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OBJECTIVE: The author's goal was to develop a pathophysiological model for neuroleptic malignant syndrome with greater explanatory power than the alternative hypotheses of hypothalamic dopamine antagonism (elevated set point) and direct myotoxicity (malignant hyperthermia variant). METHOD: Published clinical findings on neuroleptic malignant syndrome were integrated with data from human and animal studies of muscle physiology, thermoregulation, and autonomic nervous system function. RESULTS: The data show that the sympathetic nervous system's latent capacity for autonomous activity is expressed when tonic inhibitory inputs from higher central nervous system centers are disrupted. These tonic inhibitory inputs are relayed to preganglionic sympathetic neurons by way of dopaminergic hypothalamospinal tracts. The sympathetic nervous system mediates hypothalamic coordination of thermoregulatory activity and is a primary regulator of muscle tone and thermogenesis, augmenting both of these when stimulated. In addition, the sympathetic nervous system modulates all of the other end-organs that function abnormally in neuroleptic malignant syndrome. CONCLUSIONS: There is substantial evidence to support the hypothesis that dysregulated sympathetic nervous system hyperactivity is responsible for most, if not all, features of neuroleptic malignant syndrome. A predisposition to more extreme sympathetic nervous system activation and/or dysfunction in response to emotional or psychological stress may constitute a trait vulnerability for neuroleptic malignant syndrome, which, when coupled with state variables such as acute psychic distress or dopamine receptor antagonism, produces the clinical syndrome of neuroleptic malignant syndrome. This hypothesis provides a more comprehensive explanation for existing clinical data than do the current alternatives.
It is widely believed that dopamine D2 (D2) receptor antagonism causes hyperthermia in neuroleptic malignant syndrome by blocking heat-loss pathways in the anterior hypothalamus, by increasing heat production secondary to extrapyramidal rigidity R15602CEBCDBAI, or both, but this model has been criticized as inadequate R15602CEBDJCIF, R15602CEBDFHDB and lacking sufficient evidence R15602CEBCAEJD. An alternative hypothesis is that neuroleptics are directly toxic to muscle tissue, as volatile anesthetics are in malignant hyperthermia R15602CEBCEJCI, but neuroleptic malignant syndrome and malignant hyperthermia likely have distinct mechanisms R15602CEBBGBDJ, R15602CEBCEEIA. Neither model enables clinicians to identify specific patients at greater risk for neuroleptic malignant syndrome or to make reliable treatment choices R15602CHDCIBGD–R15602CHDBGGBI.
Autonomic dysfunction is a core component of neuroleptic malignant syndrome R15602CHDECGAH, R15602CHDBCJAJ, DSM-IV), and peripheral catecholamines are typically elevated R15602CHDBHIDC–R15602CHDCEEEG, but a pathophysiological role for excess catecholamines in neuroleptic malignant syndrome has been relatively overlooked. This paper provides an overview of the sympathetic nervous system and its regulatory role in body temperature, muscle function, and other organ systems that are affected in neuroleptic malignant syndrome. These data are then integrated with published clinical observations in support of the hypothesis that dysregulated sympathetic nervous system hyperactivity is the pathophysiological basis of neuroleptic malignant syndrome. The central premises of this hypothesis are the intrinsic capacity of the sympathetic nervous system for autonomous, fragmented function and its ubiquitous involvement in all of the physiological processes relevant to neuroleptic malignant syndrome. F1 summarizes this thesis schematically, and the reader will find it helpful to consult it frequently.
Most organs are innervated by sympathetic and parasympathetic divisions of the autonomic nervous system, but the adrenal medulla, sweat glands, and somatic blood vessels are regulated exclusively by the sympathetic nervous system R15602CHDEAFFC. Preganglionic sympathetic nervous system fibers synapse within the adrenal medulla R15602CHDEAFFC and promote catecholamine secretion R15602CHDCAFIH. Sympathetic nervous system and adrenomedullary responses are often dissociated R15602CHDCJFJD and can be complementary R15602CHDBDBFI, R15602CHDDHJAG. The relative independence of the sympathetic nervous system from central nervous system (CNS) regulation R15602CHDEAFFC, its more permeable blood-nerve barrier R15602CHDCADBF, and the ability of its end-organs to continue functioning when autonomic nerves are interrupted R15602CHDEAFFC all contribute to its capacity for autonomous function.
The sympathetic nervous system is regulated by the frontal cortex and hypothalamus. The sulcal prefrontal cortex tonically influences the hypothalamus to lower body temperature R15602CHDBBEFI. Sympathetic nervous system hyperactivity ensues when the hypothalamus is released from cortical control R15602CHDEAGBC, and systems lower in the neuraxis operate independently following hypothalamic lesion R15602CHDDJCCB. Sweating is tonically inhibited by the frontal cortex R15602CHDBGEFD, and a similar hierarchical inhibitory relationship exists between spinal cervicothoracic and thoracolumbar sudomotor (sweat gland) regulatory centers R15602CHDCJAFC.
The sympathetic nervous system is regulated by the lateral and posterior hypothalamus, whereas the parasympathetic division is controlled by the anterior and medial hypothalamus R15602CHDEAFFC, R15602CHDEAGBC. Stimulation of the lateral hypothalamus increases adrenal nerve activity R15602CHDCAFIH, and the lateral hypothalamic area provides organ- or site-specific regulation of sympathetic nervous system activity R15602CHDCDDEA. Most dorsal hypothalamic spinal projection neurons are dopaminergic and appear to be involved in autonomic function R15602CHDDBAFJ. Dopamine terminal axon density is highest in the intermediolateral cell columns of the spinal cord, where preganglionic sympathetic nervous system neurons originate, and microelectrophoretic dopamine application there inhibits sympathetic preganglionic neurons R15602CHDBBCGG. Retrograde labeling has identified caudal lateral hypothalamic area neurons as likely sympathetic nervous system "central command neurons" R15602CHDDJCCC.
Autopsy findings have implicated only the posterior hypothalamus in neuroleptic malignant syndrome R15602CHDCBJCF. Other autopsy results are inconclusive R15602CHDBIAJB or negative R15602CHDCDEAC, R15602CHDBGJBB, R15602CHDCCJDI with respect to hypothalamic pathology.
Preganglionic sympathetic nervous system neurons release acetylcholine, but postganglionic sympathetic nervous system neurons release norepinephrine. Exceptions are sudomotor neurons and vasodilator neurons in the muscle, whose postganglionic neurons release acetylcholine, and the adrenal medulla, whose preganglionic neurons release norepinephrine R15602CHDEAFFC, R15602CHDBIDGA. Norepinephrine acts only within the neuroeffector junction into which it is released R15602CHDBFIFF. Plasma norepinephrine levels reflect overflow from sympathetic nervous system neuroeffector junctions, and there is good correlation between muscle sympathetic nerve activity and plasma norepinephrine levels R15602CHDEADJA. Norepinephrine promotes its own release by means of prejunctional β-adrenoceptors; at higher concentrations it inhibits its own release by means of prejunctional α-adrenoceptors R15602CHDDBCAF. Trains of high frequency action potentials may cause norepinephrine to accumulate, potentiating its functional effects R15602CHDDCHJG. Symptoms of norepinephrine toxicity include anxiety, pallor, and intense diaphoresis R15602CHDBIGCE.
Epinephrine is the major catecholamine produced by the adrenal medulla; in contrast to norepinephrine, it is released into the circulation and acts at distant receptor sites R15602CHDBFIFF. Symptoms of epinephrine toxicity include fear, anxiety, tenseness, restlessness, tremor, weakness, dizziness, pallor, respiratory difficulty, and palpitations R15602CHDBIGCE. Norepinephrine constitutes no more than 20% of the catecholamine content of the adrenal medulla R15602CHDBIGCE, and epinephrine has no significant activity at sympathetic nerve endings R15602CHDBFIFF.
Norepinephrine activates predominantly α- and β1-adrenoceptors R15602CHDDEDBI and is more potent at α1 than α2 receptors R15602CHDBBCIA. Epinephrine is active primarily at β-adrenoceptors R15602CHDDEDBI and is much more potent than norepinephrine at β2 receptors, where norepinephrine has minimal activity R15602CHDCCAGC. Second messengers for adrenoceptors are adenylate cyclase (activated by β, inhibited by α2) and intracellular Ca2+ (increased by α1) R15602CHDDBJGG. Adrenoceptors in smooth muscle and glands are predominantly α1R15602CHDCJFJD, whereas vasodilator β2-adrenoceptors in skeletal muscle normally predominate over vasoconstrictor α-adrenoceptors R15602CHDCCAGC. Skeletal muscle contractility is increased by β2-adrenoceptors R15602CHDCCAGC, and cardiac rate and contraction strength are both increased by β-adrenoceptors R15602CHDBIDGA. A newly identified β-adrenoceptor subtype, β3, promotes lipolysis and plays a functional role in sympathetically induced thermogenesis R15602CHDBBCIA, R15602CHDECCJH.
High levels of D2 receptor mRNA are expressed in the normal adrenal gland R15602CHDBACFA and increased in human pheochromocytoma tissue R15602CHDDHEID. In animals, D2 agonists inhibit catecholamine release from adrenal glands, and D2 presynaptic receptors located on norepinephrine nerve terminals inhibit norepinephrine release if activated during nerve stimulation R15602CHDBDFCD. In humans, D2 agonists cause inhibition of sympathetic output that is abolished by D2 antagonists, but only at higher degrees of sympathetic stimulation R15602CHDBDFCD. These data are consistent with previously discussed anatomical evidence for dopaminergic inhibition of sympathetic nervous system function and indicate that state-dependent factors mediate D2 antagonist effects.
The functional components of the sympathetic nervous system exhibit considerable autonomy. For example, sympathetic vasoconstrictor pathways are distinct from pilomotor and visceromotor pathways and can be activated differentially R15602CHDCFFID. In cats, vasoconstrictor pathways for skin and muscle are independent of one another R15602CHDDIJFC and exercise-induced sympathetic discharge is regulated differently in the kidney and muscle R15602CHDCEEAF. Individual peripheral sympathetic nerves exhibit a high degree of coherence at rest but respond uniquely to experimentally induced cerebral ischemia, indicating that sympathetic nervous system circuits can convert a generalized excitatory stimulus into specific and desynchronized discharge patterns R15602CHDCIGFJ.
Sympathoadrenomedullary responses also vary according to stressor: some stressors increase sympathetic nervous system activity but not adrenomedullary secretion, and others have the opposite effect R15602CHDCEGII. Moreover, sympathetic nervous system outflows to different organs vary depending on the nature and intensity of the stressor R15602CHDCEGII. Autonomous and uncoordinated activity of sympathetic nervous system functional components following disruption of regulatory (hierarchical) inputs, coupled with varying affinities of norepinephrine and epinephrine for diverse and widely distributed adrenoceptor subtypes, could account for many of the clinical features of neuroleptic malignant syndrome, including its fluctuating course.
The two principal sources of thermogenesis in mammals are uncoupled oxidative phosphorylation in mitochondria and the contractile apparatus of skeletal muscle.
Brown adipose tissue is specialized to generate large amounts of heat rapidly, a process referred to as "nonshivering thermogenesis." Brown adipose tissue is rich in mitochondria containing uncoupling protein, which permits respiratory chain oxidation to liberate energy in the form of heat R15602CHDBFBEI. Norepinephrine is a major regulator of uncoupling protein synthesis R15602CHDDICFC, R15602CHDBEIID but may also have a direct thermogenic effect on brown adipose tissue R15602CHDBEIID. Hypertrophy of brown adipose tissue and increased uncoupling protein synthesis have been induced in the skeletal muscle of mice following 2 weeks of treatment with a β3 agonist R15602CHDDBDHE.
The contraction-relaxation cycle of skeletal muscle tissue is another important thermal energy source in mammals; the term for heat generated by the contractile apparatus is "shivering thermogenesis." Contraction is initiated when Ca2+ is released from its intracellular storage site in the sarcoplasmic reticulum and binds to contractile proteins (mainly troponin) in the sarcoplasm. Relaxation begins when intracellular [Ca2+] reaches a critical level, terminating further Ca2+ release and activating Ca2+ reuptake pumps in the sarcoplasmic reticulum membrane to move Ca2+ from sarcoplasm to sarcoplasmic reticulum against a steep gradient.
Ca2+ release from the sarcoplasmic reticulum, Ca2+ binding to troponin, Ca2+ reuptake by the sarcoplasmic reticulum, and the oxidative chemical reactions of the postcontraction recovery phase all produce heat R15602CHDBAEGE, and intracellular Ca2+ transport plays a role in normal thermogenesis R15602CHDDBDIC. Intracellular free [Ca2+] regulates contraction-relaxation R15602CHDCHEDB, and agents that lead to sustained elevation of sarcoplasmic [Ca2+] can induce persistent contraction in the absence of an action potential R15602CHDBAEGE. Creatine phosphokinase participates in regenerating high-energy cellular stores during the relaxation phase R15602CHDCHEDB and is an integral component of intracellular energy metabolism.
Homeothermy evolved as existing physiological reflexes were recruited for thermoregulatory functions, gradually creating a hierarchically organized collection of parallel subsystems, each of which regulates its phylogenetic predecessor. The neutral zone, defined as the body temperature range within which no thermoeffectors (heating or cooling reflexes) are activated, narrows progressively at each level of this hierarchy, so there is an illusion of a single fixed set point (in humans, about 98.6˚F) R15602CHDBBIFJ. However, homeothermy represents the interaction of two separate groups of neurons—warm-sensitive and cold-sensitive R15602CHDBJFCI. Warm sensitivity is mediated primarily by temperature-sensitive membrane ion conductances R15602CHDDCBCG, whereas cold sensitivity requires intact local synaptic networks R15602CHDDCBCG, R15602CHDDFAEJ. Warm-sensitive neurons activate cold effectors (e.g., sweat glands) to lower body temperature, and cold-sensitive neurons activate warm effectors (e.g., brown adipose tissue) to raise body temperature. Warm and cold effectors are never activated simultaneously by an intact thermoregulatory system R15602CHDBJFCI.
Thermoregulation can be dissociated in a variety of ways. The neurotoxin capsaicin disables heat-defense responses but leaves cold-defense responses intact R15602CHDBBEFI. Shivering and nonshivering thermogenesis are modulated separately following CNS lesion, and stimulation of the hypothalamus and spinal cord by opposing temperatures produces mutually independent and antagonistic thermoeffector (heating and cooling) responses R15602CHDBBIFJ. Almost all thermoeffectors also serve nonthermoregulatory functions, so competition between thermal and nonthermal drives is likely R15602CHDBBEFI, R15602CHDDEFID. Thermosensitive neurons in the hypothalamus are very sensitive to emotional and behavioral inputs, and their response is determined by perturbation magnitude rather than hedonic attributes R15602CHDBBEFI. Sympathetic nervous system activity in human skin is increased by mental stress as well as thermal inputs R15602CHDDEFJD, and many dorsal horn spinal neurons are excited by both mechanical and thermal stimuli R15602CHDCAHGF. Emotional fever is provoked by restraint or novel stimuli in some species, and anticipation can elevate body temperature in humans. These are true fevers in that they result from coordinated thermoeffector function (heat effectors turned on, cold effectors turned off) R15602CHDBABEE, R15602CHDBDABE.
Stimulation of the preoptic hypothalamus can induce fever, but this structure is not essential because fever is under the control of multiple CNS structures R15602CHDBABEE. The mammalian spinal cord has thermosensory and thermoregulatory properties R15602CHDDIJFC, but only extreme changes in body temperature elicit thermoregulatory responses in the absence of the hypothalamus R15602CHDBBIFJ. Humans with spinal cord transections have wider core temperature fluctuations R15602CHDBDABE, and subjects with complete cervical cord transections have increased core temperatures despite preserved regional heat-induced sweating R15602CHDCJAFC. Some capacity for thermoregulation is preserved when hypothalamic regulatory inputs are interrupted, so hypothalamic dysfunction alone cannot explain the extreme hyperthermia sometimes encountered in neuroleptic malignant syndrome.
It is widely believed that central dopamine receptor antagonism within the hypothalamus is necessary for neuroleptic malignant syndrome to occur, but the thermoregulatory role of dopamine is more complex. d-Amphetamine (an indirect dopamine agonist) produces hypothermia or hyperthermia in rats, depending on the ambient temperature, apparently by way of independent pathways R15602CHDCDDFD, R15602CHDDIBCJ. Acutely and chronically reserpinized rats demonstrate a reciprocal and state-dependent D1-D2 receptor interaction in their thermoregulatory responses R15602CHDCECHA. Neuroleptic malignant syndrome has followed neuroleptic dose reduction R15602CHDCEJDI, discontinuation R15602CHDCAEJI, and long-term stable dosing R15602CHDCBABC. Also, there is a report of severe extrapyramidal symptoms and hypothermia with fluphenazine, followed by rebound hyperthermia when this drug was discontinued R15602CHDBGBFA. Body temperature is highly correlated with plasma prolactin in thermally stressed men R15602CHDCDCHH, suggesting that normal heat defense is associated with decreased central dopamine, and intraventricular haloperidol produces a coordinated heat-defense response R15602CHDDGBDH. These reports refute a unique or essential role for central dopamine antagonism in neuroleptic malignant syndrome hyperthermia and provide additional evidence that state-dependent factors are important mediators of dopamine antagonist effects.
The sympathetic nervous system plays an integral role in normal muscle function. Force is potentiated by β-adrenoceptor agonists in mammalian skeletal muscle, and adrenoceptors on skeletal myocyte membranes are predominantly β2R15602CHDDFBHA, indicating that epinephrine normally is directly involved in regulating skeletal muscle contraction. In skeletal and heart muscle fibers, β-adrenoceptor agonists promote phosphorylation of Ca2+ channels, increasing the probability of their being open R15602CHDCABFH. Epinephrine increases contraction strength by way of this altered Ca2+ influx R15602CHDCABFH, apparently by increasing the amount of Ca2+ released from the sarcoplasmic reticulum into sarcoplasm during activation R15602CHDBAAAG. Epinephrine-induced Ca2+ influx by way of myocyte membrane channels also increases intracellular [Ca2+], and the same effect is seen with the α1-adrenoceptor agonist phenylephrine R15602CHDBAAAG. Liver Ca2+ homeostasis and muscle Ca2+ homeostasis are similar, and norepinephrine induces a sustained rise in hepatocellular [Ca2+] R15602CHDDBDIC. In rabbits, α1-adrenoceptor agonists cause dose-dependent increases in peak skeletal muscle tension R15602CHDBHIDA. Thus, norepinephrine and epinephrine are both potent activators of skeletal muscle and exert this effect by altering intracellular [Ca2+].
Norepinephrine has similar effects on smooth muscle. In rabbits, norepinephrine triggers Ca2+-induced Ca2+ release R15602CHDBGCHE, a process whereby a large amount of Ca2+ is released from the sarcoplasmic reticulum in response to a much smaller amount of Ca2+ outside the sarcoplasmic reticulum R15602CHDCFDHH. Norepinephrine-induced Ca2+ release can activate smooth muscle contraction fully R15602CHDDDGEE, and in guinea pig myocytes, norepinephrine produces spontaneous Ca2+-induced transmembrane electrical transients that can cause depolarization R15602CHDCAGEG. Ca2+-induced Ca2+ release is responsible for caffeine-induced contractures in skeletal muscle R15602CHDBFBCD.
All thermoeffector activity is regulated by the sympathetic nervous system. Both the sympathetic nervous system and the adrenal medulla are capable of preventing fatal hypothermia when the other is incapacitated R15602CHDEBDII. Norepinephrine is the primary regulator of brown adipose tissue metabolic activity and growth R15602CHDDJCCB, and norepinephrine also stimulates hormone-sensitive lipase, the principal lipolytic enzyme in white adipose tissue R15602CHDEBDII. Persistent β-adrenergic stimulation induces brown adipose tissue hypertrophy and accelerated uncoupling protein gene transcription in rats R15602CHDDBDHE, and although brown adipose tissue is probably not a major thermogenic tissue in man R15602CHDEBDII, it does persist throughout adulthood R15602CHDBHEAE and can be reactivated following intense sympathetic stimulation (e.g., in cold acclimation or by a pheochromocytoma) R15602CHDDJCCB. Repeated norepinephrine infusions potentiate thermogenesis in humans R15602CHDEBHBA.
Uncoupling protein synthesis can be induced in rat skeletal muscle following persistent adrenergic stimulation R15602CHDDBDHE, and skeletal muscle is the primary site of sympathomimetic-induced thermogenesis in humans R15602CHDBHEAE. Catecholamine-induced increases in intracellular [Ca2+] generate heat because chemical-mechanical transduction efficiency is low R15602CHDCGGDJ. Salbutamol, a selective β2-adrenergic agonist, is thermogenic in humans R15602CHDECFIH. Ephedrine, a mixed α- and β-adrenoceptor agonist, has a potent thermogenic effect in humans R15602CHDBHEAE that is mediated by norepinephrine and probably involves β3-adrenoceptors R15602CHDECCJH. Isoproterenol, a nonselective β-adrenoceptor agonist, substantially increases the metabolic rate in humans, apparently through β1- and β3-adrenoceptors R15602CHDCDIGB. In one mammal, norepinephrine substantially increases skeletal muscle thermogenesis through α1-adrenoceptors, independent of uncoupling protein R15602CHDCIJDI.
Nonsteroidal anti-inflammatory agents are ineffective against the hyperthermia of neuroleptic malignant syndrome, and dantrolene provides only inconsistent benefit, so it is worth noting that both indomethacin and dantrolene fail to inhibit phenylephrine-stimulated thermogenesis in small mammals R15602CHDCIJDI. These treatments would not be expected to reverse hyperthermia caused by a hyperadrenergic state in which unregulated thermogenesis, due to uncoupled phosphorylation and/or disrupted intracellular Ca2+ homeostasis, predominates.
The following general principles should now be evident:
Hierarchically organized thermoregulatory centers are located at all levels of the CNS.
The sympathetic nervous system is intimately involved in all aspects of thermoregulation.
The sympathetic nervous system consists of potentially autonomous components whose functions are normally coordinated and integrated by the hypothalamus, but which function independently when these regulatory inputs are disrupted.
Dopamine antagonists interrupt tonic inhibitory modulation of sympathetic nervous system function at the spinal cord level, an effect that is most evident when the sympathetic nervous system is hyperactive.
Sympathetic nervous system hyperactivity is associated with intense emotional stress and frontal cortical dysfunction.
The sympathetic nervous system can augment or initiate skeletal muscle contractile activity by means of adrenoceptor-mediated increases in intracellular Ca2+ levels.
The following sections explore the role of sympathetic nervous system hyperactivity in the clinical presentation of neuroleptic malignant syndrome. Again, the reader will find F1 helpful in following the discussion.
Organic brain disease is a risk factor for neuroleptic malignant syndrome R15602CHDCIBGD, R15602CHDCGFFC– R15602CHDBIJBC and for increased morbidity and mortality from this disorder R15602CHDCFCIG, R15602CHDBJJEG. Mental retardation is relatively frequent among cases of neuroleptic malignant syndrome R15602CHDCIBGD, R15602CHDBIAJB, R15602CHDCCEBG, and in one small series the most severe syndrome was associated with bilateral frontal lesions R15602CHDBCDGA. Catatonia, considered a harbinger of neuroleptic malignant syndrome by some R15602CHDBBGGD, is likely a frontal lobe syndrome R15602CHDBDHFI, R15602CHDCIJEE.
Affective illness is another risk factor for neuroleptic malignant syndrome R15602CHDBIJBC, R15602CHDBJJEG, R15602CHDEAIAE, R15602CHDBDHIH. Sympathetic nervous system activity is increased in major depression R15602CHDBIAFB; the relative contributions of the sympathetic nervous system and adrenomedullary components vary by depression subtype R15602CHDDJIHJ. In manic patients, adrenomedullary activity is associated with affective and behavioral symptoms but sympathetic nervous system activity is correlated more strongly with agitation R15602CHDBDBFI. Rhabdomyolysis has been observed in mania R15602CHDEBIJE. Plasma catecholamines and their metabolites are elevated in periodic catatonia R15602CHDCJCGG, R15602CHDCACIB, which may be a variant of bipolar disorder R15602CHDBDHFI and bears a strong clinical resemblance to neuroleptic malignant syndrome.
The temporal pattern in which specific features of neuroleptic malignant syndrome emerge is inconsistent across cases R15602CHDBJJEG, R15602CHDBCDGA, R15602CHDCCEHE, but autonomic hyperactivity is often the earliest clinical finding. Although fulminant neuroleptic malignant syndrome may present suddenly, more often the course is indolent, with unexplained episodic tachycardia and blood pressure fluctuations observed early on R15602CHDCCEHE. In particular, elevated diastolic blood pressure may be antecedent R15602CHDDBHDD. In the prodrome that frequently precedes a full-blown syndrome R15602CHDBHJHD, dysautonomic features typically predominate R15602CHDBJJEG, R15602CHDCHADH, R15602CHDBHJBF. Dysautonomia can appear without hyperthermia R15602CHDDJADC or precede hyperthermia R15602CHDCAEJI, R15602CHDDBHDD, R15602CHDBHJBF, R15602CHDCDIDF, which sometimes emerges relatively late R15602CHDBCDGA, R15602CHDCCEHE. Individual differences in the rates of catecholamine release and clearance, which are the primary determinants of their physiological effect R15602CHDEBACI, may contribute to the variability of the clinical course. Opposing effects of α- and β-adrenoceptor stimulation, as well as differing affinities of epinephrine and norepinephrine for these receptors, provide additional sources of variability in clinical presentation over time.
Altered consciousness is considered by some R15602CHDBEFFI to be a sine qua non for the diagnosis of neuroleptic malignant syndrome. In one relatively large series R15602CHDBIJBC, "a striking, frightened facial expression was observed in all cases," accompanied by "a sense of doom" and "overwhelming anxiety" (p. 719). Tollefson R15602CEBBGBDJ described a mute and akinetic patient with neuroleptic malignant syndrome as having "an exaggerated startle response." Catatonic patients retrospectively report intense, uncontrollable anxieties R15602CHDCIJEE. Healthy volunteers viewing a frightening film have increased plasma norepinephrine, but their other catecholamine and endocrine levels are normal R15602CHDBHFIB. Psychological stress is positively correlated with plasma vanillylmandelic acid but not 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, or 5-hydroxyindoleacetic acid, suggesting that the sympathetic nervous system is activated more by transient emotional stress than by persistent emotional conditions R15602CHDBFGED.
Acute, but not subacute or chronic, psychosis and Brief Psychiatric Rating Scale scores indicating global psychopathology and anxiety are positively correlated with serum creatine phosphokinase levels R15602CHDCICCE. Catatonic excitement has been promoted as a highly reliable risk factor for neuroleptic malignant syndrome R15602CHDBBGGD, and labile mood and insomnia consistently precede lethal catatonia R15602CHDBCGHB. "Emotional disturbance" can trigger hyperthermia and many of the clinical features usually associated with neuroleptic malignant syndrome R15602CHDBGGGG, as can acute phencyclidine-induced psychosis R15602CHDCCHFF. Intense emotional or psychological disturbance, with altered frontal cortical function, could be a pathophysiological link between these syndromes and neuroleptic malignant syndrome.
Diaphoresis is common in neuroleptic malignant syndrome R15602CHDBCGHB, with rates from 50% to 100% R15602CHDBIJBC, R15602CHDBJJEG, R15602CHDEAIAE, and is due to direct sympathetic nervous system stimulation rather than circulating catecholamines R15602CHDEAFFC, R15602CHDBIDGA. In contrast to its role in true fever, diaphoresis in neuroleptic malignant syndrome is not part of a coordinated effort to lower body temperature R15602CHDBFFAE. Eccrine sweat glands are the only mammalian organs with a purely thermoregulatory function R15602CHDBBEFI and have the capacity to dissipate heat faster than it can be generated R15602CHDDGGJB, so hyperthermia in neuroleptic malignant syndrome implicates a defective heat-loss mechanism in addition to any increase in thermogenesis. Excessive sweat gland activity is probably responsible for neuroleptic-malignant-syndrome-associated dehydration in some cases R15602CHDBHCGF, and dehydration may contribute to hyperthermia.
Tachypnea and tachycardia in neuroleptic malignant syndrome reflect a hyperadrenergic state, but increased metabolism makes additional demands on the cardiopulmonary system. In one drug-induced syndrome similar to neuroleptic malignant syndrome, body temperature increased in tandem with blood pressure and heart rate R15602CHDCBCII, and body temperature accounts for as much as 16% of the respiratory rate variance in neuroleptic malignant syndrome R15602CHDBFFAE.
Urinary incontinence is another clinical manifestation of autonomic dysfunction in neuroleptic malignant syndrome. The bladder base and internal sphincter consist of smooth muscle innervated exclusively by predominantly α-adrenergic sympathetic nervous system fibers. Voluntary restraint of micturition requires the frontal lobes, and lesions in either hemisphere can cause bladder incontinence R15602CHDEAFFC, R15602CHDDEFJD. In spinal cord patients, diaphoresis and bladder incontinence are associated with flexor spasms of the lower extremities, suggesting an intrinsic relationship among these motor responses R15602CHDCJAFC.
Catecholamine excess alone can produce a syndrome similar to neuroleptic malignant syndrome, as illustrated by the case of a 34-year-old woman who experienced the sudden onset of palpitations, inability to move or speak, and labile postural tachycardia and hypertension R15602CHDCACIB. Mutism, increased muscle tone, hyperactive tendon reflexes, and catalepsy were reproduced reliably by physical activity and anxiety-provoking situations and were always associated with hypertension and tachycardia. Plasma epinephrine and norepinephrine were markedly elevated and correlated with amount of time upright, but urine 24-hour catecholamine and monoamine metabolite levels were normal. She was found to have a hyperactive sympathetic response and peripheral α1-adrenoceptor subsensitivity R15602CHDCACIB.
Hyperthermia can occur when the heat-loss apparatus is defective or when intact thermoeffectors are poorly coordinated. The ineffectiveness of diaphoresis, normally a potent cold effector, in neuroleptic malignant syndrome has already been discussed. The simultaneous activation of both warm and cold effectors in neuroleptic malignant syndrome indicates that although thermoeffectors remain operational, their activities are not coordinated R15602CHDCBABC, R15602CHDBFFAE, R15602CHDCJHCD. This condition alone would be sufficient for hyperthermia to supervene, but in addition there are two likely sources of excess thermogenesis in neuroleptic malignant syndrome: accelerated brown-adipose-tissue-like metabolism (uncoupled phosphorylation) and excessive catecholamine-induced Ca2+ release from the sarcoplasmic reticulum.
Persistent stimulation of sarcoplasmic reticulum Ca2+ release would lead to continuous activation of Ca2+ reuptake mechanisms, releasing heat as a by-product. This could account for the observation that serum creatine phosphokinase levels are positively correlated with 24-hour urinary catecholamine metabolite excretion in neuroleptic malignant syndrome R15602CHDCEEEG. The appearance of elevated muscle enzyme levels in neuroleptic malignant syndrome before clinical signs of autonomic instability are evident indicates that hypermetabolism may precede the full syndrome R15602CHDDFDCE. Hypermetabolism related to hyperthyroidism, in the absence of central dopamine blockade, can produce a syndrome similar to neuroleptic malignant syndrome R15602CHDDDFCG.
Peripheral catecholamines also directly stimulate uncoupled phosphorylation in mitochondria, as occurs in some cases of pheochromocytoma, cold exposure, and treatment with sympathomimetic agents. As in these other examples, prolonged elevation of peripheral catecholamine levels in neuroleptic malignant syndrome may even lead to induction of uncoupling protein mRNA and increased thermogenic tissue mass, suggesting a possible physiological basis for persistent hyperthermia during recovery from neuroleptic malignant syndrome. This thermogenic mechanism is distinct from that related to intracellular Ca2+ homeostasis. Hyperthermia in neuroleptic malignant syndrome can be dissociated from muscle rigidity R15602CHDBIAJB, R15602CHDCAGGD and creatine phosphokinase levels R15602CHDBGEAF, precede extrapyramidal signs R15602CHDCHADH, and persist despite curarization-induced flaccidity R15602CHDBIAJB. The lack of glycogen and lipid stores in muscle biopsies strongly suggests that uncoupled phosphorylation contributes to hyperthermia in neuroleptic malignant syndrome R15602CHDCEJEB.
Asymptomatic creatine phosphokinase elevations occur in patients with psychotic disorders, whether clinically stable or acutely ill, following oral treatment with typical or atypical neuroleptics R15602CHDCFCEH–R15602CHDCAABC. Clozapine is associated with more frequent and higher creatine phosphokinase elevations than are typical neuroleptics R15602CHDCAABC; this is noteworthy because clozapine has significantly greater α2-adrenoceptor activity R15602CHDBCDBE, which is probably the cause of de novo diabetes mellitus in clozapine-treated patients R15602CHDECCEF. Substantial creatine phosphokinase elevations accompanied only by tachycardia and elevated blood pressure may follow neuroleptic treatment R15602CHDDGHEJ, suggesting a hypermetabolic effect mediated by the sympathetic nervous system.
Cardiac lesions caused by elevated catecholamines are indistinguishable from atherosclerotic lesions R15602CHDDJHFA. Short-term hypoxia permits creatine phosphokinase-MB to escape without necrosis R15602CHDBFCCC, and intravenous isoproterenol causes elevated creatine phosphokinase-MB in childhood asthmatics R15602CHDEBHCF. Elevated creatine phosphokinase and focal skeletal myositis occur in pheochromocytoma R15602CHDBAFBD, which releases mainly norepinephrine R15602CHDEBACI. Ischemia mediated by catecholamine-induced vasoconstriction in skeletal muscle is probably the cause of muscle injury in pheochromocytoma R15602CHDDDIBI. Creatine phosphokinase elevations and myoglobinuria in neuroleptic malignant syndrome may exist without rigidity or tremor R15602CHDCHECJ, and haloperidol-induced rhabdomyolysis is associated with autonomic dysfunction but not rigidity R15602CHDBJBHH.
Urinary catecholamines and catecholamine metabolites are positively correlated with blood creatine phosphokinase levels in acute neuroleptic malignant syndrome, but other clinical features are not R15602CHDCEEEG. In patients with neuroleptic malignant syndrome, serum creatine phosphokinase covaries nonlinearly with other muscle enzymes and exceeds by as much as 15-fold the normal extracellular-intracellular gradient, indicating that muscle necrosis alone cannot account for elevated creatine phosphokinase levels R15602CHDEAJIA. Experimental tissue injury models suggest that increased enzyme synthesis represents a reparative response to a noxious agent R15602CHDDAEIC. The noxious event in neuroleptic malignant syndrome could be a relative hypoxia created by a metabolism-perfusion mismatch caused by a hyperactive and unregulated sympathetic nervous system.
Catecholamine-induced Ca2+ release from the sarcoplasmic reticulum may also cause cell death R15602CHDCFCGE. Focal myocardial necrosis occurs in patients with pheochromocytoma R15602CHDEAADE, in rats infused with epinephrine and norepinephrine R15602CHDDJHFA, and in dogs infused with inotropic amines R15602CHDBEBAI. Muscle necrosis in these settings is apparently due to a direct effect of catecholamines on Ca2+ influx R15602CHDCABFH, R15602CHDEAADE. Oxidation of excess catecholamines to catecholamine-O-quinones, with subsequent formation of superoxide radicals that attack cellular membrane and protein constituents essential to energy metabolism, is another mechanism by which excess catecholamines can damage myocytes R15602CHDBADAI.
Muscle biopsy findings in patients with neuroleptic malignant syndrome have yielded minimal or inconsistent results (compare references R15602CEBBGBDJ and R15602CHDBEBGF with references R15602CHDBGJBB, R15602CHDBEFFI, R15602CHDCEJEB, and R15602CHDBDGCD. Muscle abnormalities that have been detected in neuroleptic malignant syndrome resemble those found in malignant hyperthermia R15602CHDBDGCD or consist of endomysial edema with a striking absence of both glycogen and lipid substrate stores R15602CHDCEJEB. Profound depletion of intracellular energy stores strongly implicates uncoupled phosphorylation as the source of hyperpyrexia R15602CHDCEJEB, and the resemblance to malignant hyperthermia in these cases implicates Ca2+ overload as a common etiological factor. A majority of patients with severe neuroleptic malignant syndrome have documented serum hypocalcemia R15602CHDBIJBC, which could reflect a sudden net influx of Ca2+ into myocytes that coincides with a "malignant" phase of the syndrome.
Extrapyramidal signs associated with neuroleptic malignant syndrome include rigidity, tremor, cogwheeling, dystonia, chorea, dyskinesia, opisthotonos, opsoclonus, and posturing R15602CEBDFHDB, R15602CEBCEJCI, DSM-IV). As the data presented here indicate, rigidity in neuroleptic malignant syndrome could be caused by catecholamine-induced changes in intracellular [Ca2+], and tremors could also reflect elevated peripheral catecholamines. Increased muscle tone caused by sympathetic nervous system hyperactivity is independent of, but may coexist with, effects of neuroleptics on the extrapyramidal system, and the presence of more complex motor signs implicates concomitant basal ganglia involvement in some cases of neuroleptic malignant syndrome.
Granulocytosis is a feature of neuroleptic malignant syndrome R15602CEBDFHDB, R15602CHDCFCIG, and sympathetic nervous system fibers innervate lymphoid tissue R15602CHDCBACC. Catecholamines stimulate lymphocytes at low concentrations, but at high concentrations they are inhibitory R15602CHDCBACC. Lymphocyte circulation is mediated mainly by plasma membrane β2-adrenoceptors, whereas granulocyte circulation increases are mediated by α-adrenoceptor stimulation R15602CHDDEDBI. An injection of norepinephrine can raise neutrophil levels to two to three times normal R15602CHDCBICE, and increased peripheral norepinephrine turnover is associated with reduced lymphocyte proliferation R15602CHDCCEHH. The net effect of sympathetic nervous system stimulation is leukocytosis with a "shift to the left."
Blood sugar homeostasis is regulated by the sympathetic nervous system and can be impaired in neuroleptic malignant syndrome. A 44-year-old man with no previous history of diabetes mellitus developed neuroleptic malignant syndrome and fatal diabetic ketoacidosis precipitously following a test dose of zuclopenthixol decanoate R15602CHDDGCDG. Under normal physiological circumstances, the sympathetic nervous system tonically suppresses insulin release through α-adrenoceptors R15602CHDCBGBE; stimulation of the pancreatic sympathetic nerve decreases insulin secretion and increases glucagon secretion R15602CHDCBDGH.
Bilateral E coli anterior tibial fasciitis in one case of neuroleptic malignant syndrome R15602CHDBFGBA may have resulted from ischemic muscle necrosis. Noncardiogenic pulmonary edema in neuroleptic malignant syndrome R15602CHDCAIEA could be caused by excess sympathetic nervous system activity because pheochromocytomas can cause pulmonary edema R15602CHDDDIBI. Necrotizing colitis without fever, possibly a result of sympathetic-nervous-system-mediated vasoconstriction, has been attributed to neuroleptic treatment R15602CHDCJAGH, and ischemic bowel followed respiratory failure in another case of neuroleptic malignant syndrome R15602CHDBHJHD. Paralytic ileus in neuroleptic malignant syndrome R15602CHDCGJAJ may be the result of intense sympathetic nervous system activation R15602CHDCCAGC.
The intrinsic capacity of the sympathetic nervous system for fragmented, autonomous activity normally is suppressed by inhibitory regulatory inputs originating in the frontal cortex and mediated by hypothalamic nuclei. The hypothalamus integrates afferent thermosensory information and coordinates thermoeffector responses by means of dopaminergic modulation of preganglionic sympathetic nervous system neurons. Disruption of these inhibitory inputs leads to dysregulated sympathetic nervous system hyperactivity with uncoordinated, excessive stimulation of end-organs by autonomous functional components of the sympathetic nervous system—vasomotor, sudomotor, inotropic, thermogenic, and others. In particular, extreme psychic distress (altered frontal lobe function) or acute dopamine antagonism (of hypothalamospinal tracts) may alter sympathetic nervous system function and lead to profound disturbances of homeostasis. Manifestations of dysregulated sympathetic nervous system hyperactivity include increased muscle metabolism and tone (due to increased intracellular [Ca2+]), of which elevated creatine phosphokinase is one indicator; increased mitochondrial thermogenesis (caused by uncoupled oxidative phosphorylation); ineffective heat dissipation related to unregulated vasomotor and sudomotor activity; fluctuations in vasomotor tone leading to labile blood pressure, flushing, and pallor; granulocytosis; and urinary incontinence.
The inherent autonomy of these circuits permits these effects to be produced independently of one another, but they may interact to destabilize homeothermic and hemodynamic systems, producing the clinical syndrome of neuroleptic malignant syndrome. F1 illustrates how such a pathophysiological cascade might occur. The relative mutual independence of neural and adrenal segments of the sympathetic nervous system, and the differential effects of norepinephrine and epinephrine at adrenoceptors, contribute to the unpredictable course and fluctuating clinical signs and symptoms that characterize this disorder. Direct effects of neuroleptics on extrapyramidal systems may interact with sympathetic nervous system dysfunction to produce the final clinical picture.
Presented in part at the 53rd Annual Scientific Convention of the Society of Biological Psychiatry, Toronto, May 27–31, 1998. Received March 2, 1998; revision received July 30, 1998; accepted Aug. 25, 1998. From the Department of Psychiatry, Harvard Medical School, Brockton-West Roxbury DVA Medical Center. Address reprint requests to Dr. Gurrera, Brockton DVAMC (116A), 940 Belmont St., Brockton, MA 02301; email@example.com (e-mail). Supported by DVA Medical Research Funds.
Pathophysiology Cascade in Neuroleptic Malignant Syndrome
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- Tim Hortons Cleaning the Capital
- Election Voters' List
- Welcome to New College and University Students
- Fall-Winter Recreation Classes
- FIFA Women's World Cup Canada 2015™
Tim Hortons Cleaning the Capital
Show your community pride and take part in this year's fall city wide cleanup campaign!
Election Voters' List
Check to see if your name is on the Voters' List before September 16. Avoid delays at your voting place.
Welcome to New College and University Students
The City welcomes first-time students by helping them explore the city and discover all they need to know about living in here.
Fall-Winter Recreation Classes
Back to fun! Register now for fall and winter activities.
FIFA Women's World Cup Canada 2015™
Tickets are on sale now! Find out more.
Use free transportation to get to TD Place for special events
Heading to TD Place? Find out how the best way to get there.
Highways 417 and 174
Take a look at the ramp closures and lane reductions on Highways 417 and 174.
Council and Committee Meetings and Reports
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subset: commoncrawl


text:
April 26, 2004
Tifton- Pat Melton started praying Sunday night that rainy weather wouldn't stop this protest.
Members of the NAACP want the Tift County School Board to remove Richard Golden as the board's president and they want him to resign.
"We are asking Mr. Richard Golden to do the best thing in the interest of the community, in the interest of the teacher's that serves and most of all the students," Melton said.
They are asking voters in Golden's district to recall him. That would take 15 percent of the voters in the district signing a petition. The NAACP has also contacted the governor's office.
"Once he's indicted, that's when they step in. We have to wait until the grand jury meets in May," she said.
Golden is charged with shooting the car of Derrick Pettiford last week when he caught him fishing on his property. Pettiford's family says he shouldn't have trespassed, but Golden should have called the police instead of taking the law into his own hands.
"I'm not condoning what my grandson did when he trespassed," said Solomon Pettiford, Jr.
Pettiford's grandfather wants people to boycott Golden Waste, a company Golden used to own, but has apparently sold.
"Every black person, including myself. I'm a Golden Waste participant. Will no longer be a Golden Waste participant," he said.
Whatever it takes, members of the NAACP say Golden's days as a public servant should be over.
By the way, Pat's prayer was answered. The rain held off, until the moment the protest ended. Richard Golden has not returned our phone calls.
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Irrational Installation (from Mike T)
My company recently shelled out $8,000 for a mobile TV conference endpoint that allows us to do a two-way video conference from the field using a fairly small device (about the size of a large digital camera). It's a pretty cool idea, but we're finding that the hardware and software design are just not quite Enterprisey enough for our liking.
As an example, here is the official company reply on their support forum explaining how to reset the device to factory default settings:
Hardware reset procedure Xcaster (all settings will be reset to factory default)
Required equipment:
- Small magnet
- Boot up the Xcaster
- Place a magnet close to the lower left or right side of the camera lens (red circle on image below).
- After 5-10 seconds, the GUI screen should turn white, and the Xcaster will reboot.
- When the screen turns white, remove the magnet and wait for the booting to complete.
- Reset procedure is now complete.
Irrational Installation (from D. Irigawa)
If you've never had to install IBM Rational ClearCase, consider yourself lucky. On the pain scale, it sits right between taking your bottom lip and stretching it over your head to the back of your neck, and actually using Rational ClearCase.
After spending several hours of pouring through generally incomprehensible documentation to try to figure out an approach for get started with the installation, I stumbled across this mind-bending sentence:
"Run a silent install of Installation Manager using the Installation Manager installer, see Installing Installation Manager with the Installation Manager installer."
Installs the Manual (from Justus)
Greetings from an installed user! No, this thing was not installed by the hard dish. The hard disk took some conventional screws to install the manual.
Re: Unstructions: The Factory Reset, Irrational Installation, and Installs the Manual
2011-06-30 12:19 • by Childish (unregistered)
The Factory Reset magnet trick takes me back to my first home computer, a Mac Plus.
Circa 1985, I got the Macintosh and Lisa Assembly Language programming kit. It had some 3.5" disks, a book, & a small plastic switch.
It turns out that the plastic switch was the reset button. Find the air slot on the side of the Mac Plus, & snap it in. Since Macintosh was user friendly, they didn't want regular people to have a reset switch.
Re: Unstructions: The Factory Reset, Irrational Installation, and Installs the Manual
2011-06-30 12:25 • by Jack (unregistered)
That's not Engrish.
That's not even bad Engrish.
That is an alien intelligence attempting to make contact with the human race. See, it isn't as easy as we thought, establishing a meaningful understanding from which to start decoding each other's languages...
Re: Unstructions: The Factory Reset, Irrational Installation, and Installs the Manual
2011-06-30 13:11 • by C-Octothorpe
Obviously the comments were written by a neural network.
Re: Unstructions: The Factory Reset, Irrational Installation, and Installs the Manual
2011-06-30 13:21 • by Aaron (unregistered)
The whole Rational tool set was designed and written by a sadist with a deep, personal hatred of developers. That's the only possible explanation for it.
The fact that it actually does some awesome stuff when it deigns to work just makes it more evil.
Re: Unstructions: The Factory Reset, Irrational Installation, and Installs the Manual
2011-06-30 14:28 • by Jochen (unregistered)
IBM's setup programs are epic.
Once, I had to install an update for IBM's WebSphere Application Server. You are supposed to install such updates using the UpdateInstaller for WAS. The only problem was that my installed version of UpdateInstaller was too old, so I had to update the UpdateInstaller first. Luckily, updates for the UpdateInstaller don't require another UpdateInstaller. The update program for the UpdateInstaller even found my existing installation of UpdateInstaller, but it hung while creating an uninstaller for the update of the UpdateInstaller. I had to uninstall the UpdateInstaller completely and re-install the updated UpdateInstaller in order to use it to install the update for WAS.
I guess that's what you should expect from a 100 year old company. Enterprise^2.
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|Redefining Near »


text:
Healthy Casserole Recipe: Lighter Stuffed Pasta Shells
We've been fans of cheese-stuffed pasta shells our whole lives. It's one of the first baked casserole dishes we can remember eating - and liking! - and it remains a favorite today. Don't let the fact that this is a "lighter" version turn you off. It's still cheesy and delicious, but now it's just a little better for us!
This recipe employs one of our favorite ways to lighten up a recipe: simply adding more vegetables. Be sure to cook these onions and mushrooms until they're completely soft and golden. The deeply savory flavors of the vegetables really enrich the final dish.
Cottage cheese has a rich flavor and creamy texture that makes it a surprisingly good stand-in for ricotta. We drain the extra liquid to give us a more compact filling and add a handful of mozzarella cheese for...well...cheese! The parmesan sprinkled on top also gives a burst of cheesy flavor in every bite.
12-ounce box jumbo pasta shells
2 cups (16 ounces) cottage cheese, whole or 2%
1 onion, diced small
10 ounces mushrooms, diced small
3-4 garlic cloves, minced
1 teaspoon oregano
pinch nutmeg
10 ounces baby spinach
3/4 cup (about 6 ounces) shredded mozzarella cheese
32-ounce can crushed tomatoes, tomato sauce, or your favorite jarred tomato sauce
1/4 cup (about 2 ounces) finely shredded Parmesan cheese
Pre-heat the oven to 375°.
Boil a large pot of water, add a tablespoon of salt, and cook the pasta shells until barely al dente. You want them a little under-cooked for this dish because they will absorb more liquid in the oven. Set the shells aside to cool.
Set a strainer over a bowl. Pour the cottage cheese into the strainer and allow it to drain for at least 15 minutes. Stir occasionally.
Heat a teaspoon of olive oil in a large skillet over medium-high heat. Add the onions and a healthy pinch of salt, and cook until translucent and beginning to brown, 5-7 minutes. Add the mushrooms and cook until the mushrooms have released their liquid and turned golden, 5-7 minutes. Stir in the garlic, oregano, nutmeg, and another good pinch of salt. Cook until fragrant, 30 seconds.
Turn the heat down to medium. Add as much of the spinach as will fit in the pan and cover with a lid. After a minute or two, uncover and stir the spinach. As it wilts and creates more space, add the remaining spinach to the pan. Continue stirring and steaming until all the spinach is wilted. Uncover the pan and stir the spinach for a few minutes to let the residual liquid evaporate. Remove from heat.
Combine the drained cottage cheese, the cooked vegetables, and the mozzarella in a large bowl. Taste a spoonful and add more salt and pepper if desired.
Pour half of the can of tomatoes into the bottom of a 9x13 casserole or other baking dish. Scoop a healthy spoonful (2-3 tablespoons) of the filling into each shell and arrange them side-by-side in the baking dish. Pour the remaining sauce over the top and cover tightly with foil.
Bake for 30 minutes covered and 10-15 minutes uncovered. The tomato sauce should be bubbling around the edges and look thickened in the pan. Sprinkle the Parmesan over the top of the shells in the last few minutes of cooking. Allow the casserole to sit for 10 minutes before serving.
Leftovers will keep refrigerated for up to a week.
Related: Five Ways to Eat Spinach
(Images: Emma Christensen)
Per serving, based on 4 servings. (% daily value)
13 Comments
This looks scrumptious! Another healthy alternative is to use cashew ricotta. I've tried it in shells and it works perfectly. Found this recipe: http://www.food.com/recipe/cashew-ricotta-284547
I love stuffed shells but i like to experiment w/ a filling that is not cheese (im in a lactose intolerant family). I already make cashew milk so i'm going to try the cashew cheese, thanks.
Would sauteed spinach work inside, or would it get too mushy or dry from being baked after being sauteed?
I'm wondering why one should use 2% or whole cottage cheese instead of fat-free ricotta (if going for a healthier version). Is cottage cheese healthier than fat-free (or regular) ricotta? Or does fat free ricotta not cook up well in a dish like this?
splim - You can certainly sub in non-fat ricotta if you'd like. I think it would work fine in the recipe.
Personally, I find that lower-fat cottage cheese is a bit healthier (in terms of fat and calories) than low-fat ricotta and tastes better than non-fat ricotta.
Try these with riced potato and spinach as a filling. Not quite the same a ricotta, but equally delicious.
I'm going to try this with sheep's milk ricotta sometime soon.
I made this last night and while it took a little bit of time, I put that on me, not the recipe. Tasted great! Fantastic second day lunch!
Looks delish. Although I think I might put the moz on top of the shells. I think I would miss the melty cheese on top. Definitely on my meal list for this week.
@Emma Christensen - Do you think I could get away with preparing this dish the night before baking it? I was thinking I could put everything together, fridge, and then bake the next evening for dinner. Would that work?
I made this dish this week and YUM! I made it the night before without baking it, placed it the fridge with the foil on top the, and baked it the next night. My husband (a meat lover) commented that they were great and the mushrooms really took the place of meat. We have had them for left overs for lunch and dinner and they continue to be delicious!
The "flavor issues" that fat free ricotta seems to have is easily remedied by using a GOOD Parmigiano Reggiano cheese.
Tried this recipe and
LOVED it! I didn't feel over stuffed like I normally do, and I even had a second helping. It was very flavorful and delicious. I will definately make this recipe again!
I just made this tonight, and my husband and I loved it! The filling is delicious -- the cottage cheese worked really well, and the spinach and mushroom gave it some more heft so it was more filling. There was just enough mozzarella to give it that melty satisfying feeling that you get with stuffed pasta without being quite as tough on your waist-line.


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Series: Heartsong Presents
A Truly Yours Digital Edition. . .Caroline is a worrier…. Her husband died and left her with little money or survival skills. Her son thinks the choices she's made since then are foolish. And every time an opportunity looks good, something makes her second guess herself. Rodney has always thought life was good—until a heart attack laid him out flat. Retired now from his executive lifestyle, he begins to realize he wasn't much more than a workaholic. Marriage isn't on either of their minds…but their minds are not God's, and He is busy taking care of the lilies of the field—and His children.


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SHERIDAN— The Sheridan Fiber Arts Guild will hold their annual show at Sheridan Fulmer Library Oct. 3 through Oct. 30 on the mezzanine.
The show features a variety of fiber arts mediums including quilting, felting, embroidery, cross stitch and knitting from local fiber artists.
A public artist reception will be held tomorrow from 5-7 p.m. Also in October, in the Inner Circle, entries from the 2014 Wyoming Junior Duck Stamp art contest will be on display. For more information call Christina Schmidt at 674-8585 ext 29.
SHERIDAN— The Sheridan-Johnson County chapter of the Wyoming Archaeological Society will meet at 6 p.m. Thursday at the Sheridan Holiday Inn, in the Le Gourmet room. Dinner will be ordered from the menu, however it is not necessary to order dinner to attend the free program. Following dinner, Wyoming State Archaeologist Greg Pierce will address the society regarding his new position as state archaeologist, and will discuss some of his latest fieldwork. Pierce succeeds Dr. Mark Miller as Wyoming State Archaeologist. Miller retired this spring after 30 years as state archaeologist. Reservations are not necessary to attend the free program. The Archaeological Society welcomes the public to attend. For more information call Scott Burgan at 673-5997.
SHERIDAN—The Sagebrush Community Art Center is having kids' Halloween costume classes Saturday, Oct. 4 and Saturday, Oct. 11.
On Oct. 4, the kids will be making masks and on Oct. 11 they will be designing their own costumes. There is a $6 registration for each class.
You can make reservations by calling 674-1970 or enroll on the same day of the class. For more information, call Sagebrush Community Art Center at 674-1970.
UCROSS—The artwork of Sheridan College art instructor Tawni Shuler will be on display this fall at the Ucross Foundation Art Gallery.
The opening reception will be held on Saturday, Oct. 4, from 3-5 p.m. Gallery hours are Monday through Friday, 8:30 a.m. to 4 p.m.
The Ucross Foundation Art Gallery is located at 30 Big Red Lane, near Clearmont. Call (307) 737-2291 for more information.
SHERIDAN—KLIFE is holding a youth rally on Monday from 4:30-5:30 p.m. at the Sheridan Junior High featuring Bethany Hamilton. Bethany Hamilton is a pro-surfer who's life story was featured in the movie 'Soul Surfer' and she is currently appearing on 'The Amazing Race' and 'Dolphin Tale 2'. This event is open to the public and tickets are $5 per person and are for sale at Roosters. For more information please call Amy Rabon at 461-0874.
SHERIDAN—Jentel Artist Residency Program is pleased to present this month's residents in an event open to the public. "Jentel Presents" will take place Tuesday, October 7, from 5:30 -7 p.m. at Sagebrush Community Art Center, on the corner of 5th and Broadway.
This month's presenters include a photographer, a creative non-fiction writer, a mixed media/collage artist, a sculptor, an encaustic artist and an essayist. "Jentel Presents" is a community outreach program that features visual presentations and readings by the visual artists and writers at the residency. Presenters include: Shigeki Yoshida, a photographer; Charlotte Austin, a creative nonfiction writer; Naomi Reis, a mixed media/collage artist; Emily Dunlap, a sculptor; Jane Guthridge, an encaustic artist; and Renee Restivo, an essayist.
There is no admission charge for "Jentel Presents" and refreshments are available. For more information please visit www.jentelarts.org or call Jentel at (307)737-2311.
SHERIDAN— Ackita Win will be holding their next fall meeting Tuesday, October 7 at 6 p.m. They will be meeting at Designing Dinners and will order from the menu. The program will feature Cadet Girl Scout Troop #1333. Designing Dinners is located at 615 Broadway St.
SHERIDAN— 'Science Saturday' continues next Saturday, Oct. 11 from 10 a.m. until Noon. The subject will be "The Hip Bone's Connected to the…" and will explore anatomy and physiology. The lecture will be at the Sheridan College Science Center, 3059 Coffeen Ave. For more information call Sarah Mentock at 763-0976.


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(Richmond, Virginia-AP) Dec. 18, 2003 - A federal Appeals Court in Virginia has reinstated a death sentence for a man convicted of killing two students during a shooting spree 14 years ago at a Greenwood elementary school.
The Fourth Circuit US Court of Appeals on Wednesday overturned an earlier ruling by US District Judge Matthew Perry. The Appeals Court's ruling also reinstates Jamie Wilson's convictions.
Perry found Wilson was not competent before he pleaded guilty but mentally ill to killing two 8-year-old girls, Shequila Bradley and Tequila Thomas, and injuring seven other students and two teachers at Oakland Elementary School in 1988.
The Appeals Court ruled that Perry was wrong in deciding Wilson was not competent to stand trial and not competent to be executed.
Wilson walked inside the lunchroom and shot at students and adults with a handgun before walking into a classroom and firing more shots. Wilson's lawyers argued the then 19-year-old's mental illness led to the shooting.
posted 7:42am by Chris Rees
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Here are 5 things to know about in the Patchogue and Medford area today. Browse the events section for more.
1. The Patchogue Village Board of Trustees met Tuesday night. Check back to Patch for updates from the meeting.
2. A Patchogue man was arrested after punching a police officer Tuesday morning. .
3. A Pat-Med alum was recently featured in the Columbia Tribune for playing saxophone at the University of Missouri. .
4. will take place at at 8 p.m.
5. Want to blog on Patch? Apply here.


text:
ntop shows the current network usage. It displays a list of hosts that are currently using the network and reports information concerning the IP (Internet Protocol) traffic generated by each host. The traffic is sorted according to host and protocol. If you haven't set ntop administrator's password, ntop could not start. Because setting this password for the first time makes some internal configurations for ntop to run.
You need a web browser to access the information captured by the ntop program. Locate your browser at
By default, ntop will permit everyone to see network activities from the above address. If you limit the access to ntop so that it asks for a password whenever a connection established, do the followings.


text:
Full size version is only available to registered users
Please Register as a New User or Login as Existing User to gain full access to all the photos on this site. Registration is quick and completely free.
Unregistered users can only view full size photos that have been added this month.
Cleaning Dragons Teeth
© Mark Collins, Mar 2012
Route: Arete des Cosmiques
Climbers: Unknown Climber
Camera used: Nikon D70s


text:
On the heels of news of loan forfeitures and low beet payments, the local sugar industry received more bad news this week: Sugar prices are likely to stay depressed in 2014, according to supply/demand outlooks released this week by the U.S. Department of Agriculture.
USDA says sugar production in the U.S. has gone up, Mexican imports of sugar are expected to remain high and it is estimated about 2.4 million tons of sugar will be sitting in storage in September 2014.
"The result of this report -- for now anyway -- is a lousy outlook for sugar prices," American Crystal Sugar CEO Dave Berg wrote on his blog.
This scenario would make 2014 the second straight year of severely depressed sugar prices. This year, Crystal Sugar defaulted on a government loan of $71.2 million under the federal government program that provides relief when sugar prices are down. It was the first time in more than a decade low sugar prices triggered loan forfeitures.
The market price for raw sugar was about 21.5 cents a pound when Crystal announced it would forfeit the sugar it put up as collateral for the government loans. The regional loan rate for sugar was about 23 cents per pound.
"Today, it's about the best place we have to sell sugar," Berg told The Forum newspaper of Fargo-Moorhead in October.
Berg told The Forum the forfeiture did not represent a financial hit for American Crystal.
"Actually, it's beneficial to our financial health," he said. "This is the way the sugar program is supposed to work."
Lower sugar prices do, however, affect payments to the 3,000 growers in the cooperative. Growers will be paid about $38 per ton for their 2013 crop, down from $68 a ton last year.
While announcing that payment on his blog last week, Berg said most of Crystal's growers will lose money and in many cases "they will lost a lot of money."
On his newest blog reporting the USDA report, Berg writes:
"I really hate to be so gloomy with these reports all the time, but this most recent set of estimates was NOT what we in the sugar producing end of the business were hoping for."
Some highlights of the USDA report:
- The sugar-cane crop in Louisiana is expected to be a record 1.7 million tons of processed sugar.
- USDA expects 2 million tons of Mexican sugar coming to the U.S. in 2014.
- USDA predicts 2.4 million tons of sugar will be in silos and warehouses on Sept. 30, 2014. Berg's blog says that's about 20 percent of the total used every year and 700,000-800,000 tons more than needed on hand.
(Mike McFeely is a talk-show host on KFGO-AM in Fargo, N.D. He can be reached at email@example.com. Follow him on Twitter @MikeMcFeelyKFGO.)


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30 Day Video Game Challenge - Day 2: Favorite Character
Link - Legend of Zelda Series.
For a character with an underdeveloped character, I really like this character. Bad wordplay aside, I think Link a is much more relatable protagonist than even the hyper-customizable ones from Mass Effect or Elder Scrolls and such, and his silence works really well towards that.
Think about it, what do you know about Link off the top of your head. He's a hero, and he wears green. The rest is up to the player to decide.
(I guess the same could be said about any silent protagonist, but Link pulls off green really well!)
I'll continue catching up later. I'm gonna rewatch the original Evil Dead.


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Today, May 31, 2006 marks the end of the University of California as the sole manager of Los Alamos National Laboratory (LANL), after a 63-year run. Tomorrow LANL will come under the management of Bechtel, the University of California, BWX Technologies, and Washington Group International, collectively known as Los Alamos National Security (LANS), LLC, a private, for profit enterprise.
When nuclear testing ended in 1992 Laboratory personnel scrambled to find new missions for the institution. The 1990s transition to the Stockpile Stewardship Program of maintaining our nuclear weapons without testing made a lot of people nervous. Some critics initially doubted this program, but more weapons specialists are now putting their faith in it. Los Alamos is at a turning point not only with a new managing entity, but in the fundamental way that weapons are designed, fielded, and managed. If successful, the Reliable Replacement Warhead (RRW) program may reinvigorate some of the lost mission or give impetus to a new mission in a focused and tangible way for the first time since testing ended.
The Stockpile Stewardship Program, by all reliable accounts, is working well enough to support yearly weapons certification. And RRW may reinvigorate excitement among employees and facilitate something of a return to normalcy and respite from the turmoil of the last several years that included the Wen Ho Lee incident, charges of missing classified computer drives, and other managerial problems that demoralized employees and drove out a good number of staff.
But change is inevitable. And usually change is good. LANS should seek to preserve what science and basic research it can. And in doing this, LANL's new managers need to reinvigorate the scientific mentoring culture that once permeated the institution. Rather than driving the final nail in the coffin of basic research and freedom of academic science at the Department of Energy Labs, this management change should be turned into an opportunity for the national laboratories and the Department of Energy to reinvigorate their missions, clean up their operating structure and oversight methods, motivate and reward their staff members, clarify their responsibilities in the post-Cold War era, and develop a strategy that maximizes return and value for every dollar invested in the national labs. Such a model will command respect from both complex supporters and critics.
(Anne Fitzpatrick spent two tenures at Los Alamos during her career, as a graduate research assistant in the mid-1990s and later as a Technical Staff Member)


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Editor's Choice 2009
Editor's Choice 2009
Balanzza Digital Luggage Scale Review
Anxiety sucks. Piece of mind is awesome. The Balanzza Digital Luggage Scale is here to keep gray hairs at bay while possibly saving you money while traveling through airports. As any traveler knows, most airlines charge you ...
Gunnar Optiks Edge Glasses Review
I spend countless hours in front of my computer. This often equates to poor posture, a strained neck and a set of eyes that feel like they've been staring into the sun for days on end. Enter the Gunnar Optik glasses. They're de...


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A collection of news and information related to Guy Fieri published by this site and its partners.
Top Guy Fieri Articles
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Amazon Drops Discovery and Scripps Shows, with Scripps the Bigger LoserStory | Mar 26, 2014 | 12:30 PMAs Amazon.com spends more money on original and exclusive content for its streaming-video service, the Internet retail giant is declining to renew deals for some TV content. Amazon Prime Instant Video, available through the Prime free-shipping program,...
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Food Network Renews 'Beat Bobby Flay' as Cabler's Ratings Perk UpStory | Apr 7, 2014 | 10:30 AMFood Network has ordered another 26 episodes of its latest Bobby Flay series, "Beat Bobby Flay," which is among a handful of new shows showing some life for the Scripps Networks Interactive cabler this past quarter. Scripps Networks has been under...
Go Away With ... Guy FieriStory | Dec 17, 2013"Life is a road trip," says celebrity chef and Food Network television personality Guy Fieri. "It's a continuous process where the destination can be secondary. It's fun and educational and is a great way to learn about your country." Fieri latest...
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Jimmy Fallon Premieres 'Tonight Show' in New York: 'I'll Be Your Host...For Now'Story | Feb 18, 2014Dance steps with Will Smith. A concert with U2 under a blood-red sky. Tributes from Robert DeNiro, Lindsay Lohan, Tina Fey, Stephen Colbert and Mike Tyson. Not bad for a first day on the job. Rather than brag about the entire affair, Jimmy Fallon, clad...


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UXmas BundlePosted by on December 05th, 2011
We're celebrating Christmas nice and early this year. If you planned on spending your left over quarterly budget on eggnog and Christmas decorations, we're hoping that you do the responsible thing instead and buy yourself a UXmas present.
We called it UXmas because it includes four great tools at a gift of a price. They are User eXperience enhancing tools that will make life easier for you and make your site better, easier and more effective.
So here's our UXmas offer:
You get 3 user testing projects for $700, saving $350. If you've already got an account we'll credit the extra time to it.
You get to vote on which three of the following three excellent tools you want us to include for free. Each option has 12 months access and is fully featured:
• OpenHallway (Worth $624)
Record screencast video and audio of users testing your website, locally or remotely – all from the comfort of your browser
• ConceptShare (Worth $600)
Markup visual designs collaboratively, sketch directly onto images, compare alternatives side-by-side and collaborate and get approval remotely.
• HotGloo (Worth $336)
Rapid collaborative wireframing – design your page layout and focus on your message, your navigation and your interaction before you add graphics.
• SnapEngage (Worth $540)
Live chat with your site visitors and customers.
• Websort (Worth $2,499)
Card sorting is a simple but effective way to discover how people think your site content should be organized.
• Plainframe (Worth $1,499)
Allows you to easily and quickly put your navigation structure into a plain, clickable site.
Hopefully that covers all the bases. $1,050 worth of user testing projects (3 studies), for $700, and 12 months access to the three most popular UX tools for free.
The UXmas offer will only be available for two days starting on Thursday 15th December, but you will be able to request an invoice/purchase order and pay within 21 days. Please start talking to whoever needs to authorise the payment and any other teams that may want to use the bonus tools.
Merry Christmas and Happy Testing!
The More You Tweet, The Bigger The Discount – Starts Today!Posted by on October 10th, 2011
Want to get Loop11 credits for as low as $11? Well here's your chance! To celebrate 11.11.2011… Loop11 is offering the usability testing opportunity of the century!
Between October 10, 2011 and November 10th 2011, the more @Loop11 tweets there are the bigger the discount will be on November 11th, 2011. You won't get a chance like this for another 100 years!
We have set five thresholds:
- 100 Tweets = $300
- 250 Tweets = $250
- 500 Tweets = $100
- 750 Tweets = $50
- 1000 Tweets = $11
This promotion starts on October 10th, 2011.Visit our promo page to learn more and Tweet about it.
Happy tweeting and testing!
Scheduled System MaintenancePosted by on July 15th, 2011
Loop11 will be conducting scheduled maintenance on Sunday July 17th, 2011 beginning at 22:00 PM UTC (Co-ordinated Universal Time), and lasting up to 4 hours.
During this time, the Loop11.com website will be temporarily inaccessible. Any content hosted on Loop11.com will not be accessible by you or your project participants. During this time a message will be posted on the Loop11 website alerting visitors of the scheduled maintenance.
This is a major service upgrade including database improvements and server updates. We appreciate your patience and can assure you the service will be restored as quickly as possible.
• Eastern Daylight Time (North America): Sunday, July 17: 6:00pm
• Greenwich Mean Time (Europe): Sunday, July 17: 11:00pm
• Eastern Standard Time (Australia): Monday, July 18: 8:00am
For additional time zones, please reference www.timeanddate.com.
We apologise for any inconvenience caused, if you have any queries relating to this notice please email us at email@example.com.
See Loop11 @ UPA 2011 and win an iPad!Posted by on June 16th, 2011
It' that time of year again, when usability professionals from around the world converge for a few days to network and engage with the greater UX community. This year UPA 2011 is in Atlanta, Georgia…. And as always, Loop11 will be there in force, giving away another iPad2 and plenty of stickers.
But it doesn't stop there…. Bill Albert, author of several UX books and Director of the Design and Usability Center at Bentley University will be showcasing Loop11 during his workshop on remote and unmoderated user testing. This a great opportunity for those of you who haven't tried remote testing or Loop11 to get a demo from one of the world's industry leaders.
Loop11 will be at booth number 2, so pop by to have a chat, try out our iPad usability test demo and grab some stickers for your chance to win an iPad2!
See you there!
Loop11 – Now with VideosPosted by on April 19th, 2011
More than anything else, the one thing our customers ask us the most is "Do we/can we/when will we provide user videos?"
Finally, we can say "Yes, now we do!"
As you know, Loop11 provides in-depth, quantitative usability metrics by tracking every aspect of a user's experience on your website and makes available all the data you need to identify usability issues and make informed decisions to improve the user experience of your website.
The one thing Loop11 hasn't been able to provide you with – until now – is videos of each participant. So, we teamed up with the guys from OpenHallway who have the only task-based video AND audio recording system available for the UX community.
Their videos allow you to see every mouse movement, click and scroll your users take when undertaking tasks specified by you on your website. Coupled with the metrics you get from Loop11 it's a powerful combination – that no other single UX tool provides – enabling you to delve deeper into the user experience of your website.
Generating the OpenHallway videos and Loop11 metrics is, in fact, something that has always been possible. We haven't needed to do a technical integration to enable this. Here's how you do it:
1: The first step is to create your project in Loop11, just as you normally would. Grab your project URL you
are provided upon launch and head over to OpenHallway.
2: With your OpenHallway account create a new project and then select Create a New Scenario
3: Follow the prompts and you'll be provided with your recording link. Simply distribute this to your
4: Watch your videos come in! Here's how they look…
It's a brilliant way to get all these metrics and videos to give you the information you need to pinpoint usability issues and understand your user's behaviour.
Happy Testing!
Loop11 Partners with Qualitative Usability ToolPosted by on March 29th, 2011
That's right, now you can get the best of both worlds… quantitative and qualitative. There's a plethora of information on quantitative versus qualitative research methods. Best practice guides suggest a mix of both to effectively capture a more holistic perspective. A challenge, however, is how to combine qualitative and quantitative testing in a productive way to obtain statistically significant usability data to drive user-centered design. That's where Loop11's partnership with TryMyUI comes in. When Loop11 and TryMyUi are used in tandem, designers, researchers and marketers have a powerful set of metrics to optimize the user experience.
What's the difference?
The difference between quantitative and qualitative research is often explained using contrasting terminology, like "hard vs. soft", "numeric vs. non-numeric", "statistics vs. insights", "measure vs. explore", "what vs. why". The quick contrasts are useful to highlight both the strengths and limitations of each approach if used solely without consideration of the other.
Broadly speaking, quantitative research can provide path and performance analyses by capturing the "what" of user behavior. Loop11 provides quantitative measures of real user behavior through clickstream analysis. It delivers quantitative metrics such as task completion rates, number of clicks, time on tasks, and detailed path analysis. Data generated from users' clickstream are automatically presented in real-time reports.
The quantitative measures from Loop11 are especially useful if researchers want to:
- Identify any usability problems
- Measure task efficiency and success
- Compare against competitor usability metrics
- Run regular usability benchmarking studies
In contrast, a goal of qualitative research is to gain valuable insight into the thought processes behind user's actions. TryMyUI is remote usability testing tools that capture the "voice of the customer" via a video recording and a written summary documented by the user. As users navigate a website, they "think aloud", verbalizing their thoughts as they complete the tasks or questions posed by the researcher. For example, a user may express surprise to find the "register" button in a particular location on the site. Quantitative research tracks that the user clicked "register" and what the user clicked on before and after. The additional insight that the user was "surprised" augments the analysis of the user's behavior and the researcher observes this first-hand by viewing the narrated video.
What you can learn from the qualitative measures from TryMyUI:
- How does the user experience match the user's natural expectations about how things work
- Why is the user experiencing this with in-context feedback
What's the linkage?
Loop11 provides the quantitative measures through metrics and reports, and TryMyUI delivers the qualitative insights via narrated videos and written answers to survey questions. With this easy-to-use, on-demand testing tool, any researcher or marketer can simultaneously gain insight into both the "what" and the "why" of user behavior.
Although there is no single usability tool that provides this powerful combination, the combined functionality can be replicated by initiating a project in Loop11 and then augmenting the testing process in TryMyUI.
The process is straightforward:
1: Open an account on TryMyUI.com and Loop11.com. Both sites offer a free trial for the first project
to help you get started and become familiar with the setup process and results.
2: At Loop11, create the task scenarios you want the participants to complete. When you launch
your project copy your unique project URL and head over to TryMyUI.
3: Paste the Loop11 project URL in "Web Site Address". There's no need to re-enter the task scenarios
as that information is already captured in the Loop11 project URL.
4: Use the default "Survey Questions" or customize as needed. Select the demographics. Select number of testers.
5: TryMyUI handles the rest and will deliver videos of each test user navigating the website with the "think aloud"
narration. Users will also provide written answers to any "Survey Questions".
Happy Testing!
Planes, trains and usability conferences.Posted by on June 07th, 2010
May was a crazy month for us at Loop11. After kicking the month off at the Conversion Conference in San Jose, we came back to Australia for a few days, before heading off to Europe for a whirlwind tour. With the Icelandic volcano wreaking havoc, and British Airways staff going on strike, the odds of us getting stranded were high. However, with some perseverance and ingenuity, we prevailed and made it to every destination on time.
We attended the NNG conference in London for 2 few days to exhibit, then whizzed off to Munich for the "piece de resistance" for usability professionals; the 2010 UPA conference in Munich. This was the first time the annual UPA conference was held outside the USA. So we were a bit unsure of what to expect. But it turned out to be a great event, not just for UPA but for Loop11 too. We talked to a lot of usability and IT professionals wanting to know more about Loop11 and giving us very insightful feedback. Based on our discussions with people in Munich, we will be fast tracking some new features and offers to our members.
The most interesting thing about UPA 2010 in Munich, is how many people already knew about Loop11 and how many people were seeking us out to give specific feedback, or discuss how they want use Loop11 more in-depth. Maybe the fact we gave away an iPad helped generate a crowd. Congratulations to Maik Klotz for winning our iPad giveaway! Maik was one of the first people in Germany to own an iPad.
In the end in May, the Loop11 team spent over 150 hours travelling, talked to over 400 people and watched over 30 in flights movies. It was all worth it, as the events were a rousing success for Loop11, and we'll definitely be attending them next year.
eMetrics & Conversion Conference 2010 – San JosePosted by on May 12th, 2010
We recently exhibited at the 2010 eMetrics / Conversion Conference in San Jose. It was great being in the Silicon Valley and meeting all sorts of internet professionals. Our booth was a rousing success and the feedback we got was very positive. We even gave away an iPad on the last day. Congratulations to Rob Love from OpinionLab. The event was well organized, and we'll definitly try to make it next year. Here are some pictures we took of the event.
Loop11 Road TripPosted by on March 17th, 2010
In May, we will be hitting the road to showcase Loop11 at three different events. So come and meet the Loop11 team, and receive exclusive offers and discounts! The three events we are exhibiting at are:
- Conversion Conference, San Jose, USA (May 4th-5th)
- NNG London, London, UK ( May 19th-20th)
- UPA 2010 Conference, Munich, Germany (May 22nd-28th)
Here's your chance to come and meet us. Get all the latest Loop11 info and a special "buy one get one free" offer available exclusively to people who visit our booth us at these events. We're also happy to answer any questions or discuss any issues or feedback you may have.
So, if you're around, pop by our stand and talk to us. We'll give you all the latest gossip and the special "buy one get one free" deal.
Happy testing!
Get 500 free participants for your next project! One Week Only!Posted by on March 08th, 2010
Yes, that's right, for every Loop11 credit purchased during the week commencing March 8th 2010, we will arrange for 500 participants to complete your user test! It's as simple as that.
How this will work:
Just purchase a credit during the week commencing March 8th 2010 and ending March 14th 2010. You can use your credit at any time during that week or at any time in the future. Contact us when you're ready to launch it and we will arrange for 500 participants to complete your user test…at no cost to you. Participants will be randomly sourced from MechanicalTurk.com. To purchase a usability testing credit and get your 500 free participants, go here: https://www.loop11.com/account/purchase/
Happy Testing


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Reader Comments (Page 1 of 1)
Netherscourge said...
All I see is Druid vs AFK Player...
I'm going to have to agree with Netherscourge.
The idea is really cool, the whole approach is very clever, and I got a lot of fun out of watching him knock people out of the sky.
That being said, he's still ganking people, because even someone who is paying full attention can't possibly do anything to save themselves or fight back. I understand ganking is a part of a PvP server, but what these guys do isn't exactly engaging in a fair fight.
vinniedcleaner said...
"The lady doth protest too much, methinks."
This isn't ganking, it's providing a service to those that have been ganked. I'd love to see this concept take hold and permeate all realms. I would bet that there's be less ganking in general if all the epeen strokers knew there'd be consequenses for their less-than-honorable behavior.
Now this is Ganking I like, it has a purpose. A lot of people just take "World PvP" as an excuse to simply prey on afk and especially levelling players.
In this case, every target has done something gank-worthy at least in the perception of the client.
Like vinniedcleaner said, if this had a larger scale, this could lead to less "ganking", but, I think, increase concerted world PvP actions, the type that according to players happened more often in Vanilla.


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You don't NEED a pink salt block for cooking, but it is really fun and delicious.
And it does a few things exceptionally well.
Like fish–very hard to overcook fish on a salt block. Ditto thin pork chops.
We made bananas foster/flambé bananas last night. Slightly salty, buttery and caramelized. Oh yes.
Cooking on the block this spring has been a fun project. It's a little tricky, the salt block. It requires about 40 minutes of heating before use. It can't be heated in an oven or on a sealed-top range. Clean-up is a bear.
This block came from The Meadow, the cooking store operated by cookbook author (and former engineer) Mark Bitterman. The site has lots of very detailed info on the salt blocks themselves and on cooking with them. Salt Block Cooking, his book on the subject and the only salt block cookbook I'm aware of, has a May 2013 publication date.
Next up we plan to use the block to cure salmon. Love gravlax.
Bananas, steak, chops, fish, gravlax. Maybe a salt block is for you, and maybe it's not. Come find out at a salt block cooking class at the Donelson Farmers Market on August 23. More details eventually.


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Since kids today are more inclined to grab a soft drink most parents think of juice as a healthy option, but it turns out that can depend on how much juice.
"If a child is getting filled with fruit juices instead of having either their formula or regular foods you can have one of two different scenarios. Either they substitute good healthy balanced foods and then may have some poor weight gain. Or they may, in addition to having their regular meals, guzzle down a whole bunch of fruit juice which then can put them at risk for obesity," says Robbyn Sockolow. M.D. Pediatrician
Another concern about too much juice is tooth decay. The American Academy of Pediatrics suggests infants should never take a bottle of juice to bed overnight, or they could end up with Bottle Mouth Syndrome,which is a fancy name for rotten teeth from all that sugar soaking the gums (pictured right).
Infants should not even have juice before their six months old and between the ages of one and six years old, juice should be limited to four to six ounces daily,and even for kids seven to 18, the AAP suggests no more than twelve ounces daily with 100 percent juice preferred to juice drinks which typically have a lot of added sweeteners.
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15 August 2011
Catherine shoots for silver success
Catherine Skinner, a chemical engineering student at RMIT University, has won a silver medal for shooting at the Summer Universiade in Shenzhen, China.
Catherine Skinner competed in and won silver in the women's shotgun trap event in Shenzhen, China.
Michael Brown represented Australia in table tennis.
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She set a new personal best during the final of the women's shotgun trap event.
Shooting coach and fellow athlete Daniel Allam said Ms Skinner held her nerve against eventual gold medallist and German shooter Jana Beckmann, who competed in the 2008 Olympics in Beijing.
"Had Jana missed her final shot, Catherine and Jana would have gone into a shootout where Catherine could have potentially won gold," Mr Allam said.
Ms Skinner is the only female trap shooter to be selected by Australian International Shooting to represent Australia on the Australian Uniroos team at the Summer Universiade.
She made Australia's World Cup team this year after competing in the World University Shooting Championships in Poland in 2010.
"I really love shooting for its social side," Ms Skinner said. "You have periods of intense focus in between times where you really get to enjoy the social aspects of a competition.
"It's more a mental sport than a physical one - most of the time you're competing against yourself."
The universiade is an international sporting and cultural festival that aims to promote peace and cultural exchange among young people through sport.
Two other RMIT students made the Australian team for the games, which are staged every two years by the International University Sports Federation:
- Michael Brown, a Bachelor of Business (Professional Accountancy) student - table tennis
- Patrice O'Neill, studying biology at RMIT through Open Universities Australia - women's water polo
RMIT Link Sport and Recreation Senior Coordinator, Janelle Farley, said the students had received sporting grants valued up to $1,500 from RMIT Link.
"Studying, training and competing at a high level is a difficult balancing act, so we're proud to support these top athletes in their efforts on the world stage," Ms Farley said.
Mr Brown, who has been competing in table tennis for 13 years, juggles his studies at RMIT with part-time work and training 15 - 20 hours a week.
"It is hard to put it all together - I manage but it's not always easy," he said.
"I usually train four or five nights a week and one day each weekend. Sounds like a lot but it's still not enough - in China they train about 60 hours a week!"
Mr Brown competed in the 2009 World University Games in Belgrade and was Fiji Open Champion in 2010.
The Summer Universiade ends on 23 August.


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Stephen Halbrook Testifies in Opposition to Eric Holder
Recorded: Friday, January 16, 2009
Stephen Halbrook testifies before the Senate Judiciary Committee in opposition to Attorney General nominee Eric Holder.
Experts: Stephen P. HalbrookType: TelevisionIssues: Constitutional Law, Criminal Justice/ Prisons, Gun Control, Law Enforcement
Alex Tabarrok on Organ Donors
Recorded: Wednesday, June 4, 2003
Alex Tabarrok on CSPANs Washington Journal discusses how to increase the amount of organs available for organ transplant surgery.
Experts: Alexander T. TabarrokType: TelevisionIssues: Free Market Economics, Health Care