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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
Both computed tomography angiography (CTA) and magnetic resonance angiography (MRA) have been proved to be effective in diagnosing intracranial vascular malformations after ICH. So frequently, a CT angiogram will be performed in order to exclude a secondary cause of hemorrhage or to detect a "spot sign".
Intraparenchymal hemorrhage can be recognized on CT scans because blood appears brighter than other tissue and is separated from the inner table of the skull by brain tissue. The tissue surrounding a bleed is often less dense than the rest of the brain because of edema, and therefore shows up darker on the CT scan.
When due to high blood pressure, they typically occur in the putamen or thalamus (60%), cerebrum (20%), cerebellum (13%) or pons (7%).
CT scan (computed tomography) is the definitive tool for accurate diagnosis of an intracranial hemorrhage. In difficult cases, a 3T-MRI scan can also be used.
When ICP is increased the heart rate may be decreased.
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.
For diagnosing ischemic stroke in the emergency setting:
- CT scans ("without" contrast enhancements)
- MRI scan
For diagnosing hemorrhagic stroke in the emergency setting:
- CT scans ("without" contrast enhancements)
- MRI scan
For detecting chronic hemorrhages, MRI scan is more sensitive.
For the assessment of stable stroke, nuclear medicine scans SPECT and PET/CT may be helpful. SPECT documents cerebral blood flow and PET with FDG isotope the metabolic activity of the neurons.
When a stroke has been diagnosed, various other studies may be performed to determine the underlying cause. With the current treatment and diagnosis options available, it is of particular importance to determine whether there is a peripheral source of emboli. Test selection may vary since the cause of stroke varies with age, comorbidity and the clinical presentation. The following are commonly used techniques:
- an ultrasound/doppler study of the carotid arteries (to detect carotid stenosis) or dissection of the precerebral arteries;
- an electrocardiogram (ECG) and echocardiogram (to identify arrhythmias and resultant clots in the heart which may spread to the brain vessels through the bloodstream);
- a Holter monitor study to identify intermittent abnormal heart rhythms;
- an angiogram of the cerebral vasculature (if a bleed is thought to have originated from an aneurysm or arteriovenous malformation);
- blood tests to determine if blood cholesterol is high, if there is an abnormal tendency to bleed, and if some rarer processes such as homocystinuria might be involved.
For hemorrhagic strokes, a CT or MRI scan with intravascular contrast may be able to identify abnormalities in the brain arteries (such as aneurysms) or other sources of bleeding, and structural MRI if this shows no cause. If this too does not identify an underlying reason for the bleeding, invasive cerebral angiography could be performed but this requires access to the bloodstream with an intravascular catheter and can cause further strokes as well as complications at the insertion site and this investigation is therefore reserved for specific situations. If there are symptoms suggesting that the hemorrhage might have occurred as a result of venous thrombosis, CT or MRI venography can be used to examine the cerebral veins.
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.
Animal models are frequently used to develop improved treatments for and a more complete understanding of PVL. A rat model that has white matter lesions and experiences seizures has been developed, as well as other rodents used in the study of PVL. These animal models can be used to examine the potential efficacy of new medications in the prevention and treatment of PVL.
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.
The capture, transportation and culture of bait fish can spread damaging organisms between ecosystems, endangering them. In 2007, several American states, including Michigan, enacted regulations designed to slow the spread of fish diseases, including viral hemorrhagic septicemia, by bait fish. Because of the risk of transmitting "Myxobolus cerebralis" (whirling disease), trout and salmon should not be used as bait. Anglers may increase the possibility of contamination by emptying bait buckets into fishing venues and collecting or using bait improperly. The transportation of fish from one location to another can break the law and cause the introduction of fish and parasites alien to the ecosystem.
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".