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INTRODUCTION — Neuroleptic malignant syndrome (NMS) is a life threatening neurologic emergency associated with the use of neuroleptic agents and characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia.
Mortality results directly from the dysautonomic manifestations of the disease and from systemic complications. Mortality has declined from the earliest reports in the 1960s of 76 percent and is more recently estimated between 10 and 20 percent [1]. This probably reflects greater awareness of the disease, earlier diagnosis, and more aggressive intervention. Requiring a high clinical suspicion for diagnosis and treatment, NMS is appropriately a syndrome more often considered than truly diagnosed.
EPIDEMIOLOGY — Incidence rates for neuroleptic malignant syndrome (NMS) range from 0.02 to 3 percent among patients taking neuroleptic agents [2,3]. This wide range probably reflects differences in the populations sampled, for example, inpatient versus outpatient psychiatric populations, as well as differences in the surveillance methods and definitions of disease used.
While most patients with NMS are young adults, the syndrome has been described in all age groups from 0.9 to 78 years [2,4-6]. Age is not a risk factor [7]. In most studies, men outnumber women twofold. Both age and gender distributions correspond with the distribution of the exposure to neuroleptic agents [4,7].
Neuroleptic agents — NMS is most often seen with the "typical" high potency neuroleptic agents (eg, haloperidol, fluphenazine) [8-10]. However, every class of neuroleptic drug has been implicated, including the low potency (eg, chlorpromazine) and the newer "atypical" antipsychotic drugs (eg, clozapine, risperidone, olanzapine) as well as antiemetic drugs (eg, metoclopramide, promethazine) [4,11]. Associated medications are listed in the Table (table 1).
While symptoms usually develop during the first two weeks of neuroleptic therapy, the association of the syndrome with drug use is idiosyncratic. NMS can occur after a single dose or after treatment with the same agent at the same dose for many years [12]. It is not a dose-dependent phenomenon, but higher doses are a risk factor [4]. Case-control studies implicate recent or rapid dose escalation, a switch from one agent to another, and parenteral administration as risk factors [1,7,13,14].
Associated risk factors — Case series and case-control studies also suggest that certain psychiatric conditions, acute catatonia, and extreme agitation are over represented in patients who develop NMS [3,13-15]. It is possible that these represent conditions of higher risk simply because of the increased use of higher doses, rapid escalation, and parenteral therapy. Other commonly listed risk factors, concomitant use of lithium or other psychotropic drugs, higher potency agents, depot formulations, comorbid substance abuse or neurologic disease, and acute medical illness (including trauma, surgery, and infection) have not been substantiated in case-control studies [2,4,8,16-18]. It is also unclear whether dehydration, present in 92 percent of patients, is a risk factor for, as well as an early complication of, NMS [4,19].
Antiparkinson medication withdrawal — NMS is also seen in patients treated for parkinsonism in the setting of withdrawal of L-Dopa or dopamine agonist therapy, as well as with dose reductions and a switch from one agent to another [1,3,20]. Infection and surgery are possible precipitants as well [21]. This may be considered a distinctive disorder from NMS and is sometimes called neuroleptic malignant-like syndrome or parkinsonism hyperpyrexia syndrome as well as acute akinesia or the malignant syndrome in Parkinson disease [21,22]. While some report that the clinical syndrome and laboratory findings are milder and the prognosis is better in this disorder [23], more severe cases and even fatalities have been reported [21,24,25].
PATHOGENESIS — The cause of NMS is unknown. Current theories are limited in their ability to explain all clinical manifestations and in supporting data. An animal model for NMS has been developed, but it does not fully correspond with the human syndrome [26,27].
Because of the class of agents with which NMS is associated, dopamine receptor blockade is central to most theories of its pathogenesis. Central dopamine receptor blockade in the hypothalamus may cause hyperthermia and other signs of dysautonomia [28,29]. Interference with nigrostriatal dopamine pathways may lead to Parkinsonian type symptoms such as rigidity and tremor [16,29]. Other neurotransmitter systems (gamma aminobutyric acid, epinephrine, serotonin, and acetylcholine) also appear to be involved, either directly or indirectly [26,30].
An alternative theory is that rigidity and muscle damage represent a primary effect on the peripheral muscle system, perhaps from direct changes in muscle mitochondrial function [16,31]. This in itself may represent a primary skeletal muscle defect or a direct toxic effect by neuroleptics on skeletal muscle.
A primary role has also been proposed for a disrupted modulation of the sympathetic nervous system, manifesting in increased muscle tone and metabolism and unregulated sudomotor and vasomotor activity leading to ineffective heat dissipation, labile blood pressure and heart rate [31]. In this model, dopamine antagonists precipitate symptoms by destabilizing normal dopamine regulation of efferent sympathetic activity.
Familial clusters of NMS suggest a genetic predisposition to the disorder [32]. Genetic studies have shown that the presence of a specific allele of the dopamine D2 receptor gene is over represented in NMS patients [33]. This allele is associated with reduced density and function of dopamine receptors as well as decreased dopaminergic activity and metabolism.
CLINICAL MANIFESTATIONS — NMS is defined by its association with a class of medications that block dopamine transmission and a tetrad of distinctive clinical features: fever, rigidity, mental status changes, and autonomic instability [3,34].
Typical symptoms — The tetrad of NMS symptoms typically evolves over one to three days. Each feature is present in 97 to 100 percent of patients:
- Mental status change is the initial symptom in 82 percent of patients [35]. It is not surprising, given the usual psychiatric comorbidity of the typical patient, that its significance is often underappreciated. This often takes the form of an agitated delirium with confusion rather than psychosis. Catatonic signs and mutism can be prominent. Evolution to profound encephalopathy with stupor and eventual coma is typical [15].
- Muscular rigidity is generalized and is often extreme. The increased tone can be demonstrated by moving the extremities and is characterized by "lead pipe rigidity" or stable resistance through all ranges of movement. Superimposed tremor may lead to a ratcheting quality or a cogwheel phenomenon. Other motor abnormalities include tremor (seen in 45 to 92 percent), and less commonly, dystonia, opisthotonus, trismus, chorea, and other dyskinesias [2,4]. Patients can also have prominent sialorrhea, dysarthria, and dysphagia.
- Hyperthermia is a defining symptom according to many diagnostic criteria. Temperatures of more than 38ºC are typical (87 percent), but even higher temperatures, greater than 40ºC, are common (40 percent) [4].
- Autonomic instability typically takes the form of tachycardia (in 88 percent), labile or high blood pressure (in 61 to 77 percent), and tachypnea (in 73 percent) [2,19]. Dysrhythmias may occur. Diaphoresis is often profuse.
In an analysis of 340 cases, 70 percent of patients followed a typical course of mental status changes appearing first, followed by rigidity, then hyperthermia, and autonomic dysfunction [35]. Some case reports document delay in the appearance of fever of more than 24 hours, leading to initial diagnostic confusion [2]. There is substantial variability in the presentation of NMS, and other reports do not necessarily substantiate a typical course.
Laboratory abnormalities
Elevated serum CK — Laboratory findings often reflect the clinical manifestations of NMS with more severe rigidity leading to more profound creatine kinase (CK) elevation. In NMS, CK is typically more than 1000 IU/L and can be as high as 100,000 IU/L [2,3,16,19,36,37]. Normal CK can be seen if rigidity is not clearly well developed, particularly early in the onset of the syndrome. Elevated CK, particularly in the mild to moderate range, is not specific for NMS and is often seen in patients with acute and chronic psychosis due to intramuscular injections and physical restraints, and sometimes without specific explanation [31,36]. CK levels greater than 1000 IU/L, however, are probably more specific for NMS, and the degree of CK elevation correlates with disease severity and prognosis [2]. A case-control study demonstrated that patients with NMS were more likely to have had elevated CK levels during previous non-NMS admissions than did controls (76 versus 30 percent) [37]. CK levels do usually normalize after an NMS episode.
Other — Other laboratory abnormalities are common but nonspecific.
- A consistent laboratory finding is leukocytosis, with a white blood cell count typically 10,000 to 40,000/mm3 [2,4,19]. A left shift may be present.
- Mild elevations of lactate dehydrogenase, alkaline phosphatase, and liver transaminases are common.
- Electrolyte abnormalities - hypocalcemia, hypomagnesemia, hypo and hypernatremia, hyperkalemia, and metabolic acidosis are frequently observed.
- Myoglobinuric acute renal failure can result from rhabdomyolysis [2,38]. (See "Clinical manifestations and diagnosis of rhabdomyolysis".)
- A low serum iron concentration (mean 5.71 µmol/L; normal 11 to 32 µmol/L) is commonly seen in NMS patients and is a sensitive (92 to 100 percent) but not specific marker for NMS among acutely ill psychiatric patients [19,39].
Atypical cases — There is debate in the literature about milder or atypical cases of NMS. A "forme fruste" of the syndrome has been suggested to occur in milder cases, those associated with lower potency agents, or those diagnosed early on. In particular, rigidity may be milder and perhaps even absent in these situations [40]. While many consider fever to be an essential feature of the diagnosis, cases are reported where it is absent [4]. Complicating this issue is the fact that the isolated appearance of dysautonomia, hyperthermia, Parkinsonian rigidity, and creatine kinase (CK) elevations all occur with antipsychotic therapy. Individually they do not necessarily appear to be a harbinger of NMS [16,41]. From a practical clinical point of view, it seems reasonable to consider the diagnosis when any two of the tetrad of symptoms are present in the setting of an offending agent.
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of NMS can be broadly defined in two categories – those conditions that are related to NMS and those unrelated to NMS but commonly considered in the differential diagnosis.
Related disorders — NMS is one of a group of acute dysautonomias that share common features: rigidity, hyperpyrexia, and dysautonomia [4,6,40,42]. These entities are usually distinguishable if only by the implicated drugs.
Serotonin syndrome — The most commonly diagnosed related disorder is serotonin syndrome [40,43,44]. This is usually caused by use of selective serotonin reuptake inhibitors and has a similar presentation that is difficult to distinguish from NMS [17]. Typical features in these patients that are not often seen in NMS patients are shivering, hyperreflexia, myoclonus, and ataxia [45,46]. Nausea, vomiting, and diarrhea are also a common part of the prodrome in serotonin syndrome and are rarely described in NMS. Rigidity and hyperthermia, when present, are less severe than in patients with NMS. (See "Serotonin syndrome (serotonin toxicity)".)
Malignant hyperthermia — A rare genetic disorder, malignant hyperthermia is distinguished from NMS by its clinical setting - occurring with use of potent halogenated inhalational anesthetic agents and succinylcholine. Its clinical appearance with hyperthermia, muscle rigidity, and dysautonomia is quite similar to NMS although often more fulminant. Studies using muscle contracture testing to evaluate malignant hyperthermia susceptibility among NMS patients have yielded conflicting results, with some finding a high and others a low prevalence of susceptibility. The test may be unreliable in the setting of acute or recent NMS [16,31,42]. (See "Malignant hyperthermia: Clinical diagnosis and management of acute crisis".)
Malignant catatonia — Most problematic in the differential diagnosis of NMS, malignant catatonia shares clinical features of hyperthermia and rigidity with NMS. However, in this syndrome, there is usually a behavioral prodrome of some weeks that is characterized by psychosis, agitation, and catatonic excitement. The motor symptoms are also characterized by more positive phenomena (dystonic posturing, waxy flexibility, and stereotyped repetitive movements) than are described in NMS [47,48]. Laboratory values are more typically normal. The two disorders can be difficult to distinguish clinically, and historical details, particularly in the typical patient population, can be hard to elicit and interpret. The two syndromes may overlap; many case descriptions exist of NMS arising in patients with malignant catatonia [3,15]. One reviewer found it impossible to distinguish between the two disorders in 22 percent of cases [27]. (See "Catatonia in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Malignant catatonia'.)
Other drug-related syndromes — Withdrawal of intrathecal baclofen therapy has been associated with an NMS-like syndrome in several case reports [49]. In these instances, the increased muscle tone is often described as rebound spasticity rather than rigidity. Otherwise, the spectrum of symptoms appears similar to NMS with dysautonomia, altered sensorium, fever, and elevated creatine kinase (CK) levels. Reduced gamma aminobutyric acid activity is believed to be the pathophysiologic cause. The symptoms reverse with reinstitution of therapy, and benzodiazepines may be helpful.
A central anticholinergic syndrome most often associated with intended or inadvertent drug overdose is better known. Patients present with encephalopathy and elevated body temperatures that are usually not as severe as NMS. Other features seen in NMS (diaphoresis, rigidity, and elevated CK levels) are absent here, while atypical features of NMS (flushing, mydriasis, bladder distension) are common. (See "Anticholinergic poisoning", section on 'Clinical features of overdose'.)
Acute intoxication with certain recreational drugs, especially cocaine and ecstasy (3,4-methylenedioxymethamphetamine, MDMA), can be confused with NMS. Both potent stimulants of the central nervous system, these agents are attractive to abusers because they produce heightened vigilance, energy, and euphoria; however, these same effects can also manifest as psychomotor agitation, delirium, and even psychosis. Hyperthermia and rhabdomyolysis can develop, usually in association with increased physical exertion and ambient temperature. Rigidity is not common in these cases. MDMA use can also cause a serotonin syndrome. These syndromes are discussed in detail separately. (See "MDMA (ecstasy) intoxication" and "Cocaine: Acute intoxication" and "Methamphetamine: Acute intoxication".)
Unrelated disorders — Alternative neurologic and medical disorders should be considered in the patient with NMS. Clinical symptoms of these disorders can overlap with NMS, particularly in patients who have extrapyramidal side effects of concomitant neuroleptic use. These diagnoses have serious prognostic and treatment implications and should not be overlooked [9,40]:
- Central nervous system infection (eg, meningitis, encephalitis)
- Systemic infections (eg, pneumonia, sepsis)
- Seizures
- Acute hydrocephalus
- Acute spinal cord injury
- Heat stroke (neuroleptics predispose to heat stroke by impairing thermoregulation)
- Acute dystonia
- Tetanus
- Central nervous system vasculitis
- Thyrotoxicosis
- Pheochromocytoma
- Drug intoxication, toxicity (eg, phencyclidine, ecstasy, cocaine, amphetamines, lithium)
- Withdrawal states
- Acute porphyria
DIAGNOSIS — Although there is no diagnostic test for NMS, testing has a crucial role in the evaluation of patients with potential NMS. Typical laboratory abnormalities help to confirm the clinical diagnosis, some tests rule out other conditions, and others are used to monitor patients for complications of NMS.
In patients with possible NMS, brain imaging studies and lumbar puncture are required to exclude structural brain disease and infection [40]. Magnetic resonance imaging (MRI) and computed tomography (CT) are typically normal. In isolated cases diffuse cerebral edema has been reported in the setting of severe metabolic derangements [50], as well as signal abnormalities in the cerebellum and basal ganglia that are similar to those seen in malignant hyperthermia [51]. Cerebrospinal fluid is usually normal, but a nonspecific elevation in protein is reported in 37 percent of cases [19].
Electroencephalography may be done to rule out nonconvulsive status epilepticus. In NMS patients, generalized slow wave activity is seen [3,19].
An international multispecialty consensus group published diagnostic criteria for NMS in 2011 (table 2) [52]. These are based on positive clinical and laboratory findings as well as the exclusion of alternative causes, each item given a priority score for its relative importance in contributing to the diagnosis. This requires independent validation before its use can be recommended in clinical practice.
Stop causative agent — Removal of the causative agent is the single most important treatment in NMS. Other potential contributing psychotropic agents (lithium, anticholinergic therapy, serotonergic agents) should also be stopped if possible. When the precipitant is discontinuation of dopaminergic therapy, it should be reinstituted.
Supportive care — The need for aggressive and supportive care in NMS is essential and uncontroversial [53]. Complications are common and severe, even fatal. These include:
- Dehydration
- Electrolyte imbalance
- Acute renal failure associated with rhabdomyolysis
- Cardiac arrhythmias including torsades de pointes and cardiac arrest
- Myocardial infarction
- Cardiomyopathy
- Respiratory failure from chest wall rigidity, aspiration pneumonia, pulmonary embolism
- Deep venous thrombophlebitis
- Thrombocytopenia
- Disseminated intravascular coagulation
- Deep venous thrombosis
- Seizures from hyperthermia and metabolic derangements
- Hepatic failure
- Sepsis
The intensive nature of the required monitoring and supportive treatment are such that admission to the intensive care unit is required. The following supportive treatment should be provided:
- Discontinue any neuroleptic agent or precipitating drug.
- Maintain cardiorespiratory stability. Mechanical ventilation, antiarrhythmic agents, or pacemakers may be required [54].
- Maintain euvolemic state using intravenous fluids. Insensible fluid loss from fever and from diaphoresis should also be considered [55]. If CK is very elevated, high volume intravenous fluids with urine alkalinization may help prevent or mitigate renal failure from rhabdomyolysis [56]. (See "Clinical manifestations and diagnosis of rhabdomyolysis".)
- Lower fever using cooling blankets. More aggressive physical measures may be required: ice water gastric lavage and ice packs in the axilla. The use of acetaminophen or aspirin may have a role in reducing temperature in NMS, but it is not established. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults".)
- Lower blood pressure if markedly elevated. The use of any specific agent over another is not supported by clinical data. Clonidine is effective in this setting [57]. Nitroprusside may have advantages by also facilitating cooling through cutaneous vasodilation [58]. (See "Drugs used for the treatment of hypertensive emergencies".)
- Prescribe heparin or low molecular weight heparin for prevention of deep venous thrombosis. (See "Prevention of venous thromboembolic disease in surgical patients".)
- Use benzodiazepines (eg, clonazepam, lorazepam 0.5 to 1.0 mg) to control agitation, if necessary [27].
Specific treatments
Medical therapy — Recommendations for specific medical treatments in NMS are based upon case reports and clinical experience, not upon data from clinical trials. Their efficacy is unclear and disputed [59]. Commonly used agents are dantrolene, bromocriptine, and amantadine.
- Dantrolene is a direct-acting skeletal muscle relaxant and is effective in treating malignant hyperthermia. Doses of 1 to 2.5 mg/kg IV is typically used in adults and can be repeated to a maximum dose of 10 mg/kg/day [60,61]. Efficacy includes reduction of heat production as well as rigidity, and effects are reported within minutes of administration. There is associated risk of hepatotoxicity, and dantrolene should probably be avoided if liver function tests are very abnormal. While some recommend discontinuing it after a few days, others suggest continuing for 10 days followed by a slow taper to minimize relapse [62].
- Bromocriptine, a dopamine agonist, is prescribed to restore lost dopaminergic tone. It is well tolerated in psychotic patients. Doses of 2.5 mg (through nasogastric tube) every six to eight hours are titrated up to a maximum dose of 40 mg/day. It is recommended that this be continued for 10 days after NMS is controlled and then tapered slowly.
- Amantadine has dopaminergic and anticholinergic effects and is used as an alternative to bromocriptine. An initial dose is 100 mg orally or via gastric tube and is titrated upward as needed to a maximum dose of 200 mg every 12 hours.
- Other medications used with anecdotal success include levodopa [29], apomorphine [63], carbamazepine [64], and benzodiazepines (lorazepam or clonazepam) [16,40,65].
The use of any of these medications is controversial and largely unsupported. In an animal model of NMS, dantrolene reduced body temperature, CK levels, and an EMG activation measure of rigidity compared with control [26]. A retrospective analysis of published cases indicates that the use of bromocriptine and/or dantrolene appeared to hasten clinical response [66]. Time to complete recovery was reduced from a mean of 15 days (with supportive care alone) to nine days (with dantrolene) and 10 days (with bromocriptine). Another analysis found reduced mortality: 8.6 percent in patients treated with dantrolene, 7.8 percent in patients treated with bromocriptine, and 5.9 percent in patients treated with amantadine compared with 21 percent in those receiving supportive care alone [67].
These and similar analyses are of questionable validity because of publication and other biases [1,67]. In contrast, a small prospective study in 20 patients showed that dantrolene and/or bromocriptine use was associated with a more prolonged course (9.9 versus 6.8 days) and a higher incidence of sequelae compared with those receiving supportive care alone [68]. However, the findings in this nonrandomized study could be explained by the fact that patients in the treated group were sicker than those not treated.
While evidence supporting the use of these agents is limited, they are frequently used because of anecdotal evidence of efficacy, lack of other proven treatments, and high morbidity and mortality of the disorder.
Electroconvulsive therapy — The rationale for the use of electroconvulsive therapy (ECT) in NMS includes its efficacy in treating malignant catatonia and reports of Parkinsonism improving with ECT. A further impetus for ECT comes from the frequent need for psychotropic therapy in a setting in which neuroleptics cannot be used.
ECT is a reasonable treatment option in NMS; however, there are no prospective, randomized, controlled data supporting its efficacy. A review of published cases found a lower mortality rate in ECT treated patients compared with those receiving supportive care alone (10.3 versus 21 percent) [69]. In another comprehensive literature review, clinical response occurred after an average of 4.1 treatments. However, interpretation of this is complicated by the variable timing of ECT in relation to symptom onset [70]. While these results are interpreted as supporting ECT use in NMS, methodological issues, including publication bias and lack of randomization preclude conclusions about the efficacy of ECT in NMS.
There are safety concerns for ECT in NMS. Cardiovascular complications occurred in 4 of 55 patients including two patients with ventricular fibrillation and cardiac arrest with permanent anoxic brain injury [70]. Another patient had status epilepticus. Other authors also report uncontrolled spontaneous seizures and aspiration pneumonia complicating ECT treatment for NMS [69-71].
The use of ECT in this setting is further challenged by the requirement for anesthesia. Because of concerns for associated malignant hyperthermia, some authors suggest the use of nondepolarizing agents. However, in over 16 reported cases of NMS patients treated with succinylcholine, there was no malignant hyperthermia [16,70]. Succinylcholine may also cause hyperkalemia and cardiac arrhythmias in patients with rhabdomyolysis and autonomic dysfunction [27].
ECT is generally reserved for patients not responding to other treatments or in whom nonpharmacologic psychotropic treatment is needed. (See "Overview of electroconvulsive therapy (ECT) for adults".)
PROGNOSIS — Most episodes resolve within two weeks. Reported mean recovery times are 7 to 11 days [4,19]. Cases persisting for six months with residual catatonia and motor signs are reported [5]. Risk factors for a prolonged course are depot antipsychotic use and concomitant structural brain disease [71]. Most patients recover without neurologic sequelae except where there is severe hypoxia or grossly elevated temperatures for a long duration.
Reported mortality rates for NMS are 5 to 20 percent [1,5,65,72]. Disease severity and the occurrence of medical complications are the strongest predictors of mortality [40]. A systematic review of published cases before 1989 revealed increased mortality in patients with myoglobinuria and renal failure compared with controls (50 versus 18.8 percent) [1]. Patients with organic brain disease including alcohol and drug addiction had a mortality of 38.5 percent. Others have documented lower mortalities associated with higher potency versus lower potency agents [5] and with atypical compared with typical antipsychotic drugs [72].
RESTARTING NEUROLEPTICS — Patients restarted on neuroleptic agents may or may not have a recurrent NMS episode. It is difficult to quantify this risk from the available data. Different case series with variable duration of follow-up and various use of precautionary measures report relapse rates between 10 and 90 percent [1,4,12,73]. Early resumption of neuroleptic therapy, use of high potency, parenteral neuroleptics, and concomitant use of lithium appear to be risk factors for recurrence [4,73]. Recurrent NMS is also idiosyncratic, with reports of patients with no sequelae after early resumption of a high potency neuroleptic, and relapses of NMS occurring on low potency agents up to two years later [12,73].
If neuroleptic medication is required, the following guidelines may minimize risk of NMS recurrence [3,19,73]; none of these guarantee either success or failure.
- Wait at least two weeks before resuming therapy, longer if any clinical residua exist.
- Use lower rather than higher potency agents.
- Start with low doses and titrate upward slowly.
- Avoid concomitant lithium.
- Avoid dehydration.
- Carefully monitor for symptoms of NMS.
SUMMARY AND RECOMMENDATIONS — Neuroleptic malignant syndrome (NMS) is a life threatening neurologic emergency associated with the use of neuroleptic agents and characterized by a distinctive clinical syndrome.
- The diagnosis should be suspected when any two of the four cardinal clinical features, mental status change, rigidity, fever, or dysautonomia, appear in the setting of neuroleptic use or dopamine withdrawal. (See 'Clinical manifestations' above.)
- Important considerations in the differential diagnosis include meningitis, encephalitis, systemic infections, heat stroke, and other drug-induced dysautonomias. (See 'Differential diagnosis' above.)
- Diagnostic testing includes tests to rule out these conditions and laboratory evaluation of common metabolic sequelae of NMS, especially elevated CK. (See 'Diagnosis' above.)
Treatment — The management of patients with NMS should be based upon a hierarchy of clinical severity and diagnostic certainty [3,27]:
- When there is any suspicion of NMS, neuroleptic agents should be withheld. Patients should have close inpatient monitoring of clinical signs and laboratory values. (See 'Supportive care' above.)
- Patients with significant hyperthermia and rigidity should be admitted to an intensive care unit setting and undergo aggressive supportive care as outlined above, as well as monitoring for potential dysautonomia and other complications. (See 'Supportive care' above.)
- In patients with CK elevations or hyperthermia on presentation, or who do not respond to withdrawal of medication and supportive care within the first day or two, the use of dantrolene, bromocriptine, and/or amantadine should be considered. (See 'Specific treatments' above.)
- ECT should be considered in patients not responding to medical therapy in the first week, those in whom residual catatonia persists after other symptoms have resolved, and those in whom lethal catatonia is suspected as an alternative or concomitant disorder. (See 'Electroconvulsive therapy' above.)
- Patients restarted on neuroleptic agents may or may not have a recurrent NMS episode. If neuroleptic medication is required, risk may be minimized by following some general guidelines. (See 'Restarting neuroleptics' above.)
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- Hermesh H, Manor I, Shiloh R, et al. High serum creatinine kinase level: possible risk factor for neuroleptic malignant syndrome. J Clin Psychopharmacol 2002; 22:252.
- Eiser AR, Neff MS, Slifkin RF. Acute myoglobinuric renal failure. A consequence of the neuroleptic malignant syndrome. Arch Intern Med 1982; 142:601.
- Lee JW. Serum iron in catatonia and neuroleptic malignant syndrome. Biol Psychiatry 1998; 44:499.
- Carbone JR. The neuroleptic malignant and serotonin syndromes. Emerg Med Clin North Am 2000; 18:317.
- Hasan S, Buckley P. Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique. Am J Psychiatry 1998; 155:1113.
- Caroff SN, Rosenberg H, Fletcher JE, et al. Malignant hyperthermia susceptibility in neuroleptic malignant syndrome. Anesthesiology 1987; 67:20.
- Bodner RA, Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurology 1995; 45:219.
- Ener RA, Meglathery SB, Van Decker WA, Gallagher RM. Serotonin syndrome and other serotonergic disorders. Pain Med 2003; 4:63.
- Lejoyeux M, Fineyre F, Adès J. The serotonin syndrome. Am J Psychiatry 1992; 149:1410.
- Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148:705.
- Fleischhacker WW, Unterweger B, Kane JM, Hinterhuber H. The neuroleptic malignant syndrome and its differentiation from lethal catatonia. Acta Psychiatr Scand 1990; 81:3.
- Castillo E, Rubin RT, Holsboer-Trachsler E. Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome. Am J Psychiatry 1989; 146:324.
- Coffey RJ, Edgar TS, Francisco GE, et al. Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome. Arch Phys Med Rehabil 2002; 83:735.
- Blasi C, D'Amore F, Levati M, Bandinelli MC. [Neuroleptic malignant syndrome: a neurologic pathology of great interest for the internist]. Ann Ital Med Int 1998; 13:111.
- Lyons JL, Cohen AB. Selective cerebellar and basal ganglia injury in neuroleptic malignant syndrome. J Neuroimaging 2013; 23:240.
- Gurrera RJ, Caroff SN, Cohen A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry 2011; 72:1222.
- Prevention and treatment of heat injury. Med Lett Drugs Ther 2003; 45:58.
- Parry AK, Ormerod LP, Hamlin GW, Saleem PT. Recurrent sinus arrest in association with neuroleptic malignant syndrome. Br J Psychiatry 1994; 164:689.
- Guzé BH, Baxter LR Jr. Current concepts. Neuroleptic malignant syndrome. N Engl J Med 1985; 313:163.
- Lappa A, Podestà M, Capelli O, et al. Successful treatment of a complicated case of neuroleptic malignant syndrome. Intensive Care Med 2002; 28:976.
- Gregorakos L, Thomaides T, Stratouli S, Sakayanni E. The use of clonidine in the management of autonomic overactivity in neuroleptic malignant syndrome. Clin Auton Res 2000; 10:193.
- Blue MG, Schneider SM, Noro S, Fraley DS. Successful treatment of neuroleptic malignant syndrome with sodium nitroprusside. Ann Intern Med 1986; 104:56.
- Reulbach U, Dütsch C, Biermann T, et al. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care 2007; 11:R4.
- Bond WS. Detection and management of the neuroleptic malignant syndrome. Clin Pharm 1984; 3:302.
- Tsutsumi Y, Yamamoto K, Matsuura S, et al. The treatment of neuroleptic malignant syndrome using dantrolene sodium. Psychiatry Clin Neurosci 1998; 52:433.
- Bhanushali MJ, Tuite PJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin 2004; 22:389.
- Wang HC, Hsieh Y. Treatment of neuroleptic malignant syndrome with subcutaneous apomorphine monotherapy. Mov Disord 2001; 16:765.
- Thomas P, Maron M, Rascle C, et al. Carbamazepine in the treatment of neuroleptic malignant syndrome. Biol Psychiatry 1998; 43:303.
- Tural U, Onder E. Clinical and pharmacologic risk factors for neuroleptic malignant syndrome and their association with death. Psychiatry Clin Neurosci 2010; 64:79.
- Rosenberg MR, Green M. Neuroleptic malignant syndrome. Review of response to therapy. Arch Intern Med 1989; 149:1927.
- Sakkas P, Davis JM, Janicak PG, Wang ZY. Drug treatment of the neuroleptic malignant syndrome. Psychopharmacol Bull 1991; 27:381.
- Rosebush PI, Stewart T, Mazurek MF. The treatment of neuroleptic malignant syndrome. Are dantrolene and bromocriptine useful adjuncts to supportive care? Br J Psychiatry 1991; 159:709.
- Davis JM, Janicak PG, Sakkas P, et al. Electroconvulsive Therapy in the Treatment of the Neuroleptic Malignant Syndrome. Convuls Ther 1991; 7:111.
- Trollor JN, Sachdev PS. Electroconvulsive treatment of neuroleptic malignant syndrome: a review and report of cases. Aust N Z J Psychiatry 1999; 33:650.
- Caroff SN, Mann SC, Keck PE Jr, Francis A. Residual catatonic state following neuroleptic malignant syndrome. J Clin Psychopharmacol 2000; 20:257.
- Nakamura M, Yasunaga H, Miyata H, et al. Mortality of neuroleptic malignant syndrome induced by typical and atypical antipsychotic drugs: a propensity-matched analysis from the Japanese Diagnosis Procedure Combination database. J Clin Psychiatry 2012; 73:427.
- Susman VL, Addonizio G. Recurrence of neuroleptic malignant syndrome. J Nerv Ment Dis 1988; 176:234.


text: Good afternoon, at http://www.cs.kent.ac.uk/people/staff/as49/c2hsPatched.tgz you find a patched version 0.13.1 of c2hs that supports precompiled headers. While parsing and name analysis takes as much time as it did before, writing and reading pre-compiled header information is quick. Hence converting several files that are based on the same header file is much quicker because the header is precompiled once and the precompiled header is used several times for each .chs module. AFAIK Manuel's main concern was that it doesn't fit with generating code and conditionals in his newer versions of c2hs since these .chs modules would output a bit of C which has to be translated together with the header file. I took a pragmatic approach to solve this. Suppose you have the header file calls.h and the binding file Calls.chs. The normal way of translating is c2hs call.h Calls.chs or with the newer verions being able to peek into the .chs file to figure out what header file to use you can simply say c2hs Calls.chs Most binding modules (at least those modules I am interested in) do not have conditionals or produce C declarations. For those you can now say c2hs --precomp=calls.h.precomp calls.h giving you a precompiled verison of calls.h. As a second step you say c2hs --precomp=calls.h.precomp Calls.chs which translates Calls.chs using the precompiled header file calls.h.precomp. You may also say c2hs --precomp=calls.h.precomp calls.h Calls.chs which generates the precompiled header and expands the module Calls.chs using the precompiled header. In case Calls.chs contains any C declarations that need to be parsed, the whole header file is parsed as normal (like in the first example) and the precompiled header information is written, but not used. There are a couple of things that need to be addressed: - the precompiled header files are quite large (about 20Mb for Gtk 2) which is mostly due to the file names in identifiers, which are written out for every identifier. Ideally a new string table should be added to the global monad and the String in the file name attribute should be replaced by a UName, which is an index into a string table. The string table of file names can then be written separately and every file name only appears once. I don't understand enough about the structure and the monads in c2hs to estimate how difficult this change is, so I'd rather leave this up to Manuel. - I applied my ForeignPtr patch we use for gtk2hs to correct argument passing of ForeignPtrs which have to be unwrapped and passed as Ptrs. This fix is still broken for newtypes of Ptrs and types without a newtype wrapper. The fix should not be too hard. - I hope the improvement that Duncan found in the token conversion is not yet applied to Manuel's version 0.13.1 since the mentioned version is incredebly slow. This has nothing to do with the precompilation stuff, it was that slow before. - To read files lazily I used memory-mapped read-only files (which are like a big constant). They work great but are not very portable. I put the non-portable bits in SysDepGHC6.hs but haven't bothered to write this code for other compilers and versions. Let me know what you think, Axel.

subset: commoncrawl


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text: I got me HTC Hero last week and ever since I installed the app it has never worked. I have uninstalled & reinstalled several times. Also, the cache is clear, and it is not being effected by my task manager so I know that isn't the problem. It keeps giving me this error message: Unexpected HTTP error occurred code: 501 while StartupAsyncTask Can ANYONE help me with this? I love pandora and I miss it so! lol


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Elvis Light of a Legend Illuminating Framed Canvas Print
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text: These are images of Dark Samus. Artwork From Metroid Prime 2: Echoes.From Metroid Prime 3: Corruption.From Metroid Prime 3: Corruption.Add a photo to this galleryConcept art Various pieces of concept art. From Corruption.Samus Aran vs. Dark Samus in Echoes.Add a photo to this galleryOther Trophy from Super Smash Bros. Brawl.Add a photo to this gallery Retrieved from "http://nintendo.wikia.com/wiki/Dark_Samus/gallery?oldid=417227" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Character galleries


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4807 Culloden Street, Vancouver MLS®: R2123864
NOTE the size of the Lot; 5,112 Sq. Ft. (111.42 ft. X 46.43 ft.) Great location, close to school, transportation and quiet street. Laneway house is possible. 2 Kitchens, suite on the main floor. Appliances have been updated over the years. New and extra wall insulation. House is solid and in good condition, well kept. One car garage and one car carport, with extra parking available.
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I won't post them here, but will provide a link to a disaster cleanup place's website. I've been the one that had the really nasty job of removing bodies from scenes like the ones they show. I warn you, it is pretty gross.
Their "mascot" seems a bit sexist, and maybe a bit tripped out on strong cleaning chemical fumes, but a lot of their site is interesting to peruse.
I don't agree with this though, but I won't get into particulars in this post. I don't 100% disagree with their statement, but I feel there are some exaggerations to these type of statements.
Violent death and body decomposition are biohazards.Through blood and air borne pathogens you risk HIV, hepatitis C, tuberculosis, e.coli and hantavirus.


text:
Stock Graphic >> Product Mockup - iPad mock up Special nutrition 163476 by White Hart Design Studio @ CreativeMarket
File Size: 35.8 MB; DPI: 300 DPI.
This mock up is very easy to use and perfect to enhance your ebook cover or any other health, nutrition, recipes or smoothies publication! It comes in a High quality PSD file if you want to use it in Photoshop or JPEG. Simply add the cover or image through the Smart Object and you have it! It is really easy!
It can be cropped the way you like!
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Personal and commercial licences. Copyrights White Hart Design Studio.
Keywords: smoothie, pdf, ebook, book, cover, publication, page, recipes, recipe, nutrition, rustic, health, well-being, ipad, mock up, mockup, fruits, berries, summer, linen.


text: Strategies and Plans Other pages in this section Funding Available for SME's from Projects awarded ERDF Test project map About ESIF ESIF ERDF Latest ERDF calls ESF ESF Infographic ESF programme updates Building Better Opportunities Programmes update Employment Hub Launch Event ESF newsletters ESF Technical Assistance Latest update on ESF provision LLEP ESF Provider Forum Skills Funding Agency (SFA) Tri-partite meeting Skills Support for the Workforce: Skills Metro – Leadership and Management – Business Enterprise Skills Events Project information and success stories Achieve – Inspire – Motivate (AIM, a project to help ex-offenders) Business Enterprise Skills-skills support for the workforce Careers Education Service (support for 16-24 year olds) Improve Your Prospects (support entry to employment for 16-24 yr olds) Links to Work (help for adults to find work) Moneywise Plus (help with finance and digital skills) Open Doors (Skills Metro) skills support for the workforce Skills 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Personal Campaign
MaryEllen is gathering 12 signatures to
Vietnam Veteran Asks You To Join His Near 34,000 Supporters
The Gov't is robbing us of our freedoms - a bit more each day & it's up to us to stop the march toward Socialism. We are a Republic-NOT a democracy!
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text:
Submitted by Charles Hugh-Smith of OfTwoMinds blog,
Survivorship bias helps us understand why success stories are not what actually helps us succeed.
There are known knowns; there are things we know that we know.There are known unknowns; that is to say, there are things that we now know we don't know.But there are also unknown unknowns – there are things we do not know we don't know.
Survivorship bias is a profound insight into how we confuse the known unknowns and the unknown unknowns.


text:
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France and Germany are ready "to do everything, absolutely everything" to ensure the stability of the eurozone, French Prime Minister Francois Fillon said in a speech in London on Thursday.
"Of this there must never be any doubt: euro area states, and especially France and Germany, are ready to do everything, absolutely everything, to ensure the euro area's stability," Fillon told business leaders.
He was speaking at the start of his first official visit to Britain since he became prime minister in 2007, during which he will hold talks with Prime Minister David Cameron and Deputy Prime Minister Nick Clegg.
Fillon added: "The euro area is Europe's monetary heart, and no one should have any doubt about the determination of the whole European Union to safeguard it. It's an absolute political and economic priority."
His comments come amid investor unease that the debt crisis that forced multi-billion-euro bailouts of Greece and Ireland last year could spread to Portugal, and possibly even to bigger economies such as Spain, Belgium and Italy.
After pulling off a successful bond sale on Wednesday worth 1.25 billion euros (1.6 billion dollars), Portugal said it had passed a key test of its credit standing on the international markets.
But analysts were cautious, arguing that a bailout remains a real possibility.
Spain succeeded on Thursday in reaching its maximum 3.0-billion-euro target in a five-year bond sale, although it paid sharply higher rates than in the last such auction in November.
In an interview with The Times newspaper ahead of his one-day visit, Fillon said he would be urging Cameron to back deeper European integration to save the euro or risk disaster in his own economy if the currency fails.
"I want to tell you that, throughout this crisis, the British authorities have been solid partners, respecting our differences," he said.
He added that Britain "has played her part in the joint effort, agreeing to a limited revision of the Treaty and contributing to the recent emergency plans -- I'm thinking particularly of Ireland."
Although Britain has not adopted the single European currency, it is a major contributor to the International Monetary Fund-European Union bailout of debt-wracked Ireland, which is a eurozone member.


text:
In every command scheme, keywords appear as words in both lower- and upper-case letters. When typing the command or
keyword in the command file, the user must at least copy literally the part with upper-case letters. SWASH reads
only this part. SWASH is case insensitive except for one instance (character strings), see below. When typing the
keyword in the command file, any extension of the part with upper-case letters is at the users discretion as long as
the extension is limited to letters or digits, as well as the characters - and _. So, in the first command outlined
above one may write: KEY or KEYW or KEY-word or keyhole, etc., whereas with the
abovementioned second command scheme, key1 KEY2 data may appear in the command file.
In the command file


text:
Bringing the Common Core Math Standards to Life: Exemplary Practices from High Schools.pdf
As high school math teachers shift to the Common Core State Standards, the question remains: What do the standards actually look like in the classroom? This book answers that question by taking you inside of real Common Core classrooms across the country. You'll see how exemplary teachers are meeting the new requirements and engaging students in math. Through these detailed examples of effective instruction, you will uncover how to bring the standards to life in your own classroom! Special Features: A clear explanation of the big shifts happening in the classroom as a result of the Common Core State Standards Real examples of how exemplary teachers are using engaging strategies and tasks to teach algebra, geometry, trigonometry, statistics, mathematics across the curriculum, and more A detailed analysis of each example to help you understand why it is effective and how you can try it with your own students Practical, ready-to-use tools you can take back to your classroom, including unit plans and classroom handouts
Yvelyne Germain-McCarthy is Professor Emerita of mathematics education at the University of New Orleans. She is a frequent speaker at conferences and a consultant to school districts. Ivan P. Gill is Assistant Professor and Science Education Coordinator at the University of New Orleans, where he has taught elementary and secondary science methods courses.
1. Trends and Issues Leading to The Common Core State Standards 2. EXEMPLARY PRACTICE: WHAT DOES IT LOOK LIKE? 3. MICHAEL LEHMAN: GROUP PERFORMANCE ASSESSMENTS 4. MICHAEL LONERGAN: THE MATHEMATICS OF THE THEATER 5. HENRY KRANENDONK: RAISIN GEOMETRY: EXPLORING THE BALANCE POINT AND ITS APPLICATIONS 6. VIRGINIA HIGHSTONE: EQUATIONS THAT MODEL GROWTH AND DECAY7. CRAIG JENSEN: A DICE GAME FOR ENGAGING TEACHERS IN DISCOURSE 8. BEN PREDDY: INTEGRATING MATHEMATICS WITH LITERACY 9. MURRAY SIEGEL: DISCOVERING THE CENTRAL LIMIT THEOREM WHITECOTTON AND ANGELA GUTHRIE: A LESSON STUDY ON TRIGONOMETRY AND THE HEIGHTS OF LIGHTS 11. CLAUDIA CARTER: HOW A RUMOR SPREADS - AN INTRODUCTION TO LOGISTIC CURVES 13. DON CROSSFIELD: MARCHING FROM ALGEBRA TO TRIGONOMETRY AND BEYOND 14. WHAT'S NEXT?


text:
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text:
Reuters Staff
1 Min Read
April 28 (Reuters) - Haier Electronics Co Ltd:
* Haier Elec-appointment Of A Director
* Sun Jing Yan has been appointed as an Executive Director Source text (bit.ly/2pFQaZo) Further company coverage:
All quotes delayed a minimum of 15 minutes. See here for a complete list of exchanges and delays.
© 2017 Reuters. All Rights Reserved.


text:
Wednesday November 22, 2017 04:17 EST (All prices and information will update automatically every minute on the home page)
Charts are based on a 24 hour time frame. The change in price reflects the difference between the current spot price and 24 hours ago.
NV The Vegas Show
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text:
Wolfman feat. Peter Doherty : For Lovers
Soulful, sublime...
[a]Libertines[/a] man tugs at the heartstrings
Pete takes his hands from the rudder of the good ship Albion to release this lovelorn ballad. Still, it should be glaringly obvious – even to those without a passing interest in the Libs' never-ending soap opera – that this brilliant. Encased within the twinkling piano arrangements of old chum Wolfman, Pete proves himself capable of weaving both hope and honesty into the lining of
his exquisite melodies. That it's actually a bittersweet dedication to Wolfman's broken marriage and the romantics they'd watch from a Paddington station bar matters little – it's Pete's choked croak that musters the shivers. Soulful, sublime.
James Jam


text:
Running Time (Estimated): Three hours including one intermission. On stage at the Four Seasons Centre, 145 Queen St. W., Toronto. Sung in Italian with English SURTITLES™.
new coc production
Bellini and his operas are synonymous with the bel canto era when the beauty and virtuosity of the human voice reigned supreme. In that tradition, our production features two of the most sought-after sopranos today as Toronto's own Sondra Radvanovsky and South African Elza van den Heever share the title role.
With the COC Orchestra and Chorus
* Oct. 23, 26, 28 and Nov. 5
A Canadian Opera Company co-production with San Francisco Opera, Lyric Opera of Chicago and Gran Teatre del Liceu (Barcelona)
Sondra Radvanovsky as Norma in Norma (COC, 2016), photo: Chris Hutcheson


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VIDEO: Bright-eyed, dimpled child movie star who lifted America's spirits during the Great Depression and later became a US diplomat, passed away peacefully at her California home
Shirley Temple
Enrolled at Meglin Dance Studio in Los Angeles at 3 years old


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Recently moved down to Devon from Yorkshire, we have run our own business since 1999. We have two daughters who have now left home so we decided to embark on a new adventure of our own. So we ended up with Dartmoor View Lodges, a delightful site in a wonderful part of the country. We are about 10 miles off the north-west corner of Dartmoor and enjoy stunning, uninterrupted views across the Devon countryside towards Dartmoor. The lodges were constructed in 2006 and are made from 8″ round logs, therefore the inside wall are the logs – they are very cosy though, well insulated, warm in winter and cool in summer.
We developed an interest in horses due to our daughters' all-consuming passion and hope soon to be able to offer 'bring your horse' holidays in addition to 'normal' lodge holidays.
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A United Nations study says an estimated two million Bangladeshi
children are suffering from acute malnutrition because of food
shortages and higher food prices.
The study released Sunday by two U.N. humanitarian agencies (UNICEF and the World Food Program) says child malnutrition in Bangladesh is a "silent emergency." They based the assessment on surveys of Bangladeshi children aged six months to five years old.
The report says 58 percent of Bangladeshi households in the survey complained of not having enough food in 2008, when natural disasters devastated food production and caused prices to rise.
The U.N. World Food Program's representative in Bangladesh (John Aylieff) says that even if food prices are now falling, the country's food crisis is far from over.
The study says Bangladeshi households now spend a greater proportion of their income on food compared to three years ago.
Bangladesh has a population of 156 million and is one of the world's poorest countries.


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We Have a New Look!
By Marcie Barnes
Big thanks to the fine folks at This is Beautiful for creating our new logo! We are excited to move forward with a more polished and futuristic look that represents all of the connections we possess with each other and our planet. Since the spherre will also be connecting people together, we think it's pretty cool.
Why the change? I created the original logo myself when I was first mapping out the concept and wanted something more sophisticated and "web 3.0″. In addition, this gives us a solid, unique look that will also be the foundation for the iconography and general look and feel of the site as we develop it. Plus, I figured it would be best to get this out of the way before launch :-).
Please feel free to leave feedback in the comments and let us know what you think.


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Graphic Design & WordPress Web Design
"Anna is not only professional but her work is excellent. Anna always went above and beyond what I asked of her. I would recommend Anna to anyone looking for fair prices, excellent work and attention to detail, and most important to me is that she is a sister in Christ!" Clyde C.
"Anna is not only professional but her work is excellent. Anna always went above and beyond what I asked of her. I would recommend Anna to anyone looking for fair prices, excellent work and attention to detail, and most important to me is that she is a sister in Christ!" Clyde C.
Logos. Re-creation Vector. Business Cards. WordPress Websites. E-Commerce. Marketing Graphics. Social Media Management. Product Photography.
About Me
What I Do
I am a freelance graphic and WordPress web designer. I am based on Lake Anna in Orange County, Virginia. My services include designing custom logos, business cards, marketing graphics for print/online use, basic and e-commerce websites.
Who I Serve
For starters, I serve an Awesome God! My business is based on bringing Him Glory and my goal in everything I do stems from that. My clients include small businesses, individuals, organizations, churches and ministries all over the world.
Why Choose Me?
I am an award-winning graphic designer, with a huge heart, that is hungry to serve. I want you to feel successful, however that looks to you. If you are sick, you go to a doctor. If you need a logo/website, you go to graphic/website designer. That's me.
Anna Martin Designs offers Award-Winning Graphic Design and Website Design Services that are compatible with all devices to help connect people to just what they are looking for. You.
A few things you might want to know…
Do I offer payment plans?
How long does a custom logo design take?
Giving your business an identity is such a big decision and it is important to not to rush the process. If you can provide an example, like a drawing or an image of the logo you want, the process takes a lot less time than if you have no idea how you envision the "face" of your organization.
Within 10 days of making the deposit, I will have several proofs for you to review. Then I take your comments and do whatever is necessary and submit more designs for your to review. We will continue this process until you have the logo you love. I do not limit the revisions or the amount of time it takes and I will do my best to incorporate your ideas and vision so the custom logo design process is pleasant.
How long will a website take to design?
What can you expect from me?
Request a Proposal
Send me a message and let's talk about your needs. I want to help you get on the right track to having an awesome online presence that will even impress your competitors. Whether you need a logo, website or some marketing graphics, I am here to help. You just need to ask.


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Alumnus speaks out for Intel: Moore's Law is not dead
ECE News
Corey Blumenthal, ECE ILLINOIS
Story Highlights
Intel Senor Fellow and ECE ILLINOIS alumnus Mark Bohr (MSEE '78) rejects rumors that Moore's Law is dead.
"Number one, too many people have been writing about the end of Moore's Law, and we have to correct that misimpression," Mark Bohr told Fast Company. "And number two, Intel has developed some pretty compelling technologies...that not only prove that Moore's law is still alive, but that it's going to continue to provide the best benefits of density, cost performance, and power."
Intel has begun "hyperscaling," which allows the companies to increase computing power while having to make fewer manufacturing changes. Although it has become increasingly harder to shrink the size of transistors Intel's rate of improvement still equals out to more than double every two years.
"Following Moore's law regarding delivering better transistor density, lower transistor costs, and improved transistor performance and power, those benefits really apply to all product lines," Bohr says, "whether we're talking about a server part, a client part, or a low-power mobile part."
For more information, read the original article in Fast Company.


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Pink Sauce Trailer (1992)
23 January 1992 Comedy 86 mins
Ana's husband is the perfect wealthy middle-class man. Koro's husband is a cook with no more ambitions. One day, Ana meets Koro in a night club and she proposes Ana to seduce each others husbands. The following morning Ana thinks this was a joke, but things are not always what it seems. Written by Dulzz
Watch the official Pink Sauce 1992 trailer in HD below or find more Pink Sauce videos on Vidimovie.


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[アップルソフト] [160626] カノン~ココア島事件簿~Ver.2016-06-30 [RJ175772]
Release Year: 2016/06/26
Original name: カノン~ココア島事件簿~
Studio Name:アップルソフト
File size: 283.9 MB
RJ175772 Ver.2016-06-30.rar
Highlight the problem fragment mouse and press CTRL + ENTER.
In the window that appears, describe the problem and send a notice of the Administration site.
For more details, please refer to [ How can I install the Japanese language pack? ] on the Frequently Asked Questions page.


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by Christopher Freeburn | March 5, 2013 11:56 am
Anxious not to miss out of the trend toward healthy eating, Cracker Barrel Old Country Store (NASDAQ:CBRL[1]) is planning to introduce a number of new low-calorie menu items[2] at its 621 restaurants.
The chain is testing breakfast and dinner meals with fewer than 600 calories developed by a Florida dietitian for its new Wholesome Fixin's menu category. The restaurant chain says it hopes to roll out the new items this summer, USA Today notes.
Changes to its menu come after the chain conducted consumer surveys that found its patrons were eating at other dining venues due to the perception that Cracker Barrel's menu wasn't healthy enough.
While the company is keeping quiet about the new items, an analyst says the new category includes a breakfast sandwich with eggs and cheese on flat bread, a grilled catfish dish with vegetables, and baked chicken with vegetables.
The new breakfast dishes are priced between $3.99 and $7.99, while dinners will be priced from $6.99 to $9.49.
Last year, McDonald's (NYSE:MCD[3]) indicated that it would shift away from menu items containing beef toward ones with chicken[4] due, in part, to rising calorie-count and health consciousness among its consumers.
Shares of Cracker Barrel fell fractionally in Tuesday morning trading.
Source URL: https://investorplace.com/2013/03/cracker-barrel-to-add-new-category-to-menu/
Short URL: http://invstplc.com/1fr4tDo
Copyright ©2017 InvestorPlace Media, LLC. All rights reserved. 700 Indian Springs Drive, Lancaster, PA 17601.


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- A unit of weight when you look at the U.S. Customary System add up to 100 pounds (45.36 kilograms). Also known as cental, brief hundredweight.
- A unit of weight within the British Imperial program corresponding to 112 pounds (50.80 kilograms). Also referred to as quintal.
- A measure of fat containing 100 weight (45.5 kg) in U.S. or 112 weight (51 kg) in the uk.
- A denomination of fat, containing 100, 112, or 120 weight avoirdupois, in accordance with differing rules or traditions. By the appropriate standard of The united kingdomt it's 112 pounds. In most for the usa, in both rehearse and also by legislation, its 100 weight avoirdupois, the corresponding ton of 2,000 weight, occasionally called the brief ton, being the appropriate ton.
- In avoirdupois fat, a denomination of fat, typically denoted by cwt., containing initially 112 pounds.
- a United States unit of body weight equal to 100 pounds
- a British device of fat equal to 112 weight
- a unit of body weight corresponding to 100 kilograms
Related Sources
Definition for "hundredweight"
- A unit of weight when you look at…
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Sentence for "hundredweight"
- 'Your honour has a cart or…
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Hypernym for "hundredweight"
- avoirdupois unit
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Same Context for "hundredweight"
- bandolier
- View More
Agriculture Dictionary for "hundredweight"
- Measure of fat corresponding to 112…
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Udyr Build Guide by Raeper Fawks
Not Updated For Current Season
This guide has not yet been updated for the current season. Please keep this in mind while reading. You can see the most recently updated guides on the browse guides page.
Thank You!
Your votes and comments encourage our guide authors to continue
creating helpful guides for the League of Legends community.
Udyr Build
Ability Sequence
Not Updated For Current Season
The masteries shown here are not yet updated for the current season, the guide author needs to set up the new masteries. As such, they will be different than the masteries you see in-game.
Hey, I'm Raeper Fawks. This is my guide to jungling in Phoenix Stance as Udyr. I've done it quite a bit in normal games and so far its seemed to work in ranked play as well. I googled "Udyr" with safe search off and got a bunch of different image results of men's underwear. Imagine there is a really neat-o picture of Udyr here though.
I chose the attack speed reds for obvious reasons: the attack speed means more phoenix procs which will help with jungling AOE on camps and also in lane especially when you're at a tower with a bunch of enemy minions around grabbing at your crotch and what not trying to shape your **** through your jeans n' ****.
The yellows are great just for all around being a tanky **** especially helps with early game protection against unwanted jungle ticklers.
The blues increasing your Magic Resist is great to have because OOOODDDEEERRR doesn't start with a lot of MR and it really help when you come into lanes where there are AP champions just come struttin' in and then bite them in the neck.
Quints? Why the **** not more Attack Speed?
The Masteries I use help make udyr more tanky without losing the point in Improved Smite. He just gets more hulking and muscly and so full of rape **** that he can't contain himself. With the stance dancing you can increase your dodge quite a bit so having the points in Evasion and Nimblness is a great idea.
My item core is Wriggle Lantern and Mercury's Treads. By the time yuo have both of those you're decently tanky and putting out enough damage to break knees like they're frail children. From here I usually purchase either a Chain Vest or Negatron Cloak depending on what resistance I need more of. Complete either Force of Nature or Warden's Mail and then Randuin's Omen. By now you should be an almost unkillable **** whos walking around biting toes and punching old men in the lower back. The Banshee's Veil is the icing on the **** cake. Having a shield and the extra health and mana means more butter more butter!
I have also been experimenting with Aegis of the Legion and Spirit Visage
Skill Sequence
The skill sequence was a ***** to do. Those bubbles cocked my eyes over big time I couldn't figure out ****. I start with Phoenix, this is a Phoenix Jungling guide after all. I then get Turtle for healing and shielding while doing camps so I don't have to go back a lot. After getting two points in Phoenix, one in Turtle and one in Bear its really up to you how you want to level your skills. I get more points in bear if I want to hustle some bums harder or more into Turtle if I need more shield etc.
Summoner Spells
Summoner Spells are pretty straight forward.
Smite is for killing jungle creep, stealing dragon and Baron.
Flash is good for getting over ****, escaping or teleporting directly onto people for to stun with bear.
Start your Jungle at Blue Buff. Get someone to leash it for ****S SAKE ********IT! Don't start anywhere else unless you're a lonely **** with no friends to leash blue. From blue go to Wolves, then Wraiths, then Golems. At this point your can decide whether you want to go back and get a Long Sword, Boots of Speed and a Ward or to continue jungling by getting red and either ganking or go back to Wolves. Rinse and Repeat.


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Selectmen Monday night voted to revoke the license of one gold-buying kiosk in the Auburn Mall and give a �stern warning� to another such kiosk after both were alleged to be connected to stolen jewelry.
The license of Buying Gold Inc., doing business as Cash for Gold, was found to have two violations of its license.
In the first case, Auburn Police Detective Eric K. Dyson said that on Dec. 7 he witnessed the sale of gold earrings to the Cash for Gold kiosk. When he asked kiosk manager Katherine R. Tompkins for a record of the sale, he was told there was no copy of the seller�s identification, which is a requirement of the kiosk�s junk dealer�s license.
Ms. Tompkins told selectmen that �we ran out of ink,� so she could not copy the seller�s identification.
Selectmen voted to revoke the kiosk�s license for one day for that violation.
The second violation hearing that resulted in the license revocation involved jewelry allegedly stolen from a Grafton home in November. Auburn Police Detective Vincent S. Ross said that stolen jewelry was sold by an acquaintance of the victim�s son to Cash for Gold.
Detective Ross said police identified the jewelry at the kiosk and asked that it be held as evidence.
He said the day after the jewelry was put on hold, it was sent to Florida, where it was allegedly melted down.
Ms. Tompkins said it was �due to miscommunication� that she shipped the jewelry to the store owner in Florida after police said to keep it as evidence.
�The jewelry should have been seized immediately. It happens all the time. Many, many times, (police) have taken it immediately.�
She said this was the first time any allegedly stolen items were put on hold.
Doreen M. Goodrich, chairman of the Board of Selectmen, said the license requires that all items be kept for 14 days.
For this second violation, the kiosk�s license was revoked by a unanimous vote of selectmen.
Police Chief Andrew J. Sluckis said, �We have consulted the district attorney, and criminal changes have been filed.�
Detective Ross said Ms. Tompkins has been charged with larceny over $250 and �additional charges may be filed.�
In the case of CPY Gold Buyers, another Auburn Mall kiosk, costume jewelry allegedly stolen from the same Grafton home was found in a display box next to the kiosk.
Kiosk manager David Marian told selectmen that the jewelry had been thrown away by someone, retrieved from the trash, and added to a pile of �junk jewelry� in a display box near the kiosk.
Ms. Goodrich said, �Can you see that doesn�t sound credible?�
Mr. Marian said he fully cooperated with police, and maintained proper documentation of all transactions, and suggested that police �catch the person who broke into her house, not someone in a kiosk.�
Chief Sluckis said that �$20,000 worth of jewelry was conspicuously absent. I find it hard to believe businesses pick through the trash. What we believe and what we can prove are two different things.�
Selectmen voted unanimously to give Mr. Marian a �stern warning.�
Ms. Goodrich said, �We don�t have enough evidence to prove you were in violation.�
Mr. Marian said the allegedly stolen costume jewelry would not have been put on display if he had known it was stolen, but, unlike the gold jewelry that was melted down, at least some of it could be returned to the owner.
�In hindsight, it probably was not a good idea, but at least she got some of her stuff back.�
� Ellie Oleson


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Discussion in 'Suggestion Box & Feedback' started by lekky, Apr 14, 2010.
Stats at the top of the page gone? I found the latest replies really useful!
The server has had a lot of stress on it. It's being worked on as we speak. Hopefully everything will be back to normal soon.
Yes, I love top stats too and if it can be brought back with minimal resource repercussions - it will. I want to wait until we get the site stable and a baseline going before I reactivate to evaluate, though. Hopefully today.
In the meantime if others find it useful or if others hate it, now would be the time to mention that.
Miss it!
I miss it as well
Back. I think it will be okay.. Will test throughout the day.
From the home page? Also, the recent posts section is missing?
I suggest that it come back?
i dont see them anymore either.. guess there gone again
New servers coming Wednesday night. Once we get that running smoothly, and the site optimized, we'll add it back in. Might take a few days but hopefully by the end of this week.
We all agree we like it and the goal is to add it back in... but won't do so at the expense of being able to load the site!
Thanks for your patience.
What about signatures and users logged in? Hopefully those will comeback with the new server too!
Users logged in, probably. Signatures - well the one signature per user per page thing was done on purpose as a long term solution, that probably won't be turned back off.
me no likes the top 10 stats, looks messy IMO, but majority rules!!
Sounds good. Look forward until wed upgrade. Feel days wont kill anyone.
Sent from my Nexus One using Tapatalk
Looking forward to the upgrade Wed. I love the top stats.
...a couple of days eh?
I really like the Top Stats info. Since I'm only on the subforums I subscribe to, it kept me up to date on what people in the other subforums are discussing. Not sure if there was an option to minimize it for people like Caddy that don't like it, they can hide it. It's been awhile so I don't remember


text: Bless you all for allowing me to join. I expect you have a testimony section which I shall find in due course. But in the meantime the following testimony seems as good a way as any for introducing myself. You will see that whilst I am a long established believer I have become a bit of a loose canon as a result of having spent many years seeking the hidden treasures of the Kingdom of Heaven without denominational allegience to prejudice my search. Nevertheless I hope you will learn to accommodate my quirks. I have been a regular contributor to my UK forum for five years and my post count on the True2Ourselves American forum is well over 1000, and I hope to replicate that in this forum. Both my other forums have members who openly appreciate my contributions and I intend to continue to post there. However those who are not prepared to give time to mulling over some of the things that I have to say quickly jump to hasty wrong conclusions as new member 'OneLight' will testify. I look to spread my wings as a means of "saying what I think I know in order to know what I ought to think"..... meaning that I am as much a 'listener' as I am a 'speaker'. Here then is my Testimony: I came to faith as a child over 60 years ago in a little chapel opposite my parent's home. (They packed me off to the chapel's Sunday school in order to get themselves a peaceful Sunday afternoon.) By the time I was 16, and in my first job, my faith and the chapel totally absorbed my life. We believed (at least I thought that we did) in total independence without denominational affiliation, and in God's development of each member to serve his purpose from cleaner and coffee maker, right up to and including the Pastorate. Based on Christ's Sermon on the mount we also majored on practicing complete deference to each other and to all Christians (turn the other cheek, go the extra mile, if asked for our coat then give our cloak, honour the lesser vessels amongst us, total love and forbearance to one another, etc.) However after National service, change of jobs and house moves, career obsessions etc., my faith was eventually shattered when I later thought to return to the place of my spiritual birth only to find that the Elderly Pastor and his two assistants had abandoned all that they had taught me and had led the chapel into bitter warfare over the question of Pastoral succession. What they had been preaching, and I had been believing, should have precluded such a complete reversal but far from it with the entire membership taking sides with one or another of the three leaders. The bitterness became so great that the leadership split up, defected to other Churches and took their supporters with them. The assembly had in fact become so unrecognisable that, after trying another church for a while only to find the same dissention, I took my shattered illusions off into the 'wilderness' to pray and seek resolution. Thus began, for me, many years of complete prayerful re-appraisal, including extensive research into the History of Christianity from the first teachings of Christ, through all the deliberations and declarations of the numerous Ecumenical Councils, and all the claims and counter claims of the subsequent 'Reformation' with all their various creeds and Articles of Faith. Consequently I have had no denominational influence for over 40 years now and have made it my practice to attend whichever is the nearest church to wherever God places me from time to time (provided of course that they will accept me into full fellowship without demanding formal acquiescence into any man made criteria beyond that which makes me a member of the Body of Christ) I guess re-appraisal remains an ongoing process, and out of the chequered 2000 year history of Christianity, who would expect the emergence of yet another denominational 'Parrot'. [FONT="]Sorry folks but I am now 'what I am' and I can only trust and pray that I have kept myself sufficiently free from prejudice, and continually seeking the hidden treasure of Heaven's Kingdom with sufficient diligence to at least be somewhere close to where God wants me to be.[/FONT]


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The Bent Brian dildo also features a curved (angled) head, that allows for direct targeting of the female g-spot. Brian has a firm core, and gentle texture so that you can indulge in your fantasy. With the suction cup base, you can mount Brian to almost any flat surface for hands free stimulation.
All prices are in USD.


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Ketamine Clarity
Ketamine is being used successfully to treat pain in children and adults yet there are some important things to know before using this drug clinically. Dr. Antevy discusses the best options for Ketamine administration when being used for pain in the ED or the field.
Croup There It is
Watch how to use Epinephrine 1:1,000 (1 mg/mL) for both Croup and Asthma.
Handtevy Minute - 5 Ways to Have a 3-Way
The 3-way stop cock should be in every emergency provider's toolbox. This valuable device has many uses when providing care to critical pediatric patients. Let us know how you use a 3-way in your day to day practice.
Handtevy Minute - Adenosine TIps and Tricks
It is well known that adenosine is rarely given in the field, especially to pediatric patients. The reason why has to do with not only the dosing (calculations) but also the logistics of administration. In this short video, Dr. Peter Antevy shows an easy way to rapidly administer Adenosine using a 3-way stopcock.


text: I know I had help figuring this out a couple years ago, but I don't remember, and it's impossible to google (the dashes are stripped if you try). On my console, on a woody 486, I see, regularly... -- MARK -- [ 30 or so seconds pass] -- MARK -- And I am quite sure I do not like feeling like a -- MARK --'ed person. Help? Thx In Advancia ------------------------------------------------------------------------------ This message is intended only for the personal and confidential use of the designated recipient(s) named above. If you are not the intended recipient of this message you are hereby notified that any review, dissemination, distribution or copying of this message is strictly prohibited. This communication is for information purposes only and should not be regarded as an offer to sell or as a solicitation of an offer to buy any financial product, an official confirmation of any transaction, or as an official statement of Lehman Brothers. Email transmission cannot be guaranteed to be secure or error-free. Therefore, we do not represent that this information is complete or accurate and it should not be relied upon as such. All information is subject to change without notice.


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At "Christmas in July", Third Degree Glass Factory will be unveiling our brand new selection of custom glass gifts during its free Third Friday Open House.
Browse our selection of customizable gifts, from engraved blown glass ornaments to wedding cake servers with custom beadwork, as well as unique awards for your next recognition ceremony. The possibilities are limitless when you buy local!
There will also be exciting guided glass art activities: Make your own paperweight, flame-worked glass beads, fused glass jewelry or nightlight for $35. The featured project this month is Christmas-themed tiles for $25.
The East Gallery presents its new installation: artwork by the teaching artists and students of local non-profit Artscope.
Jam out to classic holiday tunes, mixed with a little blues at 8 pm with live music by the Diamond Cut Blues Band.
The St. Louis Fire Technicians will spin fire at 8:45pm.


text: I need some suggestions on what type of ground cover to install on an island in the middle of a 1/2 acre pond. The area recieves sun all day and the soil is clay. The objective is to put on a ground cover that will spread quickley and over hang the banks to the water level. The island has a small bridge to it but not big enough to get any equipment over to it except hand tools. I tried the usual ivey, pacha,etc. The island is about 35 by 50 ft. and in the northern part of Ohio. And before anyone tells me not to take the job becouse its to much work, I already know becouse its in my back yard! any suggestion would be greatley appreciated.


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SILO — The Silo Rebels (29-2) are headed back to the state tournament after a dominating 19-0 run-rule victory over the Coalgate Wildcats on Friday to become the regional champions.
The highlight of the game was Trenton Long's grand slam home run in the second inning. His teammate Parker Holland had five RBIs on two hits, also in the second inning.
Rebel hurler Bubba Roberts tossed five innings with nine strike outs and no runs allowed.
Silo 19, Coalgate 0
The Rebels took a early 3-0 lead in the first inning, then exploded for 14 runs in the bottom half of the second inning.
The inning started with Jacob Savage gifted a base and Lukas Long hit a seeing-eye single. Holland then crushed the ball into the outfield for a 2-RBI double to start the scoring frenzy, and later scored on a wild throw to second base.
Hunter Ratcliffe was hit-by-pitch, Roberts hit a infield single and T. Long drew a walk to load the bases. Then Karson Rogers drove in two runs on double to left field and Trevor Daily hit a sacrifice fly.
With two outs, the Rebels loaded the bases again. Jake Hamilton hit a single and Savage and L. Long both drew walks. Then T. Long dug into the batters box and hammered a grand slam homer over the right field wall and the Rebels led 17-0.
Coalgate went down in order in the top of the third inning as Roberts struck out two batters and made the other ground out.
Silo added another run in the bottom half of the third inning when Savage got on base due to a throwing error and L. Long drove in his teammate on a ball hit into the outfield gap for a double.
In the top of the fourth inning, Coalgate couldn't solve Silo's defense and went down in order again on two ground outs and a strike out.
Silo put one more run on the scoreboard in the bottom of the fourth and Roberts closed out the in the top of the fifth as he struck out three batters.
The Rebels are on track to win back-to-back titles as the won the state tournament in the fall.
Contact Randy Bruce at email@example.com or Twitter @SportsBruce


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Evie Jade Events is an event planning created to make your wedding day easier!
Whatever your event Jade from Evie Jade Events will go above & beyond and meet all your expectations not only saving you money but time. Jade comes up with so many ideas her imagination is endless. Jade has been planning my wedding & don't know how I would of pulled it together without her help not only has she made the day seamless but she has also taken away the stress so I can just enjoy the lead up to my big day without worrying thanks again & I would highly recommend her services
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