Catholic parents Marita (née Curtin; 1919–2007) and Frank Bisceglia (1915–1998), who owned a successful plastering business with relatives. Her mother was Irish American and her father was Italian American.


title: Betty Broderick

text: The Bisceglias were strict parents, and much was expected of all the Bisceglia children. As Broderick later recalled, she was being trained to be a housewife since the day she was born, or as she recalled: "Go to Catholic schools, be careful with dating until you find a Catholic man, support him while he works, be blessed in your later years with beautiful grandchildren".


title: Betty Broderick

text: Broderick graduated from Maria Regina High School, in Hartsdale, New York, in 1965. She graduated from the College of Mount Saint Vincent in the Bronx, where she earned a degree in early childhood education through an accelerated program. Her credits also earned her a minor in English.


title: Betty Broderick

text: In 1965, Elizabeth (Betty) met her future husband, Dan Broderick (1944–1989), at the University of Notre Dame, Indiana. Dan was born in Pittsburgh, Pennsylvania, the eldest son of a very large Irish Catholic family. The couple married on April 12, 1969 at the Immaculate Conception Church in Tuckahoe, New York. Betty returned from the honeymoon pregnant with their first child, daughter Kim (b. 1970). She gave birth to four more children: daughter Lee (b. 1971), sons named Daniel (b. 1976) and Rhett (b. 1979), and an unnamed boy, who died four days after birth.


title: Betty Broderick

text: After Kim's birth, Dan completed his M.D. degree. He then announced his intention to combine his medical expertise with a J.D. degree and enrolled at Harvard Law School. Betty was the main provider for the family while Dan attended law school with the help of a student loan. Dan was quickly hired by a law firm in San Diego, California, and moved his family to the San Diego community of La Jolla. Betty continued working part-time, often selling Tupperware or Avon products while raising the children.


title: Betty Broderick

text: In the fall of 1982, Dan hired 21-year-old Dutch American Linda Kolkena (1961–1989), a former Delta Air Lines flight attendant, to be his legal assistant. As early as October 1983, Betty suspected that Dan was having an affair with Kolkena, but Dan denied it. Against Betty's wishes, Dan moved out in February 1985. He eventually took custody of their children after Betty left the children on his doorstep one by one. Betty claimed that Dan confessed he had in fact been having an affair with Kolkena, and a long, drawn-out, and hostile divorce ensued.


title: Betty Broderick

text: By this time, Dan Broderick had become a prominent local lawyer, serving as the president of the San Diego Bar Association. Betty claimed that Dan made it extremely difficult for her to find a lawyer willing to represent her in the divorce, which put her at a distinct disadvantage. Betty also believed that Dan used his legal influence to win sole custody of their children, sell their house against her wishes and cheat her out of her rightful share of his income.


title: Betty Broderick

text: The divorce was finalized in 1989, four years after Dan filed the petition. Betty Broderick's behavior became increasingly erratic. She left hundreds of profane messages on Dan's answering machine, and ignored numerous restraining orders that forbade her from setting foot on Dan's property. She vandalized his new home, and even drove her car into his front door despite the fact that their children were inside the house at the time.


title: Betty Broderick

text: On April 22, 1989, Dan and Kolkena were married. Kolkena had been concerned about Betty's behavior and even urged Dan to wear a bulletproof vest to their wedding. However, Betty did not arrive and the wedding proceeded without incident. After the wedding, Betty Broderick claimed that Linda Broderick taunted her by mailing her facial cream and slimming treatment ads.