For individuals living with a treatment-resistant form of the seizure disorders known as “the epilepsies,” each day can bring debilitating seizures as well as challenges from co-occurring conditions that dramatically impair quality of life. This brochure, for people with the disorders, their caregivers, and advocates, outlines the state of progress made in the past decade toward achieving the Epilepsy Research Benchmarks, a set of widely recognized objectives aimed at prioritizing the efforts of scientists and health care providers to find cures for the epilepsies. Much of this work has been funded by grants from the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH).
At least 2.3 million adults and nearly 500,000 children in the U.S. currently live with some form of epilepsy, a disorder in which clusters of nerve cells, or neurons, in the brain sometimes signal abnormally, causing seizures. Each year, another 150,000 people are diagnosed with epilepsy. The disorders affect both males and females and can develop at any age. In the U.S. alone, the annual costs associated with the epilepsies are estimated to be $15.5 billion in direct medical expenses and lost or reduced earnings and productivity.
The disturbances of neuronal activity that occur during seizures may cause strange sensations, emotions, and behaviors. They also sometimes cause convulsions, abnormal movements, and loss of consciousness. In some people, seizures happen only occasionally. Other people may experience hundreds of seizures a day. There are many different forms of epilepsy, and symptoms vary greatly from one person to another. Recent adoption of the term “the epilepsies” underscores the diversity of types and causes.
About three-quarters of the individuals diagnosed with the epilepsies can control their seizures with medicine or surgery. However, about 25 to 30 percent will continue to experience seizures even with the best available treatment. Doctors call this treatment-resistant epilepsy. In some cases, people experience a type of seizure called status epilepticus, defined as seizures that last for more than five minutes or seizures that recur without recovery of consciousness. Prolonged status epilepticus can damage the brain and may be life-threatening.
Section 1: About Epilepsies
Seizures can be classified as focal or generalized. Focal seizures begin in one area of the brain and may or may not spread to other areas. Generalized seizures are the result of abnormal neuronal (nerve cell) activity on both sides of the brain from the beginning of the seizure.
About 60 percent of people with epilepsy have focal seizures. Some focal seizures cause unusual sensations, feelings, or movements, but do not cause loss of consciousness. Other focal seizures cause a change in or loss of consciousness and may produce a dreamlike experience or strange, repetitive behavior. Focal seizures are often named for the area of the brain in which they originate. For example, temporal lobe epilepsy, or TLE, begins in the temporal lobe located on either side of the brain. TLE is the most common type of epilepsy to feature focal seizures and can sometimes be difficult to treat with available medications.
Generalized seizures impair consciousness and distort electrical activity of the whole or a large portion of the brain, leading to falls or abnormal movements. There are several different types of generalized seizures. In absence seizures, which usually begin in childhood or adolescence, an individual may appear to be staring into space or may have jerking or twitching muscles. Tonic seizures cause stiffening of muscles. Clonic seizures cause repeated jerking movements of muscles on both sides of the body. Myoclonic seizures cause jerks or twitches of the upper body, arms, or legs. Atonic seizures cause a loss of normal muscle tone, which may lead to falls or sudden drops of the head. Tonic-clonic seizures cause a combination of symptoms, including stiffening of the body and repeated jerks of the arms or legs as well as loss of consciousness.
Epilepsies with Childhood Onset
Compared to adults, infants and children have a relatively high risk of developing the epilepsies. Many epilepsy syndromes, such as infantile spasms, Lennox-Gastaut syndrome, and Rasmussen’s encephalitis, begin in childhood. Infantile spasms usually begin before the age of six months and may cause a baby to bend forward and stiffen. Children with Lennox-Gastaut syndrome have severe epilepsy with several different types of seizures, including atonic seizures, which cause sudden falls called drop attacks. Rasmussen’s encephalitis is a rare, chronic inflammatory neurological disease that usually affects only one hemisphere of the brain. It causes frequent and severe seizures and a loss of motor skills, and can lead to severe intellectual disability. Hypothalamic hamartomas can cause another rare form of epilepsy that presents during childhood and is associated with malformations in the hypothalamus at the base of the brain. People with hypothalamic harmatomas have seizures that can resemble laughing (gelastic) or crying (dacrystic). Such seizures frequently go unrecognized or are difficult to diagnose.
Some childhood epilepsy syndromes, such as childhood absence epilepsy, may go into remission or stop entirely as a child matures, although this is not true in all cases. Other syndromes, such as juvenile myoclonic epilepsy and Lennox-Gastaut syndrome, are usually present for the rest of the person’s life.
Children with delayed brain development and neurological disorders are more likely to have seizures. Seizures are more common, for example, among children with autism spectrum disorder, cerebral palsy, tuberous sclerosis complex (TSC), or Rett, Aicardi, or Down syndromes. In one study, one-third of children with autism spectrum disorder had treatmentresistant epilepsy.
For about half of all people with an epilepsy, a cause for the disorder is not identified. In other cases, the epilepsies are clearly linked to genetic factors, infection, head trauma, stroke, brain tumors, or other identifiable problems.
The epilepsies have many possible causes. Almost anything that disturbs the normal pattern of brain circuit activity—from abnormal brain development to traumatic brain injury (TBI) or illness—can lead to seizures and epilepsy. For example, seizures may develop because of an abnormality in brain wiring that occurs during brain development, an imbalance of neuronsignaling chemicals called neurotransmitters, or a combination of these factors. Researchers believe that some people with epilepsies have abnormally high levels of responsiveness to excitatory neurotransmitters, chemicals that increase the activity of nerve cells. Other people may have an abnormally low level of responsiveness to neurotransmitters that inhibit nerve cell activity. Either situation can result in too much neuronal activity and cause epilepsy. In some cases, inflammation and neuronal damage after a head injury, stroke, or other trauma may lead to epilepsy. In addition, the brain’s attempts to repair itself after such injury may inadvertently generate abnormal nerve connections that lead to seizures. Supportive cells (known as glial cells) in the brain may play a role in certain types of epilepsy.
Sidebar: The Role of the National Institutes of Health
The U.S. Federal government supports research to better understand the epilepsies and to reduce their burden through improved treatments and prevention. Much of this research support comes from the National Institutes of Health (NIH). The National Institute of Neurological Disorders and Stroke (NINDS) is the lead NIH institute for research on the epilepsies. Several other NIH Institutes also fund epilepsy-related research. Representatives from NIH institutes, the Centers for Disease Control and Prevention (CDC), the Department of Defense, the Department of Veterans Affairs, and the U.S. Food and Drug Administration (FDA) work together as part of the Interagency Collaborative to Advance Research in Epilepsy (ICARE), which was formed to facilitate communication and opportunities for coordination among institutes and agencies sponsoring research related to the epilepsies.
Section 2: Research Progress on the Epilepsies
In 2000, NINDS and epilepsy research and advocacy organizations co-sponsored a White House initiated conference, “Curing Epilepsy: Focus on the Future.” The conference has been viewed as a turning point for research on the epilepsies by shifting the focus from treating seizures to identifying cures, defined as “no seizures, no side effects, and the prevention of epilepsy in those at risk.” The first Epilepsy Research Benchmarks grew out of the momentum created by this conference, as a way to communicate and address important research priorities and as a framework for periodically “benchmarking” progress. A second conference in 2007, “Curing Epilepsy: Translating Discoveries into Therapies,” reassessed the state of research on the epilepsies and revised the Epilepsy Research Benchmarks, adding emphasis to the conditions that co-occur with the epilepsies and sudden unexpected death in epilepsy (SUDEP). A third conference in 2013, “Curing the Epilepsies: Pathways Forward,” provided an update on the state of research and will result in another revision of the Benchmarks.
Today, more than a decade since they were first developed, the Benchmarks are increasingly embraced by the entire epilepsy community, including NIH, researchers, and professional and advocacy organizations. While the ultimate goal of curing the epilepsies has not yet been achieved, researchers have made substantial progress. Research on the epilepsies has yielded exciting advances across all areas of the Benchmarks.
What New Discoveries Have Been Made About the Causes of the Epilepsies?
To understand how to prevent, treat, and cure the epilepsies, researchers first must learn how they develop. Where, how, when, and why do neurons begin to display the abnormal firing patterns that cause epileptic seizures? This process, known as epileptogenesis, is the key to understanding the epilepsies. Researchers are learning more about the fundamental processes—known as mechanisms—that lead to epileptogenesis. The discovery of each new mechanism involved in epileptogenesis has the potential to yield new targets that can be affected by medications or other therapies to block that mechanism. Among this growing list of candidate mechanisms, two stand out as being closest to yielding potential targets for drug therapy: 1) the mTOR (mammalian target of rapamycin) signal transduction pathway; and 2) activation of the cytokine protein interleukin-1ß (IL-1ß).
- The mTOR pathway is a master regulator that is involved in several genetic and acquired forms of epilepsy. An inhibitor of the mTOR pathway is being studied for the prevention of seizures related to tuberous sclerosis complex (TSC), a rare genetic disease that causes the growth of noncancerous tumors in the brain and in other organs such as the kidney, heart, eyes, lungs, and skin.
- In various types of epilepsy, inflammatory processes may play a key role. Cytokines are signaling molecules that, among other functions, help regulate the body’s inflammatory responses. Researchers are exploring why IL-1ß appears to be activated in different types of epilepsy. An inhibitor of IL-1ß synthesis is being tested in people with treatment-resistant epilepsy.
Other Areas of Epileptogenesis Research Include:
- Proteins in the cell membrane are crucial for generating the electrical impulses that neurons use to communicate with one another. For this reason, researchers are studying the membrane structure and the channels that allow molecules like sodium, calcium, and potassium to move across them to generate electrical impulses. A disruption in any of these processes can cause changes that may lead to epilepsy.
- Studies have suggested how a breakdown of the blood-brain barrier may lead to seizures. When proteins from the blood cross this important barrier between the circulatory system and fluid surrounding the brain, they trigger a reaction that leads to hyperactivity of neurons in the area of the brain surrounding the breakdown.
- Glial cells are non-neuronal cells that play a critical supportive role in the brain. For example, astrocytes are a type of glial cell that acts as a “housekeeper” by removing excessive levels of glutamate, a major neurotransmitter that mediates excitatory signals in the central nervous system. When astrocytes are impaired, levels of glutamate rise excessively in the spaces between brain cells, which may then contribute to the onset of seizures. In animal studies, the introduction of ceftriaxone, an antibiotic that supports the housekeeping role of astrocytes, has been shown to reduce seizure frequency.
- The body’s immune system may contribute to the development of certain forms of epilepsy. In aggressive forms of the disorders, antibodies may impair the function of brain receptors, leading to abnormal neuronal activity. Testing for many of these antibodies is already available, and findings from early-stage clinical trials suggest that strategies aimed at adjusting the body’s immune system may provide a means of treating these otherwise untreatable forms of epilepsy.
Researchers are studying the membrane structure and the channels that allow molecules like sodium, calcium, and potassium to move across them to generate electrical impulses. A disruption in any of these processes can cause changes that may lead to epilepsy.
Recent studies have yielded substantial progress in the identification of genetic mutations involved in the epilepsies. Several types of epilepsy have been linked to defective genes for ion channels, the “gates” that control the flow of ions in and out of cells and that regulate neuronal activity.
Mutations in single genes have been found among family members affected by certain epilepsy syndromes. For example, some infants with Dravet syndrome, a type of epilepsy associated with seizures that begin before the age of one year, carry a mutation in the SCN1A gene that is believed to cause seizures by affecting sodium channels in the brain. Surprisingly, the SCN1A mutations and other epilepsy mutations are often de novo mutations, meaning that they are not present in the parents. Building on that genetic discovery, researchers have created models of Dravet syndrome in the fruit fly, zebrafish, and mouse that are now being used to test potential therapies for controlling seizures. In addition, researchers have successfully taken connective tissue cells from individuals with Dravet syndrome, reprogrammed them to create induced pluripotent stem cells (cells that can become any type of cell in the body), and differentiated them into neurons that also can be used to test potential drugs and to study the mechanisms that lead to Dravet syndrome.
Continued progress in the identification of genetic causes of the epilepsies could guide the care and medical management of individuals. In the case of heritable mutations, this will help affected families understand their risks.
A major driver of success on the genetics front is the advent of next-generation sequencing—highthroughput methods of genetic sequencing that have revolutionized the search for the genetic underpinnings of diseases and disorders. Next-generation sequencing has significantly cut the time and costs required to identify genes involved with the epilepsies, as well as other diseases.
Major collaborative efforts have enabled researchers to efficiently investigate the effects of many risk factors, including genetic ones, among large populations of people affected by the epilepsies.
Researchers have taken skin cells from people with Dravet syndrome, turned them into stem cells, and then turned those stem cells into brain cells. Electrical activity among the brain cells can be measured, creating a testing ground for studying the disorder.
Identify Biomarkers of Seizure Onset and Epileptogenesis
Researchers see a potential opportunity to prevent the epilepsies before the onset of recurrent spontaneous seizures. Surrogate measures of epileptogenic processes, or biomarkers, could aid in the development of interventions that would prevent epilepsy in at-risk individuals. Other types of biomarkers could help researchers and health care providers better identify and monitor seizure-onset zones or predict seizure occurrence, which could enable more targeted treatments. The identification of reliable biomarkers for the epilepsies is one of the more critical areas in need of research advances.
A number of changes in the brain shown on imaging and electroencephalography (EEG) are known to be associated with epilepsy-related processes. The challenge is that people without epilepsy also can have similar brain changes and there is little evidence to show clearly which of these changes is predictive of someone who will develop a form of epilepsy.
Newer technologies are allowing researchers to map epileptic networks and track seizure generation with increasing resolution. Implantable “microelectrodes” are revealing complex brain activity during seizures. Using microelectrodes, researchers are able to better characterize high-frequency oscillations (HFOs). Abnormal HFOs have been linked to seizureonset zones and may serve as a biomarker of epileptogenesis; this could help identify people at risk for developing epilepsy after an initial insult to the brain, such as a stroke or TBI.
Investigators also have improved devices for measuring electrical activity in the brain. New electrode arrays are flexible enough to mold to the brain’s complex surface, providing unprecedented access for recording and stimulating brain activity. While these arrays have not yet been used in humans, they are a promising advance toward expanded options for epilepsy diagnosis and treatment.
Epilepsy researchers have increasingly explored how connections between different brain regions—structurally and functionally—may explain how seizures start in the first place. Much of this research grows out of observations that seizures are not merely the result of focal areas of hyperactivity, but arise from the complex interactions of the network. A better understanding of how this network operates may explain, for example, why some people do not improve even after focal areas of hyperactivity, which appeared to be the source of seizure, are surgically removed.
Diffusion tensor imaging, a type of magnetic resonance imaging (MRI) that shows microstructural detail of tissues based on the diffusion of water molecules, has shown abnormal structural connectivity during focal and generalized seizures. Advances in MRI have shown that functional connectivity patterns in people with epilepsy differ from those of normal controls. Interestingly, patterns of abnormal functioning occur both during seizures and during the “resting-state” period between seizures.
Newer technologies are allowing researchers to map epileptic networks and track seizure generation with increasing resolution. Implantable “microelectrodes” are revealing complex brainactivity during seizures. Using microelectrodes, researchers are able to better characterize high-frequency oscillations.
Develop New Animal Models for Studying Epileptogenesis and for Testing Treatments
The diversity of epilepsy syndromes and their causes precludes investigators from using any single animal model system for learning about the epilepsies and for testing potential therapies. Multiple syndrome-specific models are therefore needed to advance research on the epilepsies.
Several substantial advances in the development of animal models have occurred over the last few years, including new models of Dravet syndrome, infantile spasms, cortical dysplasia, and viral encephalitis, as well as for stroke, TBI, and other conditions that can lead to acquired forms of epilepsy.
The zebrafish has emerged as a promising model for screening new drug compounds for antiseizure activity. Fish that are bred to express mutations known to be associated with particular types of epilepsy can be quickly and cost-effectively produced for research. The drosophila, or fruit fly, is another model developed to investigate the cellular mechanisms of the epilepsies.
Paramedics stopped status epilepticus seizures earlier thanks to drug delivery with an autoinjector. Similar to the EpiPen used by people with serious allergic reactions, the autoinjector may someday be on hand for people with epilepsy and their families.
Develop New Treatment Strategies and Optimize Existing Treatments
There have been several key advances in diagnostics, therapeutics, and technologies that are either approved or in various stages of approval in the U.S. and Europe. New chemical entities have been developed for treatment-resistant epilepsy. For example, ezogabine (also called retigabine) was approved by the U.S. Food and Drug Administration (FDA) in 2011 for the prevention of focal seizures by a novel mechanism of action. Several other potential drugs and chemical compounds (brivaracetam, perampanel, YKP3089, VX-765) are in development and also are aimed at preventing seizures by novel mechanisms.
In addition, several agents have been approved for specific seizure types or syndromes: rufinamide (Lennox-Gastaut syndrome), stiripentol (Dravet syndrome), adrenocorticotropic hormone also known as ACTH (infantile spasms), and vigabatrin (infantile spasms). mTOR inhibitors (such as everolimus) are being tested for the treatment of seizures and other manifestations of tuberous sclerosis complex (TSC). The drug everolimus has been approved by the FDA for preventing the growth of tumors in individuals with TSC.
Progress has been made in determining the best single-agent therapy for childhood absence epilepsy (CAE), the most common pediatric epilepsy syndrome, occurring in 10 to 17 percent of all children with epilepsy. People with CAE tend to have several seizures each day. In the interest of finding a drug regimen that would limit an individual’s exposure to drug-related side effects, researchers compared ethosuximide, lamotrigine, and valproic acid to treat CAE. Ethosuximide was found to be the best single-agent therapy because of its optimal balance between effectiveness and relatively few side effects.
NINDS-funded researchers have made significant strides in improving the management of individuals with status epilepticus seizures. These prolonged seizures can be particularly challenging to treat given the difficulty of establishing an intravenous line (IV) when a person is having convulsions. The results of the randomized controlled trial, known as Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), showed that seizures stopped significantly earlier in people treated with midazolam delivered by an autoinjector compared to individuals treated with lorazepam by IV. The autoinjector is similar to the EpiPen drug delivery system used to treat serious drug reactions. Faster resolution of seizures also translated into fewer people requiring hospitalization.
Ongoing basic research efforts continue to identify targets for therapy development. For example, studies have focused on the role of gamma-aminobutyric acid (GABA), a key neurotransmitter that inhibits activity in the central nervous system. Other studies are investigating ways of blocking the activity of the excitatory neurotransmitter glutamate.
Given that the epilepsies involve so many different underlying mechanisms, the development of a single therapy is unlikely. Instead, management approaches will need to be tailored for specific syndromes.
Sidebar: Anticonvulsant Screening Program
In 1975, NINDS established the Anticonvulsant Screening Program (ASP) to promote the development and evaluation of new antiseizure drugs. At the time, few incentives existed for the pharmaceutical industry to support epilepsy research on the development of therapeutic agents. Since its launch, the ASP has been instrumental in bringing new antiseizure medications to the marketplace by giving researchers a common platform for submitting potential therapeutic agents to standardized testing in animal models. The resources provided to researchers through the ASP can save years in development time.
ASP’s priorities have evolved to focus on the development of therapies aimed at preventing epileptogenesis, modifying the course of disease progression, finding therapies for the cases that do not respond to currently available treatments, and identifying specific epilepsy subtypes and their unmet needs. The ASP maintains a database of more than 30,000 submitted compounds, and plans are underway to improve the usefulness of the data for researchers pursuing novel compounds. NINDS continues to look for new ways to improve the ASP. New assays and procedures are being developed and implemented to significantly expand the sensitivity of the traditional screening approach to identify novel pharmacotherapies targeting the major unmet medical needs in epilepsy.
Surgery remains an effective option for individuals with treatment-resistant epilepsies. The most common type of surgery involves the removal of a seizure focus, the small area of the brain where seizures originate. In some extremely severe cases, surgeons perform a procedure called multiple subpial transection, which involves making cuts designed to prevent seizures from spreading into other parts of the brain while leaving the person’s normal abilities intact. Doctors also may use surgical procedures called corpus callosotomy (severing of the nerve fibers that connect the two sides of the brain) or hemispherectomy (removal of half of the brain). Researchers continue to refine surgical techniques to make them less invasive and to prevent cognitive and other neurological deficits that can result from surgery.
- New imaging technologies are key advances for localizing the effects of surgery and minimizing adverse events. Many epilepsy centers have begun to use functional magnetic resonance imaging (fMRI) to “map” language and memory zones prior to surgery. NIH-funded researchers are aiming to verify whether fMRI actually improves surgical outcomes and to standardize best practices for its use.
- Researchers also are looking for ways to combine imaging modalities to more accurately map language zones. In one study, for example, diffusion tensor imaging (DTI) is being used along with fMRI and magnetoencephalography (MEG), another brain mapping technique based on magnetic fields, to evaluate preoperative language processing and preserve key language zones during surgery for temporal lobe epilepsy.
- Evidence suggests that high-frequency oscillations (HFOs) measured in the neocortex and temporal lobe may be biomarkers of epileptic networks, and can therefore help in surgical mapping and predicting outcomes after epilepsy surgery. Retrospective studies show that the removal of zones generating HFOs is associated with improved results following surgery.
- Minimally invasive MRI-guided laser surgery is being studied for the treatment of epilepsies associated with tumors, such as hypothalamic hamartomas and tuberous sclerosis complex. The technique involves drilling a very small hole in the skull through which a thermal laser is inserted to ablate an epileptogenic zone under MRI-guidance.
New imaging technologies are key advances for localizing the effects of surgery and minimizing adverse events. Many epilepsy centers have begun to use functional magnetic resonance imaging to “map” language and memory zones prior to surgery.
Electrical stimulation of the brain remains a therapeutic strategy of interest. The types of stimulation include: deep brain, intracranial cortical, peripheral nerve, vagal nerve, and trigeminal nerve. So far, deep brain stimulation has involved either the thalamus or the hippocampus, and only thalamic stimulation has been tested in a large clinical trial.
A clinical trial of deep brain stimulation in the anterior thalamic nucleus showed significant seizure reduction over the long term, and the majority of participants saw benefit. Thalamic stimulation has been cleared for use in Europe, but not in the U.S.
A report on trigeminal nerve stimulation showed efficacy rates similar to those for vagal nerve stimulation, with about half of the people responding (a responder is defined as having greater than a 50 percent reduction in seizure frequency). Freedom from seizures, although reported, remains rare for both methods.
NINDS-supported investigators are developing methods to predict seizures by analyzing brain activity patterns that precede their onset. A promising application of this research is the development of implantable devices that can detect a forthcoming seizure. Once detected, the implanted device administers an intervention, such as electrical stimulation or a fast-acting drug to prevent the seizure from occurring. The first generation of seizure control devices in clinical trials uses such seizure prediction technology. The NeuroPace RNS system is among these devices, known as responsive stimulation or closed-loop devices.
Optogenetics is an emerging experimental technique that may eventually lead to future generations of closed-loop devices. It involves the genetic delivery of light-sensitive proteins to specific populations of brain cells. The lightsensitive proteins can be inhibited or stimulated by exposure to light delivered by fiber optics. Although optogenetic methods are not currently used in humans, such an approach could allow highly targeted regulation of network excitability, providing a means for intervening at or before the onset of a seizure.
A high-fat, very low carbohydrate ketogenic diet is an age-old treatment for medicationresistant epilepsies and there has been a renewed interest in recent years in how it works. The diet effectively reduces seizures for some people, especially children with certain forms of epilepsy. Studies have shown that more than 50 percent of people who try the ketogenic diet have a greater than 50 percent improvement in seizure control and 10 percent experience seizure freedom. However, for some people, the regimen is difficult to maintain.
Researchers are trying to learn exactly how the ketogenic diet prevents seizures. They hope to find ways to mimic its seizure-blocking effects without the dietary restrictions. Studies have advanced the understanding of the connection between energy metabolism and neuronal excitability, and in the process and may contribute to a better understanding of how the ketogenic diet promotes seizure control.
In addition, researchers are looking at modified versions of and alternatives to the ketogenic diet. For example, studies show promising results for a modified Atkins diet and for a low-glycemicindex diet, both of which are less restrictive and easier to follow than the ketogenic diet. However, well-controlled randomized controlled trials have yet to assess the approaches, and many questions remain about the optimal circumstances of their use.
Researchers are trying to learn exactly how the ketogenic diet prevents seizures. They hope to find ways to mimic its seizure-blocking effects without the dietary restrictions. Studies have advanced the understanding of the connection between energy metabolism and neuronal excitability..
Gene and Cell Therapies
The discovery of genetic mutations that are linked to specific epilepsy syndromes suggests the possibility of using gene-directed therapies to counter the effects of these mutations. Gene therapies remain the subject of many studies in animal models of epilepsy, and the number of potential approaches continues to expand. A common approach in gene therapy research, called transfection, uses modified components of viruses to introduce new genes into brain cells, which then act as “factories” to produce potentially therapeutic proteins.
Several proteins have been targeted for transfection. Animal studies have shown that it is possible to introduce a new protein into a cell, and in some cases, there has been an associated reduction in the frequency, duration, and severity of seizures.
Cell therapy differs from gene therapy in that instead of introducing genetic material, it involves the transplantation of whole cells into a brain. In animal studies, for example, NINDS-funded researchers have successfully controlled seizures in mice by grafting special types of neurons that produce the inhibitory neurotransmitter GABA into the hippocampus of their brains.
Gene and cell therapies remain attractive and promising strategies for treating, and potentially curing, some forms of epilepsy. However, their advancement as a viable treatment option in people will require new technologies and methods that can target specific neurons in the brain. These approaches need to be able to create more long-lasting changes.
Viruses are introduced into brain cells, which then act as “factories” to produce potentially therapeutic proteins.
Preventing the Development of the Epilepsies
Until recently, therapy development for the epilepsies focused largely on treating seizures in people already affected by the disorders. Now, in addition to efforts to develop new and improved antiseizure treatments, researchers are striving to prevent the epilepsies among people at risk.
Measures that reduce the risk of head injury and trauma—such as improvements in automobile safety and the use of seat belts and bicycle helmets—can prevent epilepsies related to TBI. Good prenatal care, including treatment of high blood pressure and infections during pregnancy, can prevent brain damage in developing babies that may lead to epilepsy and other neurological problems later in life. Treating cardiovascular disease, high blood pressure, infections, and other disorders that affect the brain during adulthood and aging also may prevent some types of epilepsy.
However, while such measures can prevent brain damage from occurring in the first place, there are currently no interventions known to specifically reduce the risk of seizure onset once damage to the brain has occurred. None of the available antiseizure medications have been shown to modify the development of the epilepsies in people. Researchers are working to change this.
- Recent animal studies have helped clarify the mechanisms of hypoxic-ischemic encephalopathy (HIE) seizures (caused by a lack of oxygen in the brain), and clinical studies involving newborns have begun to assess potential treatment strategies. These include drugs both alone and in combination with each other or in combination with a strategy that involves deliberately cooling babies with HIE for the prevention of epilepsy.
- Adenosine is an inhibitory neuromodulator that is believed to promote sleep and suppress arousal. Studies in animal models have shown that increasing adenosine levels in the brain can inhibit the development of spontaneous recurrent seizures after an initial injury.
Section 3: Reducing the Risk of Conditions that Co-occur with the Epilepsies
Co-occurring psychiatric conditions are relatively common in individuals with epilepsy. In adults, depression and anxiety disorders are the two most frequent psychiatric diagnoses. Attention Deficit Hyperactivity Disorder and anxiety frequently affect children with epilepsy.
Therapies commonly used to treat depression in the general population have been shown in randomized controlled trials to be effective in treating depression in people with epilepsy. In those trials, depression medications did not appear to be associated with an increased risk of seizures. However, larger trials with longer followup would be required to provide reliable estimates of seizure exacerbation risk.
Basic research investigations currently are exploring the possibility that the development of depression, anxiety, and seizures may involve similar causes. In addition, studies of antiseizure drugs have focused on determining whether there may be an increased risk of suicide associated with specific medications.
People with neurodevelopmental disabilities, such as autism spectrum disorder, attention deficit disorder, and learning disabilities are known to be at higher risk for epilepsy. Further investigation is needed to better understand these associations and if there is a shared mechanism between these neurodevelopmental disabilities and the epilepsies. Sleep disorders are common among people
with the epilepsies. By one estimate, fully 70 percent of people with epilepsy had some form of disordered breathing during sleep. In another study, researchers found that certain types of seizures were associated with sleeping, while others were more common during times of wakefulness—suggesting that more research is needed on how these patterns might inform medication adjustment.
Sudden Unexpected Death in Epilepsy (SUDEP)
Some people with epilepsy are at risk of SUDEP, which for years was largely unrecognized. Estimates of SUDEP risk vary, but some studies suggest that each year approximately one case of SUDEP occurs for every 1,000 people with the epilepsies. For some, this risk can be higher, depending on several factors. People with more difficult-to-control seizures tend to have a higher incidence of SUDEP.
One study suggested that use of more than two antiseizure drugs at one time is a risk factor for SUDEP. However, it is not clear whether the use of multiple drugs causes SUDEP, or whether people who use multiple antiseizure drugs have a greater risk of death because their epilepsy is more severe or more difficult to control. People with tonic-clonic seizures, uncontrolled seizures, or epilepsy combined with other neurological disorders also have an elevated risk for SUDEP.
Findings from an analysis of four studies showed that the highest risk of SUDEP can be seen in men younger than 60 years of age with at least a 15-year history of epilepsy from unexplained causes, who had frequent generalized tonicclonic seizures, and who were taking multiple antiseizure drugs. Although SUDEP is considered rare in children, some evidence suggests that children with certain types of epilepsies, such as Dravet syndrome, may have an elevated risk for SUDEP.
Seizures are known to alter breathing and cardiac activity. Research suggests that drug therapies that address respiratory arrest and implantation of cardiac devices may reduce the risk of SUDEP in some individuals.
Early studies have described certain EEG patterns that may help identify people at elevated risk for SUDEP. In addition, several devices in the early stages of development aim to provide a warning when a seizure has the potential to put someone at risk for SUDEP.
NINDS, nonprofit lay and professional organizations, and the CDC are providing significant funding toward studies aimed at better understanding SUDEP risk factors and mechanisms, which may yield strategies for screening and prevention. Plans are underway for an Epilepsy Center without Walls initiative devoted to multi-disciplinary research on SUDEP and increased surveillance and epidemiology studies.
Progress in Managing Specific Populations
Pregnancy and the Epilepsies
Understanding how to treat epilepsy in pregnant women and the impact of antiseizure medications on an unborn child are of paramount importance and have been the focus of several studies. The American Academy of Neurology and the American Epilepsy Society conducted evidence-based systematic reviews of pregnancy-related studies among women with epilepsy.
Emerging data from the NINDS-funded Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study, as well as multiple hospital- and population-based registries, are helping to better characterize the risk of birth defects associated with antiseizure medications. In general, higher doses of these
medications are associated with an increased risk of major congenital malformations. Findings from the registries and other studies include:
- Valproate is consistently associated with an increased risk of major congenital malformations, and studies suggest a specific increased risk of neural tube defects, such as spina bifida. Prenatal exposure to valproate has been shown to be associated with symptoms of autism in humans and animals. Valproate exposure in utero also has been shown to adversely affect a child’s cognitive function, particularly verbal abilities.
- Carbamazepine may increase the risk of neural tube defects, but this is not a consistent finding. Verbal cognitive skills also have been shown to be impaired among children who were exposed to carbamazepine during gestation.
- Topiramate increases the risk of oral clefts (birth defects in which the tissues of the lip or mouth do not form correctly during fetal development) as demonstrated in multiple studies. The FDA has classified it as a category D drug in pregnancy, meaning that evidence shows that the drug involves risk to a developing fetus, but the potential benefits from the drug may warrant its use in pregnant women despite potential risks.
- Levetiracetam appears to have a lower risk of major congenital malformations than other antiseizure drugs.
- Motor, adaptive, and emotional behavioral functioning were impaired in children of mothers who had taken phenytoin, lamotrigine, valproate, or carbamazepine during pregnancy, with dose-response effects seen with valproate and carbamazepine. Breastfeeding did not affect cognitive health of the studied children.
Infants and Children
Febrile seizures occur in infants and young children and involve convulsions brought on by high fever. The vast majority of febrile seizures are brief and harmless. In rare cases, however, some children—including those with cerebral palsy, delayed development, or other neurological abnormalities—have an increased risk of developing epilepsy.
Results from an ongoing NINDS-funded study suggested that MRI and EEG may help determine which children with febrile seizures are subsequently at increased risk of developing epilepsy.
Epidemiological studies demonstrate that the elderly are at a substantially higher risk for the development of the epilepsies. In addition to stroke (hemorrhagic and ischemic), seizures in the elderly may be associated with brain tumors, TBI, and Alzheimer’s disease.
NIH-funded researchers have found that blood concentrations of antiseizure medications fluctuate markedly among many residents of nursing homes even when there is no change in dosage and no change in other medications the resident may be taking. Prospective studies will continue to follow older adults in nursing homes to help determine optimal levels of antiseizure drugs and to identify factors that may contribute to such fluctuations in drug levels.
Diagnosing, Treating, and Preventing Non-epileptic Seizures
An estimated five to 20 percent of people diagnosed with epilepsy actually have nonepileptic seizures (NES) which outwardly resemble epileptic seizures but are not associated with seizure-like electrical discharges in the brain. A history of traumatic events is among the known risk factors for psychogenic nonepileptic seizures, which are largely thought to be psychological in origin.
A NINDS-funded pilot trial showed a reduction in NES frequency when individuals with psychogenic non-epileptic seizures were treated with sertraline compared with a placebo. Two other studies showed a reduction in seizures and fewer comorbid symptoms following treatment with cognitive behavioral therapy.
Section 4: Furthering Research on the Epilepsies
There are several ways in which individuals with epilepsy and their families can help move research forward. Resources include:
- People with epilepsy can help researchers test new medications, surgical techniques, and other treatments by enrolling in clinical studies. Information about finding and participating in clinical studies can be found at the NIH Clinical Trials and You website (www.nih.gov/health/clinicaltrials). Additional studies can be found at www.clinicaltrials.gov and through many pharmaceutical and biotech companies, universities, and other organizations. A person who wishes to participate in a clinical trial must ask his or her physician to work with the doctor in charge of the trial and to forward all necessary medical records.
- To learn more about why clinical trial research is important, visit the Human Epilepsy Research Opportunities (HERO) website at www.epilepsyhero.org.
- Pregnant women with epilepsy who are taking antiseizure drugs can help researchers learn how these drugs affect unborn children by participating in the Antiepileptic Drug Pregnancy Registry. This registry is maintained by the Genetics and Teratology Unit of Massachusetts General Hospital. For more information, call 1-888-233-2334 or visit the website at
- People with epilepsies can help further research by making arrangements to donate tissue either at the time of surgery for epilepsy or at the time of death. Researchers utilize the tissue to study epilepsy and other disorders so they can better understand what causes seizures. Some brain banks accept tissue from individuals with epilepsy. Each brain bank may have different protocols for registering a potential donor. Individuals are strongly encouraged to contact a brain bank directly to learn what needs to be done ahead of the time of tissue donation. These banks include:
NICHD Brain and Tissue Bank for Developmental Disorders
University of Maryland School of Pediatrics
655 West Baltimore Street, 13-013 BRB
Baltimore, MD 21201-1559
University of Miami Brain Endowment Bank
University of Miami Department of Neurology
1951 NW 7th Avenue, Suite 240
Miami, FL 33136
305-243-6219 or 800-862-7246
National Disease Research Interchange/National Human Tissue Resource Center
8 Penn Center, 15th Floor
1628 JFK Boulevard
Philadelphia, PA 19103
215-557-7361 or 800-222-6374
The Human Brain and Spinal Fluid
11301 Wilshire Boulevard (127A)
Building 212, Room 16
Los Angeles, CA 90073
The pace of research on the epilepsies has accelerated considerably over the past few decades. Progress has been made in understanding how and why the epilepsies develop and how they might be prevented. Investigators have identified a variety of potential new treatments, and they may soon be able to use knowledge about genetic variations and other individual differences to tailor treatment for each person. With time and continued work, the missing pieces of the puzzle will be filled in to form a complete picture of how to treat and prevent all types of epilepsy


As a commonly used insulating material in industry, glass fiber not only has many types, but also has outstanding performance, and has applications in many fields.
Glass fiber cloth overview:
Glass fiber is a kind of inorganic non-metallic materials with excellent performance, and there are many kinds of them. The advantages are good insulation, strong heat resistance, good corrosion resistance and high mechanical strength; but the disadvantages are brittleness and poor wear resistance. Glass fiber is usually used as a reinforcing material in composite materials, electrical insulation materials, thermal insulation materials, and circuit boards in various fields of the national economy.
Glass fiber cloth features:
1. Used for low temperature -196℃ to high temperature 300℃, with weather resistance.
2. Non-adhesive, not easy to adhere to any substance.
3. Chemical resistance, resistance to strong acid, strong alkali, aqua regia and various organic solvents.
4. With low friction coefficient, it is the best choice for oil-free self-lubrication.
5. The light transmittance is 6-13%.
6. With high insulation performance, anti-ultraviolet, anti-static.
7. High strength. Has good mechanical properties.
8. Drug resistance.
Glass fiber cloth application:
Glass fiber cloth is mostly used in hand lay-up process. Glass fiber reinforced material grid cloth is mainly used in ship hulls, storage tanks, cooling towers, ships, vehicles, tanks, and building structural materials. Glass fiber cloth is mainly used in industry: heat insulation, fire prevention and flame retardant. The material absorbs a lot of heat when it is burned by a flame and can prevent the flame from passing through and isolate the air.


State of the World's Minorities and Indigenous Peoples 2013 - New Zealand
|Publisher||Minority Rights Group International|
|Publication Date||24 September 2013|
|Cite as||Minority Rights Group International, State of the World's Minorities and Indigenous Peoples 2013 - New Zealand, 24 September 2013, available at: http://www.refworld.org/docid/526fb739b.html [accessed 20 August 2017]|
|Disclaimer||This is not a UNHCR publication. UNHCR is not responsible for, nor does it necessarily endorse, its content. Any views expressed are solely those of the author or publisher and do not necessarily reflect those of UNHCR, the United Nations or its Member States.|
Māori, New Zealand's indigenous people, make up approximately 15.4 per cent of the country's population, with nearly a quarter living in the greater Auckland area. The relationship between the Māori and the New Zealand government is grounded in the Treaty of Waitangi, which contains a powerful expression of the Crown's moral obligations to act honourably in its dealings with Māori.
There are also more than 22 different Pacific communities in New Zealand – each with its own distinctive culture, language, history and health status. Collectively known as Pasifika, the biggest Pacific groups in New Zealand are the Samoan, Cook Islander, Tongan, Niuean, Fijian, Tokelauan, and Tuvaluan communities. To date, the majority of the Pacific communities in New Zealand originate from Polynesian states, however migration to New Zealand from Melanesian states has also increased, and predictions indicate that New Zealand can expect much larger numbers of migrants from Melanesia in the coming decades.
It is also important to note that there has been a rapid increase in the last decade of the number of Asians in New Zealand. By 2001, Asians had displaced the Pasifika communities as the third most populous ethnic group, with the 2006 Census data estimating the Asian population of New Zealand at around 9.2 per cent, with predicted growth to up to 16 per cent of the national population by 2016. Chinese (46 per cent) and Indian (29 per cent) are the majority groups, with populations from other Asian communities including Koreans, Filipinos, Japanese, Sri Lankans, Cambodians and Thais.
Despite significant gains in recent years, Māori continue to have the poorest health of any New Zealand group. Māori have a higher mortality rate than non-Māori, as well as higher rates of illness. Māori infants die more frequently from SIDS (sudden infant death syndrome), have lower birth weight than non-Māori and also experience higher rates of illness. Māori are 2.3 times more likely to experience and die from cardiovascular disease than non-Māori and Māori life expectancy is also significantly lower than the life expectancy for non-Māori.
Other minority groups in New Zealand also experience poorer health than the majority New Zealand European population. In particular, Pasifika still experience poorer health outcomes than the majority population. For example, Māori and Pacific communities have higher rates of diabetes. Māori and Pacific communities experience consistently higher infant mortality rates than the total New Zealand population, although this appears to be decreasing. Moreover, the obesity rates are greater for Māori and Pasifika.
The New Zealand government has taken some important strides to address Māori health disparity. He Korowai Oranga: Māori Health Strategy sets the direction for Māori health development in the health and disability sector. The vision of He Korowai Oranga is the achievement of whānau ora (healthy families), and recognizes the desire of Māori to have control over their future, and to seek their own solutions and to manage their own services.
The New Zealand government has developed targeted action plans that set objectives for Māori health. Whakatātaka – the Māori Health Action Plan – was implemented in 2002, and was built upon by the second Māori Health Action Plan, Whakatātaka Tuarua 2006-2011.
As part of Whakatātaka Tuarua, the Ministry of Health has identified the following areas for priority: building quality data and monitoring Māori health; developing whānau-ora-based models; ensuring Māori participation; and improving primary health care.
Under the 2000 New Zealand Public Health and Disability Act, health services require community participation and have been decentralized. The Act created 21 district health boards (DHBs), which provide services that meet local needs. This system is important for Māori health as every board is legally required to have at least 2 Māori members out of its 11, and Māori membership of the board must also be proportional to the number of Māori in the district's resident population. Moreover, DHBs must include Māori health and whānau ora as priority criteria in resource allocation and disincentives decisions, and should set funding targets for investment in Māori health and disability, and report on targets for their regions to increase funding for Māori initiatives. However, in the 2012 assessment the auditor general found that DHBs have not always performed adequately and noted a lack of monitoring and reporting.
Another important initiative for Māori health is the fact that each DHB must develop a Māori Health Plan (MHP), which aims to improve Māori health and reduce the disparities between Māori and non-Māori. As key planning and monitoring documents, the MHPs provide a summary of a DHB's Māori population and their health needs. The plan then documents and details the interventions and actions the DHB plans to undertake to address health issues in order to achieve indicator targets set nationally, regionally and at district level.
The New Zealand Ministry of Health has also been working together with Māori traditional healing practitioners. Rongoā Māori, the traditional healing, is formulated in a Māori cultural context; it encompasses the understanding of events leading to ill health and its impacts are addressed through a range of culturally bounded responses. These responses include rakau rongoā (native fauna herbal preparations), mirimiri (massage) and karakia (prayer). In December 2011, a new national Rongoā governance body – Te Kāhui Rongoā Trust – was established to protect, nurture and promote Rongoā Māori, and aimed to become fully operational by June 2012.
Although it is too early to measure the success of the initiative, it remains significant, in particular in light of old repressive laws which banned traditional Maori healers (Tohunga) and outlawed Rongoā Māori. Although the law was repealed in 1962, the new Trust is one of the first initiatives to formally promote Rongoā Māori on the national level.
Health of Asian New Zealanders
It appears that many Asian migrants who arrive in New Zealand are relatively healthy, however this has been attributed to the 'healthy immigrant effect', which requires most migrants to be in good health in order to be allowed to immigrate to a new host country. However, this positive effect on health is reported to gradually diminish with increased length of residency.
In particular, data has demonstrated low use of primary health care, emergency health care and cancer screening for Asian people in New Zealand, particularly for Chinese New Zealanders. For youth this is particularly worrying, and 15 per cent of young Chinese New Zealanders reported accessing no health services at all, which was over three times the rate reported by other New Zealanders.
Another key issue is cardiovascular disease and diabetes for South Asian people. Indian people show the highest rates of self-reported diabetes of any ethnic group in New Zealand and they also show high levels of cardiovascular disease, similar to Māori.
Some of these challenges appear to arise from underlying structural obstacles for Asian New Zealanders as a minority group: these include a lack of knowledge of the New Zealand health system, cultural beliefs and approaches to health care that differ from the New Zealand system, and linguistic barriers. Mental health also remains a challenging area because of the degree of stigma attached to such illness in many Asian cultures, resulting in potential treatment delay and possible worsening of prognosis.
17. New Zealand Government, Third periodic report to the CESCR, E/C.12/ NZL/3, para. 472, available at: http://www2.ohchr.org/english/bodies/cescr/cescrs48.htm.
18. See: Controller and Auditor-General NZ, 'Part 5: Reducing health disparities for Māori', in Health Sector: Results of the 2010/11 Audits, retrieved July 2013, http://www.oag.govt.nz/2012/health-sector/part5.htm.


The Problems of Obesity, Obesity is problematic overweight caused by excessive accumulation of fat. It is a serious problem that can have serious ramifications in the long run. Recently, it has become a worrying issue due to numerous public health problems.
Obese people encounter social stigmatization, negative stereotypes and discrimination in society. They are endangered to many life-threatening diseases, such as diabetes, high blood pressure, sleep apnea, cancer, heart disorders, etc. Additionally, the World Health Organization reveals that the greatest epidemic in the 21st century is obesity.
In this essay, I will discuss several bad effects that cause obesity. Thus, there are three main causes of obesity involved in eating unhealthy foods, neglecting physical activities and following wrong practices.
First and foremost, obesity is caused as a result of eating unhealthy foods. There are plenty of unhealthy food items which people think are healthy. A very good example is fast food and food additives. The former is like hot pies, burgers, chips, pasties, donuts, pizza, etc. The latter is like flavored yoghurt, flavored milk, flavored ketchup, flavored beverages, etc. People are tempted to eat fast foods because they have no time to wait for fresh foods. They also crave for food additives because of its flavor and delicious taste. In addition, frozen foods and some snacks fall under unhealthy foods which are the best friend of obesity. Therefore, if we believe in avoiding such types of foods is not the problem; then, eating unhealthy foods is will not be the solution. In fact, fast food is typically low in nutrition and high in sodium, calories, saturated fat and trans fat that lead to fatness.
Moreover, it is found that neglecting physical activities gives rise to obesity. Many people neglect aerobics, and are lazy to do different types of physical activities in their life, such as walking, jogging, bicycling, swimming, etc. Because of ignoring aerobics and the state of laziness, fats are heaped up in the body with the course of time.
Consequently, the body gains weight and brings about fatness. For this reason, people need to be taught the significance of these physical activities, and that ignoring them would lead to overweight and obesity.
Furthermore, obesity is caused as a consequence of following wrong practices. For instance, obesity results when people regularly take in imbalanced diet, immoderate calories and excessive sleep. For this reason, the body stores these undue calories as body fat, and over time the extra pounds add up.
Nowadays, some people go for a serious diet or toe the line of unhealthy foods that affect the metabolism which ends up with fatness. Therefore, they endanger themselves to obesity by following their own prescriptions and false instructions. So, metabolism affects the body as a result of following wrong practices in life.
In summary, obesity is merely caused by consuming too many calories, lack of physical exercises, unbalanced diet, flavored drinks etc. In this regard, Lee Haney recommends that “exercise is one of the best ways in preventing the rapid growth of obesity”. Besides, we should bear in mind that “rich, fatty foods are like destiny: they too, shape our ends”. Meanwhile, unbalanced diet leads to the illness of obesity. In short, this essay demonstrates several factors that cause obesity, such as eating unhealthy foods, neglecting physical activities and following wrong practices.


Misidentifying Twos and Fives
This is an extremely unlikely mistype. Few people of either type would be likely to mistype themselves as the other type, but others might occasionally be fooled. Surprisingly, it is more likely for some Fives to be mistaken for Twos, but only in very narrow circumstances. Because Fives do not form emotional bonds easily, they can be highly dependent on the few they do form, and can become needy with their significant others. At such times, they do not want their loved ones far from them, somewhat like average Twos.
Otherwise, these types are almost opposites. Twos are emotionally expressive and highly people-oriented. Fives are emotionally detached and can be the true loners of the Enneagram. Both feel rejected easily, but Twos cope by winning people over and Fives cope by detaching from the hurt and isolating themselves further. Twos go by their feelings and can get flustered or irritated by overly intellectual approaches or complex ideas and procedures. Fives get flustered or irritated by sentimentality and gushiness: Fives feel that they are in their element with intellectual concepts and complexity. Twos tend to move toward others: Fives tend to withdraw from others, and so forth.


Stress hormones help firm up memories of emotional events so that we can avoid or deal with the challenge if it occurs again. For example, cortisol, produced by the adrenal glands, has receptors in many parts of the brain—especially the hippocampus, a nexus of emotion and memory.
Many disorders can result from improperly functioning cortisol, including anxiety, post-traumatic stress disorder, and some forms of depression. Scientists seeking treatments need a detailed picture of how cortisol works through its receptors to affect the brain. One player in the relay appears to be mitogen-activated protein kinase (MAPK), which previous studies show is activated in tandem with cortisol receptors.
In the May issue of Nature Neuroscience, Pier Vincenzo Piazza of the Bordeaux Institute for Neurosciences, France, and colleagues set out to establish cause and effect. They found that in cultured cells, activating cortisol receptors with the hormone increased levels of MAPK and the genes under its control.
In mice, the researchers found that the stress of being briefly restrained increased MAPK expression. When the mice were injected with a MAPK inhibitor, they lost the ability to form fear-related memories: in a conditioning test involving a mild shock to the foot, the treated mice showed none of the normal “freezing” behavior.
“Our data indicate a direct link between cortisol receptor activation, the MAPK signaling pathway and its target genes, and stress-induced enhanced memories of emotionally arousing experiences,” the researchers write.


“How Shall We Then Laugh?” in his Literature and Theology as Amiable Companions
Van der Weele, Steve J.
privately published, 2010
“Just what it is that prompts laughter has engaged some of the best minds in history. It is a phenomenon which Christopher Fry calls ‘the surest touch of genius in creation.’ From Aristotle and Plato down to the present, the fact that man is the only creature that laughs has evoked great interest and voluminous comment.” Freud, for example, in a two-hundred-page treatment said that laughter, comedy, humor are deeply connected with the highest of human gifts, with music, literature, the arts. “Laughter, he says, happens when a breakthrough in one’s perception occurs, when old things are suddenly exhibited in new patterns.” Laughter can also be a potent weapon to expose folly, as every satirist knows. But the great comedic writers (especially Shakespeare) know that laughter is cousin to joy. In Shakespeare, satire is relegated to the subplots, and joy to the main street. There are plenty of troubles, but in the end, restoration, reconciliation, joy. Every one of Shakespeare’s comedies ends “with multiple weddings.”


White Paper: Medical
The Liquid Lens Evolution
Before liquid lenses, a user would have to design some type of mechanical focusing into their optical system, which meant having a device to raise and lower the optics to enable them to refocus on different heights of an object. With liquid lenses and EDOF software, a user can expand depth of field and eliminate the need for mechanical refocusing, leading to simpler and faster inspection.
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Mesothelioma is a rare but deadly form of cancer that occurs in the mesothelium, the thin layer of issue surrounding major organs. Mesothelioma can grow in a number of places within the body including the lungs (pleural mesothelioma), the abdomen (peritoneal mesothelioma), testicles, and the heart (pericardial mesothelioma). Pleural mesothelioma accounts for about 70% of all cases. Mesothelimoa rarely appears without the negligence of someone else. If you or a loved one has or had mesothelimoa, call 800-553-8082 or get a free on-line case review.Overview of the Asbestos Exposure
Mesothelioma is caused by exposure to asbestos. Asbestos is a naturally occurring mineral. Because asbestos fibers are resistance to heat, asbestos has been used for insulation, brakes, flooring, electrical wiring, and many other common products.
During the process of mining and using asbestos, dust is often created. If inhaled or ingested, the dust particles settle in the lungs or stomach and can eventually lead to mesothelioma. It usually takes between 30 and 40 years for exposure to result in cancer. Mesothelioma has also been reported in people who were not directly exposed to the asbestos particles. Common examples include spouses who washed the clothes of contaminated workers or who were otherwise in close contact with those workers. This is referred to as second hand mesothelioma and can be deadly.Symptoms and Treatment
Mesothelioma symptoms vary depending on where the cancer has grown. Plural mesothelioma symptoms include shortness of breath, chest pain, painful coughing, weight loss, and lumpy tissue in the chest area. Symptoms of peritoneal mesothelioma include abdominal pain, swelling, and weight loss.
Treatment options often combine surgery, chemotherapy, and radiation therapy. After diagnosis the average patient lives, tragically, only for 18 months.The Mesothelimoa Tragedy
People working with asbestos and those living with exposed workers are at an increased risk for developing mesothelioma. Even after the risks of exposure had been established, asbestos companies continued to use the mineral thus exposing thousands of construction workers, military members, and others. Because of the industry's efforts to profit off of a substance they knew to be dangerous, US courts have established asbestos trusts in the amount of $30 billion. These trusts are meant to compensate victims who developed cancer after exposure. Most asbestos settlements are tied to the costs of related medical expenses. Where a plaintiff can prove that a manufacturer actively concealed the dangerous nature of their product or where they failed to provide adequate worker protections, the damages can be much higher.Maryland Asbestos History
Maryland holds a unique place in the history of asbestos use, exposure, and litigation. The state is home to over 20 asbestos deposits and at least four have been mined. Further, Maryland residents have a statistically increased risk of exposure because of the state's shipyards, power plants, chemical factories, and construction companies that boomed during and after World War II. Overall, Maryland ranks 16th in a nationwide survey of mesothelioma cases. There were 1,074 mesothelioma deaths from 1979-2001. At least 553 - more than half - of these fatalities were in Baltimore.
Maryland has a statute of limitations for asbestos claims that applies to injured parties as well as their heirs. The statute begins to run when the plaintiff has knowledge of the asbestos- related injury. If you or a relative have been exposed to asbestos, we encourage quick action to ensure that your claim can be considered.
Strict liability - also called "enterprise liability" or "absolute legal responsibility" is when a defendant has legal responsibility for damages or injures regardless of whether or not the person or company was at fault for the harm caused. In its pure form, it means that the defendant is responsible for the plaintiffs losses even if they did absolutely nothing wrong.


A Fulbright Teacher in Bogota, Colombia, A Special Series – Air Travel in Colombia – by Laura Blasena. The North Star Reports: Global Citizenship and Digital Literacy, at NorthStarReports.org and facebook.com/NorthStarReports
Colombia isn’t a big country. About 1.15 km2. For comparison (because that number means very little by itself), the United States is about 9.85 km2.
Therefore, traveling using the country’s extensive private bus companies is easy, right? Wrong. The issues is that three giant ridges of the Andes mountains run right through Colombia, meaning that, historically, ground travel in the country was an issue (which lead to the huge regional differences that we see today) and remains an issue today.
(The different regions of Colombia presented on a clay map made by one of my elementary students. Learning the geography of the country seems to be a very integral part of the school system here.)
To get from Bogota…
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At least 40 visible sea stars were alive and well in the Treasure Island tide pools in South Laguna at noon this past Saturday. But by 3 p.m., eight had disintegrated like wet bread.
An epidemic, which has destroyed sea stars along the West Coast beginning last June, has reached the shores of Laguna Beach.
Snorkelers reported finding sea star legs piling up in underwater rocky crevices near Crescent Bay and Shaw’s Coves in North Laguna and rolling eerily along the ocean bottom. The limbs will eventually wash up on shore.
Of 76 sea stars spotted last Sunday at Treasure Island, a quarter of the population exhibited signs of what scientists have named sea star wasting disease, said Jeff Rosaler, director of education and research at the Laguna Ocean Foundation and a Treasure Island tide pool educator.
Scientists categorize sea stars as a “keystone” species, which means they keep their prey – mussels, snails and urchins — in check. Without them, as with the extinction of other species, the balance of nature runs amuck. Urchins have been known to overpopulate and do deadly damage to local kelp forests.
In the tide pools on Sunday, observers watched as legs fell off the sea stars, their bodies split in half, small lesions became rips in the sea stars’ spiky skin, and white flesh and orange gills spilled out.
An octopus, about 15 inches long, crept out from under a nearby rock and tore a dangling leg off a melting sea star. The next day, only the empty external skeleton of two limbs remained. Seagulls fought and feasted over other dismantled sea stars lodged in rock crannies.
While the affliction is not an anomaly, scientists are stumped and finding the massive outbreak “particularly troubling,” said Pete Raimondi, of UC Santa Cruz, who is the lead investigator into the disease.
In the past, unusually warm water caused the wasting of sea stars, particularly during an El Nino, but that’s clearly not the case this time, said Raimondi. “That’s what’s so concerning about this. In the past, when the die-off was associated with warm water, you had this idea that things would get back to normal. But it’s not warm water. We’re in a cool water period.” Sea stars usually thrive in normally cool Pacific Ocean temperatures.
Also disturbing to Raimondi is how far the disease is spreading and the number of sea stars it’s affecting.
The culprit is believed to be an infectious microorganism, which appears to be attacking a specific marine species and would not likely affect humans, scientists say. Raimondi said researchers are “pretty clear” what the infectious agent is but they are unsure of its origin and decline to disclose whether it’s naturally occurring or manmade.
“These guys are epidemiologists and they have a protocol that they follow,” said Raimondi. ”They don’t release anything until they follow the protocol. They’re in the process now of challenging organisms. Once that work is done, they’ll be able to release the information.”
The sea star death-rate along the West Coast was described as “catastrophic” by Ian Hewson, an assistant professor in microbiology at New York’s Cornell University, who is collaborating with Raimondi in collecting data and testing possible causes of sea star wasting. Raimondi contributed to a report released last month, published by UCSC’s ecology and evolutionary biology department’s Pacific Rocky Intertidal Monitoring project.
Hewson is overseeing experiments at UCSC and the University of Washington to establish the suspected cause of the disease. Scientists are inoculating two healthy sea stars with possible infectious agents. If healthy sea stars also contract the disease, which could be as soon as two days, the cause will then be definitive and results will be published in scientific journals before being released to the public, which could take up to six weeks.
Tsunami debris and radioactive fallout from the Fukushima nuclear power plant melt-down in Japan have not been entirely ruled out as a cause Hewson said, but Raimondi called it unlikely.
“The path of the debris and presumably the radiation is far to the north of here,” said Raimondi. “It’s mostly in the Pacific Northwest. No one’s been able to detect levels of radiation that are even above background in North America. There’s no possibility at this point that the stuff has gotten here.”
Hewson added that human pollutants are also being considered. “The ocean is really subject to a great deal of human influence,” he said, “everything from run-off and fertilizer use to actual toxicants in various products and treatments that end up in the sea. We haven’t been able to disprove any of these pollutants as a cause.”
Signs of the current epidemic in Laguna were noticed last fall, when water temperatures were more summerlike, hovering around 70 degrees, said Laguna Ocean Foundation’s chair, Louise Thornton.
Over the past two weeks, the mortality rate has become epidemic, said Rosaler, the tide pool educator.
Former episodes of the wasting disease occurred in the early 1980s and late ‘90s. Warm El Nino currents washed in from Mexico and destroyed sea stars as well as the local kelp forests, which were scavenged by ravenous sea urchins that had lost a once-abundant food source.
Biologist Nancy Caruso, who helped replant the 100-acre kelp forest now flourishing off Laguna’s coastline, doesn’t expect a surge in the urchin population or damage to kelp forests because of the die-off of sea stars.
“I don’t see anything going on with the kelp,” she said. “It’s a stress-induced problem with the sea stars and we need to figure out what the stress is.”