Search

Vagal nerve stimulation (VNS) is currently under investigation for the treatment of various cardiovascular diseases including heart failure, arrhythmia, and hypertension. In preclinical and clinical studies, VNS stimulation parameters are heuristically determined in the open loop. However, its therapeutic efficacy remains inconclusive, strongly suggesting the need for a closed-loop approach to optimize patient-specific stimulation parameters. In this paper, we develop a multiple model predictive control (MMPC) algorithm for automated regulation of heart rate (HR) and mean arterial pressure by optimally adjusting the amplitude and frequency of electrical pulses applied to three locations of the vagal nerve. The multiple local models are identified from our previously reported pulsatile rat cardiac model that emulates symptoms of hypertension in rest and exercise states. The computational expense of the proposed method is verified in simulation with rigorous hardware-in-the-loop (HIL) implementation.

The present research aims to enhance heat transfer in straight and wavy profile heat sinks using the same length and hydraulic diameter with different microchannel geometries (triangular, rectangular, trapezoidal, semi-circular, and circular) for uses in electronics, inkjet printing, high heat flux cooling of lasers, and other domains. The nanofluid employed is water/aluminum oxide (water/Al2O3), and the flow regime is laminar. The range of Reynolds number (Re) in this study was 220 ≤ Re ≤ 550, and the concentrations of nanoparticle Al2O3with Heavy Water (2H2O) were 1.2 % volume. This investigation uses 3-dimensional Computational Fluid Dynamics (CFD) simulation software to investigate the heat transfer characteristics of several cross-sectioned microchannels. The numerical investigation utilizes the finite volume approach, and the CFD analysis is validated with accessible literature with different wavy profiles. According to the CFD simulation results, the microchannel with a circular cross-section has the highest heat transfer performance (up to 18 %) among the other cross-sections. The circular cross-section microchannel seemed to have the most significant increase in coolant temperature (by 9–22 %). The analysis outcomes prove that the microchannel with a circular cross-section has the highest performance for heat transfer; the triangular channel has the lowest performance under the same geometric parameters and boundary conditions. So, it is suggested that a circular microchannel can be used for a heat-carrying capacity of 150 W/cm2, a hydraulic diameter of 500 µm, and a Reynolds number equal to 500.

We propose a nonlinear model-based control technique for regulating the heart rate and blood pressure using vagus nerve neuromodulation. The closed-loop framework is based on an in silico model of the rat cardiovascular system for the simulation of the hemodynamic response to multi-location vagal nerve stimulation. The in silico model is derived by compartmentalizing the various physiological components involved in the closed-loop cardiovascular system with intrinsic baroreflex regulation to virtually generate nominal and hypertension-related heart dynamics of rats in rest and exercise states. The controller, using a reduced cycle-averaged model, monitors the outputs from the in silico model, estimates the current state of the reduced model, and computes the optimum stimulation locations and the corresponding parameters using a nonlinear model predictive control algorithm. The results demonstrate that the proposed control strategy is robust with respect to its ability to handle setpoint tracking and disturbance rejection in different simulation scenarios.

Various pre-clinical investigations indicate that the electrical stimulation of the cervical branch of the vagus that innervates the heart has therapeutic value in the management of various cardiac diseases. In theory, the design of a closed-loop control mechanism that automatically adjusts vagal nerve stimulation (VNS) parameters based on real-time physiological feedback can eliminate intra-patient variability in VNS outcomes and therefore represents a major step towards patient-specific therapy. This study develops a nonlinear model predictive control (NMPC) approach for VNS of a pulsatile, human cardio-baroreflex system. The manipulated variables are the frequency and amplitude of a charge-balanced biphasic current. The effects of these variables on hemodynamic quantities such as heart rate, blood pressure, heart contractility e.t.c. are estimated under the assumption that the desired activation of efferent vagal nerve fibers within the vagosympathetic complex can not be realistically isolated from the off-target activation of afferent fibers. An approximate, cycle-averaged cardiovascular model is derived to eliminate pulsatility and is used for prediction in the controller. The feasibility of this NMPC scheme is explored with a set-point tracking example.

CC-90009 (1) is a cereblon E3 ligase modulating drug (CELMoD) in clinical trials for the treatment of acute myeloid leukemia (AML). An efficient synthesis of 1was required to support drug substance supply for clinical trials. The structure features an isoindolinone core, an α,α-difluorophenylacetamide, and a chemically sensitive α-amidoglutaramide moiety prone to hydrolysis or ring opening under basic or Lewis acidic conditions. A key feature of the synthesis was the transformation of a phthalide to the corresponding o-(chloromethyl)benzoate ester while managing the tendency of intermediates to relactonize. The realization of this transformation under mild conditions also serves as a model for a broadly applicable strategy to access these valuable motifs. Optimization of the nitrile hydrogenation and the amide bond formation to form 1afforded the API in significantly improved yield and with high purity. This route was scaled up to supply early clinical trials and served as the basis for commercial route development.

PCDH19-related epilepsy is a developmental and epileptic encephalopathy typically presenting with epilepsy and varying degrees of intellectual disability. Seizures typically present in clusters of focal or generalized seizures, sometimes in the setting of fever. We present the case of a 7-month-old girl presenting with new-onset refractory status epilepticus that followed routine vaccine administration and ensuing cytokine storm. She was diagnosed with a pathogenic variant in PCDH19. The patient required 5 antiseizure medications and pentobarbital-induced burst suppression for control of seizures. She was noted to have elevated serum cytokine levels (interleukin [IL]-2, IL-4, IL-10, IL-13, IL-17, IL-1, IL-1β, and IL-8) and CSF cytokine levels (IL-6 and IL-13). Anakinra was initiated and titrated based on serial cytokine levels, with doses ranging from 5 to 20 mg/kg/d resulting in reduction in cytokine levels and seizure reduction. By age 14 months, she was able to be maintained on 3 active antiseizure medications and ketogenic diet for seizure control.

Sleep disorders are common after traumatic brain injury (TBI). This study will review the spectrum and proposed mechanisms of TBI-associated sleep disorders and discuss the clinical approach to diagnosis and management of them. Disordered and fragmented sleep with insomnia and daytime sleepiness is very common after TBI. Sleep disruption contributes to morbidity and neurocognitive and neurobehavioral deficits and prolongs the recovery phase after injury. Early recognition and correction of these problems may limit the secondary effects of TBI and improve patient outcomes. Evaluating sleep disorders in TBI should be an important component of TBI assessment and management. Finally, newer research techniques for early diagnosis, prognosis, and improved outcomes after TBI will also be addressed.

Research has shown that sleep is beneficial for the long-term retention of memories. According to theories of memory consolidation, memories are gradually reorganized, becoming supported by widespread, distributed cortical networks, particularly during postencoding periods of sleep. However, the effects of sleep on the organization of memories in the hippocampus itself remains less clear. In a 3-d study, participants encoded separate lists of word–image pairs differing in their opportunity for sleep-dependent consolidation. Pairs were initially studied either before or after an overnight sleep period, and were then restudied in a functional magnetic resonance imaging (fMRI) scan session. We used multivariate pattern similarity analyses to examine fine-grained effects of consolidation on memory representations in the hippocampus. We provide evidence for a dissociation along the long axis of the hippocampus that emerges with consolidation, such that representational patterns for object–word memories initially formed prior to sleep become differentiated in anterior hippocampus and more similar, or overlapping, in posterior hippocampus. Differentiation in anterior hippocampal representations correlated with subsequent behavioral performance. Furthermore, representational overlap in posterior hippocampus correlated with the duration of intervening slow wave sleep. Together, these results demonstrate that sleep-dependent consolidation promotes the reorganization of memory traces along the long axis of the hippocampus.

Responsive neurostimulation (RNS) is an emerging therapy for patients with refractory focal epilepsy who are not candidates for surgical resection, with limited published experience in the pediatric population. We report a case of refractory multifocal epilepsy following febrile infection related epilepsy syndrome (FIRES) in which surgical resection was not feasible due to multifocal independent seizures and risk of cognitive deficit, and RNS was pursued. Relevant RNS data and neuropsychological testing results were reviewed. By eight months after implantation, decreased frequency and severity of clinical seizures were noted, and RNS data revealed decreased “long episodes,” reduced spread of electrographic seizures, and fewer detections. Neuropsychological assessment, though potentially confounded by stimulant medication, revealed significant improvement in multiple cognitive domains, particularly working memory and processing speed, at six months. These findings illustrate success in detecting and aborting seizures, and additionally suggest a neuromodulatory effect of RNS stimulation. Our case demonstrates feasibility, efficacy and safety of RNS in a pediatric patient with FIRES, with evidence to also suggest cognitive improvement.

Deep carious lesions in immature permanent molars with pulp necrosis pose a serious challenge to contemporary paedodontic practice. A further complex clinical scenario is an immature permanent molar with varying root formation in both roots. This case report demonstrates the successful management of an immature permanent mandibular first molar. An 8-year-old boy was referred for endodontic management of 36 by a general practitioner. After clinical and radiographic evaluation, a diagnosis of recurrent chronic periapical abscess with abrupt root closure in the mesial root and cessation of root closure in the distal root was made. Apexification was undertaken in three appointments. In the first appointment, under local analgesia and isolation, the mesial canals were prepared to size #F3 with rotary Protaper Universal and the distal canal was left unprepared. Both canals were irrigated with 5% sodium hypochlorite and calcium hydroxide intracanal medicament was placed. One week later, the mesial canals were obturated and a 4 mm white MTA apical plug was placed in the distal canal. Partial extrusion of the MTA was seen periapically. After 24 h, the hard-setting of the MTA plug was verified, remainder of the distal canal was obturated and core filling was placed followed by a preformed metal crown as an intermediate restoration. The patient was asymptomatic and showed resolution of the lesion, normal thickness of the PDL space with continuity of the lamina dura after 12 months. Extruded MTA was partially resorbed. Three years follow-up showed complete resorption of the extruded MTA and an intact lamina dura.

An algorithm is presented that might identify discard of donor livers and be used to optimize allocation sequences and inform policy development.

Aims. The objective of this study was to gather evidence‐based data on the educational needs of neuropediatricians. A needs assessment was conducted to identify the clinical challenges of physicians when diagnosing, medically treating, and managing pediatric patients with epilepsy; which could be addressed through educational interventions. Methods. A two‐phase mixed‐methods approach was used to conduct the needs assessment in Germany, Spain, and the US. Phase 1 consisted of qualitative data collection through multiple sources: a literature review, semi‐structured interviews with clinicians and nurses working in pediatric epilepsy, and interpretation and input from faculty experts. Qualitative data were coded (NVivo) and analyzed using a thematic analysis, and findings were then used to design the second phase. Phase 2 consisted of quantitative data collection through an online survey that aimed to validate the identified challenges and underlying causes using a larger sample than in Phase 1. Data from the survey were analyzed using frequency tabulations and chi‐square tests (SPSS). Results. A total of 267 participants were included in the study. Phase 1 included 88 participants (neurologists, pediatricians, neuropediatricians, and nurses). Phase 2 included 179 participants (neurologists, pediatricians, and neuropediatricians). The main areas of challenge which emerged from the triangulated data included: the integration of guidelines into practice, identification of epilepsy and epilepsy events, integration of genetic testing into practice, integration of non‐pharmacological treatments, transition from pediatric to adult care, and involvement and engagement with caregivers. Underlying causes of these challenges are reported, along with supporting qualitative findings. Conclusions. This study identified the educational needs of physicians working in pediatric epilepsy in Germany, Spain and the USA. Increasingly, educational interventions are required to be evidence‐based. The results of this study could be used to design such interventions to support neuropediatricians who wish to specialize in pediatric epileptology, in order to manage the identified challenges.

Epilepsy is common in people with intellectual and developmental disabilities (IDD). In adulthood, patients with IDD and epilepsy (IDD-E) have neurologic, psychiatric, medical, and social challenges compounded by fragmented and limited care. With increasing neurologic disability, there is a higher frequency of epilepsy, especially symptomatic generalized and treatment-resistant epilepsies. The causes of IDD-E are increasingly recognized to be genetic based on chromosomal microarray analysis to identify copy number variants, gene panels (epilepsy, autism spectrum disorder, intellectual disability), and whole-exome sequencing. A specific genetic diagnosis may guide care by pointing to comorbid disorders and best therapy. Therapy to control seizures should be individualized, with drug selection based on seizure types, epilepsy syndrome, concomitant medications, and comorbid disorders. There are limited comparative antiepileptic drug data in the IDD-E population. Vagus nerve and responsive neural stimulation therapies and resective surgery should be considered. Among the many comorbid disorders that affect patients with IDD-E, psychiatric and sleep disorders are common but often unrecognized and typically not treated. Transition from holistic and coordinated pediatric to adult care is often a vulnerable period. Communication among adult health care providers is complex but essential to ensure best care when these patients are seen in outpatient, emergency room, and inpatient settings. We propose specific recommendations for minimum care standards for people with IDD-E.

The problem of optimal sparse output feedback control design for continuous linear time invariant systems is considered. This work adopts the concept of %p-approximation to develop an optimization algorithm capable of synthesizing a structured sparse static controller gain for which the overall closed loop system exhibits empirical frequency characteristics resembling that of the system controlled with a pre-designed centralized controller. We, moreover, modify our optimization problem so that the control signal generated by the sparse controller falls into the vicinity of the centralized control input, in the sense of L norm. Furthermore, we show that our optimization problem can be equivalently reformulated into a rank constrained problem for which we propose to use a tailored version of Alternating Direction Method of Multipliers (ADMM) as a computationally efficient algorithm to sub-optimally solve it. Finally, we illuminate the effectiveness of our proposed method by testing it on randomly generated sample network models.

Aim. To identify factors that influence diurnal and sleep/wake seizure timing in children undergoing tapered drug withdrawal in an epilepsy monitoring unit. Methods. Medical charts of patients that underwent video‐EEG were reviewed. Seizures were evaluated based on their occurrence in three‐hour time intervals (bins) and between wakefulness and sleep. Patients were classified according to EEG localisation and age: infants (≤3 years), children (3–12 years), and adolescents (>12–21 years). Analysis utilising generalised estimating equations with a negative binomial distribution was performed. Results. A total of 390 patients (188 girls; mean age: 9.2 years; SD: 6.0) had 1,754 seizures. Generalised seizures (109 patients; 490 seizures) occurred more during wakefulness (p<0.001) and during the day (p<0.001). Modelling revealed a greater occurrence of seizures at night with increasing age (p=0.046). Temporal lobe seizures (62 patients; 271 seizures) occurred overall more frequently during wakefulness (p=0.03). Frontal lobe seizures (41 patients; 184 seizures) occurred more frequently during wakefulness in infants (p<0.05) and more frequently during sleep in adolescents (p<0.0001). Adolescents with frontal lobe seizures were 3.6 times more likely to have seizures during sleep compared to other children (95% CI: 1.8–7.2). Conclusion. These findings are suggestive of changes in circadian rhythmicity that may alter seizure susceptibility in different age groups. The results may assist in prediction of periods of greatest seizure propensity.

To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA).

Rufinamide is a triazole derivative structurally unrelated to other antiepileptic drugs that is indicated for the adjunctive treatment of seizures associated with Lennox‐Gastaut syndrome (LGS) in patients aged ≥4 years. Originally granted orphan drug status, marketing authorisation was obtained on the basis of a randomised, double‐blind, placebo‐controlled trial conducted in 138 LGS patients. An open‐label extension study subsequently demonstrated that rufinamide's efficacy and tolerability were maintained over the longer term (median duration of treatment, 432 days). Recently published reports from Europe and the United States have described the use of adjunctive rufinamide to treat LGS in clinical practice. These data complement the clinical trial results, by providing information on the efficacy and tolerability of rufinamide when used on an individualised basis in real‐world practice, under less tightly restricted conditions in terms of patient population and dosing strategies. A comparison of the data reveals that a “lower and slower” dosing strategy tends to be adopted in clinical practice, in comparison with the clinical trial, which does not appear to compromise efficacy, but may provide improvements in tolerability. Individual case reports provide additional valuable information on how rufinamide is being used to treat different seizure types associated with LGS. Since clinical experience with rufinamide is currently at an early stage, there are still unanswered questions relating to its use, and it is likely that its place in the adjunctive treatment of LGS will evolve as further data emerge.

The syndrome of malignant migrating partial seizures of infancy (MMPEI) is characterized by early onset of multiple seizures types, highly pharmaco‐resistant seizures, and overall poor prognosis. In this study, we investigated retrospectively the efficacy of rufinamide (RUF) in five infants with MMPEI, by examining seizure type and frequency, EEG features and antiepileptic drug use. The data demonstrate that two of the five patients showed good efficacy and tolerability for RUF with a >50% reduction in seizure frequency. The use of RUF for the treatment of MMPEI may therefore provide some hope for such infants and should be further validated. [Published with video sequences] Content available: Video

The syndrome of malignant migrating partial seizures of infancy (MMPEI) is characterized by early onset of multiple seizures types, highly pharmaco-resistant seizures, and overall poor prognosis. In this study, we investigated retrospectively the efficacy of rufinamide (RUF) in five infants with MMPEI, by examining seizure type and frequency, EEG features and antiepileptic drug use. The data demonstrate that two of the five patients showed good efficacy and tolerability for RUF with a > 50% reduction in seizure frequency. The use of RUF for the treatment of MMPEI may therefore provide some hope for such infants and should be further validated.

To evaluate the relationship of sleep/wake and day/night pattern to various seizure subtypes and epilepsy localizations.

Health-related quality-of-life measures in childhood epilepsy are typically limited to a particular functional domain, specific age group, parent proxy-report, or child self-report. Generic health-related quality-of-life instruments in paediatric epilepsy comparing child self-reports with simultaneous parent proxy-reports have not been previously investigated. A previously validated generic questionnaire, the Pediatric Quality of Life version 4 (PedsQL.v4.0), was used to prospectively assess parental and child perceptions of health-related quality of life in 100 children with epilepsy. The correlation between child and parental health-related quality-of-life perceptions across all domains was excellent (p < 0.001) and both were significantly lower than those for healthy controls (p < 0.001). Parents’ perceptions of their children’s healthrelated quality of life were lower than those for other chronic illnesses (p < 0.001), especially for refractory epilepsy. The presence of neurological or psychiatric comorbidities also had an adverse impact on health-related quality of life. The PedsQL.v4.0 measures health-related quality of life from both the parent’s and child’s perspective. Ease of use makes this instrument attractive for routine clinical use.

Health‐related quality‐of‐life measures in childhood epilepsy are typically limited to a particular functional domain, specific age group, parent proxy‐report, or child self‐report. Generic health‐related quality‐of‐life instruments in paediatric epilepsy comparing child self‐reports with simultaneous parent proxy‐reports have not been previously investigated. A previously validated generic questionnaire, the Pediatric Quality of Life version 4 (PedsQL.v4.0), was used to prospectively assess parental and child perceptions of health‐related quality of life in 100 children with epilepsy. The correlation between child and parental health‐related quality‐of‐life perceptions across all domains was excellent (p < 0.001) and both were significantly lower than those for healthy controls (p < 0.001). Parents' perceptions of their children's health‐related quality of life were lower than those for other chronic illnesses (p < 0.001), especially for refractory epilepsy. The presence of neurological or psychiatric comorbidities also had an adverse impact on health‐related quality of life. The PedsQL.v4.0 measures health‐related quality of life from both the parent's and child's perspective. Ease of use makes this instrument attractive for routine clinical use.

Restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS) are common neurological disorders in childhood which are usually underdiagnosed. As many pediatricians and pediatric pulmonologists with interest in sleep medicine will be encountering children with RLS and PLMS in their practice, we feel a comprehensive review of these disorders from a pediatric perspective would be very important in understanding basic pathophysiology, clinical features in early diagnosis, and effective management.

Interictal occipital epileptiform abnormalities have not been well characterized. The objective of this pilot study was to assess their significance in children. A search was performed on the EEG database for the keywords “occipital”, “spike”, “sharp wave” and “epileptiform”. Patients were divided into two groups based on the absence of all (group 1) or presence of any (group 2) of the following criteria: mental retardation, cerebral palsy, neurological deficits, abnormal MRI and/or intractable epilepsy. Special attention was given to the spike/sharp wave amplitude/duration and background slowing. A total of 44 children (eight months to 15 years) were studied. Groups 1 and 2 were each composed of 22 children. Background slowing was more frequent in group 2 (10/22, 45%) compared to group 1 (1/22, 4.5%; p = 0.002). In group 2, 8/22 (36%) had spikes or sharp waves with amplitudes below 50 µV or above 150 µV with a positive predictive value of 89%, and a negative predictive value of 39%. Only 1/22 (4.5%) in group 1 had epileptiform activity outside of the 50–150 µV range. The presence of very high or low-amplitude occipital epileptiform abnormalities or background slowing may be indicative of encephalopathy.

Interictal occipital epileptiform abnormalities have not been well characterized. The objective of this pilot study was to assess their significance in children. A search was performed on the EEG database for the keywords “occipital”, “spike”, “sharp wave” and “epileptiform”. Patients were divided into two groups based on the absence of all (group 1) or presence of any (group 2) of the following criteria: mental retardation, cerebral palsy, neurological deficits, abnormal MRI and/or intractable epilepsy. Special attention was given to the spike/sharp wave amplitude/duration and background slowing. A total of 44 children (eight months to 15 years) were studied. Groups 1 and 2 were each composed of 22 children. Background slowing was more frequent in group 2 (10/22, 45%) compared to group 1 (1/22, 4.5%; p = 0.002). In group 2, 8/22 (36%) had spikes or sharp waves with amplitudes below 50 μV or above 150 μV with a positive predictive value of 89%, and a negative predictive value of 39%. Only 1/22 (4.5%) in group 1 had epileptiform activity outside of the 50‐150 μV range. The presence of very high or low‐amplitude occipital epileptiform abnormalities or background slowing may be indicative of encephalopathy.

We provide an update on the pathogenesis, diagnosis, assessment (clinical and laboratory), and treatment options for children with narcolepsy and other hypersomnias of central origin in order to raise awareness of these diseases and to highlight the clinical findings that should make the pediatrician suspect the diagnosis.

Insomnia is a major public health problem and is the most common sleep disturbance in both adults and children. The causes of sleeplessness are age-dependent and have potentially enormous effects on cognitive development, behavior, family dynamics, and the metabolic health of children. Here we review the epidemiology, cause, pathophysiology, and clinical approach to pediatric insomnia.

To characterize polysomnographic (PSG) findings of children with sickle cell disease (SCD) suspected of having sleep disordered breathing (SDB).

Background: Zonisamide (ZNS), a sulphonamide derivative, is a new-generation anticonvulsant with multiple potential mechanisms that contribute to its antiepileptic efficacy and may also explain its as yet incompletely assessed utility for non-seizure disorders such as headaches, neuropathic pain, and weight loss. Objective: A review of the pharmacokinetics, pharmacodynamics, evidence for efficacy in different seizure types and non-seizure conditions, adverse effects, and tolerability of ZNS is presented. Methods: A review of all manuscripts published in the English literature on ZNS was performed in preparing this manuscript. Results/conclusions: ZNS has a broad label for use in Japan, while the regulatory bodies in the USA and Europe have approved it for use only as an adjunctive therapy for partial seizures in adults. It has favorable pharmacokinetic characteristics, proven efficacy in seizure disorders, and is well tolerated in long-term use.

Efficacy of antiepileptic drugs (AEDs) are often equivalent, hence selection of an AED is often determined by the adverse effects (AEs). The development of neurocognitive AEs is almost inevitable with use of AEDs, especially in high-risk groups. Teratogenesis with major or minor malformations is of great concern during the first trimester of pregnancy, but an increasing body of information suggests that potential neurocognitive developmental delay may also occur with use of AEDs in the latter part of pregnancy. Decreased bone mineral density has been found in adults and children receiving both enzyme-inducing AEDs and valproate, an enzyme-inhibiting drug. AEDs may influence the lipid profile, body weight, reproductive, hormonal and other endocrine functions, and sleep architecture. There are age-specific AEs related to pharmacokinetic differences that have been highlighted in this review with emphasis on the pediatric population. A classification of AEs using different parameters is also included.

Epilepsy, a common problem in child neurology, affects the entire family. There is a potential for such psychosocial consequences as parental chronic sorrow and alterations in coping. In this study, 67 parents completed brief questionnaires about their sorrow and coping styles. Results demonstrated chronic sorrow as measured by the Adapted Burke Questionnaire 10.45±7.9. Interestingly, the total score was not significantly different between parents of children with refractory and nonrefractory epilepsy or parents of children with comorbid or without comorbid conditions. Selection of the individual item disbelief,however, was significantly increased in parents of children with nonrefractory epilepsy, and selection of the item angerwas significantly increased in parents of children with comorbid conditions. Parental coping styles were similar to those reported in the normative data for the instrument used, the Coping Health Inventory for Parents CHIP. The correlation between chronic sorrow and coping was significant between the grief component of sorrow and Coping Pattern II of the CHIP. Implications for practice include earlier identification of parental feelings of sorrow and coping styles, which may contribute to a positive outcome.

The clinical features of seizures occurring in the pediatric intensive care unit (PICU) setting are not well characterized. Adult ICU studies reveal an incidence of seizures ranging from 0.8% to 3.3%, with vascular, metabolic abnormalities, and drug withdrawal being the most common etiologies. The objective of this study is to investigate the clinical characteristics of seizures in children admitted to the PICU at our institution. We performed a retrospective review of all patients with diagnoses of seizures or epilepsy, admitted to our PICU from 2002 to 2004. Of 6,820 admissions, 32 patients, aged one month to 19 years had seizures in the PICU. The incidence of seizures was 0.5%. Developmental delay or mental retardation was present in 37% of patients. Seizures were generalized in 26 (81%), and focal in 6 (19%); 34% had status epilepticus. The etiology of seizures was epilepsy in 11 (34%). Seizures that do not meet the diagnosis of epilepsy were diagnosed in 21 (66%) including post‐craniotomy in five (23%), febrile seizures in three (14%), encephalitis in three (14%), and hydrocephalus in three (14%). Thirty‐one patients (97%) were initially treated with either lorazepam or fosphenytoin. Seizures in PICU have different clinical characteristics from those in adults. Recognizing the common seizure etiologies in PICU is likely to lead to a more prompt and effective treatment. Antiepileptic drug prophylaxis may be useful in post‐craniotomy patients. A neurological consultation and EEG evaluation are of the utmost importance to help rule in or out epileptic disorders in the PICU.

Abstract: Background: Aicardi–Goutierés syndrome (AGS) is a severe and progressive familial encephalopathy that is characterized by acquired microcephaly, intracranial calcification, white matter lesions, and chronic lymphocytosis with elevated levels of interferon-α in the cerebrospinal fluid. Although the degree of calcification and the severity of brain atrophy are variable, typically, the brain lesions appear to progress on successive examinations.Case report: We report a 7-year-old male patient who showed relative regression of white matter lesions with nonprogression of basal ganglia calcification and atrophy on follow-up magnetic resonance imaging and computed tomography scans.Results: Magnetic resonance spectroscopy findings were normal. This, to our knowledge, is the first case report, which describes relative regression of the white matter changes in AGS.

Exenatide, a treatment for type 2 diabetes, slows gastric emptying as part of its pharmacologic action and may alter the absorption of concomitant oral drugs. This open‐label, 2‐period, fixed‐sequence study evaluated the influence of exenatide coadministration on the pharmacokinetics and pharmacodynamics of warfarin, a narrow therapeutic index drug, in healthy men (N = 16). A single, 25‐mg oral dose of warfarin, with a standardized breakfast, was administered alone in period 1 and concomitantly with 10 μg exenatide subcutaneous twice daily in period 2. Exenatide did not produce significant changes in R‐ or S‐warfarin pharmacokinetics. Although there were minor reductions in warfarin anticoagulant effect, the ratios of geometric means for the area under the international normalized ratio (INR)–time curve from dosing until the time of the last measurable INR value or maximum‐observed INR response being 0.94 (0.93‐0.96) and 0.88 (0.84‐0.92), respectively, the magnitude and direction of these changes do not suggest a safety concern from this interaction.

We study the problem of hydrodynamic regulation of a flow stream in a microfluidic geometry using model predictive control (MPC). Via bit-accurate emulations we mimic, on a 32-bit microcontroller, the optimization operations associated with MPC. Additionally, we use finite element method simulations to solve the coupled partial differential equation problem that describes the flow and diffusive transport in the examined microfluidic geometry. This combination of simulations and hardware emulations allows us to examine the feasibility of a real-time embedded MPC chip in closed loop with a microsystem, and provide estimates of the performance.

Sleep bruxism is an involuntary mandibular movement with tooth grinding during sleep. The prevalence of sleep bruxism in children is high and may lead to frequent arousals with altered daytime functioning. We investigated the sleep architecture, the incidence of gastroesophageal reflux, and the daytime cognitive behavioral functioning in a group of children with sleep bruxism. DESIGN-PATIENTS: This prospective pilot study included 10 children. Polysomnographic data with pH-probe analysis was compared with 10 age- and sex-matched controls. Each patient completed a dental evaluation, a nighttime polysomnogram, and cognitive behavioral tests (Kaufman Brief Intelligence Test and Achenbach Child Behavior Checklist).

Intrathecal baclofen (ITB) therapy is being used increasingly to treat medically intractable spasticity in children with cerebral palsy and spinal cord injuries. Baclofen overdose and withdrawal are potentially life-threatening complications of pump and spinal catheter system malfunction. We report a case of a 12-year-old boy, on long-term ITB therapy, who presents to our emergency department with an overdose of ITB, which is followed by withdrawal symptoms. The patient initially presented obtunded and in respiratory arrest. His symptoms of respiratory arrest, obtundation, fixed pupils, and hypotension mimicked other diagnoses, such as head trauma. The history obtained from the family about the pump reservoir being refilled just before the onset of symptoms led to the diagnosis. During hospitalization, as the patient recovered from the overdose, he began to experience symptoms of baclofen withdrawal, including hypertension, hyperthermia, and hallucinations. The pump was found to be disconnected and was revised. The patient was discharged home without permanent sequelae. With increased use of ITB, emergency medicine physicians must be aware of the mechanics of these pumps and the management of baclofen toxicity and withdrawal.

In this paper, we study the problem of modeling multicomponent concentration profiles in a membrane-based microreactor. Using basic constitutive laws of mass balance, we derive a low-order model of a generic membrane microreactor, incorporating chemical reaction and permeation through a selective micro-membrane and utilizing a pressure distribution formula for slipping flows from our previous work. Without loss of generality, the model can address nonisothermal conditions and can be extended to allow flow compressibility. We study the utility of our model in evaluating the optimal design and operation of a palladium-based membrane microreactor for conducting hydrogen purification and water gas shift (WGS) reforming in microfuel processing applications.

This open‐label study investigated the effect of exenatide coadministration on the steady‐state plasma pharmacokinetics of digoxin. A total of 21 healthy male subjects received digoxin (day 1, 0.5 mg twice daily; days 2–12, 0.25 mg once daily) and exenatide (days 8–12, 10 μg twice daily). Digoxin plasma and urine concentrations were measured on days 7 and 12. Exenatide coadministration did not change the overall 24‐hour steady‐state digoxin exposure (AUCτ,ss) and Cmin,ssbut caused a 17% decrease in mean plasma digoxin Cmax,ss(1.40 to 1.16 ng/mL) and an increase in digoxin tmax,ss(median increase, 2.5 hours). Although the decrease in digoxin Cmax,sswas statistically significant, peak concentrations were within the therapeutic concentration range in all subjects. Digoxin urinary pharmacokinetic parameters were not altered. Gastrointestinal symptoms, the most common adverse effects of exenatide, decreased over time. Exenatide administration does not cause any changes in digoxin steady‐state pharmacokinetics that would be expected to have clinical sequelae; thus, dosage adjustment does not appear warranted, based on pharmacokinetic considerations.

The recommended treatment for juvenile myoclonic epilepsy (JME) is valproate (VPA). Recently, topiramate and lamotrigine have also been shown to be effective. The objective of this study was to evaluate the efficacy and tolerability of zonisamide (ZNS) in the treatment of JME. We retrospectively analyzed the records of 15 patients (three M, 12 F, ages 11‐20 years) diagnosed with JME at our institution during 2001‐2003, and treated with ZNS. Generalized tonic‐clonic (GTC), myoclonic and absence seizure response was assessed. The ZNS dose range was 200‐500 mg/day (2.0‐8.5 mg/kg/day). ZNS was started as the first drug, and as monotherapy, in 13 and was added to VPA in two patients. Follow‐up range was 2‐24 months (mean 12 months). Overall, 80% of patients on ZNS monotherapy showed good control (≥ 50% seizure reduction). Sixty‐nine, 62 and 38% of patients were free of GTC, myoclonic, and absence seizures, respectively. Seizure control was achieved within four to eight weeks of attaining the maintenance dose. One patient on polytherapy had a 75% reduction in seizure frequency, whereas the other patient showed no response. There were no ZNS‐VPA interactions. One patient stopped ZNS and was switched to VPA because of poor seizure control. Three patients (20%) experienced side effects (weight loss, headache, dizziness) during escalation, which resolved during maintenance. In this open‐label, retrospective study, ZNS was shown to be an effective and well‐tolerated drug in the treatment of patients with JME. The ease of titration, good safety profile, once‐a‐day dosing, lack of significant drug interaction, and short latency for onset of efficacy make ZNS an attractive therapeutic alternative for the treatment of JME.

We propose a framework for embedding model predictive control for Systems-on-a-Chip applications. In order to allow the implementation of such a computationally expensive controller on chip, we propose reducing the precision of the operations coupled with using logarithmic number system arithmetic. Two particular control problems are examined. We provide the methodology for choosing the design parameters; we emulate the performance of the embedded controller for the examined cases and we give the microprocessor architecture details.