bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence, Etiology, and Management of Cerebrospinal Fluid Leaks Following Trans‐Sphenoidal Surgery
Authors: Shiley Samuel G. , Limonadi Farhad , Delashaw Johnny B. , Barnwell Stanley L. , Andersen Peter E. , Hwang Peter H. , Wax Mark K.
Published: November 2003

Objectives/Hypothesis The incidence of cerebrospinal fluid (CSF) leak following trans‐sphenoidal surgery ranges from 0.5% to 15.0%. Factors predicting which patients are likely to develop postoperative leaks and optimal management of these patients are poorly defined. The objective was to determine 1) the incidence of CSF leak following trans‐sphenoidal surgery; 2) demographic or intraoperative factors associated with postoperative leaks; 3) techniques and efficacy of postoperative leak management at Oregon Health and Science University, (Portland, OR).

Study Design Retrospective chart review.

Methods Two hundred thirty‐five trans‐sphenoidal surgeries were performed on 216 patients between 1994 and 2001. Follow‐up data were available for 217 operations (92.3%) performed on 202 patients (93.5%).

Results Postoperative CSF leaks occurred in 6.0% (13 of 217) of patients. Leaks were more common in the setting of revision surgery versus primary surgery (14.6% vs. 4.0%, P = .0096), nonadenomatous disease versus pituitary adenoma (15.8% vs. 5.1%, P = .059), or if an intraoperative leak occurred (12.7% vs. 2.7%, P = .004). However, on multivariate analysis, only the presence of intraoperative leak (P = .008) and nonadenomatous disease (P = .047) were found to be independently associated with postoperative CSF leak. Size of adenoma was not associated with occurrence of postoperative CSF leak (6.4% for microadenoma vs. 4.2% for macroadenoma) on both univariate and multivariate analysis. There were 13 postoperative CSF leaks: 2 resolved with lumbar drainage and 11 required operative management (three required multiple procedures). Of the three patients who required multiple operations, two had hospital courses complicated by meningitis and postinfectious hydrocephalus and ultimately required ventriculoperitoneal shunts. Endoscopic re‐exploration was successful in 87.5% (7 of 8) of cases.

Conclusions Cerebrospinal fluid leaks following trans‐sphenoidal surgery occurred in 6.0% of cases. Nonadenomatous disease and presence of an intraoperative leak were independent predictors of a postoperative leak. Endoscopic re‐exploration combined with packing was an effective technique in managing uncomplicated postoperative leaks. In the setting of meningitis and postinfectious hydrocephalus, more invasive techniques such as ventriculoperitoneal shunt may be necessary.
The Impact of Malignant Disease on Facial Nerve Function After Parotidectomy
Authors: Ellingson Todd W. , Cohen James I. , Andersen Peter
Published: November 2003

Objectives/Hypothesis Studies of immediate postoperative facial nerve function following parotidectomy focus on benign disease. The purpose of the study was to compare facial nerve function with regard to benign or malignant disease in patients undergoing superficial parotidectomy.

Study Design Retrospective cohort study of consecutive patients undergoing parotidectomy between 1995 to 2002.

Methods House‐Brackmann (HB) grade was recorded or assigned at the first postoperative visit. For patients with HB grade of III or greater, final resolution of facial nerve function was recorded. A χ2 analysis for independence was conducted between patients with HB grade of II or less and those with HB grade of III or greater and final pathological finding (benign vs. malignant disease). Mean and median times to resolution were determined for patients with HB grade of III or greater. Times to resolution for benign and malignant disease for those with HB grade of III or greater were compared (Kaplan‐Meier method).

Results Sixty‐seven patients with benign disease and 52 with malignant disease were included. Ninety‐four percent of patients with benign disease had HB grade of II or less at first postoperative visit (mean period, 11.6 d) compared with 76.9% of patients with malignant disease (mean period, 12.4 d). A χ2 analysis found this difference significant (χ2 = 7.36, P = .0067). Time to resolution for HB grade of III or greater was 253.8 days (±168.2 d) with median time of 229.5 days for benign disease and 182.4 days (±134.6 d) with median time of 138 days for malignant disease. Kaplan‐Meier comparison found no significant differences in time to final resolution (P = .83). Three patients in the group with malignant disease had unresolved dysfunction (one patient for >2 y).

Conclusions Patients with benign disease have a greater chance of having HB grade of II or less immediately following surgery; however, whether the disease is benign or malignant, long‐term final facial nerve function is the same.
Tacrolimus and Mycophenolate Mofetil Provide Effective Immunosuppression in Rat Laryngeal Transplantation
Authors: Nelson Marc , Fritz Michael , Dan Olivia , Worley Sarah , Strome Marshall
Published: November 2003

Objectives/Hypothesis Tacrolimus is efficacious in several transplantation settings. Some studies have demonstrated improved results using combination therapy with mycophenolate mofetil. Our primary objective was to evaluate the efficacy and optimal dosing of tacrolimus in preventing rejection, using an established rat model of laryngeal transplantation. Further, the ability of mycophenolate to allow lower dosing of tacrolimus while achieving equivalent immunosuppression was investigated.

Study Design A dosage efficacy study with 10 experimental arms was conducted.

Methods Dosage groups were 0.1, 0.2, 0.3, and 0.6 mg/kg tacrolimus alone and 0.1 mg/kg tacrolimus combined with 15 mg/kg mycophenolate mofetil, 0.1 mg/kg tacrolimus combined with 30 mg/kg mycophenolate mofetil, 0.1 mg/kg tacrolimus combined with 40 mg/kg mycophenolate mofetil, 0.2 mg/kg tacrolimus combined with 15 mg/kg mycophenolate mofetil, 0.2 mg/kg tacrolimus combined with 30 mg/kg mycophenolate mofetil (30 d only), and 0.2 mg/kg tacrolimus combined with 40 mg/kg mycophenolate mofetil. Each group contained 8 to 10 rats. Grafts were harvested for histopathological analysis on day 15 or 30 after transplantation. Histopathological appearance of the graft was blindly graded according to an established scale. Dosage groups were compared on rejection score using Wilcoxon's rank sum test and the Jonckheere‐Terpstra test for trend.

Results There was a significant association between increasing dose of tacrolimus and decreasing rejection score at both 15 and 30 days (P <.001). In the groups treated with 0.1 mg/kg T, an increasing dose of mycophenolate was associated with lower rejection scores at both 15 and 30 days (P = .001). In the group treated with 0.2 mg/kg T, there was no evidence that the addition of mycophenolate resulted in lower rejection at 15 days. However, at 30 days, combination therapy with increasing doses of mycophenolate was associated with decreasing rejection score (P = .002).

Conclusions Tacrolimus is an effective immunosuppressive agent for laryngeal transplantation. Mycophenolate mofetil allows lower doses of tacrolimus to be used while preserving graft viability in the early post‐transplantation period.
The Role of Nuclear Factor‐κB in Interleukin‐8 Expression by Human Adenoidal Fibroblasts
Authors: Takaki Minoru , Ushikai Masoto , Deguchi Kohji , Nishimoto Kengo , Matsune Shoji , Kurono Yuichi
Published: November 2003

Objectives/Hypothesis The production of cytokines by adenoids is known to be associated with inflammation of nasopharynx and the pathogenesis of otitis media with effusion. However, the role of adenoids in producing inflammatory cytokines such as interleukin‐8 (IL‐8) is not yet clear. In the present study, expression of IL‐8 in adenoidal fibroblasts was investigated at the level of transcription factors. Further, the effects of clarithromycin, a 14‐member ring macrolide, on IL‐8 gene expression and nuclear factor‐κB (NF‐κB) activation in adenoidal fibroblasts were evaluated.

Study Design In vitro study for the production of inflammatory cytokine from human adenoidal fibroblasts.

Methods Adenoidal fibroblasts were incubated with nontypeable Haemophilus influenzae endotoxin or interleukin‐1β. Then the expression of IL‐8 and the influence of NF‐κB inhibitor and clarithromycin were evaluated. Interleukin‐8 protein production was assessed by ELISA, and IL‐8 messenger RNA production was measured by Northern blot analysis and reverse transcriptase–polymerase chain reaction. Activation of NF‐κB and inhibition of its activation were determined by electrophoretic mobility shift assay.

Results The expression of both IL‐8 protein and messenger RNA in adenoidal fibroblasts was enhanced by Haemophilus influenzae endotoxin and interleukin‐1β and was positively correlated with increases in NF‐κB activity. Treatment of cells with the NF‐κB inhibitor N‐tosyl‐L‐phenylalanine chloromethyl ketone, as well as with clarithromycin, reduced expression of IL‐8 and NF‐κB activity in a dose‐dependent manner.

Conclusions Results suggest that adenoidal fibroblasts produce IL‐8 in response to endotoxin through NF‐κB activation. The inhibitory effects of clarithromycin on NF‐κB activation and IL‐8 production in adenoidal fibroblasts might explain, in part, the mechanism of this drug in improving otitis media with effusion.
Long‐Term Results of Endonasal Sinus Surgery in Sinonasal Papillomas
Authors: Kraft Marcel , Simmen Daniel , Kaufmann Thomas , Holzmann David
Published: November 2003

Objective To assess the value of endonasal sinus surgery in the management of sinonasal papillomas.

Study Design Retrospective study including 43 patients operated on for sinonasal papilloma in a long‐term follow‐up.

Methods In 26 cases (60%) an endonasal approach, in eight cases (19%) an external approach, and in four cases (9%) a combined procedure was performed to remove these tumors. Five septal lesions (12%) were resected under direct vision. The original sections and charts of all patients were reviewed to assess clinical data. Follow‐up information was available for 42 of our patients (98%) with a mean follow‐up of 62 months.

Results Histologic examination revealed 34 cases of inverted papilloma (79%), five cases of exophytic papilloma (12%), and four cases of columnar cell papilloma (9%). Malignancy occurred in 4 of 43 patients (9%), and recurrences developed in 8 of 42 patients (19%). Two of these recurrences happened after endoscopic sinus surgery (two inverted papillomas), three after lateral rhinotomy (three inverted papillomas), one after a combined procedure (one inverted papilloma), and two after simple resection (two exophytic papilloma).

Conclusions In keeping with our experience, the endonasal endoscopic approach, often in combination with a medial maxillectomy, is favored for the treatment of sinonasal papilloma because of a lower recurrence rate and a better cosmetic result. In some larger tumors and lesions in difficult locations, better visualization can be obtained by a combined external and endonasal approach.
Cell Proliferation in the Endolymphatic Sac In Situ After the Rat Waldeyer Ring Equivalent Immunostimulation
Authors: Yan Zhen , Wang Ji‐Bao , Gong Shu‐Sheng , Huang Xiang
Published: November 2003

Objectives/Hypothesis It has been recognized that immunological mechanisms could be involved in the pathogenesis of different inner ear disorders, such as progressive sensorineural hearing loss, Meniere's disease, and even sudden deafness. The endolymphatic sac acts as an immune control organ for the inner ear and has been considered as an effector site of the mucosa‐associated lymphoid tissue. The purpose of the study was to determine the potentially immunological relationship between endolymphatic sac and Waldeyer ring equivalent, one of the most important affector organs in mucosa‐associated lymphoid tissue.

Study Design Animal model.

Methods Thirty‐six rats were employed. Two animals were killed for histological observation of Waldeyer ring equivalent, and another 34 animals were randomly divided into experimental and control groups and received bilateral intranasal immunizations with keyhole limpet hemocyanin or Freund adjuvant, respectively. The ears of immunized animals and control animals were examined for keyhole limpet hemocyanin–positive memory cells and immunoglobulin G–positive plasma cells with the technique of immunohistochemical analysis. The histopathological changes and cell proliferation in those ears were also assessed.

Results There were paired and organized lymphoid tissues in the lateral wall of the first choana in the rat. Keyhole limpet hemocyanin–positive lymphocytes appeared within the endolymphatic sac at 3 days after the first anti‐genetic stimulus of the Waldeyer ring equivalent. Endolymphatic hydrops in the cochlea, elevated amounts of immunocompetent cells, and increased activity of cell proliferation within the endolymphatic sac were also considered after four intranasal injections of keyhole limpet hemocyanin.

Conclusion Presumably, endolymphatic sac is supplied with immunocompetent cells from Waldeyer ring equivalent and has an ability of co‐reaction with Waldeyer ring equivalent.
Natural history of untreated otitis media
Authors: Rosenfeld Richard M. , Kay David
Published: November 2003

Objective/Hypothesis: Data from cohort studies and untreated groups in randomized controlled trials can be identified through systematic literature review and synthesized with meta‐analysis to estimate natural history of acute otitis media (AOM) and otitis media with effusion (OME). Study Design: Systematic literature review and meta‐analysis. Method: Source articles were identified by MEDLINE search through August 2002 plus manual crosschecks of bibliographies and published meta‐analyses. Data were abstracted independently by two investigators and combined with random effects meta‐analysis to estimate spontaneous resolution, 95% confidence intervals (CI), and heterogeneity. Sensitivity analysis was performed. Results: Sixty‐three articles met inclusion criteria. AOM symptoms improved within 24 hours without antibiotics in 61% of children (95% CI, 50–72%), rising to 80% by 2 to 3 days (95% CI, 69–90%). Suppurative complications were comparable if antibiotics were withheld (0.12%) or provided (0.24%). Children entered recurrent AOM trials with a mean rate of 5.5 or more annual episodes but averaged only 2.8 annual episodes while on placebo (95% CI, 2.2–3.4). No AOM episodes occurred in 41%, and only 17% remained otitis prone (3 or more episodes). OME after untreated AOM had 59% resolution by 1 month (95% CI, 50–68%) and 74% resolution by 3 months (95% CI, 68–80%). OME of unknown duration had 28% spontaneous resolution by 3 months (95%, CI 14–41%), rising to 42% by 6 months (95% CI, 35–49%). In contrast, chronic OME had only 26% resolution by 6 months and 33% resolution by 1 year. Conclusions: The natural history of otitis media is very favorable. Combined estimates of spontaneous resolution provide a benchmark against which to judge new or established interventions. The need for surgery in children with recurrent AOM or chronic OME should be balanced against the likelihood of timely spontaneous resolution and the potential risk of learning, language, or other adverse sequelae from persistent middle ear effusion. Further research is needed to identify prognostic factors that can target children unlikely to improve spontaneously for earlier intervention.
Ossicular chain reconstruction: Titanium versus plastipore
Authors: Hillman Todd A. , Shelton Clough
Published: November 2003

Objective: To compare the complication rate and hearing results of a new, lightweight, titanium ossicular replacement prosthesis with Plastipore prostheses (Xomed, Jacksonville, FL). Study Design: Retrospective. Methods: Charts were reviewed for type of operation, type of prosthesis used, extrusion rate, prostheses failure rate, and hearing thresholds at multiple frequencies and at multiple follow‐up points. The dependant variable for hearing results was the four‐frequency average air‐bone gap. Results: There were 84 patients undergoing tympanoplasty with the Plastipore prosthesis and 53 with the titanium. There was one extrusion in the titanium group. There was an additional single incidence of prosthesis failure in the titanium group. Overall hearing results were comparable with an air‐bone gap average of 19.3 dB in the Plastipore group compared with the titanium group with an air‐bone gap of 22.0 dB (P = .08). Sixty percent of patients had a postoperative air‐bone gap of 20 dB or less in the Plastipore group. In the titanium group, 45.3% achieved a 20 dB or less postoperative air‐bone gap. Plastipore had a lower air‐bone gap than the titanium when a canal wall up operation was performed (17.8 vs. 23.9 dB) and tended toward a lower air‐bone gap when a total ossicular prosthesis was needed (22 vs. 27 dB) (P < .07). Conclusion: The titanium prosthesis is a new ossicular replacement prosthesis that provides excellent visualization during insertion and provides hearing results that are comparable with Plastipore. The Plastipore prosthesis performed better in canal wall up mastoidectomy situations and tended toward better performance when a total ossicular replacement prosthesis was needed.
Connexin 26 mutations and nonsyndromic hearing impairment in Northern Finland
Authors: Löppönen Tuija , Väisänen Marja‐Leena , Luotonen Mirja , Allinen Minna , Uusimaa Johanna , Lindholm PÄIvi , Mäki‐Torkko Elina , Väyrynen Mirja , Löppönen Heikki , Leisti Jaakko
Published: November 2003

Objective: The aims of the present study were to evaluate the role of the gap junction protein β‐2 gene (GJB2), encoding connexin 26 (Cx26), in children with moderate to profound prelingual nonsyndromic sensorineural hearing impairment (HI) and to investigate the carrier frequencies of the GJB2 gene mutations in a control population in Northern Finland. Methods: Mutation analysis was performed by direct sequencing and carrier detection by conformation sensitive gel electrophoresis further confirmed by direct sequencing. Results: Cx26 mutations were found in 15 of 71 (21.1%) (67 families) children with HI. Homozygosity for the mutation 35delG was shown to be the cause of HI in 13 of 15 (86.7%) children. Homozygosity for the M34T genotype was found in one child, and compound heterozygosity for the M34T/V37I genotype was found in another. Five families of those with suspected familial HI (29.4%) and six families out of those with sporadic HI (12.0%) had a homozygous or compound heterozygous mutation. The carrier frequency for the mutation 35delG was 1 of 78 (4 of 313) and that for the M34T was 1 of 26 (12 of 313). Conclusion: 35delG/35delG genotype was found to be a significant cause of moderate to profound prelingual nonsyndromic sensorineural HI in Northern Finland. M34T/M34T genotype was seen in only one child, but the carrier frequency of the M34T allele was about three times higher than that of the 35delG mutation.
Total thyroidectomy for benign thyroid disease
Authors: Friguglietti Celso U. M. , Lin Chin S. , Kulcsar Marco A. V.
Published: November 2003

Objectives/Hypothesis: The use of total thyroidectomy in thyroid cancer treatment is not unanimous, and it is even more controversial when this procedure is advocated for benign diseases. On the other hand, the complication risk may have an increase up to 20 times in repeat operations for recurrence. The objective of the study was to evaluate the use of total thyroidectomy in benign diseases, multinodular goiter, and Graves disease to justify the authors' preference. Study Design: Retrospective study of use of total thyroidectomy in benign diseases. Methods: Retrospective study of 1789 patients who underwent thyroidectomies from June 1990 to December 2000. Indication, extension of thyroidectomy, cancer incidence, and complications were analyzed. Results: Total thyroidectomy was performed in 81.19% of 456 patients with nontoxic multinodular goiter, 93.93% of 33 with toxic multinodular goiter, 93.93% of 66 with recurrent multinodular goiter, and 49.18% of 122 with Graves disease. Thyroid cancer was found in 16.62%, 9.09%, 3.03% and 5.73% of patients, respectively. Transitory and permanent hypoparathyroidism, hematoma requiring surgical intervention, and transitory and permanent recurrent laryngeal nerve injury occurred in 12.27%, 1.61%, 0.26%, 1.88%, and 0.35% of the patients undergoing total thyroidectomy, respectively. Permanent complications of total thyroidectomy for nontoxic multinodular goiter and Graves disease were similar to nontotal thyroidectomy. Use of total thyroidectomy for nontoxic multinodular goiter increased from 53.33% of the patient to 81.19%, on average, with a concomitant increase of cancer diagnosis from 11.11% to 16,62%. The authors performed total thyroidectomy for all patients with Graves disease. Conclusion: Total thyroidectomy is the treatment of choice for multinodular goiter and thyroiditis, when there is bilateral gland involvement posterior to middle thyroid veins, and for Graves disease because it decreases the likelihood of future repeat operations for recurrent disease and thus the associated risks, when performed safely.
Foresight and courage: Levi Cooper Lane, MD, a model head and neck surgeon
Authors: Abemayor Elliot
Published: November 2003

Objectives: To detail the life and achievements of Levi Cooper Lane, MD, author of the first American textbook on surgery of the head and neck. Methods: Literature search and analysis. Results/Conclusions: While some of Lane's observations have been diluted by the passage of time, the lessons imparted by his life and work merit continued study by contemporary head and neck surgeons.
Lateral pharyngoplasty: A new treatment for obstructive sleep apnea hypopnea syndrome
Authors: Cahali Michel B.
Published: November 2003

Objective: The role of the lateral pharyngeal muscular walls in the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) is crucial. My objective is to describe a surgical procedure for splinting the lateral pharyngeal walls in patients with OSAHS and report the initial results. Study Design: Prospective randomized pilot study performed in an academic tertiary center as part of a doctoral thesis. Patients and Methods: Ten adults with OSAHS, originally selected for treatment with uvulopalatopharyngoplasty, underwent the lateral pharyngoplasty procedure, which consists of a microdissection of the superior pharyngeal constrictor muscle within the tonsillar fossa, sectioning of this muscle, and suturing of the created laterally based flap of that muscle to the same‐side palatoglossus muscle. In addition, a palatopharyngeal Z‐plasty is performed to prevent retropalatal collapse. Results: Lateral pharyngoplasty improved sleep and daytime symptoms related to OSAHS. After at least 6 months of follow‐up, the median apnea‐hypopnea index decreased from 41.2 to 9.5 (P = .009) and the median total sleep time spent in rapid eye movement (REM) sleep and in stages 3 plus 4 non‐REM sleep increased from 14.1% to 22.1% (P = .059) and from 5.3% to 16.3% (P = .037), respectively. Also, there was statistically significant improvement in snoring, daytime sleepiness, and overall impact of the disease on quality of life. Swallowing disturbances lasted a median of 14.5 days after the surgeries, and all patients returned to normal subjective swallowing function in the follow‐up. Conclusions: Lateral pharyngoplasty is a safe and straightforward approach to lateral pharyngeal muscles and has produced appreciable benefits for OSAHS patients.
Combined reconstruction of congenital auricular atresia and severe microtia
Authors: Siegert Ralf
Published: November 2003

Objectives: Due to their embryologic developments, auricular atresia and severe microtia are in most cases combined malformations. The aims of this study were to develop a surgical technique for combined esthetic and functional reconstruction with a minimum of operations and to evaluate the results. Study Design: Prospective clinical evaluation. Patients and Methods: Fifty‐two patients with third‐degree microtia and congenital aural atresia with a sound‐conducting block of about 50 dB were treated as described here. In the first operation, autogenous cartilage is harvested and the auricular framework fabricated and implanted. In addition, the tympanic membrane and the external ear canal are prefabricated and stored in a subcutaneous pocket. In the second step, the elevation of the new framework is combined with the operation for atresia utilizing the prefabricated tympanic membrane and external ear canal. In the third step, the cavum conchae is deepened and the external ear canal opened and covered with a skin graft. Results: Seventy‐six percent of the patients had a final conducting hearing loss of 30 dB or less. No restenosis of the new external ear canal was observed. The esthetic results of the constructed auricles are shown. Conclusion: With this combination of plastic surgery for the auricle and functional surgery for the middle ear, no additional operations are necessary, and the prefabrication of the external ear canal and the tympanic membrane gives stable and reliable results. Therefore, we think that this combined technique offers the best chance for an optimal esthetic and functional rehabilitation of patients with these malformations.
Temporal bone abnormalities associated with hearing loss in waardenburg syndrome
Authors: Madden Colm , Halsted Mark J. , Hopkin Robert J. , Choo Daniel I. , Benton Corning , Greinwald John H.
Published: November 2003

Objectives/Hypothesis: The objectives were to correlate audiometric thresholds with radiological findings and to determine the prevalence of inner ear radiological abnormalities in patients with hearing loss and Waardenburg syndrome. Study Design: The study was a retrospective review of patients with Waardenburg syndrome identified in a pediatric hearing‐impaired population and human genetics clinic. Methods: Nine children with Waardenburg syndrome were identified. Eighty‐nine children without sensorineural hearing loss served as control subjects. Clinical data, audiometric thresholds, and radiographic temporal bone measurements in these children were analyzed. Results: Seven children were identified with hearing loss and Waardenburg syndrome. Four children had Waardenburg syndrome type 1, and three children had Waardenburg syndrome type 2. The overall prevalence of hearing loss in the total study population with Waardenburg syndrome was 78%. The mean pure‐tone average was 99 dB. All of the children had sensorineural hearing loss. The hearing outcome was stable in 86% of the children. Twelve temporal bones were available for radiological analysis by computed tomography. Enlargement of the vestibular aqueduct was found in 50% of the CT scans. There was a significant difference in measurements of vestibular aqueduct width at the midpoint between the patients with Waardenburg syndrome and the control group (P < .05). There were also significant differences in the measurements of the vestibule (P = .0484), internal auditory canal (P = .0092), and modiolus (P = .0045) between the children with Waardenburg syndrome and the control group. Conclusion: A profound sensorineural hearing loss was characteristic of the study population with Waardenburg syndrome. Overall, 100% of patients with hearing loss and Waardenburg syndrome had temporal bone anomalies on at least one measurement of their inner ear, and 50% had an enlargement of the vestibular aqueduct at the midpoint. As shown by computed tomography, enlargement of the vestibular aqueduct and the upper vestibule, narrowing of the internal auditory canal porus, and hypoplasia of the modiolus are features of Waardenburg syndrome.
Modeling the structure of the respiratory syncytial virus small hydrophobic protein by silent‐mutation analysis of global searching molecular dynamics
Authors: Kochva Uzi , Leonov Hadas , Arkin Isaiah T.
Published: November 2003

Human respiratory syncytial virus (RSV) encodes a small hydrophobic (SH) protein, whose function in the life cycle of the virus is unknown. Recent channel activity measurements of the protein suggest that like other viroporins, SH may assemble into a homo‐oligomeric ion channel. To further our understanding of this potentially important protein, a new strategy was implemented in order to model the transmembrane oligomeric bundle of the protein. Global searching molecular dynamic simulations of SH proteins from eight different viral strains, each at different oligomeric states, as well as different lengths of the putative transmembrane domain, were undertaken. Taken together, a total of 45 different global molecular dynamic simulations pointed to a single pentameric structure for the protein that was found in all of the different variants. The model of the structure obtained is a channel‐like homopentamer whose minimal transmembrane pore diameter is 1.46 Å.
The Humicola grisea Cel12A enzyme structure at 1.2 Å resolution and the impact of its free cysteine residues on thermal stability
Authors: Sandgren Mats , Gualfetti Peter J. , Paech Christian , Paech Sigrid , Shaw Andrew , Gross Laurie S. , Saldajeno Mae , Berglund Gunnar I. , Jones T. Alwyn , Mitchinson Colin
Published: November 2003

As part of a program to discover improved glycoside hydrolase family 12 (GH 12) endoglucanases, we have extended our previous work on the structural and biochemical diversity of GH 12 homologs to include the most stable fungal GH 12 found, Humicola grisea Cel12A. The H. grisea enzyme was much more stable to irreversible thermal denaturation than the Trichoderma reesei enzyme. It had an apparent denaturation midpoint (Tm) of 68.7°C, 14.3°C higher than the T. reesei enzyme. There are an additional three cysteines found in the H. grisea Cel12A enzyme. To determine their importance for thermal stability, we constructed three H. grisea Cel12A single mutants in which these cysteines were exchanged with the corresponding residues in the T. reesei enzyme. We also introduced these cysteine residues into the T. reesei enzyme. The thermal stability of these variants was determined. Substitutions at any of the three positions affected stability, with the largest effect seen in H. grisea C206P, which has a Tm 9.1°C lower than that of the wild type. The T. reesei cysteine variant that gave the largest increase in stability, with a Tm 3.9°C higher than wild type, was the P201C mutation, the converse of the destabilizing C206P mutation in H. grisea. To help rationalize the results, we have determined the crystal structure of the H. grisea enzyme and of the most stable T. reesei cysteine variant, P201C. The three cysteines in H. grisea Cel12A play an important role in the thermal stability of this protein, although they are not involved in a disulfide bond.
‘Teaching an inclusive classroom can be rather tedious’: an international perspective, Israel, 1998–2000
Authors: Avissar Gilada
Published: November 2003

Inclusion of students with disabilities into regular classrooms has been practised on a voluntary basis in Israel for the past 30–40 years. Special education legislation passed in 1988 included as one of its touchstones the mandate to mainstream students with disabilities into regular classrooms to the maximum extent possible. The ‘Plan for Inclusion’ began in 1996 and since 2000 it has been implemented in schools all over Israel.
BEHAVIOURAL RESPONSES TO CONSPECIFIC DISTURBANCE CHEMICALS ENHANCE SURVIVAL OF JUVENILE BROOK CHARR, SALVELINUS FONTINALIS, DURING ENCOUNTERS WITH PREDATORS
Authors: Mirza Reehan , Chivers Douglas
Published: November 2003

Several species of aquatic organisms release chemical cues upon detecting predators. These chemicals may serve to 'warn' nearby conspecifics of the predator and hence have been termed disturbance cues. Disturbance cues are thought to be low-level indicators of risk to which prey animals respond with antipredator behaviour. However, little is known about the distribution of disturbance cues among different taxa or how prey animals use these cues to mediate their risk of predation. In this study we exposed brook charr (Salvelinus fontinalis) to water from a tank containing cues of disturbed or undisturbed conspecifics at the same time as we exposed them to cues of an unknown predator, northern pike (Esox lucius). In subsequent trials, we staged encounters between the charr and a pike and tested for differences in survival. We found that charr that were exposed to simultaneous cues from disturbed conspecifics and pike odour subsequently avoided the pike significantly more than charr that had been previously exposed to chemical stimuli from undisturbed charr plus pike odour. Moreover, pike took significantly longer to capture charr that had been previously exposed to disturbance cues from conspecifics plus pike stimuli compared to charr previously exposed to cues from undisturbed charr plus pike stimuli. Ours is the first study to demonstrate that detection of disturbance cues can provide a survival benefit during an encounter with a predator.
Grotius and his Followers on Treaty Construction
Authors:   Bederman
Published: November 2003

No Abstract
Early Development of Modern International Law in East Asia
Authors:   Lee
Published: November 2003

No Abstract
The European Court of Justice and the EC External Trade Relations: A Legal Analysis of the Court's Problems with Regard to International Agreements
Authors: Leal-Arcas Rafael
Published: November 2003

This article explains why the WTOand the various agreements that form an integral part of the Agreement establishing the WTO raise problems and challenges for the Court of Justice of the European Communities (ECJ). It focuses on the role of the ECJ in relation to exclusive and shared competence. The European Community's (EC) specific problems and challenges for the ECJ are partly related to the EC's position in the WTO. In this sense, the opinion of Advocate General Tesauro in Hermès International v. FHT Marketing Choice is helpful for understanding the unitary character of the EC's external trade relations. This article includes a discussion of Hermès v. FHT Marketing concerning the interpretation of Article 50 of the Agreement on TRIPS, annexed to the 1994 Agreement establishing the WTO. The new mechanisms introduced by the WTO Dispute Settlement Understanding are perhaps not comparable to the full judicial system within the EU, but they have changed both the rules and the legal culture concerning the adjudication and enforcement obligations. Although the WTO is still an intergovernmental organization, powerful private actors have already learned to manipulate the system to reach legal adjudication under the guise of intergovernmental disputes. This paper concludes that the EC wants to deny 'direct effect' to the WTO. This article offers the conclusion that we must aim at the creation of new standards to judge the applicability of international agreements. Otherwise, by allowing policy makers to decide rather than ECJ, the EC legal order may be at risk.
Australian water closet developments and their role in sustainable sanitation
Authors: Cummings S J , Wright G B , Bonollo E
Published: November 2003

Australia's unique climatic and demographic conditions have resulted in a long standing appreciation of the importance of water conservation issues. With respect to sanitation provisions, this has resulted in the development of 6/3 litre dual flush water closets (WC). In addition to the obvious environmental benefits associated with using lower flush volumes, such technology has also had significant financial implications, both for the nation and the domestic consumer. This paper outlines the development of low flush volume WCs in Australia, along with other technologies aimed at improving the sustainability of the water based sanitation systems used in Australia and throughout the industrialized world.
Unsupervised adaptive resonance theory neural networks for control chart pattern recognition
Authors: Pham D T , Chan A B
Published: November 2003

This paper describes the use of unsupervised adaptive resonance theory ART2 neural networks for recognizing patterns in statistical process control charts. To improve the classification accuracy, three schemes are proposed. The first scheme involves using information on changes between consecutive points in a pattern. The second scheme modifies the ART2 vigilance parameter during training. The third scheme merges class neurons representing the same class after training. The paper gives results which demonstrate the improvements achieved.
Preparation and Reactivity of N-Substituted S,S,S-Triphenyliminosulfonium Salts
Authors: Yoshimura Toshiaki , Fujii Takayoshi , Hamata Kouki , Imado Masahiro , Morita Hiroyuki , Ono Shin , Horn Ernst
Published: November 2003

N-Substituted S,S,S-triphenyliminosulfonium salts were prepared by the reaction of S,S,S-triphenylthiazyne with several electrophiles. The molecular structure of N-methyl-S,S,S-triphenyliminosulfonium perchlorate was determined by the X-ray crystallographic analysis. Furthermore, their reactivities were investigated.
Double Stereocontrol in α-Alkylation of Chiral Lithium Dienolates Generated from (E)-α,β-Olefinic Amides and Esters
Authors: Tomooka Katsuhiko , Nagasawa Atsushi , Nakai Takeshi
Published: November 2003

The methylation of the lithium dienolate generated from (E)-α,β-olefinic amide with Katsuki’s chiral auxiliary affords the α-methylated β,γ-enamide in an exceptionally high Z-selectivity (99%) over the terminal olefinic bond along with 99% de at the α-chiral center. The origin of the high Z-selectivity is discussed.
ortho-Halogeno Substituents Effect in Asymmetric Cyclization of 4-Aryl-4-pentenals Using a Rhodium Catalyst
Authors: Fujio Masakazu , Tanaka Masakazu , Wu Xiao-Ming , Funakoshi Kazuhisa , Sakai Kiyoshi , Suemune Hiroshi
Published: November 2003

Asymmetric cyclization of 4-aryl-4-pentenals by using a cationic [Rh((R)-BINAP)]ClO4 afforded (3R)-3-substituted cyclopentanones; on the other hand, the cyclization of 4-pentenals bearing ortho-halogeno phenyl groups afforded the opposite (3S)-ones.
pH-Dependent Photocurrent Response from Bacteriorhodopsin at Electrode-Electrolyte Interfaces
Authors: Saga Yoshitaka , Watanabe Tadashi , Koyama Koichi , Miyasaka Tsutomu
Published: November 2003

The transient photocurrent response of bacteriorhodopsin (bR) at electrode-electrolyte interfaces showed a drastic pH dependence, reversing at a low pH. The ratio of the photocurrent by turning the light off to that at the onset of illumination, Ioff/Ion, decreased systematically from 0.92 to 0 by raising pH. These results can neatly be correlated with the proton release/uptake sequence in the bR photocycle.
Synthesis of Chlorophyll Doped Silica-mesostructure Materials
Authors: Zhou HaoShen , Honma Itaru
Published: November 2003

The photosynthetic molecule chlorophyll(Chl) doping silica mesostructure material can be directly synthesized by self-organized co-assembly of mixing Chl with hexadecyltrimethylammonium chloride (C16-TMA) surfactant, successfully. X-ray diffraction pattern (XRD) shows a typical hexagonal diffraction pattern of the mesoporous materials with d100 about 35.3 Å. The optical absorption spectra show the typical band (located at about 680 nm) of Chl.
Application of the Integral Equation Approach to the Study of Enthalpic Effects Accompanying Mixed-Gas Adsorption on Heterogeneous Solid Surfaces
Authors: Nieszporek Krzysztof
Published: November 2003

The possibilities of the Integral Equation approach for describing mixed-gas adsorption equilibria are presented. In this study, the energetic heterogeneity was described through the use of the Gaussian-like adsorption energy distribution function. As a result, very simple equations describing the isosteric heats of mixture components were obtained. The advantage of the model presented is the possibility of predicting the phase diagrams and enthalpic effects accompanying mixed-gas adsorption from a theoretical viewpoint based on pure-component adsorption data.

New equations for isosteric heats of component mixtures were examined using the experimental data obtained by Dunne et al. (1996a, b, 1997), i.e. C2H6, CH4 adsorbed on silicalite and CO2, C2H6 adsorbed on NaX zeolite.

The calculations are relatively simple and can be applied industrially.
Designing Conjoint Choice Experiments Using Managers' Prior Beliefs
Authors: SÁndor Zsolt , Wedel Michel
Published: November 2003

The authors provide more efficient designs for conjoint choice experiments based on prior information elicited from managers about the parameters and their associated uncertainty. The authors use a Bayesian design procedure that assumes a prior distribution of likely parameter values and optimizes the design over that distribution. The authors propose a way to elicit prior information from managers and show in Monte Carlo studies that the procedure provides more efficient designs than the current procedures. The authors provide an empirical application, in which they elicit prior information on the parameter values and the associated uncertainty from managers. Here, the Bayesian design provides 30%-50% lower standard errors of the estimates and an expected predictive validity that is approximately 20% higher.
Marketing-Mix Variables and the Diffusion of Successive Generations of a Technological Innovation
Authors: Danaher Peter J. , Hardie Bruce G.S. , Putsis William P.
Published: November 2003

Research addressing the diffusion of successive generations of technological innovations has generally ignored the impact of marketing-mix variables. As a result, there have been several calls for the development of multiple-generation models that incorporate marketing-mix variables. The authors develop a model of first-time sales and subscriptions for successive generations of a technological innovation, which explicitly captures the effects of marketing-mix variables through a proportional hazards framework. The empirical analysis estimates the impact of price for two generations of cellular telephones in a European country. The results suggest that there are important substantive insights to be gained from the parameter estimates for this marketing-mix variable when intergenerational interdependencies are considered. For example, although the time path of the estimated price elasticities in a multiple-generation setting closely follows those reported previously for single generations, the authors find evidence of an important interaction in price response across generations. Therefore, empirical estimates in single-generation models may be missing an important part of the pricing equation.
Perceptual Organization in Vision
Authors: Palmer Stephen E.
Published: November 2003

The field of perceptual organization in vision is surveyed and analyzed from phenomenological, empirical, and theoretical perspectives. Structuralist, Gestaltist, and ecological principles are discussed as a historical backdrop for modern computational theories. A set of basic organizational processes—region segregation, border assignment (orfigure‐ground organization), grouping, and parsing—are presented as underlying the visual system's ability to construct a part‐whole hierarchy of groups, objects, parts, and subparts from input images. Hypotheses about how these processes might be computed and interrelated in the stream of visual processing are also considered in light of both logical and empirical constraints. Further processes ofvisual interpolationand depth perception are required to account for the perception of amodal completion, illusory contours, translucency, and figural scission. Other organizational phenomena are also discussed, including global precedence,frames of reference,figural goodness, andmultistability. Explanations in terms of structural simplicity and ecological likelihood are presented, and their interrelations are discussed.
Attention
Authors: Luck Steven J. , Vecera Shaun P.
Published: November 2003

The termattentionis used to describe the focusing of cognitive processes onto a subset of the information that is currently available. This focusing is useful whenever a given cognitive process is faced with multiple sources of input, and attention is therefore important across a wide variety of tasks. Attention plays several distinct computational roles, including binding together the features of an object, minimizing interference in working memory, and mitigating the deleterious effects of noise. Recent research also indicates that attention can operate on a variety of different representational formats, including spatial representations and abstract object‐based representations. Most theories of attention have assumed that attention is a unitary process that operates at a single stage of processing, but it is now clear that it operates within different cognitive systems under different conditions. Thus, attentional focusing does not appear to be achieved by a unitary attentional process; instead, focusing appears to be implemented by a collection of partially independent attentional processes that are embedded within other cognitive processes. However, these attentional processes must work together to produce unified behavioral output, and recent research has focused extensively on the control systems that coordinate the allocation of attention.
Knowledge Representation
Authors: Markman Arthur B.
Published: November 2003

Psychological theories make assumptions about how knowledge is represented and processed. In this chapter, I begin by defining the concept of representation and discussing the ways that mental representations come to have meaning. Then, I present four different types of representations: spatial representations, featural representations, semantic networks, and structured representations. For each type of representation, I first give an overview of the basic assumptions of the representation, and then present examples of its use in psychological theories. Next, I discuss the strengths and weaknesses of each approach. At the end of the chapter, I consider ways that multiple approaches to representation may be combined. I also discuss principles of testing models of representation.
Reasoning
Authors: Rips Lance J.
Published: November 2003

Some current theories portray human reasoning as the result of a single cognitive process that operates in a uniform way across all domains of knowledge. This unitary process handles both entailments (given information guarantees the conclusion) and inductively strong inferences (given information makes the conclusion more likely). Other theories partition reasoning into two or more types that differ according to the domain of knowledge to which they apply, the kind of inference (entailment vs. inductively strong inference) they implement, or other psychological properties (rule‐based vs. similarity‐based, explicit vs. implicit, analytic vs. holistic, decontextual vs. context‐bound, and so on). This chapter surveys both unitary and partitioning theories, as well as the experimental evidence that supports them. Unitary theories run into difficulties with simple inferences that people endorse but the favored method doesn't explain. Partitioning theories gain from flexibility, but often fail to distinguish their component processes in an adequate way. In some cases, evidence for multiple processes may be due instead to multiple knowledge sources; in others, the processes are described too vaguely to do serious psychological work.
Single versus Multiple Systems of Learning and Memory
Authors: Ashby F. Gregory , Ell Shawn W.
Published: November 2003

This chapter explores the debate between single and multiple systems. The focus is on the methodologies that have been proposed for testing between these two positions: an explicit system that is rule‐based, and an implicit system that operates largely without conscious awareness. In particular, we ask the following questions: 1) What constitutes a separate system? 2) What is the appropriate way to resolve this debate empirically?, and 3) What are the best empirical methodologies for testing between single and multiple systems? Finally, as a model of this debate, we focus on the question of whether human category learning is mediated by single or multiple systems.