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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.
Skin cancer may occur following ionizing radiation exposure following a latent period averaging 20 to 40 years. A Chronic radiation keratosis is a precancerous keratotic skin lesion that may arise on the skin many years after exposure to ionizing radiation. Various malignancies may develop, most frequency basal-cell carcinoma followed by squamous-cell carcinoma. Elevated risk is confined to the site of radiation exposure. Several studies have also suggested the possibility of a causal relationship between melanoma and ionizing radiation exposure. The degree of carcinogenic risk arising from low levels of exposure is more contentious, but the available evidence points to an increased risk that is approximately proportional to the dose received. Radiologists and radiographers are among the earliest occupational groups exposed to radiation. It was the observation of the earliest radiologists that led to the recognition of radiation-induced skin cancer—the first solid cancer linked to radiation—in 1902. While the incidence of skin cancer secondary to medical ionizing radiation was higher in the past, there is also some evidence that risks of certain cancers, notably skin cancer, may be increased among more recent medical radiation workers, and this may be related to specific or changing radiologic practices. Available evidence indicates that the excess risk of skin cancer lasts for 45 years or more following irradiation.
Cancer is a stochastic effect of radiation, meaning that it only has a probability of occurrence, as opposed to deterministic effects which always happen over a certain dose threshold. The consensus of the nuclear industry, nuclear regulators, and governments, is that the incidence of cancers due to ionizing radiation can be modeled as increasing linearly with effective radiation dose at a rate of 5.5% per sievert. Individual studies, alternate models, and earlier versions of the industry consensus have produced other risk estimates scattered around this consensus model. There is general agreement that the risk is much higher for infants and fetuses than adults, higher for the middle-aged than for seniors, and higher for women than for men, though there is no quantitative consensus about this. This model is widely accepted for external radiation, but its application to internal contamination is disputed. For example, the model fails to account for the low rates of cancer in early workers at Los Alamos National Laboratory who were exposed to plutonium dust, and the high rates of thyroid cancer in children following the Chernobyl accident, both of which were internal exposure events. The European Committee on Radiation Risk calls the ICRP model "fatally flawed" when it comes to internal exposure.
Radiation can cause cancer in most parts of the body, in all animals, and at any age, although radiation-induced solid tumors usually take 10–15 years, and can take up to 40 years, to become clinically manifest, and radiation-induced leukemias typically require 2–10 years to appear. Some people, such as those with nevoid basal cell carcinoma syndrome or retinoblastoma, are more susceptible than average to developing cancer from radiation exposure. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.
Radiation exposure can cause cancer in any living tissue, but high-dose whole-body external exposure is most closely associated with leukemia, reflecting the high radiosensitivity of bone marrow. Internal exposures tend to cause cancer in the organs where the radioactive material concentrates, so that radon predominantly causes lung cancer, iodine-131 is most likely to cause thyroid cancer, etc.
According to the linear no-threshold model, any exposure to ionizing radiation, even at doses too low to produce any symptoms of radiation sickness, can induce cancer due to cellular and genetic damage. Under the assumption, survivors of acute radiation syndrome face an increased risk of developing cancer later in life. The probability of developing cancer is a linear function with respect to the effective radiation dose. In radiation-induced cancer, the speed at which the condition advances, the prognosis, the degree of pain, and every other feature of the disease are not believed to be functions of the radiation dosage.
However, some studies contradict the linear no-threshold model. These studies indicate that some low levels of radiation do not increase cancer risk at all, and that there may exist a threshold dosage of ionizing radiation below which exposure should be considered safe. Nonetheless the 'no safe amount' assumption is the basis of US and most national regulatory policies regarding "man-made" sources of radiation.
Radiation sickness is caused by exposure to a large dose of ionizing radiation (> ~0.1 Gy) over a short period of time. (> ~0.1 Gy/h) This might be the result of a nuclear explosion, a criticality accident, a radiotherapy accident as in Therac-25, a solar flare during interplanetary travel, misplacement of radioactive waste as in the 1987 Goiânia accident, human error in a nuclear reactor, or other possibilities. Acute radiation sickness due to ingestion of radioactive material is possible, but rare; examples include the 1987 contamination of Leide das Neves Ferreira and the 2006 poisoning of Alexander Litvinenko.
Alpha and beta radiation have low penetrating power and are unlikely to affect vital internal organs from outside the body. Any type of ionizing radiation can cause burns, but alpha and beta radiation can only do so if radioactive contamination or nuclear fallout is deposited on the individual's skin or clothing. Gamma and neutron radiation can travel much further distances and penetrate the body easily, so whole-body irradiation generally causes ARS before skin effects are evident. Local gamma irradiation can cause skin effects without any sickness. In the early twentieth century, radiographers would commonly calibrate their machines by irradiating their own hand and measuring the time to onset of erythema.
Adult survivors of childhood cancer have some physical, psychological, and social difficulties.
Premature heart disease is a major long-term complication in adult survivors of childhood cancer. Adult survivors are eight times more likely to die of heart disease than other people, and more than half of children treated for cancer develop some type of cardiac abnormality, although this may be asymptomatic or too mild to qualify for a clinical diagnosis of heart disease.
Radiation burns are caused by exposure to high levels of radiation. Levels high enough to cause burn are generally lethal if received as a whole-body dose, whereas they may be treatable if received as a shallow or local dose.
Fluoroscopy may cause burns if performed repeatedly or for too long.
Similarly, Computed Tomography and traditional Projectional Radiography have the potential to cause radiation burns if the exposure factors and exposure time are not appropriately controlled by the operator.
A study of radiation induced skin injuries has been performed by the Food and Drug Administration (FDA) based on results from 1994, followed by an advisory to minimize further fluoroscopy-induced injuries. The problem of radiation injuries due to fluoroscopy has been further investigated in review articles in 2000, 2001, 2009 and 2010.
Children with cancer are at risk for developing various cognitive or learning problems. These difficulties may be related to brain injury stemming from the cancer itself, such as a brain tumor or central nervous system metastasis or from side effects of cancer treatments such as chemotherapy and radiation therapy. Studies have shown that chemo and radiation therapies may damage brain white matter and disrupt brain activity.
Chronic radiation syndrome is a constellation of health effects that occur after months or years of chronic exposure to high amounts of ionizing radiation. Chronic radiation syndrome develops with a speed and severity proportional to the radiation dose received, i.e., it is a deterministic effect of radiation exposure, unlike radiation-induced cancer. It is distinct from acute radiation syndrome in that it occurs at dose rates low enough to permit natural repair mechanisms to compete with the radiation damage during the exposure period. Dose rates high enough to cause the acute form (> ~0.1 Gy/h) are fatal long before onset of the chronic form. The lower threshold for chronic radiation syndrome is between 0.7 and 1.5 Gy, at dose rates above 0.1 Gy/yr. This condition is primarily known from the Kyshtym disaster, where 66 cases were diagnosed, and has received little mention in Western literature. A future ICRP publication, currently in draft, may recognize the condition but with higher thresholds.
In 2013, Alexander V. Akleyev described the chronology of the clinical course or CRS while presenting at ConRad in Munich, Germany. In his presentation, he defined the latent period as being 1-5 years, and the formation coinciding with the period of maximum radiation dose. The recovery period was described as being 3-12 months after exposure ceased. He concluded that "CRS represents a systemic response of the body as a whole to the chronic total body exposure in man." In 2014, Akleyev's book "Comprehensive analysis of chronic radiation syndrome, covering epidemiology, pathogenesis, pathoanatomy, diagnosis and treatment" was published by Springer.
Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation. Additionally, the majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.
Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. Radiation can cause cancer in most parts of the body, in all animals and at any age. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.
Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.
Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.
Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources have been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer. However, studies have not found a consistent link between mobile phone radiation and cancer risk.
Exposure to particular substances have been linked to specific types of cancer. These substances are called "carcinogens".
Tobacco smoke, for example, causes 90% of lung cancer. It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.
Tobacco is responsible for about one in five cancer deaths worldwide and about one in three in the developed world. Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.
In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers. Cancer from work-related substance exposures may cause between 2 and 20% of cases, causing at least 200,000 deaths. Cancers such as lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.
In the United States, fire and hot liquids are the most common causes of burns. Of house fires that result in death, smoking causes 25% and heating devices cause 22%. Almost half of injuries are due to efforts to fight a fire. Scalding is caused by hot liquids or gases and most commonly occurs from exposure to hot drinks, high temperature tap water in baths or showers, hot cooking oil, or steam. Scald injuries are most common in children under the age of five and, in the United States and Australia, this population makes up about two-thirds of all burns. Contact with hot objects is the cause of about 20–30% of burns in children. Generally, scalds are first- or second-degree burns, but third-degree burns may also result, especially with prolonged contact. Fireworks are a common cause of burns during holiday seasons in many countries. This is a particular risk for adolescent males.
In India, about 700,000 to 800,000 people per year sustain significant burns, though very few are looked after in specialist burn units. The highest rates occur in women 16–35 years of age. Part of this high rate is related to unsafe kitchens and loose-fitting clothing typical to India. It is estimated that one-third of all burns in India are due to clothing catching fire from open flames. Intentional burns are also a common cause and occur at high rates in young women, secondary to domestic violence and self-harm.
An occupational injury is bodily damage resulting from working. The most common organs involved are the spine, hands, the head, lungs, eyes, skeleton, and skin. Occupational injuries can result from exposure to occupational hazards (physical, chemical, biological, or psychosocial), such as temperature, noise, insect or animal bites, blood-borne pathogens, aerosols, hazardous chemicals, radiation, and occupational burnout.
While many prevention methods are set in place, injuries may still occur due to poor ergonomics, manual handling of heavy loads, misuse or failure of equipment, exposure to general hazards, and inadequate safety training.
Common causes of head injury are motor vehicle traffic collisions, home and occupational accidents, falls, and assaults. Wilson's disease has also been indicative of head injury. According to the United States CDC, 32% of traumatic brain injuries (another, more specific, term for head injuries) are caused by falls, 10% by assaults, 16.5% by being struck or against something, 17% by motor vehicle accidents, 21% by other/unknown ways. In addition, the highest rate of injury is among children ages 0–14 and adults age 65 and older.
The lungs are a radiosensitive organ, and radiation pneumonitis can occur leading to pulmonary insufficiency and death (100% after exposure to 50 gray of radiation), in a few months. Radiation pneumonitis is characterized by:
- Loss of epithelial cells
- Edema
- Inflammation
- Occlusions airways, air sacs and blood vessels
- Fibrosis
In children with uncomplicated minor head injuries the risk of intra cranial bleeding over the next year is rare at 2 cases per 1 million. In some cases transient neurological disturbances may occur, lasting minutes to hours. Malignant post traumatic cerebral swelling can develop unexpectedly in stable patients after an injury, as can post traumatic seizures. Recovery in children with neurologic deficits will vary. Children with neurologic deficits who improve daily are more likely to recover, while those who are vegetative for months are less likely to improve. Most patients without deficits have full recovery. However, persons who sustain head trauma resulting in unconsciousness for an hour or more have twice the risk of developing Alzheimer's disease later in life.
Head injury may be associated with a neck injury. Bruises on the back or neck, neck pain, or pain radiating to the arms are signs of cervical spine injury and merit spinal immobilization via application of a cervical collar and possibly a long board.If the neurological exam is normal this is reassuring. Reassessment is needed if there is a worsening headache, seizure, one sided weakness, or has persistent vomiting.
To combat overuse of Head CT Scans yielding negative intracranial hemorrhage, which unnecessarily expose patients to radiation and increase time in the hospital and cost of the visit, multiple clinical decision support rules have been developed to help clinicians weigh the option to scan a patient with a head injury. Among these are the Canadian Head CT rule, the PECARN Head Injury/Trauma Algorithm, and the New Orleans/Charity Head Injury/Trauma Rule all help clinicians make these decisions using easily obtained information and noninvasive practices.
Radiation-induced lung injury is a general term for damage to the lungs which occurs as a result of exposure to ionizing radiation. In general terms, such damage is divided into early inflammatory damage ("radiation pneumonitis") and later complications of chronic scarring ("radiation fibrosis"). Pulmonary radiation injury most commonly occurs as a result of radiation therapy administered to treat cancer.
Ionizing radiation is classified as a neurotoxicant. A 2004 cohort study concluded that irradiation of the brain with dose levels overlapping those imparted by computed tomography can, in at least some instances, adversely affect intellectual development. Prenatal exposure to ionizing radiation at the 8-15 and 16–25 weeks after ovulation was found to induce severe mental retardation as well as variation in intelligence quotient (IQ) and school performance. It is uncertain, if there exist a threshold, under which one or more of these effects, of prenatal exposure to ionizing radiation, do not exist. Cumulative equivalent doses above 500 mSv of ionizing radiation to the head were proven with epidemiological evidences to cause cerebro-vascular atherosclerotic damage. The equivalent dose of 500 mGy x-rays is 500 mSv.
Radiation therapy was found to cause cognitive decline. Cognitive decline was especially apparent in young children, between the ages of 5 to 11. Studies found, for example, that the IQ of 5-year-old children declined each year after treatment by additional several IQ points, thereby the child's IQ decreased and decreased while growing older.
As in the United Kingdom, slips, trips and falls are common and account for 20-40% of disabling occupational injuries. Often these accidents result in a back injury that can persist to a permanent disability. In the United States, a high risk of back injuries occurs in the health care industry. 25% of reported injuries in health care workers in the state of Pennsylvania are for back pain. Among nurses, the prevalence of lower back pain may be as high as 72% mostly as a result of transferring patients. Fortunately, some of these injuries can be prevented with the availability of patient lifts, improved worker training, and allocation of more time to perform work procedures. Another common type of injury is carpal tunnel syndrome associated with overuse of the hands and wrists. Studies on a cohort of newly hired workers have thus far identified forceful gripping, repetitive lifting of > 1 kg, and using vibrating power tools as high risk work activities.
Additionally, noise exposure in the workplace can cause hearing loss, which accounted for 14% of reported occupational illnesses in 2007. Many initiatives have been created to prevent this common workplace injury. For example, the Buy Quiet program encourages employers to purchase tools and machines that produce less noise and the Safe-In-Sound Award was created to recognize companies and program that excel in the area of hearing loss prevention.
Accidental injection or needlestick injuries are a common injury that plague agriculture workers and veterinarians. The majority of these injuries are located to the hands or legs, and can result in mild to severe reactions, including possible hospitalization. Due to the wide variety of biologics used in animal agriculture, needlestick injuries can result in bacterial or fungal infections, lacerations, local inflammation, vaccine/antibiotic reactions, amputations, miscarriage, and death. Due to daily human-animal interactions, livestock related injuries are also a prevalent injury of agriculture workers, and are responsible for the majoriy of nonfatal worker injuries on dairy farms. Additionally, approximately 30 people die of cattle and horse-related deaths in the United States annually.
In rare cases where large tumors infringe on the brainstem which controls motor nerves, with or without surgery, paralysis or death can result. This occurs in less than 1% of large tumors.
Taste disturbance and mouth dryness are frequent for a few weeks following surgery. In a few patients this disturbance is longer or permanent.
Research shows that children with cancer are at risk for developing various cognitive or learning problems. These difficulties may be related to brain injury stemming from the cancer itself, such as a brain tumor or central nervous system metastasis or from side effects of cancer treatments such as chemotherapy and radiation therapy. Studies have shown that chemo and radiation therapies may damage brain white matter and disrupt brain activity.
Cognitive problems that have been associated with cancer and its treatments in children include deficits in attention, working memory, processing speed, mental flexibility, persistence, verbal fluency, memory, motor skills, academic achievement and social function. These deficits have been shown to occur irrespective of age, socioeconomic status, months since onset or cessation of treatment, anxiety, fatigue and dosage schedule.
Most soft-tissue sarcomas are not associated with any known risk factors or identifiable cause. There are some exceptions:
- Studies suggest that workers who are exposed to chlorophenols in wood preservatives and phenoxy herbicides may have an increased risk of developing soft-tissue sarcomas. An unusual percentage of patients with a rare blood vessel tumor, angiosarcoma of the liver, have been exposed to vinyl chloride in their work. This substance is used in the manufacture of certain plastics, notably PVC.
- In the early 1900s, when scientists were just discovering the potential uses of radiation to treat disease, little was known about safe dosage levels and precise methods of delivery. At that time, radiation was used to treat a variety of noncancerous medical problems, including enlargement of the tonsils, adenoids, and thymus gland. Later, researchers found that high doses of radiation caused soft-tissue sarcomas in some patients. Because of this risk, radiation treatment for cancer is now planned to ensure that the maximum dosage of radiation is delivered to diseased tissue while surrounding healthy tissue is protected as much as possible.
- Kaposi's sarcoma, a rare cancer of the cells that line blood vessels in the skin and mucus membranes, is caused by Human herpesvirus 8. Kaposi's sarcoma often occurs in patients with AIDS (acquired immune deficiency syndrome). Kaposi's sarcoma, however, has different characteristics than typical soft-tissue sarcomas and is treated differently.
- In a very small fraction of cases, sarcoma may be related to a rare inherited genetic alteration of the p53 gene and is known as Li-Fraumeni syndrome. Certain other inherited diseases are associated with an increased risk of developing soft-tissue sarcomas. For example, people with neurofibromatosis type I (also called von Recklinghausen's disease, associated with alterations in the NF1 gene) are at an increased risk of developing soft-tissue sarcomas known as malignant peripheral nerve sheath tumors. Patients with inherited retinoblastoma have alterations in the RB1 gene, a tumor suppressor gene, and are likely to develop soft-tissue sarcomas as they mature into adulthood.
Radiation-induced cognitive decline describes the possible correlation between radiation therapy and mild cognitive impairment. Radiation therapy is used mainly in the treatment of cancer. Radiation therapy can be used to cure care or shrink tumors that are interfering with quality of life. Sometimes radiation therapy is used alone; other times it is used in conjunction with chemotherapy and surgery. For people with brain tumors, radiation can be an effective treatment because chemotherapy is often less effective due to the blood–brain barrier. Unfortunately for some patients, as time passes, people who received radiation therapy may begin experiencing deficits in their learning, memory, and spatial information processing abilities. The learning, memory, and spatial information processing abilities are dependent on proper hippocampus functionality. Therefore, any hippocampus dysfunction will result in deficits in learning, memory, and spatial information processing ability.
The hippocampus is one of two structures of the central nervous system where neurogenesis continues after birth. The other structure that undergoes neurogenesis is the olfactory bulb. Therefore, it has been proposed that neurogenesis plays some role in the proper functionality of the hippocampus and the olfactory bulb. To test this proposal, a group of rats with normal hippocampal neurogenesis (control) were subjected to a placement recognition exercise that required proper hippocampus function to complete. Afterwards a second group of rats (experimental) were subjected to the same exercise but in that trial their neurogenesis in the hippocampus was arrested. It was found that the experimental group was not able to distinguish between its familiar and unexplored territory. The experimental group spent more time exploring the familiar territory, while the control group spent more time exploring the new territory. The results indicate that neurogenesis in the hippocampus is important for memory and proper hippocampal functionality. Therefore, if radiation therapy inhibits neurogenesis in the hippocampus it would lead to the cognitive decline observed in patients who have received this radiation therapy.
In animal studies discussed by Monje and Palmer in "Radiation Injury and Neurogenesis", it has been proven that radiation does indeed decrease or arrest neurogenesis altogether in the hippocampus. This decrease in neurogenesis is due to apoptosis of the neurons which usually occurs after irradiation. However it has not been proven whether the apoptosis is a direct result of the radiation itself or if there are other factors that cause neuronal apoptosis, namely changes in the hippocampus micro-environment or damage to the precursor pool. Determining the exact cause of the cell apoptosis is important because then it may be possible to inhibit the apoptosis and reverse the effects of the arrested neurogenesis.