Capacity Limits Lead to Information Bottlenecks in Ongoing Rapid Motor Behaviors.

Studies of ongoing, rapid motor behaviors have often focused on the decision-making implicit in the task. Here, we instead study how decision-making integrates with the perceptual and motor systems and propose a framework of limited-capacity, pipelined processing with flexible resources to understand rapid motor behaviors. Results from three experiments show that human performance is consistent with our framework: participants perform objectively worse as task difficulty increases, and, surprisingly, this drop in performance is largest for the most skilled performers. As well, our analysis shows that the worst-performing participants can perform equally well under increased task demands, which is consistent with flexible neural resources being allocated to reduce bottleneck effects and improve overall performance. We conclude that capacity limits lead to information bottlenecks and that processes like attention help reduce the effects that these bottlenecks have on maximal performance.

Quantitatively assessing aging effects in rapid motor behaviours: a cross-sectional study.

BACKGROUND: An individual's rapid motor skills allow them to perform many daily activities and are a hallmark of physical health. Although age and sex are both known to affect motor performance, standardized methods for assessing their impact on upper limb function are limited. METHODS: Here we perform a cross-sectional study of 643 healthy human participants in two interactive motor tasks developed to quantify sensorimotor abilities, Object-Hit (OH) and Object-Hit-and-Avoid (OHA). The tasks required participants to hit virtual objects with and without the presence of distractor objects. Velocities and positions of hands and objects were recorded by a robotic exoskeleton, allowing a variety of parameters to be calculated for each trial. We verified that these tasks are viable for measuring performance in healthy humans and we examined whether any of our recorded parameters were related to age or sex. RESULTS: Our analysis shows that both OH and OHA can assess rapid motor behaviours in healthy human participants. It also shows that while some parameters in these tasks decline with age, those most associated with the motor system do not. Three parameters show significant sex-related effects in OH, but these effects disappear in OHA. CONCLUSIONS: This study suggests that the underlying effect of aging on rapid motor behaviours is not on the capabilities of the motor system, but on the brain's capacity for processing inputs into motor actions. Additionally, this study provides a baseline description of healthy human performance in OH and OHA when using these tasks to investigate age-related declines in sensorimotor ability.

Canadian neurosurgeons' views on medical assistance in dying (MAID): a cross-sectional survey of Canadian Neurosurgical Society (CNSS) members.

BACKGROUND: The Supreme Court of Canada removed the prohibition on physicians assisting in patients dying on 6 February 2015. Bill C-14, legalising medical assistance in dying (MAID) in Canada, was subsequently passed by the House of Commons and the Senate on 17 June 2016. As this remains a divisive issue for physicians, the Canadian Neurosurgical Society (CNSS) has recently published a position statement on MAID. METHODS: We conducted a cross-sectional survey to understand the views and perceptions among CNSS members regarding MAID to inform its position statement on the issue. Data was collected from May to June 2016. RESULTS: Of the 300 active membes of the CNSS who recevied the survey, 89 respondents completed the survey, 71% of whom were attending neurosurgeons and 29% were neurosurgery residents. Most respondents,74.2%, supported the right of physicians to participate in MAID with 7.8% opposing. 37% had current patients in their practice fitting the criteria for MAID. 23.6% had been asked by patients to assist with MAID, but only 11% would consider personally providing it. 84% of neurosurgeons surveyed supported the physicians' right to conscientious objection to MAID while 21% thought attending surgeons should be removed from the inquiry and decision-making process. 43.8% agreed that the requirment to refer a patient to a MAID service should be mandatory. Glioblastoma multiforme (65%), quadriplegia/quadriparesis secondary to spinal tumour/trauma (54%) and Parkinson's disease (24%) were the most common suggested potential indications for MAID among the neurosurgical population. CONCLUSIONS: Our results demonstrate that most neurosurgeons in Canada are generally supportive of MAID in select patients. However, they also strongly support the physicians' right to conscientious objection.

Clinical prediction of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

OBJECTIVEThe aim of this study was to derive a clinically applicable decision rule using clinical, radiological, and laboratory data to predict the development of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients.METHODSPatients presenting over a consecutive 9-year period with subarachnoid hemorrhage (SAH) and at least 1 angiographically evident aneurysm were included. Variables significantly associated with DCI in univariate analysis underwent multivariable logistic regression. Using the beta coefficients, points were assigned to each predictor to establish a scoring system with estimated risks. DCI was defined as neurological deterioration attributable to arterial narrowing detected by transcranial Doppler ultrasonography, CT angiography, MR angiography, or catheter angiography, after exclusion of competing diagnoses.RESULTSOf 463 patients, 58% experienced angiographic vasospasm with an overall DCI incidence of 21%. Age, modified Fisher grade, and ruptured aneurysm location were significantly associated with DCI. This combination of predictors had a greater area under the receiver operating characteristic curve than the modified Fisher grade alone (0.73 [95% CI 0.67-0.78] vs 0.66 [95% CI 0.60-0.71]). Patients 70 years or older with modified Fisher grade 0 or 1 SAH and a posterior circulation aneurysm had the lowest risk of DCI at 1.2% (0 points). The highest estimated risk was 38% (17 points) in patients 40-59 years old with modified Fisher grade 4 SAH following rupture of an anterior circulation aneurysm.CONCLUSIONSAmong patients presenting with aSAH, this score-based clinical prediction tool exhibits increased accuracy over the modified Fisher grade alone and may serve as a useful tool to individualize DCI risk.

Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats.

The Zucker diabetic fatty (ZDF) rat, an inbred strain of obese Zucker fatty rat, develops early onset of insulin resistance and displays hyperglycemia and hyperlipidemia. The phenotypic changes resemble human type 2 diabetes associated with obesity and therefore the strain is used as a pharmacological model for type 2 diabetes. The aim of the current study was to compare the pharmacokinetics and hepatic metabolism in male ZDF and Sprague-Dawley (SD) rats of five antidiabetic drugs that are known to be cleared via various mechanisms. Among the drugs examined, metformin, cleared through renal excretion, and rosiglitazone, metabolized by hepatic cytochrome P450 2C, did not exhibit differences in the plasma clearance in ZDF and SD rats. In contrast, glibenclamide, metabolized by hepatic CYP3A, canagliflozin, metabolized mainly by UDP-glucuronosyltransferases (UGT), and troglitazone, metabolized by sulfotransferase and UGT, exhibited significantly lower plasma clearance in ZDF than in SD rats after a single intravenous administration. To elucidate the mechanisms for the difference in the drug clearance, studies were performed to characterize the activity of hepatic drug-metabolizing enzymes using liver S9 fractions from the two strains. The results revealed that the activity for CYP3A and UGT was decreased in ZDF rats using the probe substrates, and decreased unbound intrinsic clearance in vitro for glibenclamide, canagliflozin, and troglitazone was consistent with lower plasma clearance in vivo. The difference in pharmacokinetics of these two strains may complicate pharmacokinetic/pharmacodynamic correlations, given that ZDF is used as a pharmacological model, and SD rat as the pharmacokinetics and toxicology strain.

Do Early Dental Visits Reduce Treatment and Treatment Costs for Children?

PURPOSE: The purpose of this paper was to determine if number and cost of dental treatments in high caries-risk children differs in children with early dental intervention compared to children with later intervention. METHODS: Billing data from children age zero to seven years old, whose first dental visit was between January 1, 2004 and December 31, 2004, were collected from 20 corporate treatment centers serving children from lower socioeconomic status backgrounds. Data included age at first visit, dental treatment codes, and associated costs for eight years after the first dental visit. Treatment included restorations, crowns, pulpotomies, and extractions. First visit age was categorized into early starters (younger than four years old) and late starters (four years of age or older). Linear regression with cluster adjustment for clinic determined a difference in costs and dental treatments by early and late starters. RESULTS: Of 42,532 subjects, 17,040 (40 percent) were early starters and 25,492 (60 percent) were late starters. There were 3.58 more dental procedures per- formed on late starters, over eight years of follow-up, than on early starters (P < .001). Late starters spent $360 more over eight years of follow-up than early starters (P < .001). CONCLUSION: In this study, number of procedures per- formed were fewer and cost of treatment less for children seen earlier versus later.

Intracranial pressure monitoring among children with severe traumatic brain injury.

OBJECT Well-designed studies linking intracranial pressure (ICP) monitoring with improved outcomes among children with severe traumatic brain injury (TBI) are lacking. The main objective of this study was to examine the relationship between ICP monitoring in children and in-hospital mortality following severe TBI. METHODS An observational study was conducted using data derived from 153 adult or mixed (adult and pediatric) trauma centers participating in the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) and 29 pediatric trauma centers participating in the pediatric pilot TQIP between 2010 and 2012. Random-intercept multilevel modeling was used to examine the association between ICP monitoring and in-hospital mortality among children with severe TBI ≤16 years of age after adjusting for important confounders. This association was evaluated at the patient level and at the hospital level. In a sensitivity analysis, this association was reexamined in a propensity-matched cohort. RESULTS A total of 1705 children with severe TBI were included in the study cohort. The overall in-hospital mortality was 14.3% of patients (n = 243), whereas the mortality of the 273 patients (16%) who underwent invasive ICP monitoring was 11% (n = 30). After adjusting for patient- and hospital-level characteristics, ICP monitoring was associated with lower in-hospital mortality (adjusted OR 0.50; 95% CI 0.30-0.85; p = 0.01). It is possible that patients who were managed with ICP monitoring were selected because of an anticipated favorable or unfavorable outcome. To further address this potential selection bias, the analysis was repeated with the hospital-specific rate of ICP monitoring use as the exposure. The adjusted OR for death of children treated at high ICP-use hospitals was 0.49 compared with those treated at low ICP-use hospitals (95% CI 0.31-0.78; p = 0.003). Variations in ICP monitoring use accounted for 15.9% of the interhospital variation in mortality among children with severe TBI. Similar results were obtained after analyzing the data using propensity score-matching methods. CONCLUSIONS In this observational study, ICP monitoring use was associated with lower hospital mortality at both the patient and hospital levels. However, the contribution of variable ICP monitoring rates to interhospital variation in pediatric TBI mortality was modest.

In vitro characterization of the bioconversion of pomaglumetad methionil, a novel metabotropic glutamate 2/3 receptor agonist peptide prodrug.

To characterize the hydrolysis of the peptide prodrug pomaglumetad methionil (LY2140023; (1R,4S,5S,6S)-4-(L-methionylamino)-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide), to the active drug LY404039 [(1R,4S,5S,6S)-4-amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 2,2-dioxide], a series of in vitro studies were performed in various matrices, including human intestinal, liver, kidney homogenate, and human plasma. The studies were performed to determine the tissue(s) and enzyme(s) responsible for the conversion of the prodrug to the active molecule. This could enable an assessment of the risk for drug interactions, an evaluation of pharmacogenomic implications, as well as the development of a Physiologically Based Pharmacokinetic (PBPK) model for formation of the active drug. Of the matrices examined, hydrolysis of pomaglumetad methionil was observed in intestinal and kidney homogenate preparations and plasma, but not in liver homogenate. Clearance values calculated after applying standard scaling factors suggest the intestine and kidney as primary sites of hydrolysis. Studies with peptidase inhibitors were performed in an attempt to identify the enzyme(s) catalyzing the conversion. Near complete inhibition of LY404039 formation was observed in intestinal and kidney homogenate and human plasma with the selective dehydropeptidase1 (DPEP1) inhibitor cilastatin. Human recombinant DPEP1 was expressed and shown to catalyze the hydrolysis, which was completely inhibited by cilastatin. These studies demonstrate pomaglumetad methionil can be converted to LY404039 via one or multiple enzymes completely inhibited by cilastatin, likely DPEP1, in plasma, the intestine, and the kidney, with the plasma and kidney involved in the clearance of the circulating prodrug. These experiments define a strategy for the characterization of enzymes responsible for the metabolism of other peptide-like compounds.

Do early dental visits reduce treatment and treatment costs for children?

PURPOSE: The purpose of this paper was to determine if number and cost of dental treatments in high caries-risk children differs in children with early dental intervention compared to children with later intervention. METHODS: Billing data from children age zero to seven years old, whose first dental visit was between January 1, 2004 and December 31, 2004, were collected from 20 corporate treatment centers serving children from lower socioeconomic status backgrounds. Data included age at first visit, dental treatment codes, and associated costs for eight years after the first dental visit. Treatment included restorations, crowns, pulpotomies, and extractions. First visit age was categorized into early starters (younger than four years old) and late starters (four years of age or older). Linear regression with cluster adjustment for clinic determined a difference in costs and dental treatments by early and late starters. RESULTS: Of 42,532 subjects, 17,040 (40 percent) were early starters and 25,492 (60 percent) were late starters. There were 3.58 more dental procedures performed on late starters, over eight years of follow-up, than on early starters (P<.001). Late starters spent $360 more over eight years of follow-up than early starters (P<.001). CONCLUSION: In this study, number of procedures performed were fewer and cost of treatment less for children seen earlier versus later.

Synchronous intravascular large B-cell lymphoma within meningioma.

Intravascular large B-cell lymphoma is a rare and aggressive lymphoma with a dismal prognosis. Synchronous intravascular large B-cell lymphoma within meningioma has not previously been documented. We report a case of a 73-year-old woman of Asian descent who presented with fever of unknown origin with generalized weakness. CT scan and MRI of the head revealed a dural-based mass lesion consistent with meningioma in the left frontal cerebral convexity. Surgery was performed to remove the tumor and histopathology showed a meningioma within which was a synchronous intravascular large B-cell lymphoma. The hematology and oncology services were consulted and palliative treatment was initiated due to the patient's poor Eastern Cooperative Oncology Group performance status. The patient died within 30 days post-surgery. To the best of our knowledge, this case represents the first report of synchronous intravascular large B-cell lymphoma within a meningioma.

Effect of neuromuscular blockade on energy expenditure in patients with severe head injury.

BACKGROUND: The purpose of this study was to determine the effect of neuromuscular blockade on energy expenditure in severely head-injured patients; to determine the effects of body temperature, nutrition support, and morphine use on metabolic rate; and to compare measured energy expenditure with values from predictive equations. METHODS: Energy expenditure was measured using indirect calorimetry in 2 groups of ventilated patients-18 with severe head injury during and after administration of pancuronium bromide and morphine, and second, 14 severely traumatized patients without severe head injury (trauma group) who received morphine without neuromuscular blockade. RESULTS: The mean energy expenditure of head-injured patients increased significantly once pancuronium was discontinued, ie, from 24.2 +/- 3.1 to 28.7 +/- 4.6 kcal/kg (p = .002). This effect was independent of other relevant variables such as morphine dose, body temperature, and nutrition support. When compared with the Harris-Benedict and World Health Organization predictive equations, neuromuscular blockade resulted in a stress factor of only 0.96 and 0.95, respectively, which increased to 1.19 and 1.18, respectively, once blockade was discontinued. Head-injured patients not on neuromuscular blockade had a significantly greater energy expenditure when compared with the trauma group (p = .02). CONCLUSIONS: Neuromuscular blockade in severely head-injured patients decreases energy expenditure to basal levels, independent of morphine use, body temperature, and feeding. Levels of hypermetabolism in both the head-injured and trauma groups were relatively low, at 19% and 5% above predicted values, respectively. This study provides useful information for the management of nutrition support in severely traumatized patients.