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Table of Contents
Residents in remote areas of Alameda and Contra Costa counties were under mandatory evacuation orders Monday morning as firefighers battle a series of lightning-sparked brush fires — one east of Mt. Diablo and the other sout of Sunol.
Alameda County vegetation fire prompts evacuations in Sunol
Alameda County vegetation fire prompts evacuations in Sunol
Alameda County sheriff's deputies evacuated residents on Welch Creek Road near Sunol, about 10 miles south of Pleasonton, on Sunday night, as fire crews respond to three vegetation flare-ups dubbed the Marsh Creek Complex Fire.
The fires, which were burning in the area of Calaveras Road and Welch Creek Road, had spread to about 850 acres and were 0% contained Sunday night. About 10 homes were impacted by the county's evacuation order. There were no reports of injuries to firefighters or members of the community.
In Contra Costa County, sheriff's deputies evacuated residents along Marsh Creek and Morgan Territory roads southeast of Brentwood and north of Livermore, as a cluster of fires broke out Sunday night. Fire officials said the Deer Zone Fires was at least 400 acres Sunday night.
All of Morgan Territory and Marsh Creek roads from Round Valley north west to Deer Valley were ordered to evacuate. Evacuees were told to go to the Community Center in Brentwood at 34 Oak St or the the Clayton Library, 6125 Clayton Rd.
Other significant fires broke out around the region after a wild weather night. In Monterey County, a rapidly growing fire east of Salinas had reached 2,000 acres Sunday night and was threatening 30 structures, with evacuations in place.
Megan Cassidy is a San Francisco Chronicle staff writer. Email: [email protected] Twitter: @meganrcassidy

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Not many 17-year-olds could walk into a dressing room containing such luminaries as Eric Abidal, Sylvain Wiltord, Giovane Elber, Sidney Govou, Michael Essien, Florent Malouda and Mahamadou Diarra and keep their composure. Yet that is exactly what the fresh-faced Karim Benzema did on a January evening back in 2005. In the two years that have elapsed since that initiation into the big time at
Like any newcomer to the
Lyon's French forward Karim Benzema (L) vies with Saint Etienne's Brazilian defender Nivaldo
Although the highly rated rookie showed flashes of brilliance in his first two seasons at the Stade Gerland, he has really come into his own at this the start of
After a spluttering start to the new campaign OL have been indebted to Benzema and his goalscoring instincts, which have helped them go five games unbeaten in the league. Not that the self-effacing hitman is taking all the credit for the sudden upturn in their fortunes. "It's not only been me," he said after firing a hat-trick in a 5-1 demolition of FC Metz. "With the likes of Juninho, Kader Keita, Kim Kallstrom and Ben Arfa we've got a lot of talent in the side and some gifted performers in midfield and at the back too. As for me, well, I don't feel tired at all. I'm hungry to play and collect more match balls. I'm on top of my game." And as the goals continue to come, there can be no arguing with that.
A dream debut
Born in Lyon in December 1987, Benzema joined the youth ranks of his hometown club as a young boy, developing his striking skills through the seasons and making his mark both at domestic and international level, teaming up with fellow wonderboys Samir Nasri, Hatem Ben Arfa and Jeremy Menez to win the UEFA U-17 European Championship with Les Bleus in 2004. His technical qualities and unusually sharp eye for goal soon attracted the interest of the then Lyon coach Paul Le Guen, and even had the experts likening him to Trezeguet for his positional sense, to Thierry Henry for his turn of pace and Nicolas Anelka for his ability to lose his markers and link up with team-mates.
Recognising these gifts Le Guen gave him his first taste of Ligue 1 action towards the end of a meeting with
In the two years that have elapsed since that initiation into the big time at
Keen to break him in gently, Le Guen and his assistants restricted the rising star to six first division appearances that season, one in which the homeboy continued to hone his finishing skills in the club's U-18 team, scoring 12 times in 14 matches.
The following season brought 13 league appearances, a solitary goal and a UEFA Champions League debut against Rosenborg. And just as he did in his maiden Ligue 1 outing, the man known as "Bigbenz" to his team-mates, made another instant impression against the unsuspecting Norwegians, latching onto a Ben Arfa pass on the edge of the penalty box, taking out two defenders with his first touch and slotting the ball just inside the post, proof that he is nothing if not consistent.
He continued his learning curve last term, showing he could compete for a place with Wiltord, Govou, Fred, John Carew and Milan Baros to notch up 21 games in all. His five-goal haul for the season included a vital strike against Dynamo Kiev in October 2006, one that secured his side's place in the last sixteen of the Champions League.
UEFA Euro 2008 the target
While the teenage sensation is developing quickly, there is no doubt that having players of the calibre of Juninho, Wiltord and Govou around makes the job of learning that much easier. "They've got a lot of experience and I listen to them because I know it can really help me," he says. "With Wiltord I learn how to prepare. With 'Juni' it's more about what you do on the pitch, and with
That hard work certainly seems to be paying dividends. The latest coach to be impressed by the Lyon man's attributes is
With less than a year to go to Euro 2008, the newly capped striker knows a productive campaign could well open the door to
It was that same dedication to their trade that took two of the club's idols to the top: Bernard Lacombe, the former France international and now an adviser to OL president Jean-Michel Aulas; and Sonny Anderson, the Brazilian goal machine who played an instrumental part in its first two championship triumphs and who now trains the
Insatiable as ever, the fans at the Stade Gerland are anxious to see another striker of their stature emerge, a goalscorer that can help


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The term "anticonvulsant" is applied to a drug used for the treatment of epileptic seizures, hence, the synonym "antiepileptic." Anticonvulsants are also being used in the treatment of neuropathic pain and as mood stabilizers in the treatment of psychiatric disorders such as bipolar disorder. In this article, the author reviews anticonvulsants as a drug class and their use in conditions other than epilepsy, such as pain and psychiatric disorders. The author also compares the mechanism of action as well as the efficacy of various anticonvulsants.
• Several drugs with different mechanisms of action have anticonvulsant properties and are used as antiepileptics.
• Some of the approved anticonvulsant drugs have been investigated for relief of pain and psychiatric disorders and some of these indications are approved.
• Several clinical trials of anticonvulsant drugs are still ongoing.
• The use of anticonvulsants should be personalized to increase efficacy and safety by matching the right drug to the right patient.
The term "anticonvulsant" is applied to a drug used for the treatment of epileptic seizures, hence, the synonym "antiepileptic," which is often denoted by the abbreviation AED. This term is applied to other agents such as ketogenic diet and procedures such as vagal nerve stimulation when used for control of seizures. Some drugs from other pharmacological categories have anticonvulsant effect, eg, acetazolamide, which is a carbonic anhydrase inhibitor. Anticonvulsants are also being used in the treatment of neuropathic pain and as mood stabilizers in the treatment of psychiatric disorders such as bipolar disorder.
The era of anticonvulsant drugs started with the introduction of bromides in 1857 and was followed by the discovery of the anticonvulsant effect of barbiturates in 1912 (12). Phenytoin (diphenylhydantoin), synthesized in 1908, was not introduced for the treatment of epilepsy until 1938 (27). Although carbamazepine was shown to have antiepileptic properties in 1954, it was first approved in 1968 for the treatment of trigeminal neuralgia and was approved in 1974 for the treatment of epilepsy. Anticonvulsant properties of valproic acid, which is structurally unrelated to other antiepileptic drugs, were discovered by chance in 1963; however, it did not become a major anticonvulsant drug until the 1970s. Older anticonvulsant drugs with new variations are still widely used and remain the mainstay for treatment of epilepsy in developing countries. During the past two decades, several new anticonvulsant drugs have been approved worldwide, and drugs remain the first-line treatment for epilepsy. Several new drugs are in development. Currently approved anticonvulsants include the following:
(1) Brivaracetam
The following drugs in clinical trials have novel modes of action compared to more established antiepileptic drugs: anakinra (a recombinant form of human interleukin-1 receptor antagonist), CVL-865 (a novel GABA modulator), and ganaxolone (a synthetic analog of the endogenous neurosteroid allopregnanolone).
Several of these anticonvulsant drugs are reviewed individually in separate clinical summaries. Use of anticonvulsant drugs in indications other than epilepsy has increased. This article compares various anticonvulsants and describes their uses for indications besides epilepsy.
Pharmacodynamics. The main actions of currently used anticonvulsants are:
(1) Modulation of voltage-gated sodium and calcium channels.
Anticonvulsants in use can be classified according to their predominant mode of action as shown in Table 1, but some drugs have more than one mechanism of action, and some of the mechanisms are not known.
Some of the newer anticonvulsant drugs do not fit into the pattern of mode of actions of older drugs. For example, retigabine primarily acts to stabilize neuronal potassium-gated ion channels (35). Currently, no other marketed anticonvulsant drug shares this mode of action. It has been approved both in Europe and in the United States for the adjunctive treatment of partial-onset seizures in adults.
Sodium channel
Calcium channel
Other mechanisms
Use of anticonvulsants in epilepsy. The primary criterion for the selection of anticonvulsant drugs is the patient's seizure type; determination is largely based on drug studies that assess the drugs' effectiveness for specific seizure types rather than the defined causes of seizures. Despite restriction to partial seizures, the response to an investigational anticonvulsant is quite variable. The reasons for this include: (1) patient-to-patient variation in the metabolism of the drug, (2) variations in the ability of drug to bind to the target, (3) variations in the amount of drug target produced by different individuals, and (4) different pathophysiological events accounting for the same seizure phenotype.
No single anticonvulsant is clearly superior to others. Causes of variability of effects of anticonvulsants include genetic differences, pathogenesis and severity of epilepsy, age, nutritional status, renal and liver function, concomitant illnesses, and drug interactions. An antiepileptic drug that is effective for one type of epilepsy may not be suitable for another type of epilepsy. For example, absence and myoclonic seizures are aggravated by carbamazepine, which is indicated for generalized tonic-clonic and complex partial seizures.
A randomized, unblinded, multicenter, parallel-group clinical trial has compared the quality-of-life (QoL) outcomes over two years following initiation of treatment with standard versus newer antiepileptic drug in adults with new-onset epilepsy (18). QoL was reduced with failure of the initial treatment, continued seizures, and adverse drug reactions with no significant differences between drugs.
Use of anticonvulsants for prophylaxis of seizures due to disorders other than epilepsy. Decision for prophylactic use of anticonvulsants for seizures due to conditions other than epilepsy should be based on available evidence. The following are some examples:
Anticonvulsants for primary and secondary prevention of seizures in viral encephalitis. Although seizures are common in viral encephalitis, no randomized placebo-controlled trial has been reported to evaluate the efficacy of this approach (31). There is insufficient evidence in the literature to support the use of anticonvulsant drugs in viral encephalitis; therefore, there is a need for controlled clinical trials.
Anticonvulsants for seizures in brain tumors. Seizures following brain tumor surgery are well-recognized, but prophylactic use of anticonvulsants is controversial particularly in patients without previous history of seizures. A study has questioned whether the cost and risk of using prophylactic anticonvulsants in postoperative patients with convexity meningiomas and no history of seizures is worth the small benefit (38).
A study that measured the effects of selected antiepileptic drugs on glioblastoma cells lines concluded that ethosuximide, levetiracetam, and vigabatrin should not be used for prophylaxis or short-term treatment of epilepsy in glioblastoma because of their growth enhancement effects (25).
Use of anticonvulsants in preeclampsia. Seizures occurring in preeclampsia denote progression to eclampsia; these seizures are life-threatening and require control by anticonvulsants. Magnesium sulphate more than halves the risk of eclampsia, and a review of controlled clinical trials indicates that it is more effective than other anticonvulsants, such as phenytoin (09).
Use of anticonvulsants in traumatic brain injury. Prophylactic anticonvulsant therapy has been considered in traumatic brain injury because early posttraumatic seizures occur in more than one fifth of patients in the intensive care unit and are associated with secondary brain injury caused by increased intracranial pressure, brain edema, and cerebral metabolic disturbances with adverse outcomes (44).
Effect of anticonvulsants as analgesics. Similarities between the pathophysiological phenomena observed in some epilepsy models and in neuropathic pain models justify the use of anticonvulsants in the symptomatic management of neuropathic pain. Although used for relief of neuropathic pain, anticonvulsant drugs do not seem to influence pain perception in epileptic patients (10). Pain-relieving effects require doses that are in each drug's antiepileptic dose range. Given their diverse chemistries and different patterns of activity in seizure models, it seems exceedingly unlikely that these anticonvulsants are all working on neuropathic pain via the same mechanism. Table 2 shows the mechanism of action as well as indications for use of various anticonvulsant drugs for management of pain.
Mechanism of action
Uses in pain
Slows recovery rate of voltage-gated sodium channels. Stabilization of cell membrane.
First line therapy of trigeminal neuralgia, glossopharyngeal neuralgia
Inhibits repetitive firing of neurons by action at calcium channels
Neuropathic pain, migraine
An epalon that modulates GABA receptors
Modulates sodium channels and interacts with the collapsin-response mediator protein-2
Neuropathic pain, diabetic neuropathy
Inhibits repetitive firing of neurons by action at sodium channels
Neuropathic pain, migraine
Enhances active sodium extrusion and inhibits passive sodium entry, leading to normalization of the sodium gradient and stabilization of the membrane.
Second line therapy of trigeminal neuralgia
Enhancement of GABA-mediated inhibition
Shown to be effective in controlled studies in diabetic neuropathy and postherpetic neuralgia; fibromyalgia
Inhibits repetitive firing of neurons by action at sodium channels
Neuropathic pain
Suppresses repetitive depolarization from injured sensory neurons.
Neuropathic pain, migraine, diabetic neuropathy
Valproic acid
Inhibits repetitive firing of neurons by action at sodium channels
Effect of anticonvulsants in psychiatric disorders. Anticonvulsant drugs are widely used in psychiatric indications. These include mainly alcohol and benzodiazepine withdrawal syndromes, panic and anxiety disorders, dementia, schizophrenia, mood disorders (bipolar affective disorders in particular), and, to some extent, personality disorders. Electroconvulsive therapy can be safely and effectively administered to patients treated with various anticonvulsants, but there is no evidence that combination of the two treatment modalities augments therapeutic efficacy.
Bipolar disorders. The relative neurocognitive effects of the various psychotropic anticonvulsant drugs in patients with bipolar disorder are consistent with relative effects in patients with epilepsy.
Mood disorders. The effectiveness of anticonvulsants in mood disorders raises the question whether the analgesic effects of antiepileptic drugs in patients with neuropathic pain may result, at least in part, from their beneficial effects on mood. For example, gabapentin treatment significantly ameliorates depression, anxiety, fatigue, and other mood symptoms and improves sleep in patients with postherpetic neuralgia and painful diabetic neuropathy.
Alcohol withdrawal. Anticonvulsants have a limited role in the treatment of alcohol withdrawal syndrome. Topiramate is the most widely used anticonvulsant in the treatment of alcohol dependence (06). A systematic review of controlled clinical trials does not provide sufficient evidence in favor of anticonvulsants for the treatment of alcohol withdrawal (28).
Neuroprotective effect of anticonvulsants. Experimental studies have shown neuroprotective effect of some anticonvulsant drugs (19). A randomized trial supports neuroprotective effect of phenytoin in patients with acute optic neuritis at concentrations at which it blocks voltage-gated Na channels selectively (33). However, clinical role of phenytoin as a neuroprotective has not been established.
Levetiracetam has been shown to have a neuroprotective effect in animal models of stroke and traumatic brain injury. Other studies have shown protective effects against cerebral edema and neuronal injury in autologous blood-induced cerebral hemorrhage (17).
Valproic acid, widely used for the treatment of epilepsy, is also used for bipolar disorder and migraine prophylaxis. Heat shock protein 70 induction in cortical neurons by valproic acid as a histone deacetylase inhibitor may contribute to its neuroprotective and therapeutic effects. One review describes the preclinical animal experimental studies as well as human clinical trials of the use of valproic acid in hemorrhagic shock and traumatic brain injury (36). Furthermore, it details the different mechanisms in which valproic acid alters gene expression and shows that valproic acid provides neuroprotection while enhancing survival in hemorrhagic shock and traumatic brain injury with potential for application in combat casualty care.
Pharmacokinetics of anticonvulsants. Pharmacokinetics is described in the articles dealing with individual anticonvulsant drugs.
Therapeutic drug monitoring. This is described along with individual anticonvulsant drugs in other articles. Considerable data have accumulated for the older first-generation antiepileptic drugs (carbamazepine, ethosuximide, phenobarbital, phenytoin, primidone, and valproic acid), and are increasing for the new antiepileptic drugs (brivaracetam, eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, piracetam, pregabalin, rufinamide, stiripentol, sulthiame, tiagabine, topiramate, vigabatrin, and zonisamide). The latest review of these data has concluded that therapeutic drug monitoring is a practical approach in the management of epilepsy because dose adjustments are based on drug concentrations to optimize efficacy and safety (32).
A simple, accurate and cost-effective liquid chromatography-tandem mass spectrometric method is available for simultaneous quantification of 22 anticonvulsant drugs in case of suspected drug abuse and forensic cases (04).
Pharmacogenetics of anticonvulsants. Pharmacogenetic alterations can affect efficacy, tolerability, and safety of anticonvulsants, including variation in genes encoding drug target, drug transport, drug metabolization, and human leucocyte antigen proteins. The current studies associating genes and their variants with seizure control or adverse events have inherent weaknesses and have not provided unifying conclusions. However, several observations (eg, that Asian patients with the HLA allele, HLA-B*1502, are at a higher risk for Stevens-Johnson syndrome when using carbamazepine) are helpful in improving our knowledge of how genetic variation affects the treatment of epilepsy. A better understanding of the genetic influences on epilepsy outcome is key to developing the much-needed new therapeutic strategies for individual patients with epilepsy.
Other categories of drugs with anticonvulsant effects. In addition to the drugs in the recognized category of anticonvulsants, there are drugs in other therapeutic categories that have anticonvulsant effects. Selective serotonin reuptake inhibitors (SSRIs) can reduce seizure frequency in humans, but no clinical trials have been done to test their value as potential anticonvulsant drugs, partly because of isolated case reports of seizures as adverse events during SSRI treatment (16).
Several herbal medicines have been used as anticonvulsants. The active medicinal components of various herbs that have shown anticonvulsant or antiepileptic activity have been reviewed and classified according to structural types such as alkaloids, flavonoids, terpenoids, saponins, and coumarins (43). This may provide the basis for development of new anticonvulsant drugs.
Cannabidiol (a component of the marijuana plant) was approved by the FDA as Epidiolex in 2018 for the treatment of seizures in Lennox-Gastaut syndrome and Dravet syndrome. It is the only form of cannabidiol available by prescription. The mechanisms for cannabidiol's anticonvulsant effects are unclear and likely involve noncannabinoid receptor pathways. An experimental study has shown inhibitory effects of cannabidiol on voltage-dependent sodium currents, which may partially explain its antiseizure activity (11). A double-blind, placebo-controlled trial showed that in patients with Lennox-Gastaut syndrome the addition of cannabidiol at a dose of 10 or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo (07). A double-blind, placebo-controlled, randomized clinical trial showed that cannabidiol significantly reduced seizures associated with tuberous sclerosis complex compared with placebo (NCT02544763) (40). The 25 mg/kg/day dosage had a better safety profile than the 50 mg/kg/day dosage.
Numerous clinical trials in epilepsy have been conducted with newer anticonvulsant drugs, often as add-on to established older drugs. These are described in the clinical summaries for individual anticonvulsants. There are fewer clinical trials comparing monotherapies using various anticonvulsants. Remarks on specific trials are given according to indication categories such as epilepsy, pain, and psychiatric disorders.
Clinical trial databases. Information about current clinical trials can be obtained from various databases accessible on the internet. As of June 2021, the largest number of clinical trials on anticonvulsants were listed on the clinical trial database of the National Institutes of Health, which can be accessed at the following website:www.ClinicalTrials.gov. Of the 3738 clinical trials, the largest numbers involved levetiracetam (255), gabapentin (503), lamotrigine (226), pregabalin (511), and topiramate (305). The rest of the trials concern other anticonvulsants including new drugs in development.
Epilepsy. Carbamazepine has been a drug of choice for the treatment of simple or complex partial seizures and secondary generalized seizures in adults and children. After introduction of vigabatrin, an open prospective trial showed that vigabatrin is safe and effective as primary monotherapy for epilepsy in children, with a similar proportion of side effects as carbamazepine. A systematic review of randomized controlled clinical trials to compare efficacy of antiepileptic drugs for patients with generalized epileptic seizures concluded that lamotrigine, levetiracetam, and topiramate are as effective as valproate for treating generalized tonic-clonic, tonic, and clonic seizures, whereas valproate and ethosuximide are the best options for the treatment of absence seizures (02).
Status epilepticus. As of June 2021, 37 clinical trials of anticonvulsants for status epilepticus are listed on the clinical trials database, which can be accessed at the following website: www.clinicaltrials.gov. The trials compare commonly used anticonvulsant drugs and route of administration (eg, intramuscular vs. intravenous). No prospective randomized trial has shown that any agent or combination of agents is more effective for the treatment of convulsive status epilepticus than a benzodiazepine followed by phenytoin or its prodrug, fosphenytoin.
In the Established Status Epilepticus Treatment Trial (ESETT), a randomized, blinded, adaptive clinical trial on patients with benzodiazepine-refractory status epilepticus, intravenous levetiracetam, fosphenytoin, and valproate each led to cessation of seizures and improved alertness within 1 hour in approximately half the patients, and the 3 drugs were associated with similar incidences of adverse events (Kapur et el 2019). Eventually, the choice of anticonvulsant medication in status epilepticus should be guided by individual patient characteristics.
Pain. Clinical trials with individual anticonvulsant medications for pain are mentioned in the clinical summaries discussing the individual drugs. Most of the trials are in patients with pain refractory to treatment with conventional analgesics. One anticonvulsant agent is usually not compared against another in clinical trials.
Cochrane Database review of clinical trials shows that anticonvulsants reduce migraine frequency by about 1.3 attacks per 28 days compared with placebo--more than double the number of patients for whom migraine frequency is reduced by 50% relative to placebo (29). Sodium valproate/divalproex sodium and topiramate were better than placebo, whereas acetazolamide, clonazepam, lamotrigine, and vigabatrin were not.
A Cochrane review has shown some benefit of pregabalin over placebo in reducing the pain of fibromyalgia (41). No definite conclusions were drawn on the efficacy and safety of gabapentin, lacosamide, and levetiracetam.
Psychiatric disorders. Clinical trials of anticonvulsant disorders are described in the clinical summaries discussing the individual anticonvulsant agents. Few studies that compare one anticonvulsant agent against another in psychiatric disorders.
Anticonvulsant medications have been approved for the treatment of epilepsy, pain, and psychiatric disorders. Details of indications are given in the clinical summaries dealing with individual anticonvulsants.
Several studies of newer anticonvulsants in epilepsy, pain and psychiatric disorders are still ongoing.
Contraindications are specified for each drug individually (see individual clinical summaries for each drug). There are no contraindications for anticonvulsants as a class.
Goals vary according to the disease and anticonvulsant used. Anticonvulsants may be used as monotherapy or polytherapy. Duration varies for acute to chronic, with most of the indications being chronic conditions.
Personalized approach to use of anticonvulsants. Physicians try to match a drug to a patient by trial and error. The final choice may take several months and depends on the efficacy and tolerability of adverse effects. Moreover, there are problems of adverse side effects and failure to control seizures in more than 30% of patients.
Use of therapeutic drug monitoring has demonstrated pharmacokinetic variability of anticonvulsant drugs and a need to individualize the treatment for an optimal outcome. Factors that contribute to pharmacokinetic variability include external factors such as food and comedication, gender, age, and genetic factors, eg, polymorphisms of drug metabolizing enzymes (23).
Control of epilepsy with phenytoin can be a difficult and lengthy process because of the wide range of doses required by different patients and the drug's narrow therapeutic index. Similarly, appropriate doses of carbamazepine take time to determine because of the drug's variable effects on patient metabolism and its potential neurologic side effects. People with epilepsy are genetically different from one another, and some of those differences affect their responses to drugs in a predictable manner. Variants of two genes have been identified that are more likely to be found in patients who required higher dosages of the antiepileptic drugs carbamazepine and phenytoin (39). One variant of the gene that encodes CYP2C9 shows a significant association with the maximum dose of phenytoin taken by patients with epilepsy. Moreover, a variant of a second gene, called SCN1A, with activity in the brain, is found significantly more often in patients on the highest doses of both carbamazepine and phenytoin. SCN1A has been implicated in many inherited forms of epilepsy and is the drug target for phenytoin. Detection of these gene variants might determine, in advance, which patients will need the higher dose and enable a more optimal dose schedule at the start. Otherwise, it could take months to get the seizures under control. These new findings provide a direction for a dosing scheme that could be tested in a clinical trial to assess whether pharmacogenetic testing can improve dosing decisions. Such a trial might also enable physicians to identify patients who might safely take a smaller dose, thereby minimizing their risk for adverse side effects.
In search of a biomarker to predict responses to antiepileptic drugs, a study was conducted in newly diagnosed epileptic patients, drug-resistant patients, as well as healthy controls by using resting-state functional MRI tools to explore changes in spontaneous brain activity (15). Abnormally increased activity in Brodmann area 17 was associated with facilitation of seizure onset in drug-resistant patients, but this was not observed in those with successful control of seizures with an antiepileptic drug. Increased activity in Brodmann area 17 indicates imbalance between brain activation and inhibition and can be considered a predictive biomarker of poor response to antiepileptic drugs.
Anticonvulsant polytherapy. Anticonvulsant drug combinations may be used in the treatment of epilepsy but there are no definite guidelines for this. Combinations of drugs with different mechanisms of action may be more effective than combinations of drugs with the same mechanisms of action. Care should be taken to avoid combinations of drugs with additive toxicity or drug interactions. The most documented combination resulting in synergistic anticonvulsant effect against focal seizures is that of valproic acid and lamotrigine (01).
Anticonvulsants for symptomatic seizures in other neurologic disorders. Frequency of seizures attacks after stroke ranges from 3% up to 60% and there is some controversy about starting use of anticonvulsants after the first seizure. In an open comparative study, in the first group of stroke patients who took anticonvulsants for one year, repeated epileptic attacks were revealed in 27.1% of patients whereas in the other group where there was no treatment with anticonvulsants for one year, repeated attacks were observed in 53.75% of patients (30). These findings favor administration of anticonvulsants after the first seizure in patients after stroke, but controlled studies are needed.
Prophylactic use of anticonvulsants in patients undergoing neurosurgical procedures involving craniotomy, who have no history of seizures, is controversial. There is a wide variation in the rates of seizures because of the variety of lesions treated as well as the types of procedures, and 15% to 50% of patients have been reported to have at least one seizure postoperatively. Routine prophylaxis is often recommended, as a seizure may aggravate the postoperative course. Duration of prophylaxis varies from days to months, but the commonly used anticonvulsant is phenytoin. A study from one center has recommended the prophylactic use of anticonvulsants for one week as safe following uneventful procedures for extradural hematomas and extraaxial brain tumors (20). In case of intraaxial tumors, the duration depends on the nature of lesion as well as the procedure. In case of intraparenchymal hemorrhage, use of anticonvulsant is continued until blood has cleared as determined by brain imaging. Controlled studies are required to assess the usefulness of this approach.
The doses are specified in the individual clinical summaries for each anticonvulsant.
Pediatric. Many of the anticonvulsants used in adults also have been used in children without any extra risk. However, safety of anticonvulsants for the treatment of psychiatric disorders in the pediatric age group is not supported by adequate clinical trials.
Geriatric. The use of anticonvulsants in the elderly for the management of epilepsy is safe.
Renal failure. Treatment of seizures in patients with renal failure, particularly those on dialysis, is challenging. Most anticonvulsants require dosage adjustment according to the degree of renal failure, and extra doses after dialysis (08).
Pregnancy. There is concern about teratogenicity as the incidence of congenital malformations in offspring of women treated with anticonvulsants during pregnancy is somewhat higher than in offspring of women not exposed to these drugs. Most anticonvulsant drugs fall into category C of the United States Food and Drug Administration. Animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate and well-controlled studies in humans. Long-term developmental effects of antiepileptic drugs in children as they grow older are still uncertain. Potential benefits may warrant use of antiepileptic drugs in pregnant women despite potential risks.
Scientific data are now becoming available for the use of second generation antiepileptic drugs during epilepsy. Lamotrigine and levetiracetam are considered to have low risks for both anatomical and behavioral teratogenesis (26). Although safety issues are favorable for lamotrigine, its therapeutic concentration may be difficult to maintain during pregnancy as its clearance from the body during pregnancy is increased due to being metabolized by uridine-diphospate glucuronosyl transferase (34).
Analysis of 20 year data from the Australian Pregnancy Register of women on antiepileptic drugs for epilepsy as well other indications showed that polytherapy did not increase fetal hazard unless valproate or topiramate was involved in the combination (42). The use of these two drugs should be avoided in pregnancy unless absolutely required for seizure control. For women on anticonvulsant therapy who are breastfeeding, there are still limited data regarding the degree to which anticonvulsants penetrate into breast milk. In general, women with epilepsy can breastfeed their babies safely with some cautions (14). Phenobarbital and primidone should be avoided, and with ethosuximide, levetiracetam, lamotrigine, topiramate, and zonisamide there is a potential for significant breast milk concentrations.
Anesthesia. There are no anesthetic implications for use of anticonvulsants.
Anticonvulsant drugs may interact with each other as well as with other drugs. These are specified in the individual clinical summaries for each agent.
The adverse effects of anticonvulsants involve practically every system of the body. These are described in the separate clinical summaries of individual anticonvulsants. However, some adverse effects are common to most anticonvulsant agents, for example, adverse skin reactions, dose-related neurotoxicity, and psychiatric complications. Long-term use of anticonvulsants may lead to some metabolic and endocrine disturbances.
Anticonvulsant hypersensitivity syndrome is a rare but potentially fatal adverse drug reaction. Clinical presentations include Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS). Most commonly involved anticonvulsants are the aromatic drugs such as phenytoin, phenobarbital, carbamazepine, and lamotrigine. Nonaromatic drugs, such as benzodiazepines and levetiracetam, are the safer alternatives in these cases (05).
In 2008, the U.S. Food and Drug Administration (FDA) conducted a review of nearly 200 studies on anticonvulsant drugs and concluded that they nearly doubled the risk of suicide compared to placebo, although in absolute terms it was still quite small. The FDA recommended the black box warning, but an expert advisory panel did not support the recommendation. However, the panel agreed on the distribution of medication guides to healthcare providers, outlining the risks of antiepileptic medications and suicidal thoughts.
Drug resistance. Problems with the use of anticonvulsants include loss of efficacy and development of drug resistance. One third of patients with epilepsy develop resistance to drugs, which is associated with an increased risk of death and debilitating psychosocial consequences. The International League Against Epilepsy defined pharmacoresistant epilepsy as the "failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom" (22). Some studies suggest an association of anticonvulsant drugs with increased risk of suicide in epileptic patients, whereas others have reported no association. Evaluation of this topic is complicated because observational studies show that suicide tendencies and depression are not uncommon in epilepsy, and persons with epilepsy have higher risk for suicide than healthy controls (13). However, there is a lack of prospective and longitudinal studies on suicide in epilepsy.
If epilepsy is resistant to multiple anticonvulsant drugs, the mode of resistance is nonspecific, involving drug-efflux transporters. Another mechanism underlying drug resistance in epilepsy may be the same as in cancer: a cellular pump called P-glycoprotein, which protects cells from toxic substances by actively exporting the offending compounds. In epilepsy resistant to phenytoin, low levels of phenytoin have been demonstrated in association with high levels of P-glycoprotein expression, the product of the MDR1 gene. Genotyping differences have been shown between responders and non-responders. Further studies in this direction might eventually enable the drugs to be tailored to the patient's profile.
Study of brain tissue removed during surgery for epilepsy has shown that the mechanism of action of carbamazepine, use-dependent block of voltage-dependent sodium channels, is completely lost in carbamazepine-resistant patients. Likewise, seizure activity elicited in human hippocampal slices is insensitive to carbamazepine. In marked contrast, carbamazepine-induced use-dependent block of sodium channels blocks seizure activity in vitro in patients clinically responsive to this drug. These observations suggest that the study of changes in ion channel pharmacology and their contribution to the loss of anticonvulsant drug efficacy in human epilepsy may provide an important impetus for the development of novel anticonvulsants specifically targeted to modified ion channels in the epileptic brain. It is possible to use human tissue for the demonstration of drug resistance in an in vitro preparation, providing a unique tool in the search for novel, more efficient anticonvulsants.
Studies of the properties of transmitter receptors of tissues removed during surgical treatment of drug-resistant temporal lobe epilepsy showed use-dependent downregulation of neocortical GABAA-receptor. This represents a temporal lobe epilepsy-specific dysfunction in contrast to stable GABAA-receptor function in the cell membranes isolated from the temporal lobe of temporal lobe epilepsy patients afflicted with neoplastic, traumatic, or ischemic temporal lesions and can be antagonized by brain-derived neurotrophic factor. These findings may help to develop new treatments for drug-resistant temporal lobe epilepsy.
Nanoparticulate formulations of antiepileptic drugs can be used as drug carriers to the brain with pharmacoresistant seizures and P-glycoprotein overexpression. Phenytoin carried by silica core iron oxide nanoparticles reduces the expression of pharmacoresistant seizures in rats (24).
Management. Treatment of adverse effects of anticonvulsants usually requires discontinuation of the offending agent and replacement with one that is better tolerated.
Concluding remarks and future prospects for anticonvulsants. Despite the large number of anticonvulsants available, there are considerable unmet needs in the management of epilepsy, eg, drug-resistant epilepsy. Newer drugs for epilepsy are still being approved. In 2016, the FDA approved brivaracetam as an add-on treatment to other medications to treat partial onset seizures in patients 16 years of age and older with epilepsy. Brivaracetam, a high-affinity synaptic vesicle protein 2A ligand, is reported to be 10- to 30-fold more potent than levetiracetam. It inhibits neuronal voltage-gated sodium channels as a partial antagonist (03). A multicenter, retrospective cohort study of brivaracetam in patients with genetic generalized epilepsies showed that it was well tolerated, with 50% responder rates like those observed in focal epilepsies, and that an immediate switch from levetiracetam to brivaracetam at a ratio of 15 to 1 is feasible (37).
Most conventional anticonvulsant drugs are directed at symptomatic control of seizures with much less effect on disease modification and neuroprotection. New antiepileptic drug discovery efforts aim to identify novel drugs that interfere with the underlying mechanisms of epilepsy. Advances in biotechnology with improved understanding of genetics and molecular pathophysiology of epilepsies will contribute to these efforts.
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
K K Jain MD†
Dr. Jain was a consultant in neurology and had no relevant financial relationships to disclose.See Profile
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Convocation 2013: the legacy of Harold Innis
It's not every day that a student graduates from a college named after his great grandfather at the University of Toronto.
On June 18, Innis College enjoyed a memorable visit from the family of the late Harold Innis, the influential scholar for whom the college is named, when Ken Cates entered Convocation Hall to receive his Bachelor of Arts degree.
The family travelled from far and wide to attend the College's convocation, meeting with President David Naylor, Chancellor Emeritus David Peterson and Chancellor Michael Wilson before the ceremony.
Harold Innis' legacy is deeply rooted in the University of Toronto, where he burnished his reputation as an influential professor of political economy and an internationally-renowned communications scholar. Considered to be one of Canada's most original thinkers, his novel ideas formed the basis of many of the works he authored on media, communication theory and Canadian economic history. Innis' writings on communication explore the role of media in shaping the culture and development of civilizations – predating and influencing the work of his colleague, Marshall McLuhan.
One of Innis' greatest admirers was his daughter, Mary Innis Cates, who followed in her father's footsteps by studying political science and economics and graduating from UofT in 1949. In fact, all four of the Innis children would go on to graduate from the University between 1943 and 1956.
Mary's connection to Innis College, and the wider U of T community, reaches far beyond the shared name and this visit was an occasion to reconnect with the College and its students, faculty and staff.
"One comment my father often made was 'The pursuit of truth is the persistence of doubt'," said Cates. "For me, seeing the vibrant young people and the huge success of Innis College was overwhelming.
"Knowing his beginnings as a farm boy living with no electricity, no running water, no indoor plumbing, and the culmination of his life and work embodied in the College is truly inspiring and gratifying for the family. "
The College also welcomed her four children who had travelled from as far as Tottori, Japan to be in attendance. With Innis College preparing to celebrate the 50th Anniversary of its founding next year, Principal Janet Paterson reflected on the historic visit and its meaning.
"It was a unique and truly special honour to welcome the Harold Innis family to the College," said Paterson. "It was a very proud moment for us, as few Colleges can claim such a distinctive personal link to their history and their identity, particularly one that bridges past and present so fittingly."
Ennis Blentic is a writer with Innis College at the University of Toronto


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65 Sad Clown Tattoos
In general, we typically see clowns in one of two ways—happy or absolutely terrifying. However, today we're talking about sad clowns. Sad clowns are frequently depicted in art and there's even the famous song, "The Tears of a Clown" by Smokey Robinson and The Miracles about them.
But there's more to sad clowns than haunting paintings or a hit song. The sad clown paradox is the contradictory connection between comedy and mental illnesses such as depression. Many comedians source their humor from dark places and use it as an outlet. Often times, this trauma revolves around early childhood, school or family relations. Several well known comedians have discussed the hardships they experienced early in life and why they leaned into comedy, notably Tommy Smothers, Johnny Carson, Woody Allen and Norman Lear. It just goes to show that there can be more to a comedian than the funny jokes they include in their sets or specials.
Comedians or not, many have taken the paradox head on through symbolic tattoos. Take a look at 65 of our favorite sad clown tattoos in the gallery below and let us know your favorite piece from this list in the comments section on social media.


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Reimagined in a daring display of natural beauty, Greenhill Farm is a modern-day retreat that elevates the standard for sophisticated country living. Surrounded by open fields and mature trees, Greenhill Farm is a project focused on the use of authentic materials while emphasizing stylistic sight lines. Luxury home specialists Patrick Pastella and Kanitha Burns of PASTELLA | BURNS sought to create Greenhill Farm, their private Solebury residence, into a home that unifies the original homes purist form with modern additions showcasing uncompromising interiors. The design and building approach went unrestricted and emphasizes the juxtaposition of old vs new and raw vs refined. Distinctive features of Greenhill Farm include the use of highly distressed wood, shadow line walls, large format porcelain and customized adobe plastering techniques throughout the homes interior. The designer kitchen is entirely customized with a 16' island. Over 11 slabs of granite weighing nearly 7,000lbs were used to create the kitchen's designer features and stone mitered ends. The porcelain floors extend across the home with radiant heat throughout. The vanities are all designer pieces from Barcelona, Spain. Fixtures utilized include luxury brands such as Dorn Bracht, Badeloft and BOCCI to name a few. The main residence consists of over 6,100 square feet of interior space with two additional guest houses and studio building. The property also boasts a large timber framed barn from the 1850's. Lose yourself walking the property's forrest and meadow trails. Greenhill Farm is stately, sexy and a master class in what is possible in a luxury home. To the core, this home is a country-side retreat fit for decerning homeowners seeking an escape from the rigors of daily life
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I didnt skew your reading but rather simplified
Reader comment on item: Claiming Jerusalem is in the Koran
Submitted by Shmuel Froman (United Kingdom), Sep 18, 2015 at 12:34
Hello, I merely simplified your reading of al isra by using "haram" and "aqsa" for the ease of my reading, yes I agree I should have used the definite article. Anyway, I have no issue with your reading of what al haram and al aqsa are. But still, I wonder what your thoughts are on my previous post.
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A massive redevelopment of Vancouver's oldest mall – one that will remake a largely single-family neighbourhood in the centre of the city – is expected to take a major step toward reality this week.
Councillors will decide Tuesday on whether to send the project to a public hearing. The planners for Oakridge Centre envision transforming the 12-hectare site into a mixed-use village, with 2,900 new apartment units (290 of them subsidized social housing, 290 market rental), a nine-acre park with a mini-lake that will sit on the roof of the mall and a main-street-style retail strip. The project will also include a community centre, a library, a daycare, a seniors' centre and more retail and office space.
"For me as a planner, this is the right location for a significant amount of density," said Vancouver's general manager of planning, Brian Jackson, who has recommended the project go to a public hearing. "It's at a crossroads of the city, one that's been identified as one of the major retail and commercial hubs."
The project's developers, Ivanhoe Cambridge, a Quebec-based credit union, and local developer Westbank Projects Corporation have been asked to put in an unprecedented $148-million in community amenities. That's significantly up from the $90-million talked about a year ago after the plan was first presented to council. As well, the developers have to pay $46-million in developer levies and $8-million toward the city's public-art fund.
That bump has meant more social-housing and market-rental units in the project than outlined last year, a bigger community centre, and a larger, more accessible rooftop park.
"The public benefits have been increased dramatically," said project architect Gregory Henriquez. "I think it's an exceptional piece of city-making. And if we're going to save the planet, other parts of the city have to densify besides downtown."
In an effort to sell the project, the developers have had a public-outreach team camped out at the Oakridge mall most Saturdays over the past year to talk to passersby, reaching more than 30,000 people.
But the $1.5-billion project has also generated dedicated bands of opponents aghast at such a dramatic change to a suburban-feeling neighbourhood in the city. The Oakridge opponents are among the many groups that have formed in recent years, unhappy about the increased development pressure – and the city planning to increase population density – they're feeling like builders have run out of available room in the downtown.
Those groups will be lining up to object to the new Oakridge plan at the anticipated public hearing beginning in March, said Allan Buium of the Riley-South Cambie community committee, as he once again looked over the Oakridge model on display at the mall last weekend.
"They have not improved anything. And this is too much – we're on our way to being Metrotown," said Mr. Buium. Like many, he said one of the main problems is that, even though the project is being sold as a transit-oriented development, the transit line it's built on is already jammed.
Development consultant Gary Pooni said current overcrowding on the Canada Line and increased traffic congestion were the two main concerns people brought up repeatedly.
Mr. Pooni said the majority of people who have looked at the model and plans are excited about what they see.
"They love having the mall as an actual amenity for people. It becomes a place to do more than just shop. People do think it's a good place for density. But traffic and the Canada Line – those are the two biggest questions we have."
That kind of reaction was on display among the non-aligned, casual visitors who dropped by last weekend.
Wan Rahardja, looking over the model with a toddler in his arms, was mostly approving.
"I think it's quite exciting. This mall is quite limited."
Senior Penny O'Donnell was just relieved to see that the seniors' centre had been moved from a second-floor spot to ground level in the new version. She did wonder, though, "what they'll do with all the people."
And Richmond resident Brett Tolley, who has seen massive development around the Canada Line in his municipality as well, was gloomily resigned.
"It's Vancouver in 2014, I guess. It's typical overdensification, with as many condos as they can jam in. There seems to be no thought to transportation or planning."


text:
Is horticulture a cause worth supporting?
By Andy McIndoe •
Perennial started life as the Gardeners' Royal Benevolent Institution back in 1839 as a pension fund for head gardeners. It was founded by wealthy landowners who wanted to offer their loyal gardeners something more than a handshake on retiring from service. You can read more about the history of Perennial here: http://perennial.org.uk/home/about-us/our-history/. Now in its 175th year, Perennial is one of the only charities in the world to offer those of us working in the horticulture industry help, advice and support in times of need.
Horticulturists – and by that I mean professionals who garden, landscape, design, prune, chop, tend, mow, measure, grow and sow for a living are not well-paid by all accounts. I heard Alan Titchmarsh, President, speak at Perennial's 175th anniversary party back in January, and he described gardening for a living as a 'calling'; I have to agree. What's more, it's high risk – especially if you have to use heavy machinery, climb trees with a chainsaw or spend your working life lifting heavy bales of compost or lugging tree roots around. Although horticulture is a healthy outdoor career, the work can eventually take its toll.
But in a low paid, high-risk industry, there's little chance of decent pension or the opportunity to put any aside in case of injury, illness or poor health in later life; this is where Perennial comes in. Dedicated case workers are trained to give specialist financial, debt, housing and social care advice to anyone working in or retired from horticulture. On contacting the charity for help you can expect a call back within three days and a caseworker visit within two weeks. Last year Perennial helped over 1,200 people assisting its clients in accessing over £1.5m in direct financial help. Not bad for a charity you've never heard of!
The Perennial 175th Birthday party in January certainly helped to raise the profile of the charity within the horticulture industry itself. Many of us know of its existence but might struggle to describe what it does. HRH Princess Alexandra, KG, GCVO Patron of Perennial, takes a great interest and her presence at the party certainly helped to endorse the importance of this charity.
In terms of activities I had little idea of how many events and activities go on during the year to raise funds for Perennial. In 2014 I pledged to help Perennial raise awareness of the importance of its work for all horticulturists by opening my garden to visitors for the evening. This event is now sold out, but there are plenty more 175th anniversary Special Events to choose from. Visit the website http://perennial.org.uk/ and find out more.
Garden retailers regularly hold charity events to attract customers and 'give something back' to the local community. They almost always choose a local charity or one that is likely to directly help their customers. They rarely choose to support the very charity that exists to look after their own staff, suppliers and contractors, maybe because it is just too difficult to explain.
But without those people who have chosen horticulture as their career our environment would be immeasurably poorer. I believe it's important we keep them fit, healthy and look after them in times of need. I find it encouraging that more industry stalwarts are getting behind the charity through partnerships, fundraisers and support in kind at flower shows and events.
I'm looking forward to seeing Jo Thompson's floral exhibit at The Chelsea Flower Show and the Perennial gardens at Harrogate Spring Flower Show and Gardening Scotland. And I've been following the antics of the #grubbygardeners on Twitter – a team of horticulturists, who have pledged to raise £20K for Perennial this year. A fantastic £5.5K has been raised so far, and you can make a donation to the team here: http://www.justgiving.com/teams/grubby-gardeners
So is horticulture a cause worth supporting? Of course it is. I would love to know of other organizations dedicated to helping horticulturists wherever you are so please post your comments below. Also do find out more about Perennial by visiting: www.perennial.org.uk
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tag:blogger.com,1999:blog-2011194091106156925.post1236586015618052073..comments2022-12-04T18:13:03.079-08:00Comments on Sillyinvestor: Coporate updates: Further liquidation of portfolio email@example.com:blogger.com,1999:blog-2011194091106156925.post-91035466455673224202021-05-18T02:26:09.872-07:002021-05-18T02:26:09.872-07:00Do you need to increase your credit score? Do you ...Do you need to increase your credit score?
Do you intend to upgrade your school grade?
Do you want to hack your cheating spouse Email, whatsapp, Facebook, instagram or any social network?
Do you need any information concerning any database.
Do you need to retrieve deleted files?
Do you need to clear your criminal records or DMV?
Do you want to remove any site or link from any blog?
you should contact this hacker, he is reliable and good at the hack jobs..
contact : cybergoldenhacker at gmail dot com
felisha greenhttps://firstname.lastname@example.com:blogger.com,1999:blog-2011194091106156925.post-64116867953956193052017-03-08T06:01:40.921-08:002017-03-08T06:01:40.921-08:00Hi B, I like your analogy of casting the net and ...Hi B,

I like your analogy of casting the net and harvesting

I hope younger and more beginning investors have this in mind when reading blogs. Then we all cast and keep at different times and we fish at different depths. Some go for big fish "in deep water", some scope the surface.

I was at a point 90% vested too; some good call and some bad call. Before Brexit, I was almost 100% vested during black Monday. Brexit scare the shit out of me and I seldom do more than 80% then.

Sillyinvestorhttps://firstname.lastname@example.com:blogger.com,1999:blog-2011194091106156925.post-23776711142965410982017-03-08T05:30:12.614-08:002017-03-08T05:30:12.614-08:00Hi SI Congrats on the gains. Privatization offer...Hi SI

Congrats on the gains.

Privatization offer soon. Special dividend.

Like LP, I am also still casting my net wide (currently 90% vested). Probably will harvest soon enough also :DBhttps://email@example.com:blogger.com,1999:blog-2011194091106156925.post-3162115120752567032017-03-08T05:02:01.426-08:002017-03-08T05:02:01.426-08:00Oh one more thing. Even if we lock in 40% gain an...Oh one more thing.

Even if we lock in 40% gain and cut loss at 15%. Our returns are forgettable if we cut twice and take profits once. Worse!! Cut thrice and take profits once. Go fly card if only cut anf cut but no take profits Sillyinvestorhttps://email@example.com:blogger.com,1999:blog-2011194091106156925.post-64111816275494114292017-03-08T04:04:05.551-08:002017-03-08T04:04:05.551-08:00SMOL, I be very honest with u. I didn't inten...SMOL,

I be very honest with u. I didn't intent to sell Venture, I was caught out by the advance order.

I remember very clearly I already cancel the order. But I guess when u have order for 7 days, u need to cancel everyday?

Because when Venture price recovered, it got sold off.

Nvm. I already think I know what I will do next time. If I really like it so much, I will just get it back at the same price later. I dun think it will cheong further Sillyinvestorhttps://firstname.lastname@example.com:blogger.com,1999:blog-2011194091106156925.post-10929749891901483582017-03-08T04:00:45.634-08:002017-03-08T04:00:45.634-08:00Wow, I remember you do guerilla tactics. This mu...Wow,

I remember you do guerilla tactics. This must be a prime target involving heavy artillery and one that will cripple Mr Market. LOL

BO chio, I can be a pest ally, take the loot but watch the fighting ...

May u have bountiful harvest Sillyinvestorhttps://firstname.lastname@example.com:blogger.com,1999:blog-2011194091106156925.post-54101944773519382492017-03-08T00:57:10.376-08:002017-03-08T00:57:10.376-08:00Hi SI, Wah, got declare special dividends or not?...Hi SI,

Wah, got declare special dividends or not? :)

I'm still on buying spree, and now about 30% cash. I let my net out to the open sea, still not time to retrieve the net and capture my harvest yet :)la papillionhttps://firstname.lastname@example.com:blogger.com,1999:blog-2011194091106156925.post-72591960579632074922017-03-07T20:15:15.488-08:002017-03-07T20:15:15.488-08:00Sillyinvestor, "Think over the next few year...Sillyinvestor,

"Think over the next few years, I will concentrate on savings rate than investment rate if no opportunity present itself."

Now this statement displayed a lot of wisdom for someone with a "silly" nick ;)

P.S. Lock in profits at above 30% plus. If can cut-loss within -15%, you'll come out on top in the long term.

Much better than profit 15% plus; realised losses -30% plus ;)

You know your math!Singapore Man of Leisurehttps://firstname.lastname@example.com:blogger.com,1999:blog-2011194091106156925.post-51852972244564110112017-03-07T14:48:27.727-08:002017-03-07T14:48:27.727-08:00Hi Farmer, Thank you very much. Trump is making e...Hi Farmer,

Thank you very much. Trump is making everyone having a honeymoon. I bet u throw a stone and u will hit an investor with profits.

Think over the next few years, I will concentrate on savings rate than investment rate if no opportunity present itself. Sillyinvestorhttps://firstname.lastname@example.com:blogger.com,1999:blog-2011194091106156925.post-215168577177475352017-03-07T06:26:44.612-08:002017-03-07T06:26:44.612-08:00Hi SI, Congrats on your profit in YZJ and Venture...Hi SI,

Congrats on your profit in YZJ and Venture. Hmm, more and more companies delisting from SG...Passive Income Farmerhttps://firstname.lastname@example.com


text:
Business Driven.
People Focused.
Business Driven. People Focused.
Global competition for businesses, jobs and talent has never been more intense. As a valued member of the local business community, we need your help to ensure the continued prosperity of Chemung County and the greater region.
ENGAGE 2026 is a carefully designed, 5-year economic development plan to ensure our existing companies continue to grow right here at home. It also looks to attract companies and people to join our community and create the conditions that will encourage them to stay. You can read more about the plan's five strategic initiatives and performance measures in this online brochure.
Your leadership and investment in ENGAGE 2026 is critical. Local private sector leaders must be actively involved in solving challenges and building synergy around the right solutions for our community. We can't afford to leave our growth up to chance.
Please contact us to learn more about how you can join the effort.
Anders Tomson, Co-Chair Chemung Canal Trust Company
Dawn Burlew, Co-Chair Corning Incorporated
Joseph Roman, President [email protected]
Jill Koski, Vice President [email protected]


text:
[Editor's Note: To preview this week's football games, Sports Editor, Phillip B. Hubbard introduces a brand new series called "Phil's Pregame Points." For each game, he briefly breaks down what he believes each team needs to do to better their chances at a win.]
Alcovy @ Lakeside (Evans)
533 Blue Ridge Dr.,
Evans, GA 30809
Kickoff at 7:30 p.m.
Last matchup:
2020 Alcovy won 35-0
• Maintain offensive rhythm
- Alcovy came out of the gate against Grovetown firing on all cylinders. After just the first quarter, the Tigers held a 20-0 advantage. However, they didn't score another point until 50 seconds before halftime. If Alcovy wants to pick up its third win of the season, it'll need to clean up those lapses on offense. Those could have a huge impact on the outcome of the game.
• Defense struggle in third quarter
- On Friday night, the Tigers defense allowed all of Grovetown's 20 points in the third quarter. This was totally opposite to how Alcovy came out in the first quarter. The Tigers need to keep their intensity coming out of halftime as they do starting the game.
Newton vs. Mill Creek
Sharp Stadium
Kickoff at 7:30 p.m.
Last matchup:
2020 Mill Creek won 31-0
• Go with what got you here
- Going into last Friday, the Rams had only lost one game and were undefeated in region play. It's largely been due to the running committee led by Rontravious Perry, Zion Johnson and Jevarra Martin Jr. However, Newton seemed to have an identity crisis at Brookwood with a bunch of different formations. If the Rams want to get back in the win column, they need to get back with what has worked.
• Feed off homecoming energy
- Every local team has lost its homecoming game this season. Newton, I'm sure, will want to break that streak. The Rams need to feed off the energy that Sharp Stadium will be filled with to help improve to 5-2.
Social Circle @ Commerce
272 Lakeview Dr.,
Commerce, GA 30529
Kickoff at 7:30 p.m.
Last matchup:
2020 Commerce won 48-22
• Forget 1-point loss
- The bye week helps with this, but it is still worth noting. The last time Social Circle was on the football field, they suffered a last second, 1-point loss to Lincoln County. If the Redskins want to bounce back, they'll have to flush that and move from the loss.
• Learn from Washington-Wilkes
- This will be like a deja vu for the Redskins. Following their first bye week of the season, the Redskins went and played a high powered Washington-Wilkes team on the road. Now, this time, Social Circle will go on the road to face a dominating Commerce team. I know each opponent is different, but the circumstances are similar. Maybe learning from their mistakes against Washington-Wilkes will help the Redskins put up a better fight against Commerce.
Eastside @ Jackson County
152 Jaxco Jct,
Hoschton, GA 30548
Kickoff at 7:30 p.m.
Last matchup:
2020 Eastside won 27-0
• Take advantage of BYE week
- The two weeks prior to Eastside's bye week were brutal for the Eagles, to say the least. They lost 13-6 against Clarke Central in a closely contested matchup and grinded out a 10-9 victory over Loganville. So, the bye week couldn't have come at a better time for Eastside. Now, going on the road to face Jackson County, the Eagles will need their star players like Dallas Johnson and Kenai Grier to make huge contributions. The positive is all of the players should be rested up now having a week off.
• Panthers playing for something more
- It's not homecoming or senior night for Jackson County, but the Eagles should still expect the Panthers to play more passionately. Why? Because Jackson County head coach, Rich McWhorter is just one win away from 300 career victories. I expect that to have the players approaching this Friday's game with a different type of determination. Therefore, Eastside needs to prepare for a more intense battle than a normal matchup with the Panthers would be.


text:
As FIFA World Cup 2022 is approaching, we're kicking off Football Carnival Campaign to celebrate the most impressive moment this year, which is collaborated with BNB Chain, Bitkeep, Space Misfits, Space Falcon, Sakura, Universe Islands, Hydraverse, Sportspace. Football Carnival is the series of 6 World Cup-themed mini events to during the Qatar World Cup for users to participate in this quadrennial sports event.
The participant will get a chance to win a bunch of tokens and exclusive NFTs from Roseon and our partners.
Carnival Period: 09:00 (UTC), November 16th – 09:00 (UTC), December 20th
Total $10,000 prize pools await during the campaign!
Follow Roseon Twitter and Roseon Community to join interesting activities launched during the World Cup (World Cup 2022 Schedule)
Campaign 1: World Cup 2022 Prediction
Campaign Period: 00:00 UTC Nov 18th – 0:00 UTC Dec 18th, 2022
We run a series of guessing score event for each match in Roseon Community:
- Event 1 – World Cup 2022 Champion: Predict the winner (champion) of FIFA World Cup 2022 (in Gleam)
Rewards: $500 worth of prizes for 40 lucky winners (including 600 Rose points to be shared – Exchange Rose points for tokens in Game Center -> Spin2Win; 1 Space Falcon NFT for the fastest correct answer).
Register with Gleam: https://gleam.io/cxSuS/guessing-score
Rules: t.me/Roseon/473823
- Event 2 – Group Winners: Predict the winners of each group via our event post
Rewards: $600 worth of prizes for 30 lucky winners (Including 450 Rose points to be shared for top 30 fastest correct answers – Exchange Rose points for tokens in Game Center -> Spin2Win; 10 Hydraverse NFT for Top 10 fastest correct answer; 1 Space Falcon NFT for 1st correct answer)
How to register: Reply to this telegram post the winner (Top 1) of all groups in World Cup 2022 before 6:00 UTC 28 Nov 2022, in format "Winner group A – Winner group B – … Winner group H"
How to claim:
– Send the email address of your Roseon account & comment link to Telegram admin @Elnino_Nguyn before Dev 10th, 2022.
– Rewards will be distributed on Dec 15th via Roseon app.
- Event 3 – Group Stage Matches: Predict the score of World Cup 2022 matches (Round of 16 – Finals) via our daily event post.
Rewards: $600 worth of prizes for 52 lucky winners (Including 520 Rose points to be shared for top 52 fastest correct answers of 26 matches in World Cup 2022 – Exchange Rose points for tokens in Game Center -> Spin2Win; 10 Hydraverse NFT for 10 lucky answers with correct winner & score; 1 Space Falcon NFT for the fastest correct winner & score).
How to register: To be announced
Rules: To be announced
Turn your notifications on, the details of each match will be announced in our community.
Rewards distribution : Dec 17th via Roseon app.
Join Roseon Community
Celebrate World Cup 2022 with us and Win a share of $10,000 Rewards
Campaign 2: Bobblehead Ball – Soccer Game Tournament
Period: 0:00 UTC November 28th – 0:00 UTC Dec 9th
BobbleHead Ball is a soccer game testing how you use your 'head'. Win the 1v1 matches using some of the most iconic personalities in the crypto space and prove that you are one 'step' ahead the rest by scoring the most goals!
Download Roseon App HERE and play Bobblehead Ball on Game Center.
Whoever earns the highest total score within this campaign period (0:00 UTC November 28th – 0:00 UTC Dec 9th) will be in the top 6. Every Wednesday, we will announce the weekly leaderboard on Telegram Announcements.
The top 6 users who have highest scores will be qualified for Bobblehead Ball – Weekly Championship Round (live on Dec 2nd and December 9th) to share the rewards pool.
🏆 Rewards pool: $1400 worth of NFT prizes
*The rules for the Weekly Championship Round will be announced later.
Campaign 3: Collect to Win
Period: 0:00 UTC November 18th – 0:00 UTC January 1st
Earn Rose Points and participate in Spin2Win to win more prizes. Any user who collect all 5 different "free NFTs" (in Roseon Kicks NFT Collection) from Spin2Win game will receive $500+ worth of tokens and bonus in NFTs from Roseon, Space Falcon, Hydraverse, Sakura, Space Misfit, Sportspace.
5 NFTs in the collection: Roseon Dynamic, Roseon Legacy, Roseon Revolution, Roseon Supremacy, Roseon Marvel. You will receive random 1 of those 5 "free NFT" in Game Center -> Spin2Win
Total winners: 6 winners
Rewards: $400 in tokens & NFT bonus / user
We will collect result of all users and distribute rewards ~14 days after the event ends.
Make sure you download and have your Roseon app account.
Campaign 4:World Cup Meme & Fanart Event
Use partner's mascots, logos and media kits to create the best memes & fanarts with World Cup theme, and share across social media channels with hashtag #RoseonFootballCarnival #WorldCupArtContest
How to register:
1. Create postive artwork/videos about World Cup content/ event referral using mascots/ characters of any event sponsors in the list
2. Share your work to Twitter/ You tube with brief introduction about the project and your idea.
– Dont forget to add hashtag and share the campaign link in your post:
#FIFAWorldCup $ROSN #RoseonFootballCarnival #Free2Play ; Roseon World Cup 2022 Carnival Series: http://ow.ly/BAMO50LIYkG (💰Total $10,000 prize pools)
3. Submit the link of your work at: https://gleam.io/Wy7f7/world-cup-meme-fanart-event
🏆 Reward Pool:
Campaign 5: Deposit Campaign
Period: 0:00 UTC November 18th – 0:00 UTC January 1st
Users deposit any of the tokens from Roseon and our project partner to your wallet in Roseon App, with the minimum value of $100 worth of below tokens, and hold until end of campaign.
List of token: BUSD, BNB, ROSN, SAK, UIM, SMCW, HDV, FCON.
Your transactions will be recorded automatically.
🏆 Rewards: On Jan 3, Roseon will host the livestream to announce winners result. 8 lucky winners will receive $300 worth of token and bonus NFTs each.
Campaign 6: Trading Competition
The trading activity will be announced in December.
And more activities with our partners will be announced on social media channels and community.
Prizes Pool
$10,000 prize pools includes:
- Roseon: $1,000 worth of ROSN, 5 UniCone NFTs and Shop Voucher
- Space Falcon: 20 NFTs and $300 worth of FCON
- Hydraverse: 100 NFT worth of $3000
- Sakura: $1,000 worth of SAK
- Space Misfit: $2,000 worth of SMCW
- Sportspace: $1,000
- Universe Island: $1,000 worth of UIM and 10 character NFTs ($100 each)
Google Play: https://play.google.com/store/apps/details?id=roseon.finance
App Store: https://apps.apple.com/vn/app/roseon-finance/id1559440997
Web app: https://app.roseon.finance/
Roseon is your one-stop crypto lifestyle app with LaunchPad, DeFi and Play-To-Earn Games. We got selected as one of the Top 9 stars in BNB Chain Web3 Stars Accelerator Vietnam.
Roseon is the entire ecosystem covering Roseon's developments in simplifying our users' crypto journey. Our one-stop solution to all crypto needs is accessible via mobile or web, and soon, with our very own metaverse. Our intuitive but user-friendly UI eases the adoption of newcomers to our ecosystem.
Website | Twitter | Litepaper | Telegram | Discord | Facebook
Related Articles
Roseon Launches New Reward Program: Conquer the World of Metaverse Hero Arena for the +$7,000 Rewards
We're launching a reward program with $7,003 in HERA up for grabs!
Join October's Sign-up Bonus and Refer & Earn Campaigns
This October, enjoy our special welcome offer as a thank you for choosing Roseon. Register and receive our special welcome bonus rewards. No KYC required!
Roseon Integrates with OKC (OKX Chain)
Roseon now integrated with OKC, the L1 blockchain backed by one of the top market crypto exchange, OKX.


text:
In this hard-hitting, dark exploration of toxic relationships Tamaki nails the experience of first year university- the good and the bad- with teens gone a little crazy on freedom and alcohol. Allison has good parents, great potential, but a dark past. When she enters her first year at university she is bewildered, unimpressed, and disconnected… Continue reading Painfully Honest: (You) Set Me on Fire Review
Tag: lesbian relationships
New Classic Alert: The Miseducation of Cameron Post Review
I am in love with this book, which falls under my favourite category, Poignant Coming-of-age Story. Cameron Post is the mother of all coming of age stories. I have been unable to stop talking or thinking about since I first read an advance reading copy in September. I have thrust it into the hands of everyone… Continue reading New Classic Alert: The Miseducation of Cameron Post Review


text:
Color Connection Toaster Covers
$4.79 - $6.79
$6.99 - $8.99
$6.99 - $8.99
Save up to 31%
Additional Information
Product Details
Protect your toaster from dust while you're not using it—and add a pop of color to your countertop! Cute, colorful cover fits right over your toaster, and it's easy to pull on or off. Woven polyester/cotton; machine wash. Imported. 2-Slice cover fits toasters up to 10 1/2" w x 7 1/2" h x 7" d. 4-Slice cover fits toasters up to 12" w x 7 1/2" h x 9 1/2" d.
Personalize it!
Name up to 15 letters (apostrophe + s and the word "Kitchen" will be added when personalized)
Personalization location: long side of cover (front on 4-Slice cover)
Personalization technique: Embroidered
Additional Information
Ratings & Reviews
Color Connection Toaster Covers is rated out of 5 by 6.
Rated 3 out of 5 by Denise from Grilled Cheese Toaster I've only used it one time, so far. I burnt my sandwiches, but I'm still experimenting. Putting butter on the outside of the bread is very messy, and I'm trying to figure out a less messy way to do it, and melted cheese gets inside of it, and I can't get to it to clean it out. I like it, but it seems like it's more trouble than it's worth.
Date published: 2022-01-02
Rated 5 out of 5 by Cherubsxo from Perfect fit Inlove the color of this cover and it fits my 4-slice toaster perfectly.
Date published: 2021-11-01
Rated 5 out of 5 by Anonymous from Color Connection Toaster Cover This toaster cover in your choice of colors is perfect for any kitchen. Love it!!
Date published: 2021-10-16
- bvseo_sdk, dw_cartridge, 16.1.1, p_sdk_3.2.0
- CLOUD, getContent, 22ms
- reviews, product
Question & Answer
- bvseo_sdk, dw_cartridge, 16.1.1, p_sdk_3.2.0
- CLOUD, getContent, 5ms
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Sponsored Content


text:
Price: 8,900.00 USD
Bitcoin Miner:
Canaan Avalon A1246 85T ASIC Bitcoin Miner New US STOCK free shipping
Condition:New Model:A1246 85T Compatible Currency:btc, bsv, bch
Voltage:200V-240V 50/60HZ Operating temperature:0~40℃ Noise:≤ 80DB
Connectivity: Power Cord ( IEC C19 ) Power Use(W):3420 W Calculate power rating:85±3%(TH/S)
Color:Silver Total Weight:14.5 kg/32.5lbs Size:331*195*292 mm
New with original box with build in power.
No power cord, if you can send us a picture of your 220V outlet. I can look for a power cord in our warehouse, if you luck enough that will be a gift to you.
Ship from Irvine, California, No headache for the import issues.
Accepted local pick up inspection.
If you would like make a big quantity order, pls feel free to contact us.
We will offer you a best solution.
Warm Reminder: Mining machine is a customized product, which is different from ordinary consumer electronic products. Its function and value are well known to all. Therefore, once sold, no return, no refund no exchange , please be sure to think carefully and make a prudent decision before buying.
If you buy the product, you agree with the policy of "no return, no refund, no exchange". Please purchase carefully.
Warranty: With the SN number in the miner, you can contact the Canaan ask about the warranty information. Also you can get technical support from them if you have any questions.


text:
Hope & Love Radio Coaching is a professional life coaching practice specializing in relationships located in Fresno, CA.
Hope & Love Radio Coaching works through a transformational coaching approach. Through this outlook, support, exercises, new information and feedback will be given to help clients effectively address personal relationship challenges. Additionally, coaching techniques will be integrated to offer a highly-personalized program tailored to you. With compassion and understanding, Hope & Love Radio Coaching works with you to help build on your strengths and helps you attain the relationship you are looking for.