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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)
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Treatment depends substantially of the type of ICH. Rapid CT scan and other diagnostic measures are used to determine proper treatment, which may include both medication and surgery.
- Tracheal intubation is indicated in people with decreased level of consciousness or other risk of airway obstruction.
- IV fluids are given to maintain fluid balance, using isotonic rather than hypotonic fluids.
Surgery is required if the hematoma is greater than , if there is a structural vascular lesion or lobar hemorrhage in a young patient.
- A catheter may be passed into the brain vasculature to close off or dilate blood vessels, avoiding invasive surgical procedures.
- Aspiration by stereotactic surgery or endoscopic drainage may be used in basal ganglia hemorrhages, although successful reports are limited.
A "subarachnoid hemorrhage" is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Besides from head injury, it may occur spontaneously, usually from a ruptured cerebral aneurysm. Symptoms of SAH include a severe headache with a rapid onset ("thunderclap headache"), vomiting, confusion or a lowered level of consciousness, and sometimes seizures. The diagnosis is generally confirmed with a CT scan of the head, or occasionally by lumbar puncture. Treatment is by prompt neurosurgery or radiologically guided interventions with medications and other treatments to help prevent recurrence of the bleeding and complications. Since the 1990s, many aneurysms are treated by a minimal invasive procedure called "coiling", which is carried out by instrumentation through large blood vessels. However, this procedure has higher recurrence rates than the more invasive craniotomy with clipping.
Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. It includes intracerebral bleeds (intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural bleeds.
Intracerebral bleeding affects 2.5 per 10,000 people each year.
Aspirin reduces the overall risk of recurrence by 13% with greater benefit early on. Definitive therapy within the first few hours is aimed at removing the blockage by breaking the clot down (thrombolysis), or by removing it mechanically (thrombectomy). The philosophical premise underlying the importance of rapid stroke intervention was summed up as "Time is Brain!" in the early 1990s. Years later, that same idea, that rapid cerebral blood flow restoration results in fewer brain cells dying, has been proved and quantified.
Tight blood sugar control in the first few hours does not improve outcomes and may cause harm. High blood pressure is also not typically lowered as this has not been found to be helpful. Cerebrolysin, a mix of pig brain tissue used to treat acute ischemic stroke in many Asian and European countries, does not improve outcomes and may increase the risk of severe adverse events.
People with intracerebral hemorrhage require supportive care, including blood pressure control if required. People are monitored for changes in the level of consciousness, and their blood sugar and oxygenation are kept at optimum levels. Anticoagulants and antithrombotics can make bleeding worse and are generally discontinued (and reversed if possible). A proportion may benefit from neurosurgical intervention to remove the blood and treat the underlying cause, but this depends on the location and the size of the hemorrhage as well as patient-related factors, and ongoing research is being conducted into the question as to which people with intracerebral hemorrhage may benefit.
In subarachnoid hemorrhage, early treatment for underlying cerebral aneurysms may reduce the risk of further hemorrhages. Depending on the site of the aneurysm this may be by surgery that involves opening the skull or endovascularly (through the blood vessels).
Currently, there are no treatments prescribed for PVL. All treatments administered are in response to secondary pathologies that develop as a consequence of the PVL. Because white matter injury in the periventricular region can result in a variety of deficits, neurologists must closely monitor infants diagnosed with PVL in order to determine the severity and extent of their conditions.
Patients are typically treated with an individualized treatment. It is crucial for doctors to observe and maintain organ function: visceral organ failure can potentially occur in untreated patients. Additionally, motor deficits and increased muscle tone are often treated with individualized physical and occupational therapy treatments.
Current clinical research ranges from studies aimed at understanding the progression and pathology of PVL to developing protocols for the prevention of PVL development. Many studies examine the trends in outcomes of individuals with PVL: a recent study by Hamrick, et al., considered the role of cystic periventricular leukomalacia (a particularly severe form of PVL, involving development of cysts) in the developmental outcome of the infant.
Other ongoing clinical studies are aimed at the prevention and treatment of PVL: clinical trials testing neuroprotectants, prevention of premature births, and examining potential medications for the attenuation of white matter damage are all currently supported by NIH funding.
Lymphocystis is a common viral disease of freshwater and saltwater fish. The viruses that cause this disease belong to the genus Lymphocystivirus of the family Iridoviridae.
Aquarists often come across this virus when their fish are stressed such as when put into a new environment and the virus is able to grow.
The fish starts growing small white pin-prick like growths on their fins or skin and this is often mistaken for Ich/Ick (Ichthyophthirius multifiliis) in the early stages. It soon clumps together to form a cauliflower-like growth on the skin, mouth, fins, and occasional gills. Lesions at the base of the dorsal fin are common among freshwater species of Central American origin, most notably Herichthys carpentis & inside the mouth of Herichthys cyanoguttatus & Geophagus steindachneri. On the tail fin of Koi, Carps, & US native sunfish (Lepomis sp.) On the side flanks of Walleye, Sauger & Flounder. On random head and/or tail areas of common goldfish, and oranda variants. This virus appears to present itself as a lesion(s) at differing locations depending on the species of fish being attacked, often complicating initial diagnosis.
Lymphocystis does show some host-specificity, i.e., each strain (or species) of lymphocystis can infect only its primary host fish, or some additional closely related, fish.
There is no known cure for this virus, though a privately owned fish research & breeding facility near Gainesville, Florida USA has reportedly been able to suppress the virus into remission using the human antiviral "Acyclovir" at the rate of 200 mg per 10 US gallons for 2 days. Otherwise, some aquarists recommend surgery to remove the affected area if it is very serious, followed by an antibiotic bath treatment to prevent a secondary bacterial infection of the open wounds.
Eventually the growths inhibit the fish's ability to swim, breathe or eat, and secondary bacterial infections usually kills the fish.
Usually the best cure is to simply give the fish a stress free life, a weekly bacteria treatment and the virus will slowly subside and the fins will repair themselves. This can take many months. Like most viral infections, even in humans, the first outbreaks are the most serious, whilst the immune system "learns" how to suppress it, the outbreaks become less severe over time assuming the organism survives the initial outbreaks.
Several health authorities have issued related guidance documents, which need to be considered for drug development:
- ICH (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use)
- M3(R2) "Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals"
- S9 "Nonclinical Evaluation for Anticancer Pharmaceuticals"
- S10 "Photosafety Evaluation"
- EMA (European Medicines Agency)
- "Note for Guidance on Photosafety Testing" (revision on-hold)
- "Question & Answers on the Note for Guidance on Photosafety Testing"
- FDA (U.S. Food and Drug Administration)
- MHLW/PMDA (Japanese Ministry of Health, Labour and Welfare / Pharmaceuticals and Medical Devices Agency)
3T3 Neutral Red Phototoxicity Test – An in vitro toxicological assessment test used to determine the cytotoxic and photo(cyto)toxicity effect of a test article to murine fibroblasts in the presence or absence of UVA light.
"The 3T3 Neutral Red Uptake Phototoxicity Assay (3T3 NRU PT) can be utilized to identify the phototoxic effect of a test substance induced by the combination of test substance and light and is based on the comparison of the cytotoxic effect of a test substance when tested after the exposure and in the absence of exposure to a non-cytotoxic dose of UVA/vis light. Cytotoxicity is expressed as a concentration-dependent reduction of the uptake of the vital dye - Neutral Red.
Substances that are phototoxic in vivo after systemic application and distribution to the skin, as well as compounds that could act as phototoxicants after topical application to the skin can be identified by the test. The reliability and relevance of the 3T3 NRU PT have been evaluated and has been shown to be predictive when compared with acute phototoxicity effects in vivo in animals and humans." Taken with permission from
Like humans and other animals, fish suffer from diseases and parasites. Fish defences against disease are specific and non-specific. Non-specific defences include skin and scales, as well as the mucus layer secreted by the epidermis that traps microorganisms and inhibits their growth. If pathogens breach these defences, fish can develop inflammatory responses that increase the flow of blood to infected areas and deliver white blood cells that attempt to destroy the pathogens.
Specific defences are specialised responses to particular pathogens recognised by the fish's body, that is adaptative immune responses. In recent years, vaccines have become widely used in aquaculture and ornamental fish, for example vaccines for furunculosis in farmed salmon and koi herpes virus in koi.
Some commercially important fish diseases are VHS, ich and whirling disease.
All fish carry pathogens and parasites. Usually this is at some cost to the fish. If the cost is sufficiently high, then the impacts can be characterised as a disease. However disease in fish is not understood well. What is known about fish disease often relates to aquaria fish, and more recently, to farmed fish.
Disease is a prime agent affecting fish mortality, especially when fish are young. Fish can limit the impacts of pathogens and parasites with behavioural or biochemical means, and such fish have reproductive advantages. Interacting factors result in low grade infection becoming fatal diseases. In particular, things that causes stress, such as natural droughts or pollution or predators, can precipitate outbreak of disease.
Disease can also be particularly problematic when pathogens and parasites carried by introduced species affect native species. An introduced species may find invading easier if potential predators and competitors have been decimated by disease.
Pathogens which can cause fish diseases comprise:
- viral infections, such as esocid lymphosarcoma found in "Esox" species.
- bacterial infections, such as "Pseudomonas fluorescens" leading to fin rot and fish dropsy
- fungal infections
- water mould infections, such as "Saprolegnia" sp.
- metazoan parasites, such as copepods
- unicellular parasites, such as "Ichthyophthirius multifiliis" leading to ich
- Certain parasites like Helminths for example "Eustrongylides"
Poena cullei (from Latin 'penalty of the sack') under Roman law was a type of death penalty imposed on a subject who had been found guilty of parricide. The punishment consisted of being sewn up in a leather sack, sometimes with an assortment of live animals, and then being thrown into water. The punishment may have varied widely in its frequency and precise form during the Roman period. For example, the earliest fully documented case is from ca. 100 BCE, although scholars think the punishment may have developed about a century earlier (earlier than that, murderers, including parricides, would be handed over to the aggrieved family for punishment, rather than punishment being enacted by Roman state officials). Inclusion of live animals in the sack is only documented from Early Imperial times, and at the beginning, only snakes are mentioned. At the time of Emperor Hadrian (2nd century CE), the most well known form of the punishment was documented, where a cock, a dog, a monkey and a viper were inserted in the sack. However, at the time of Hadrian "poena cullei" was made into an optional form of punishment for parricides (the alternate being thrown to the beasts in the arena). During the 3rd century CE up to the accession of Emperor Constantine, "poena cullei" fell out of use; Constantine revived it, now with only serpents to be added in the sack. Well over 200 years later, Emperor Justinian reinstituted the punishment with the four animals, and "poena cullei" remained the statutory penalty for parricides within Byzantine law for the next 400 years, when it was replaced with the punishment for parricides to be burnt alive instead.
"Poena cullei" gained a revival of sorts in late medieval and early modern Germany, with late cases of being drowned in a sack along with live animals being documented from Saxony in the first half of the 18th century.
The "Wenxian Tongkao", written by Chinese historian Ma Duanlin (1245-1322), and the "History of Song" describe how the Byzantine emperor Michael VII Parapinakēs Caesar ("Mie li sha ling kai sa" 滅力沙靈改撒) of "Fu lin" (拂菻, i.e. Byzantium) sent an embassy to China's Song dynasty, arriving in November 1081, during the reign of Emperor Shenzong of Song (r. 1067-1085). The "History of Song" described the tributary gifts given by the Byzantine embassy as well as the products made in Byzantium. It also described forms of punishment in Byzantine law, such as caning, as well as the capital punishment of being stuffed into a "feather bag" and thrown into the sea. This description seems to correspond with the Romano-Byzantine punishment of "poena cullei".