bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional constraint underlies 60 million year stasis of Dipteran testis‐specific β‐tubulin
Authors: Nielsen Mark G. , Caserta Justin M. , Kidd Sarah J. , Phillips Christopher M.
Published: January 2006

How do proteins evolve while maintaining their function? Previous studies find a highly stringent structure/function relationship between the Drosophila melanogaster testis‐specific tubulin β2 and the spermtail axoneme, such that small changes in the β2 protein render it unable to generate a motile axoneme. This raises the question, how does β2 evolve while maintaining its function? To address this question we cloned full‐ and partial‐length β2 sequences from 17 species of Drosophila and Hirtodrosophila flies spanning 60 Myr of evolution. Not a single amino acid difference is coded among them—β2 maintains its function by not evolving. We also performed gene genealogical analyses to determine ortholog/paralog relationships among insect tubulins. We find that the Lepidopteran and Dipteran testis‐specific β‐tubulins are likely orthologs, and surprisingly, despite functioning in the same structure, the Lepidopteran orthologs are evolving rapidly. We argue that differences in tubulin isoform use in the testes cause the Dipteran axoneme to be less evolvable than the Lepidopteran axoneme, which has facilitated the evolution of a unique amino acid synergism in Drosophila and Hirtodrosophilaβ2 that is resistant to change, contributing to its evolutionary stasis.
Conservation and divergence in the AGAMOUS subfamily of MADS‐box genes: evidence of independent sub‐ and neofunctionalization events
Authors: Zahn Laura M. , Leebens‐Mack James H. , Arrington Jennifer M. , Hu Yi , Landherr Lena L. , DePamphilis Claude W. , Becker Annette , Theissen Günter , Ma Hong
Published: January 2006

The MADS‐box gene AGAMOUS (AG) plays a key role in determining floral meristem and organ identities. We identified three AG homologs, EScaAG1, EScaAG2, and EScaAGL11 from the basal eudicot Eschscholzia californica (California poppy). Phylogenetic analyses indicate that EScaAG1 and EScaAG2 are recent paralogs within the AG clade, independent of the duplication in ancestral core eudicots that gave rise to the euAG and PLENA (PLE) orthologs. EScaAGL11 is basal to core eudicot AGL11 orthologs in a clade representing an older duplication event after the divergence of the angiosperm and gymnosperm lineages. Detailed in situ hybridization experiments show that expression of EScaAG1 and EScaAG2 is similar to AG; however, both genes appear to be expressed earlier in floral development than described in the core eudicots. A thorough examination of available expression and functional data in a phylogenetic context for members of the AG and AGL11 clades reveals that gene expression has been quite variable throughout the evolutionary history of the AG subfamily and that ovule‐specific expression might have evolved more than twice. Although sub‐ and neofunctionalization are inferred to have occurred following gene duplication, functional divergence among orthologs is evident, as is convergence, among paralogs sampled from different species. We propose that retention of multiple AG homologs in several paralogous lineages can be explained by the conservation of ancestral protein activity combined with evolutionarily labile regulation of expression in the AG and AGL11 clades such that the collective functions of the AG subfamily in stamen and carpel development are maintained following gene duplication.
Developmental regulation of skull morphology II: ontogenetic dynamics of covariance
Authors: Zelditch Miriam Leah , Mezey Jason , Sheets H. David , Lundrigan Barbara L. , Garland Theodore
Published: January 2006

SUMMARY
Canalization may play a critical role in molding patterns of integration when variability is regulated by the balance between processes that generate and remove variation. Under these conditions, the interaction among those processes may produce a dynamic structure of integration even when the level of variability is constant. To determine whether the constancy of variance in skull shape throughout most of postnatal growth results from a balance between processes generating and removing variation, we compare covariance structures from age to age in two rodent species, cotton rats (Sigmodon fulviventer) and house mice (Mus musculus domesticus). We assess the overall similarity of covariance matrices by the matrix correlation, and compare the structures of covariance matrices using common subspace analysis, a method related to common principal components (PCs) analysis but suited to cases in which variation is so nearly spherical that PCs are ambiguous. We find significant differences from age to age in covariance structure and the more effectively canalized ones tend to be least stable in covariance structure. We find no evidence that canalization gradually and preferentially removes deviations arising early in development as we might expect if canalization results from compensatory differential growth. Our results suggest that (co)variation patterns are continually restructured by processes that equilibrate variance, and thus that canalization plays a critical role in molding patterns of integration.
The brachymorph mouse and the developmental‐genetic basis for canalization and morphological integration
Authors: Hallgrímsson Benedikt , Brown Jevon J. Y. , Ford‐Hutchinson Alice F. , Sheets H. David , Zelditch Miriam L. , Jirik Frank R.
Published: January 2006

SUMMARYAlthough it is well known that many mutations influence phenotypic variability as well as the mean, the underlying mechanisms for variability effects are very poorly understood. The brachymorph (bm) phenotype results from an autosomal recessive mutation in the phosphoadenosine‐phosphosulfate synthetase 2 gene (Papps2). A major cranial manifestation is a dramatic reduction in the growth of the chondrocranium which results from undersulfation of glycosaminoglycans (GAGs) in the cartilage matrix. We found that this reduction in the growth of the chondrocranium is associated with an altered pattern of craniofacial shape variation, a significant increase in phenotypic variance and a dramatic increase in morphological integration for craniofacial shape. Both effects are largest in the basicranium. The altered variation pattern indicates that the mutation produces developmental influences on shape that are not present in the wildtype. As the mutation dramatically reduces sulfation of GAGs, we infer that this influence is variation among individuals in the degree of sulfation, or variable expressivity of the mutation. This variation may be because of genetic variation at other loci that influence sulfation, environmental effects, or intrinsic effects. We infer that chondrocranial development exhibits greater sensitivity to variation in the sulfation of chondroitin sulfate when the degree of sulfation is low. At normal levels, sulfation probably contributes minimally to phenotypic variation. This case illustrates canalization in a particular developmental‐genetic context.
Developmental origin of shark electrosensory organs
Authors: Freitas Renata , Zhang GuangJun , Albert James S. , Evans David H. , Cohn Martin J.
Published: January 2006

Vertebrates have evolved electrosensory receptors that detect electrical stimuli on the surface of the skin and transmit them somatotopically to the brain. In chondrichthyans, the electrosensory system is composed of a cephalic network of ampullary organs, known as the ampullae of Lorenzini, that can detect extremely weak electric fields during hunting and navigation. Each ampullary organ consists of a gel‐filled epidermal pit containing sensory hair cells, and synaptic connections with primary afferent neurons at the base of the pit that facilitate detection of voltage gradients over large regions of the body. The developmental origin of electroreceptors and the mechanisms that determine their spatial arrangement in the vertebrate head are not well understood. We have analyzed electroreceptor development in the lesser spotted catshark (Scyliorhinus canicula) and show thatSox8and HNK1, two markers of the neural crest lineage, selectively mark sensory cells in ampullary organs. This represents the first evidence that the neural crest gives rise to electrosensory cells. We also show that pathfinding by cephalic mechanosensory and electrosensory axons follows the expression pattern ofEphA4, a well‐known guidance cue for axons and neural crest cells in osteichthyans. Expression ofEphrinB2, which encodes a ligand for EphA4, marks the positions at which ampullary placodes are initiated in the epidermis, andEphA4is expressed in surrounding mesenchyme. These results suggest thatEph–Ephrinsignaling may establish an early molecular map for neural crest migration, axon guidance and placodal morphogenesis during development of the shark electrosensory system.
Pleiotropic mutation, modularity and evolvability
Authors: Griswold Cortland K.
Published: January 2006

The relationship between pleiotropy and the rate of evolution of a phenotypic character (evolvability) in a population is explored using computer simulations. I present results that suggest the rate of evolution of a phenotypic character may not decline when that character is pleiotropically associated to an increasing number of other characters, provided that the characters are under pure directional selection such that they are far from their optima relative to the average magnitude of a mutation. These conditions may be relevant during adaptive radiations. Adding pleiotropic associations to a set of characters in which one is under directional selection and the other is under stabilizing selection increases the rate of adaptation of the character under directional selection provided that the new characters that come to be pleiotropically associated are under directional selection. Thus, increasing the number of pleiotropic associations under these conditions increases the rate of adaptation of a character.
Generality of vertebrate developmental patterns: evidence for a dermomyotome in fish
Authors: Devoto S. H. , Stoiber W. , Hammond C. L. , Steinbacher P. , Haslett J. R. , Barresi M. J. F. , Patterson S. E. , Adiarte E. G. , Hughes S. M.
Published: January 2006

SUMMARYThe somitic compartment that gives rise to trunk muscle and dermis in amniotes is an epithelial sheet on the external surface of the somite, and is known as the dermomyotome. However, despite its central role in the development of the trunk and limbs, the evolutionary history of the dermomyotome and its role in nonamniotes is poorly understood. We have tested whether a tissue with the morphological and molecular characteristics of a dermomyotome exists in nonamniotes. We show that representatives of the agnathans and of all major clades of gnathostomes each have a layer of cells on the surface of the somite, external to the embryonic myotome. These external cells do not show any signs of terminal myogenic or dermogenic differentiation. Moreover, in the embryos of bony fishes as diverse as sturgeons (Chondrostei) and zebrafish (Teleostei) this layer of cells expresses thepax3andpax7genes that mark myogenic precursors. Some of thepax7‐expressing cells also express the differentiation‐promoting myogenic regulatory factor Myogenin and appear to enter into the myotome. We therefore suggest that the dermomyotome is an ancient and conserved structure that evolved prior to the last common ancestor of all vertebrates. The identification of a dermomyotome in fish makes it possible to apply the powerful cellular and genetic approaches available in zebrafish to the understanding of this key developmental structure.
Oral Sumatriptan for the Acute Treatment of Probable Migraine: First Randomized, Controlled Study
Authors: Tepper Stewart J. , Cady Roger , Dodick David , Freitag Frederick G. , Hutchinson Susan L. , Twomey Colleen , Kuhn Timothy A.
Published: January 2006

Objective.—To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura.

Background.—Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed.

Methods.—This was a randomized, multicenter, double‐blind, placebo‐controlled, parallel‐group study. Adults (18 to 65 years) with a 1‐year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan‐ and ergot‐naïve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders.

Results.—At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2‐hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0–4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported.

Conclusion.—These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.
Zolmitriptan Intranasal: A Review of the Pharmacokinetics and Clinical Efficacy
Authors: Goadsby Peter J. , Yates Roger
Published: January 2006

Migraine is a common disabling neurological disorder, associated with headache, nausea, and on occasions vomiting. Zolmitriptan is a widely available serotonin 5HT1B/1D receptor agonist with a long track record in clinical studies and in the treatment of acute migraine. A nasal formulation has been developed that has clear evidence for local absorption, resulting in plasma drug concentrations within 2 minutes of dosing, central nervous system penetration 3 minutes later, and a significant efficacy benefit versus placebo 10 to 15 minutes after dosing. Intranasal zolmitriptan offers advantages to migraineurs, particularly those seeking a more rapid onset of effect without wishing to self‐inject, or those with gastrointestinal upset. The comparison of pharmacokinetic and clinical data available from different formulations of zolmitriptan contributes both to the understanding of its mode of action and the characteristics required of an acute migraine treatment if it is to meet patient needs.
Symptoms of Premenstrual Syndrome and Their Association With Migraine Headache
Authors: Martin Vincent T. , Wernke Suzanne , Mandell Karen , Ramadan Nabih , Kao Lily , Bean Judy , Liu James , Zoma Willie , Rebar Robert
Published: January 2006

Objectives.—To determine the association between the severity of premenstrual (PMS) symptoms and headache outcome measures during natural menstrual cycles and after medical oophorectomy.

Background.—Premenstrual syndrome may occur in 64% of those with pure menstrual migraine and 33% of those with menstrually related migraine. Few past studies have examined the relationship between the severity of PMS symptoms and migraine headache.

Methods.—Data were obtained from a 6.5‐month randomized‐controlled trial examining the role of medical oophorectomy in the prevention of migraine headache and later divided into two data sets for analysis purposes. The menstrual cycle data set was composed of data from three natural menstrual cycles obtained from 21 participants during lead‐in and placebo run‐in phases. Each menstrual cycle was subdivided into seven 3‐day intervals based on urine hormone metabolites. The medical oophorectomy data set included data from a 2‐month treatment period in which a medical oophorectomy was induced by gonadotropin‐releasing hormone agonists (GnRHa) and participants were randomized to transdermal estradiol or a matching placebo (GnRHa/estradiol and GnRHa/placebo groups, respectively). All participants completed a daily diary recording the severity of PMS symptoms and headache outcome measures. The primary outcome measures were the PMS index (mean of the daily PMS severity scores) and the headache index (mean of the headache severity scores). Pearson correlation coefficients were used to assess the degree of association between the outcome measures.

Results.—Menstrual Cycle Data Set.—The PMS index was significantly correlated with the headache index during native menstrual cycles (correlation coefficient of 0.47; P < .05) and during all seven intervals of the menstrual cycle (correlation coefficients of 0.39 to 0.65; all P values < .05).

Medical Oophorectomy Data Set.—Correlation coefficients between the PMS and headache indices were 0.58 and 0.47 for the GnRHa/estradiol (n = 9) and GnRHa/placebo groups, respectively (P‐values of <.05).

Conclusions.—Moderate correlations exist within female migraineurs between the severity of PMS symptoms and headache outcome measures throughout natural menstrual cycles as well as after medical oophorectomy. Our data would suggest that the presence and severity of headache might modulate PMS symptoms in female migraineurs.
Effects of a Website Designed to Improve the Management of Migraines
Authors: Sciamanna Christopher N. , Nicholson Robert A. , Lofland Jennifer H. , Manocchia Michael , Mui Sarah , Hartman Christine W.
Published: January 2006

Objective.—The aim was to examine the effect of using a Web‐based computer program that provides personalized feedback to migraine patients, on the interactions of patients and providers.

Background.—Despite the widespread availability of evidence‐based migraine treatment guidelines, patients often do not receive optimal treatment to reduce migraine pain and disability.

Methods.—To address these quality gaps in migraine care, we developed a Web‐based computer program, to be used by migraine patients before doctor visits. The feedback is designed to prompt patients to ask questions that lead to higher quality of care. This study was conducted to examine the effect of using the program on migraine‐specific doctor‐patient communications. Patients were randomized to use the Website before (intervention) or after (control) a visit with their provider. The outcome measures were the migraine‐specific topics discussed during the visit, measured by an exit survey after the visit.

Results.—Fifty of 53 subjects randomized completed the postvisit measures (94%). Overall, the mean age was 42.0 years, most patients were female (86.5%), all were white, and 58.5% saw a headache specialist during their visit. Most (75.0%) reported having headaches at least once per week and 48.1% rated their headaches as “severe.” Intervention patients were significantly more likely to “discuss whether you had migraine headaches or some other type of headache?” (89.3% vs 54.5%; P < .01) and to “discuss whether or not there may be a more serious cause of your headaches?” (50.0% vs 13.6%; P < .01). Intervention patients were more likely to report discussing 8 of 12 migraine‐related topics more frequently and a greater overall number of topics (5.5 vs 4.3) than control patients. This difference was not statistically significant.

Conclusions.—These results suggest that the Website may have a positive impact on migraine‐specific doctor‐patient communications. A larger study, including important quality of life and utilization outcomes, is warranted.
Zolmitriptan Oral Tablet in Migraine Treatment: High Placebo Responses in Adolescents
Authors: Rothner A. David , Wasiewski Warren , Winner Paul , Lewis Donald , Stankowski Jill
Published: January 2006

Objective.—The objective of this randomized, double‐blind, placebo‐controlled study was to evaluate the efficacy and tolerability of the zolmitriptan conventional tablet at three different doses for the treatment of a single migraine attack in adolescents.

Background.—Preliminary data from an open‐label study suggested that the zolmitriptan conventional tablet could be effective in the treatment of acute migraine in adolescent patients.

Methods.—Migraine patients aged 12 to 17 years (n = 850) were randomized to receive zolmitriptan 2.5, 5, or 10 mg, or placebo for treatment of a single migraine attack. Patients recorded migraine headache intensity before and after treatment using a 4‐point scale.

Results.—There was no statistically significant improvement between zolmitriptan 10 mg (2 × 5 mg tablet) and placebo for the primary efficacy variable, headache response at 2 hours, nor any of the secondary variables tested. Two‐hour headache response rates were 54%, 53%, and 57% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 58% for placebo. Two‐hour pain‐free rates were 25%, 19%, and 23% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 20% for placebo. Zolmitriptan was well tolerated, with a tolerability profile similar to the pattern seen in adults.

Conclusion.—The similar efficacy between zolmitriptan and placebo appears to be the result of the high placebo response rate. This is a recognized issue in pediatric migraine studies and there is an ongoing debate on ways to address this problem. Since this study was initiated, there has been some debate on the appropriateness of the 2‐hour endpoint for response rates in adolescent studies, given the shorter duration of headache pain in adolescents compared with adults. Furthermore, accurate information regarding the timeliness of treatment and reporting of headache‐related information by adolescents is difficult.
Exertional Headache and Coronary Ischemia Despite Normal Electrocardiographic Stress Testing
Authors: Cutrer F. Michael , Huerter Karina
Published: January 2006

Exertional headaches may under certain conditions reflect coronary ischemia. We report the case of a patient seen in a neurology referral practice whose exertional headaches, even in the face of two normal electrocardiographic stress tests and in the absence of underlying chest pain were the sole symptoms of coronary ischemia as detected by Tc‐99m Sestamibi testing SPECT stress testing. Stent placement resulted in complete resolution of headaches. Exertional headache in the absence of chest pain may reflect underlying symptomatic coronary artery disease (CAD) even when conventional electrocardiographic stress testing does not indicate ischemia.
Fatal Paranasal Sinusitis Presenting as Trigeminal Neuralgia
Authors: Lin Yen‐Wen , Lin Shinn‐Kuang , Weng I‐Hsin
Published: January 2006

Trigeminal neuralgia is rare in patients with paranasal sinusitis. The authors describe a case of paranasal sinusitis that appeared as an insidious onset of trigeminal neuralgia along the distribution of ophthalmic and maxillary branches, followed by rapid intracranial invasion with temporal meningoencephalitis and subdural empyema, and finally a fatal outcome.
Identification of the Epileptogenic Tuber in Patients with Tuberous Sclerosis: A Comparison of High‐resolution EEG and MEG
Authors: Jansen Floor E. , Huiskamp Geertjan , van Huffelen Alexander C. , Bourez‐Swart Mireille , Boere Elvira , Gebbink Tineke , Vincken Koen L. , van Nieuwenhuizen Onno
Published: January 2006

Summary:  Purpose: We compared epileptiform activity recorded with EEG and magnetoencephalography (MEG) in 19 patients with tuberous sclerosis complex (TSC) and epilepsy.

Methods: High‐resolution (HR) EEG, HR‐MEG, and 1.5‐T MRI scans were performed. Epileptiform spikes were identified in EEG and MEG recordings offline by three observers. Spikes for which the interobserver agreement (spike consensus) was >0.40 were used for source localization with CURRYV 3.0 software. MUSIC analysis was performed. The distance between the source determined from EEG and MEG recordings and the border of the closest tuber was calculated and compared.

Results: Consensus spikes (kappa >0.4) were identified in 12 patients in the EEG recording and in 14 patients in the MEG recording. MEG sources were closer to tubers in all but one patient. Three patients underwent epilepsy surgery, two of whom are seizure free after complete resection of the tuber.

Conclusions: In patients with TSC, epileptogenic sources identified on MEG are closer to the presumed epileptogenic tuber than are similar sources identified on EEG. Moreover, spike consensus is greater with MEG. Clear identification of the epileptogenic zone may offer opportunities for surgery in patients with TSC with intractable epilepsy.
Periventricular Nodular Heterotopia: Classification, Epileptic History, and Genesis of Epileptic Discharges
Authors: Battaglia Giorgio , Chiapparini Luisa , Franceschetti Silvana , Freri Elena , Tassi Laura , Bassanini Stefania , Villani Flavio , Spreafico Roberto , D'Incerti Ludovico , Granata Tiziana
Published: January 2006

Summary:  Purpose. Periventricular nodular heterotopia (PNH) is among the most common malformations of cortical development, and affected patients are frequently characterized by focal drug‐resistant epilepsy. Here we analyzed clinical, MRI, and electrophysiologic findings in 54 PNH patients to reevaluate the classification of PNH, relate the anatomic features to epileptic outcome, and ascertain the contribution of PNH nodules to the onset of epileptic discharges.

Methods: The patients were followed up for a prolonged period at the Epilepsy Center of our Institute. In all cases, we related MRI findings to clinical and epileptic outcome and analyzed interictal and ictal EEG abnormalities. In one patient, EEG and stereo‐EEG (SEEG) recordings of seizures were compared.

Results: We included cases with periventricular nodules, also extending to white matter and cortex, provided that anatomic continuity was present between nodules and malformed cortex. Based on imaging and clinical data, patients were subdivided into five PNH groups: (a) bilateral and symmetrical; (b) bilateral single‐noduled; (c) bilateral and asymmetrical; (d) unilateral; and (e) unilateral with extension to neocortex. The latter three groups were characterized by worse epileptic outcome. No differences in outcome were found between unilateral PNH patients regardless the presence of cortical involvement. Interictal as well as ictal EEG abnormalities were always related to PNH location.

Conclusions: The distinctive clinical features and epileptic outcomes in each group of patients confirm the reliability of the proposed classification. Ictal EEG and SEEG recordings suggest that seizures are generated by abnormal anatomic circuitries including the heterotopic nodules and adjacent cortical areas.
Involvement of Medial Pulvinar Thalamic Nucleus in Human Temporal Lobe Seizures
Authors: Rosenberg Dominique S. , Mauguière François , Demarquay Geneviève , Ryvlin Philippe , Isnard Jean , Fischer Catherine , Guénot Marc , Magnin Michel
Published: January 2006

Summary:  Purpose: Several animal studies suggest that the thalamus might be involved in the maintenance and propagation of epileptic seizures. However, electrophysiologic evidence for this implication in human partial epileptic seizures is still lacking. Considering the rich and reciprocal connectivity of the medial pulvinar (PuM) with the temporal lobe, we evaluated a potential participation of this thalamic nucleus in temporal lobe epilepsy (TLE).

Methods: The electrophysiologic activity of PuM was recorded during stereoelectroencephalographic exploration of spontaneous temporal lobe seizures in 14 patients referred for presurgical assessment of refractory TLE.

Results: We recorded PuM ictal activity in 80% of the 74 seizures that we analyzed. This activity was characterized by rhythmic slow‐waves or rhythmic spikes (RSW‐RS) or both or by low‐voltage fast activity (LVFA) in 64% and 36% of seizures, respectively. RSW‐RS occurred mostly in seizures arising from mesiotemporal structures, whereas LVFA was more frequently observed in seizures of neocortical origin. In the 15 seizures without PuM ictal activity, spreading of the seizure outside the onset zone never occurred, whereas it did in 78% of seizures with PuM ictal involvement. Discharge propagation was systematic when PuM involvement corresponded to LVFA, whatever the seizure onset zone was, whereas it represented only 66% of the seizures when PuM exhibited RSW‐RS.

Conclusions: This study shows that ictal changes in PuM activity are frequently observed during temporal lobe seizures and suggests that this thalamic nucleus might participate in their propagation.
Efficacy of Dexamathasone on Cerebral Swelling and Seizures during Subdural Grid EEG Recording in Children
Authors: Araki Takashi , Otsubo Hiroshi , Makino Yuko , Elliott Irene , Iida Koji , Ochi Ayako , Weiss Shelly K. , Chuang Sylvester H. , Rutka James T. , Snead O. Carter
Published: January 2006

Summary:  Purpose: To evaluate the impact of steroid treatment on cerebral swelling and seizures during subdural grid EEG (SGEEG) monitoring.

Methods: We reviewed data from 37 pediatric patients with intractable epilepsy who underwent SGEEG monitoring and divided the patients into those who received dexamethasone and those who did not. We then correlated administration of steroids to incidence of cerebral swelling on computed tomography (CT) scans and to frequency of seizures during SGEEG.

Results: Twenty‐three patients received dexamethasone prophylactically every 6 hours (dosage range, 1–7.5 mg; mean, 3.2 mg) from the first day of SGEEG placement (group A); 14 patients received no dexamethasone (group B). Eight (21.6%) of 37 patients experienced cerebral swelling on CT: two (9%) were in group A, and six (42.9%) were in group B (p < 0.05). SGEEG monitoring time for recording habitual seizures that localized cortical areas for surgical excision was longer in group A (1–6 days; mean, 3.0) than it was in group B (1–3 days; mean, 2.2), (p < 0.05). Habitual seizures were recorded in 36 patients. One group A patient experienced obtundation due to cerebral swelling, and monitoring in this patient was discontinued.

Conclusions: The prophylactic administration of steroids to pediatric patients during SGEEG monitoring is efficacious for reducing cerebral swelling. Although it decreases the frequency of habitual seizures and increases seizure‐monitoring time, dexamethasone reduces the risk of complications from cerebral swelling during the SGEEG procedure.
Long‐term Follow‐up of Patients with Benign Partial Epilepsy in Infancy
Authors: Okumura Akihisa , Watanabe Kazuyoshi , Negoro Tamiko , Hayakawa Fumio , Kato Toru , Maruyama Koichi , Kubota Tetsuo , Suzuki Motomasa , Kurahashi Hirokazu , Azuma Yoshiteru
Published: January 2006

Summary:  Purpose: The aim of this study was to investigate the long‐term outcome of children with benign partial epilepsy in infancy (BPEI).

Methods: A telephone‐interview survey using a structured questionnaire was conducted with patients who were diagnosed as having possible BPEI at age 2 years and who were 8 years or older at the time of the survey. The data from 39 of 48 patients were available. The median age at the time of the survey was 11.3 years; 18 boys and 21 girls were included.

Results: Three patients had a recurrence of unprovoked seizure beyond age 2 years. Four patients had cognitive problems (mild mental retardation in three and Asperger syndrome in one). An association of paroxysmal kinesigenic choreoathetosis was observed in three patients, and another three had experienced seizures associated with mild gastroenteritis. Major behavioral problems were not recognized in any patients. Four patients were excluded from having definite BPEI at age 5 years, and another two were excluded for having definite BPEI at the last follow‐up. Eventually, 33 of 39 patients were categorized as having definite BPEI beyond 8 years of age.

Conclusions: A large majority of patients diagnosed as possibly having BPEI at age 2 years did not have a recurrence of unprovoked seizures and cognitive problems beyond 8 years of age.
Real Options in an Asymmetric Duopoly: Who Benefits from Your Competitive Disadvantage?
Authors: Pawlina Grzegorz , Kort Peter M.
Published: January 2006

This paper analyzes the impact of investment cost asymmetry on the optimal real option exercise strategies and the value of firms in duopoly. Both firms have an opportunity to invest in a project enhancing (ceteris paribus) the profit flow. We show that three types of equilibrium strategies exist. Furthermore, we express the critical levels of cost asymmetry delineating the equilibrium regions as functions of basic economic variables. The presence of strategic interactions among the firms leads to counterintuitive results. First, for a certain range of the asymmetry level, a marginal increase in the investment cost of the firm with the cost disadvantage can enhance this firm's own value. Moreover, such a cost increase can reduce the value of the competitor. Finally, we discuss the welfare implications of the optimal exercise strategies and show that the presence of identical firms can result in a socially less desirable outcome than if one of the competitors has a significant cost (dis)advantage.
Dynamic Competition with Experience Goods
Authors: Villas‐Boas J. Miguel
Published: January 2006

This paper considers dynamic competition in the case in which consumers are only able to learn about their preferences for a certain product after experiencing it. After trying a product a consumer has more information about that product than about untried products. When competing in such a market firms with more sales in the past have an informational advantage because more consumers know their products. If products provide a better‐than‐expected fit with greater likelihood, taking advantage of that informational advantage may lead to an informational disadvantage in the future. This paper considers this competition with an infinite horizon model in a duopoly market with overlapping generations of consumers. Two effects are identified: On one hand marginal forward‐looking consumers realize that by purchasing a product in the current period will be charged a higher expected price in the future. This effect results in reduced price sensitivity and higher equilibrium prices. On the other hand, forward‐looking firms realize that they gain in the future from having a greater market share in the current period and compete more aggressively in prices. For similar discount factors for consumers and firms, the former effect is more important, and prices are higher the greater the informational advantages. The paper also characterizes oscillating market share dynamics, and comparative statics of the equilibrium with respect to consumer and firm patience, and the importance of the experience in the ex post valuation of the product.
Nationalism in Winter Sports Judging and Its Lessons for Organizational Decision Making
Authors: Zitzewitz Eric
Published: January 2006

This paper exploits nationalistic biases in Olympic winter sports judging to study the problem of designing a decision‐making process that uses the input of potentially biased agents. Judges score athletes from their own countries higher than other judges do, and they appear to vary their biases strategically in response to the stakes, the scrutiny given the event, and the degree of subjectivity of the performance aspect being scored. Ski jumping judges display a taste for fairness in that they compensate for the nationalistic biases of other panel members, while figure skating judges appear to engage in vote trading and bloc judging. Career concerns create incentives for judges: biased judges are less likely to be chosen to judge the Olympics in ski jumping but more likely in figure skating; this is consistent with judges being chosen centrally in ski jumping and by national federations in figure skating. The sports truncate extreme scores to different degrees; both ski jumping and, especially, figure skating are shown to truncate too aggressively. Extreme truncation not only discards information, but may also make the vote trading in figure skating easier to implement. These findings have implications for both the current proposals for reforming the judging of figure skating and for designing decision making in organizations more generally.
Marketing Innovation
Authors: Chen Yongmin
Published: January 2006

This paper provides an economic analysis of marketing innovation. A dynamic duopoly model is developed to study two forms of marketing innovation: γ, which allows a firm to acquire consumer information effectively; and σ, which reduces consumer transaction costs. The incentives and effects of marketing innovation differ markedly from those of product or process innovations. Although γ benefits the innovating firm, it hurts some consumers; and, while σ benefits all consumers, it may or may not benefit the innovating firm. Increased competition intensity reduces the value of γ but increases the value of σ. The private incentive is too high for γ but too low for σ.
Consumer Cognition and Pricing in the Nines in Oligopolistic Markets
Authors: Basu Kaushik
Published: January 2006

The paper fully characterizes the Bertrand equilibria of oligopolistic markets where consumers may ignore the last (i.e., the right‐most) digits of prices. Consumers, in this model, do not do this reflexively or out of irrationality, but only when they expect the time cost of acquiring full cognizance of the exact price to exceed the expected loss caused by the slightly erroneous amounts that are likely to be purchased or the slightly higher price that may be paid by virtue of ignoring the information concerning the last digits of prices. It is shown that in this setting there will always exist firms that set prices that end in nine though there may also be some (nonstrict) equilibria where a non‐nine price ending occurs. It is shown that all firms earn positive profits even in Bertrand equilibria. The model helps us understand in what kinds of markets we are most likely to encounter pricing in the nines.
Entry‐Deterring Capacity in the Texas Lodging Industry
Authors: Conlin Michael , Kadiyali Vrinda
Published: January 2006

This paper empirically tests whether capacity is used to deter entry and whether the amount invested in entry‐deterring capacity is related to market concentration and market presence. We use a unique dataset containing 3,830 lodging properties in Texas from 1991 through 1997. We find that there is higher investment in capacity relative to demand (i.e., idle capacity) in markets with a larger Herfindahl index and by firms with a larger share of market capacity. These results are consistent with the entry deterrence literature that suggests firms in more concentrated markets and firms with a larger market share have greater incentive to invest in entry‐deterring capacity.
Team Incentives under Relative Performance Evaluation
Authors: Ishida Junichiro
Published: January 2006

This paper examines the optimal provision of incentives in the repeated setting with many agents under the restriction that only relative performance evaluation is feasible for contracting. We show that the optimal contract in the repeated setting may take a different form than that in the static setting. In the repeated setting, it may be optimal for the principal to arbitrarily divide the agents into teams and compensate them based on team ranking, as it allows the principal to motivate the agents through peer sanctions. The situation draws a clear contrast to the static setting where such a strategy is never optimal. The result indicates that the concept of team plays an important role in the repeated setting even when performances can only be evaluated in relative terms.
Quality and Location Choices under Price Regulation
Authors: Brekke Kurt R. , Nuscheler Robert , Rune Straume Odd
Published: January 2006

In a model of spatial competition, we analyze the equilibrium outcomes in markets where the product price is exogenous. Using an extended version of the Hotelling model, we assume that firms choose their locations and the quality of the product they supply. We derive the optimal price set by a welfarist regulator. If the regulator can commit to a price prior to the choice of locations, the optimal (second‐best) price causes overinvestment in quality and an insufficient degree of horizontal differentiation (compared with the first‐best solution) if the transportation cost of consumers is sufficiently high. Under partial commitment, where the regulator is not able to commit prior to location choices, the optimal price induces first‐best quality, but horizontal differentiation is inefficiently high.
Defensive Publications in an R&D Race
Authors: Bar Talia
Published: January 2006

This paper considers a multistage dynamic R&D race in which the competitors strategically publish research findings. Publications change the prior art, thus affecting patentability. Firms publish when they are behind in the race and their rival is close to winning it. Publication sets back both competitors and gives the follower a chance to catch up. Publications prolong the race. Firms are more likely to publish the more patient they are, and the higher their probability of success. Asymmetry between the firms generates additional incentives to publish such as protecting profits from a previous patent and increasing a strong firm's probability of winning. When firms face a joint decision on publications and the intensity of research, publications substitute investment.
Tools for Financial Innovation: Neoclassical versus Behavioral Finance
Authors: Shiller Robert J.
Published: January 2006

The behavioral finance revolution in academic finance in the last several decades is best described as a return to a more eclectic approach to financial modeling. The earlier neoclassical finance revolution that had swept the finance profession in the 1960s and 1970s represented the overly‐enthusiastic pursuit of only one model. Freed from the tyranny of just one model, financial research is now making faster progress, and that progress can be expected to show material benefits. An example of the application of both behavioral finance and neoclassical finance is discussed: the reform of Social Security and the introduction of personal accounts.
Estimating Incremental Cost‐Effectiveness Ratios and Their Confidence Intervals with Differentially Censored Data
Authors: Wang Hongkun , Zhao Hongwei
Published: January 2006

SummaryWith medical costs escalating over recent years, cost analysis is being conducted more and more to assess economic impact of new treatment options. An incremental cost‐effectiveness ratio (ICER) is a measure that assesses the additional cost for a new treatment for each additional unit of effectiveness, such as saving 1 year of life. In this article, we consider cost‐effectiveness analysis for new treatments evaluated in a randomized clinical trial setting with staggered entries. In particular, the censoring times are different for cost and survival data. We propose a method for estimating the ICER and obtaining its confidence interval when differential censoring exists. Simulation experiments are conducted to evaluate our proposed method. We also apply our methods to a clinical trial example comparing the cost‐effectiveness of implanted defibrillators with conventional therapy for individuals with reduced left ventricular function after myocardial infarction.
Spatial Event Cluster Detection Using a Compound Poisson Distribution
Authors: Rosychuk Rhonda J. , Huston Carolyn , Prasad Narasimha G. N.
Published: January 2006

Summary Geographic disease surveillance methods identify regions that have higher disease rates than expected. These approaches are generally applied to incident or prevalent cases of disease. In some contexts, disease‐related events rather than individuals are the appropriate units of analysis for geographic surveillance. We propose a compound Poisson approach that detects event clusters by testing individual areas that may be combined with their nearest neighbors. The method is applicable to situations where the population sizes are diverse and the population distribution by important strata may differ by area. For example, a geographical region might have sparse population in the northern areas, and other areas which are predominantly retirement communities. The approach requires a coarse geographical relationship and administrative data for the numbers of population, cases, and events in each area. Pediatric self‐inflicted injuries requiring presentation to Alberta emergency departments provide an illustration.
Multiscale Processing of Mass Spectrometry Data
Authors: Randolph T. W. , Yasui Y.
Published: January 2006

Summary This work addresses the problem of extracting signal content from protein mass spectrometry data. A multiscale decomposition of these spectra is used to focus on local scale‐based structure by defining scale‐specific features. Quantification of features is accompanied by an efficient method for calculating the location of features which avoids estimation of signal‐to‐noise ratios or bandwidths. Scale‐based histograms serve as spectral‐density‐like functions indicating the regions of high density of features in the data. These regions provide bins within which features are quantified and compared across samples. As a preliminary step, the locations of prominent features within coarse‐scale bins may be used for a crude registration of spectra. The multiscale decomposition, the scale‐based feature definition, the calculation of feature locations, and subsequent quantification of features are carried out by way of a translation‐invariant wavelet analysis.
Functional Hierarchical Models for Identifying Genes with Different Time‐Course Expression Profiles
Authors: Hong F. , Li H.
Published: January 2006

Summary Time‐course studies of gene expression are essential in biomedical research to understand biological phenomena that evolve in a temporal fashion. We introduce a functional hierarchical model for detecting temporally differentially expressed (TDE) genes between two experimental conditions for cross‐sectional designs, where the gene expression profiles are treated as functional data and modeled by basis function expansions. A Monte Carlo EM algorithm was developed for estimating both the gene‐specific parameters and the hyperparameters in the second level of modeling. We use a direct posterior probability approach to bound the rate of false discovery at a pre‐specified level and evaluate the methods by simulations and application to microarray time‐course gene expression data on Caenorhabditis elegans developmental processes. Simulation results suggested that the procedure performs better than the two‐way ANOVA in identifying TDE genes, resulting in both higher sensitivity and specificity. Genes identified from the C. elegans developmental data set show clear patterns of changes between the two experimental conditions.