bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic relationships among Spanish goats breeds
Authors: Azor P. J. , Monteagudo L. V. , Luque M. , Tejedor M. T. , Rodero E. , Sierra I. , Herrera M. , Rodero A. , Arruga M. V.
Published: September 2005

We partially sequenced the mitochondrial hypervariable region 1 (HVR1) in 60 goats belonging to six Spanish breeds. The analysis of these and previously published sequences reveals a weak phylogeographical structure in the Iberian Peninsula breeds. Individuals from a single breed did not group into a single cluster. Furthermore, individuals from different breeds often shared single phylogenetic tree branches after UPGMA analysis. This could reflect the non‐existence of breed isolation because of traditional seasonal pastoralism and annual long‐distance migrations. Three goats belonging to the C maternal lineage were found, demonstrating a wider than previously thought distribution for this lineage.
Mapping of 443 porcine EST improves the comparative maps for SSC1 and SSC7 with the human genome
Authors: Demeure O. , Pomp D. , Milan D. , Rothschild M. F. , Tuggle C. K.
Published: September 2005

Numerous mapping studies of complex traits in the pig have resulted in quantitative trait loci (QTL) intervals of 10–20 cM. To improve the chances to identify the genes located in such intervals, increased expressed sequence tags (EST)‐based marker density, coupled with comparative mapping with species whose genomes have been sequenced such as human and mouse, is the most efficient tool. In this study, we mapped 443 porcine EST with a radiation hybrid (RH) panel (384 had LOD > 6.0) and a somatic cell hybrid panel. Requiring no discrepancy between two‐point and multipoint RH data allowed robust assignment of 309 EST, of which most were located on porcine chromosomes (SSC) 1, 4, 7, 8 and X. Moreover, we built framework maps for two chromosomes, SSC1 and SSC7, with mapped QTL in regions with known rearrangement between pig and human genomes. Using the Blast tool, we found orthologies between 407 of the 443 pig cDNA sequences and human genes, or to existing pig genes. Our porcine/human comparative mapping results reveal possible new homologies for SSC1, SSC3, SSC5, SSC6, SSC12 and SSC14 and add markers in synteny breakpoints for chromosome 7.
Comparative linkage mapping of the Grey coat colour gene in horses1
Authors: Pielberg G. , Mikko S. , Sandberg K. , Andersson L.
Published: September 2005

Grey horses are born coloured, turn progressively grey and often develop melanomas late in life. Grey shows an autosomal dominant inheritance and the locus has previously been mapped to horse chromosome 25 (ECA25), around the TXN gene. We have now developed eight new single nucleotide polymorphisms (SNPs) associated with genes on ECA25 using information on the linear order of genes on human chromosome 9q, as well as the human and mouse coding sequences. These SNPs were mapped in relation to the Grey locus using more than 300 progeny from matings between two Swedish Warmblood grey stallions and non‐grey mares. Grey was firmly assigned to an interval with flanking markers NANS and ABCA1. This corresponds to a region of approximately 6.9 Mb on human chromosome 9q. Furthermore, no recombination was observed between Grey, TGFBR1 and TMEFF1, the last two being 1.4 Mb apart in human. There are no obvious candidate genes in this region and none of the genes has been associated with pigmentation disorders or melanoma development, suggesting that the grey phenotype is caused by a mutation in a novel gene.
Nasal biomarker profiles in acute and chronic rhinosinusitis
Authors: Riechelmann H. , Deutschle T. , Rozsasi A. , Keck T. , Polzehl D. , Bürner H.
Published: September 2005

Background
Clinical manifestations of rhinosinusitis include acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyps and CRS without polyps.

Objective
Possible mechanisms defining these three forms of rhinosinusitis should be investigated assessing biomarker profiles in nasal secretions.

Methods
Fifteen cytokines, three cellular activation markers and total IgE were determined in nasal secretions of seven patients with acute rhinosinusitis, 12 patients with CRS without polyps, 13 patients with CRS with polyps and six healthy controls. Principal component analysis was used to extract relevant factors.

Results
Irrespective of the clinical manifestation, all biomarkers assessed were increased in patients with rhinosinusitis when compared with controls (P<0.001). Principal component analysis allowed the extraction of three factors explaining 83% of data variance. The general inflammatory activation was mainly reflected by the first factor. The second factor differentiated acute from CRS. This factor correlated with IL‐12, which is involved in pathogen‐related immune activation by antigen‐presenting cells. It was also positively correlated with IL‐4, IL‐10 and IL‐13, which play an important role in the resolution of infections. The third factor differentiated CRS with polyps from CRS without polyps (P=0.001). It represented IL‐5 and nasal IgE (nIgE), whereas eosinophil cationic protein and tryptase were not specific for CRS with polyps.

Conclusion
In mucosal infection, numerous inflammatory mediators are activated. Simple correlations of few biomarkers with a specific disease process bear the risk of overestimating a possibly unspecific effect. To assess biomarker profiles, more complex analytic tools may be more appropriate to delineate mechanisms underlying mucosal disease. Using principal component analysis, it was found that high nIgE and IL‐5 levels are specific for CRS with nasal polyps.
Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years
Authors: Brierley J. , Tsang R. , Panzarella T. , Bana N.
Published: September 2005

Objectives  To assess the prognostic factors and the role of radioactive iodine (RAI) and external beam radiotherapy (RT) in patients with differentiated thyroid cancer.

Design  A retrospective review of 729 patients treated between 1958 and 1998. The median follow‐up was 11·3 years (range 0·3–39·8 years). Primary outcomes included time to cause‐specific survival and time to local–regional relapse. Baseline and treatment variables were assessed for statistical significance using the Cox proportional hazards model.

Results  The 10‐year cause‐specific survival (CSS) was 87·3% and the 10‐year local–regional relapse‐free rate (LRFR) was 84·9%. In multivariate analysis there was no statistically significant improvement in CSS with more aggressive treatment (i.e. more extensive surgery, the administration of RAI and/or RT). By multivariate analysis the use of RAI resulted in a statistically significant improvement in LRFR (hazard ratio 0·5; 95% confidence interval 0·3–0·8; P = 0·007). In low‐risk patients at AJCC stage I ≤ 45 years, there was no apparent benefit from RAI. For patients over 60, with extrathyroid extension but no gross residual disease (n = 70), adjuvant external RT resulted in statistically significantly higher CSS (10‐year CSS 81·0%vs. 64·6%, P = 0·04) and LRFR (10‐year LRFR 86·4%vs. 65·7%, P = 0·01).

Conclusions  The use of RAI was associated with improved LRFR but not in low‐risk patients. External beam RT improved LRFR and CSS in high‐risk patients.
Phosphorus decrease and climate variability: mediators of synchrony in phytoplankton changes among European peri‐alpine lakes
Authors: ANNEVILLE ORLANE , GAMMETER SONJA , STRAILE DIETMAR
Published: September 2005

1. In an attempt to discern long‐term regional patterns in phytoplankton community composition we analysed data from five deep peri‐alpine lake basins that have been included in long‐term monitoring programmes since the beginning of the 1970s. Local management measures have led to synchronous declines in phosphorus concentrations by more than 50% in all four lakes. Their trophic state now ranges from mesotrophic to oligotrophic.

2. No coherence in phytoplankton biomass was observed among lakes, or any significant decrease in response to phosphorus (P)‐reduction (oligotrophication), except in Lakes Constance and Walen.

3. Multivariate analyses identified long‐term changes in phytoplankton composition, which occurred coherently in all lakes despite the differing absolute phosphorus concentrations.

4. In all lakes, the phytoplankton species benefiting from oligotrophication included mixotrophic species and/or species indicative of oligo‐mesotrophic conditions.

5. A major change in community composition occurred in all lakes at the end of the 1980s. During this period there was also a major shift in climatic conditions during winter and early spring, suggesting an impact of climatic factors.

6. Our results provide evidence that synchronous long‐term changes in geographically separated phytoplankton communities may occur even when overall biomass changes are not synchronous.
How virtual are we? Measuring virtuality and understanding its impact in a global organization
Authors: Chudoba Katherine M. , Wynn Eleanor , Lu Mei , Watson‐Manheim Mary B.
Published: September 2005

Abstract. Employees in global corporations are increasingly involved in ‘virtual teams’ on a regular basis. Conflicting definitions of virtuality make it hard to measure such things as how much virtual teaming occurs and how virtual teaming affects performance. As a consequence, it is hard to allocate funding and to design infrastructures and software to support this specific mode of working. Using the concept of discontinuities, or changes in expected conditions, we propose a virtuality index to assess how ‘virtual’ a given setting is. The discontinuities used include geography, time zone, organization, national culture, work practices, and technology. The index separately measures these aspects of virtuality and their effect on perceived team performance. Data collected at a large multinational corporation clustered into three overarching discontinuities: team distribution, workplace mobility, and variety of work practices. The study revealed that being distributed in and of itself had no impact on self‐assessed team performance. Work practice predictability and sociability mitigated effects of working in discontinuous environments, while variety of practices (cultural and work process diversity) and employee mobility negatively impacted performance.
Treatment recommendations in patients diagnosed with high‐risk cutaneous squamous cell carcinoma
Authors: Veness MJ
Published: September 2005

Non‐melanoma cutaneous cancers occur at an epidemic rate in Australia. With an ageing population, more Australians will develop these cancers and at an increasing rate. In the majority of cases local treatment is highly curative. However, a subset of the population will be diagnosed with a high‐risk cutaneous squamous cell carcinoma. These can be defined as patients at risk of having subclinical metastases to regional lymph nodes based on unfavourable primary lesion features (including inadequately excised and recurrent lesions), patients with metastatic squamous cell carcinoma to regional lymph nodes, and squamous cell carcinoma in immunosuppressed patients. The mortality and morbidity associated with high‐risk cutaneous squamous cell carcinoma is usually as a consequence of uncontrolled metastatic nodal disease and, to a lesser extent, distant metastases. Radiotherapy has an essential role in treating these patients and in many cases the addition of adjuvant radiotherapy may be life saving. It is therefore important that all clinicians treating skin cancers have an understanding and awareness of the optimal approach to these patients. The aim of this article is to present treatment recommendations based on an overview of the current published literature.
REDUCING THE RISK OF PERISTOMAL INFECTION AFTER PEG PLACEMENT
Authors: Maetani Iruru , Sakai Yoshihiro
Published: September 2005

Percutaneous endoscopic gastrostomy (PEG) was first described in 1980 as an effective means of enteral nutrition where oral intake is not possible. PEG placement is safe and has now replaced the nasogastric tube in patients who need long‐term feeding. Although it is relatively safe with a very low associated mortality, minor complications, especially local and systemic infection, remain a problem. Of these, peristomal wound infections are the most common complication of PEG. In patients indicated for this procedure who are aged and/or frail, this complication may pose a critical problem. In the commonly used pull or push methods for PEG placement, the PEG tube is readily colonized by oropharyngeal bacteria. Infection of the PEG site is considered to be associated with contamination of the PEG catheter. There are important measures that should be taken to prevent peristomal infection. A number of rigorous studies have shown that prophylactic antibiotics are effective in reducing the risk of peristomal infection. As methicillin‐resistant Staphylococcus aureus (MRSA) or other resistant organisms are emerging as a major pathogen in peristomal infection, however, currently recommended antibiotic prophylaxis regimens might be inappropriate. Alternative regimens and other approaches to prevent contamination of the PEG tube during the procedure are required.
CLINICAL APPLICATION OF AN INDWELLING NEEDLE FOR ESOPHAGEAL VARICES IN ENDOSCOPIC INJECTION SCLEROTHERAPY WITH SIMULTANEOUS LIGATION
Authors: Nishikawa Yoshiyuki , Chikamori Fumio , Murakami Masato , Nasu Junichirou
Published: September 2005

Endoscopic injection sclerotherapy (EIS), in which a sclerosing agent is infused into esophageal varices, is advantageous in obstructing a blood‐supplying route; however, accurate intravascular infusion is technically difficult. To achieve accurate continuous intravascular infusion that does not depend on respiration or vomiting reflex, we developed an indwelling needle for esophageal varices. This indwelling needle facilitated intravascular puncture, as demonstrated for conventional puncture needles, and stabilized infusion of a sclerosing agent. Furthermore, EIS with ligation (EISL) prevented hemorrhage after the needle was removed. EISL with an indwelling needle may improve the treatment results.
SPECIFIC DIAGNOSIS OF BILIARY STRICTURES BY QUANTITATIVE ASSESSMENT USING A CHOLANGIOSCOPICALLY DERIVED HEMOGLOBIN INDEX
Authors: Inui Kazuo , Yoshino Junji , Miyoshi Hironao , Wakabayashi Takao , Okushima Kazumu , Nakamura Yuta , Hattori Toshiyuki , Nakazawa Saburo
Published: September 2005

Background:  We used percutaneous transhepatic cholangioscopy for detailed assessment of biliary tumors. Among the most important endoscopic findings is greater mucosal vascularity in malignant than in benign biliary strictures. Development of digital image processing now permits measurement of mucosal hemoglobin volume as a hemoglobin index. We studied the clinical usefulness of this hemoglobin index for differentiating malignant from benign biliary strictures.

Methods:  From 2000 to 2002 we determined the hemoglobin index in 22 patients with biliary stricture (8 with bile duct carcinoma; 1 with carcinoma of the duodenum; 5 with pancreatic carcinoma and 8 with benign stricture). Eight patients with malignant stricture were diagnosed by the histological examinations of resected specimens; six with malignant stricture and eight with benign stricture were diagnosed by examination of biopsy specimens. The ratio of hemoglobin indices in a given patient of lesional and uninvolved mucosa was determined from cholangioscopic imaging data.

Results:  The mean hemoglobin index ratio for bile duct carcinoma was 1.83; for carcinoma of the duodenum 1.98; and for pancreatic carcinoma, 1.35. For benign strictures, the ratio was only 1.09. The mean hemoglobin index ratio in patients with bile duct or pancreatic carcinoma was significantly higher than in patients with benign stricture (P < 0.05, paired t‐test).

Conclusions:  An image‐derived hemoglobin index is useful for diagnostic assessment of biliary stricture.
Induction of LTP in the human auditory cortex by sensory stimulation
Authors: Clapp W. C. , Kirk I. J. , Hamm J. P. , Shepherd D. , Teyler T. J.
Published: September 2005

High‐frequency, repetitive, auditory stimulation was used to determine whether induction of a long‐lasting increase of the human auditory evoked potential (AEP) was possible. Recording non‐invasively with electroencephalogram scalp electrodes, stable increases in amplitude were observed in the N1 component of the AEP, which is thought to reflect activity within auditory cortex (N1). The increase was maintained over an hour and was shown to be independent of alterations in the state of arousal. This is the first demonstration of the induction of long‐lasting plastic changes in AEPs, and suggest that this represents the first direct demonstration of long‐term potentiation in the auditory cortex of normal, intact humans.
Anterior cingulate cortex contributes to the descending facilitatory modulation of pain via dorsal reticular nucleus
Authors: Zhang Ling , Zhang Yuqiu , Zhao Zhi‐Qi
Published: September 2005

Supraspinal centres biphasically modulate spinal nociceptive transmission, including descending inhibition and facilitation. Recent studies have revealed that descending facilitatory modulation is a key mechanism underlying induction and maintenance of neuropathic and inflammatory pain. The anterior cingulate cortex (ACC) is not only involved in the transmission of pain sensation but also plays a role in processing pain‐related emotion. The ACC also widely connects with relevant regions of the descending modulation system. Here we used electrophysiological and behavioural techniques to study the possible pathways behind the modulation of spinal nociceptive transmission from the ACC. C‐fibre‐evoked field potentials in the spinal dorsal horn were produced by electrical stimulation of the sciatic nerve at an intensity high enough to excite C fibres, and paw withdrawal latencies (PWLs) to noxious heating were recorded. The results showed that high‐frequency tetanic electrical stimulation of the ACC both unilaterally enhanced the C‐fibre‐evoked field potentials in the spinal dorsal horn and bilaterally shortened PWLs, indicating a facilitation of spinal nociception. A similar effect was observed after microinjection of N‐methyl‐d‐aspartic acid (NMDA; 10 nm, 1 µL) or homocysteic acid (HCA; 0.1 m, 1 µL) into the ACC. When the dorsal reticular nucleus (DRt) was electrolytically lesioned, ACC‐induced facilitation of spinal nociception was blocked. These results imply that: (i) activation of the ACC may facilitate spinal nociception; (ii) NMDA receptors in the ACC may be involved in descending facilitation; and (iii) the DRt plays a crucial role in mediating ACC‐induced facilitation of spinal nociception.
Persistent changes in motivation to self‐administer cocaine following modulation of cyclic AMP‐dependent protein kinase A (PKA) activity in the nucleus accumbens
Authors: Lynch W. J. , Taylor J. R.
Published: September 2005

Drug‐induced neuroadaptations within the nucleus accumbens, including activation of cAMP‐dependent protein kinase A (PKA), may contribute to the synaptic plasticity and behavioural changes that underlie drug addiction. As a direct test of this hypothesis, we examined the effects in rats of PKA activation (Sp‐cAMPS infusions of 10 and 20 nmol/side) and inhibition (Rp‐cAMPS infusions of 10 and 20 nmol/side) in the nucleus accumbens on motivation to obtain cocaine as measured by responding under the progressive‐ratio schedule. Bilateral infusions of Sp‐cAMPS (20 nmol/side) resulted in an increase in progressive‐ratio responding for cocaine and this effect persisted for several days. In contrast, Rp‐cAMPS (20 nmol/side) produced persistent decreases in progressive‐ratio responding for cocaine beginning on the day of administration and lasting for several days. These data suggest that alternations in PKA activity within the nucleus accumbens as a consequence of repeated cocaine exposure may contribute to addiction by producing persistent increases in motivation to obtain cocaine.
Excessive activation of cyclic nucleotide‐gated channels contributes to neuronal degeneration of photoreceptors
Authors: Vallazza‐Deschamps Géraldine , Cia David , Gong Jie , Jellali Abdeljelil , Duboc Agnès , Forster Valérie , Sahel Jose A. , Tessier Luc‐Henri , Picaud Serge
Published: September 2005

In different animal models, photoreceptor degeneration was correlated to an abnormal increase in cGMP concentration. The cGMP‐induced photoreceptor toxicity was demonstrated by applying the phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine on retinal explants. To assess the role of cGMP‐gated channels in this cGMP toxicity, the Ca2+ channel blockers verapamil and l‐ and d‐diltiazem, which block cGMP‐gated channels with different efficacies, were applied to in vitro animal models of photoreceptor degeneration. These models included: (i) adult rat retinal explants incubated with zaprinast, a more specific inhibitor of the rod phosphodiesterase than 3‐isobutyl‐1‐methylxanthine and (ii) rd mouse retinal explants. Photoreceptor apoptosis was assessed by terminal dUTP nick end labelling and caspase 3 activation. Effects of the blockers on the synaptic rod Ca2+ channels were measured by patch‐clamp recording. In the zaprinast‐induced photoreceptor degeneration model, both diltiazem isomers rescued photoreceptors whereas verapamil had no influence. Their neuroprotective efficacy was correlated to their inhibition of cGMP‐gated channels (l‐diltiazem > d‐diltiazem > verapamil = 0). In contrast, all three Ca2+ channel blockers suppressed rod Ca2+ channel currents similarly. This suppression of the currents by the diltiazem isomers was very weak (16.5%) at the neuroprotective concentration (10 µm). In rd retinal explants, both diltiazem isomers also slowed down rod degeneration in contrast to verapamil. l‐diltiazem exhibited this effect at concentrations ranging from 1 to 20 µm. This study further supports the photoreceptor neuroprotection by diltiazem particularly in the rd mouse retina, whereas the absence of neuroprotection by verapamil further suggests the role of cGMP‐gated channel activation in the induction of photoreceptor degeneration.
Growth and maturation of metatarsals and their taxonomic significance in the jerboas Allactaga and Jaculus (Rodentia: Dipodidae)
Authors: Shahin A. A. B.
Published: September 2005

The development of metatarsals in Allactaga tetradactyla, Jaculus jaculus jaculus and J. orientalis was studied and their taxonomic significance was elucidated. The five metatarsals, as a rule, are developed and ossified in the three species, but variation in the fate of the first and fifth metatarsals was found. Ossification begins in the median part of the metatarsals; however, it appears in the distal part of the digits’ phalanges, beginning with the third phalanx. The first metatarsal appears just distal to the entocuneiform and develops as a small, separate bone located either in close contact with the distal end of the entocuneiform in A. tetradactyla or completely fused with it, forming a compound bone, in both of J. j. jaculus and J. orientalis. The second, third and fourth metatarsals differentiate distal to the mesocuneiform, ectocuneiform and cuboid, respectively, and fuse with one another into a single long cannon bone in all species. Nevertheless, the fifth metatarsal differentiates ventro‐lateral to the head of the fourth metatarsal and ossifies ventral to the head process of the developing cannon bone. The fifth metatarsal either extends to articulate with the phalanges of the fourth digit in A. tetradactyla or persists as a separate, small bone in both of J. j. jaculus and J. orientalis. On this basis, it is concluded that J. jaculus and J. orientalis are both distinct congeneric species and are somewhat more distant from A. tetradactyla.
The Fixed Combination of Acetylsalicylic acid, Paracetamol and Caffeine is more Effective than Single Substances and Dual Combination for the Treatment of Headache: a Multicentre, Randomized, Double-Blind, Single-Dose, Placebo-Controlled Parallel Group Study
Authors: Diener HC , Pfaffenrath V , Pageler L , Peil H , Aicher B
Published: September 2005

We investigated efficacy, safety, and tolerability of two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA) + 200 mg paracetamol + 50 mg caffeine (Thomapyrin®) in comparison with two tablets of 250 mg ASA + 200 mg paracetamol, two tablets of 500 mg ASA, two tablets of 500 mg paracetamol, two tablets of 50 mg caffeine, and placebo in patients who were used to treating their episodic tension-type headache or migraine attacks with non-prescription analgesics. For the primary endpoint ‘time to 50% pain relief’ in the intention-to-treat dataset ( n = 1743 patients), the fixed combination of ASA, paracetamol and caffeine was statistically significantly superior to the combination without caffeine ( P = 0.0181), the mono-substances ASA ( P = 0.0398), paracetamol ( P = 0.0016), caffeine ( P < 0.0001) and placebo ( P < 0.0001). All active treatments except caffeine differed significantly ( P < 0.0001) from placebo. The superior efficacy of the triple combination could also be shown for all secondary endpoints such as time until reduction of pain intensity to 10 mm, weighted sum of pain intensity difference (%SPIDweighted), extent of impairment of daily activities, global assessment of efficacy. All treatments were well tolerated. The incidence of adverse events observed was low.
Altered Motion Perception in Migraineurs: Evidence for Interictal Cortical Hyperexcitability
Authors: Antal A , Temme J , Nitsche MA , Varga ET , Lang N , Paulus W
Published: September 2005

Much research on visual functions in migraine has pinpointed the existence of abnormal visual processing between attacks. However, it is not clear if this is due to cortical hyper- or hypoexcitability. We aimed to clarify this issue by comparing motion perception thresholds of subjects with migraine with (MA) or without aura (MoA) and control subjects. Two types of dot kinetograms were used: in the first experiment coherently moving dots were presented in an incoherent environment, while in the second only coherent motion was seen. Subjects with migraine displayed significantly impaired motion perception compared with controls when they had to detect the direction of the coherently moving dots in an incoherent environment, while they were slightly better in a direction discrimination task, where only coherent motion was presented. This pattern of results is comparable to those achieved by an external excitability enhancement of V5 induced in healthy human subjects in a former study of our group. According to this, a cortical excitability enhancement can result in an impaired focusing on a given signal against a noisy background, but improves perception of non-ambiguous stimuli. Thus we conclude that migraineurs display enhanced visual cortical excitability between attacks in V5.
A single-fibre EMG Study of Neuromuscular Transmission in Migraine Patients
Authors: Domitrz I , Kostera-Pruszczyk A , Kwieciñski H
Published: September 2005

It is known that mutations of CACNA1A, which encodes a neuronal P/Q Ca2+ channel, are present in patients with familial hemiplegic migraine, and possibly in other types of migraine as well. This calcium channel is also involved in neuromuscular transmission. To assess if the single-fibre EMG (SFEMG) method can demonstrate a neuromuscular transmission deficit in migraine, a group of 26 patients with different types of migraine and 20 healthy control subjects were studied. The migraine patients were divided into three groups: 8 patients with migraine without aura (MoA), 12 with migraine with aura excluding visual aura (MA) and 6 with visual aura (VA). A SFEMG of the voluntarily activated extensor digitorum communis muscle was performed. The SFEMG results were normal in the healthy controls and the MoA group (migraine without aura). Slight neuromuscular transmission disturbances were present in 6/12 (50%) of patients with MA and in 1/6 (17%) of patients with VA. We suggest that abnormal neuromuscular transmission detectable by SFEMG may reflect a genetically determined dysfunction of the P/Q Ca2+ channels in a subgroup of migraineurs with aura.
Tetanus toxin fragment C fusion facilitates protein delivery to CNS neurons from cerebrospinal fluid in mice
Authors: Benn Susanna C. , Ay Ilknur , Bastia Elena , Chian Ru‐Ju , Celia Samuel A. , Pepinsky R. Blake , Fishman Paul S. , Brown Robert H. , Francis Jonathan W.
Published: September 2005

To improve protein delivery to the CNS following intracerebroventricular administration, we compared the distribution of a human Cu/Zn superoxide dismutase:tetanus toxin fragment C fusion protein (SOD1:TTC) in mouse brain and spinal cord with that of tetanus toxin fragment C (TTC) or human SOD1 (hSOD1) alone, following continuous infusion into the lateral ventricle. Mice infused with TTC or SOD1:TTC showed intense anti‐TTC or anti‐hSOD1 labeling, respectively, throughout the CNS. In contrast, animals treated with hSOD1 revealed moderate staining in periventricular tissues. In spinal cord sections from animals infused with SOD1:TTC, the fusion protein was found in neuron nuclear antigen‐positive (NeuN+) neurons and not glial fibrillary acidic protein‐positive (GFAP+) astrocytes. The percentage of NeuN+ ventral horn cells that were co‐labeled with hSOD1 antibody was greater in mice treated with SOD1:TTC (cervical cord = 73 ± 8.5%; lumbar cord = 62 ± 7.7%) than in mice treated with hSOD1 alone (cervical cord = 15 ± 3.9%; lumbar cord = 27 ±4.7%). Enzyme‐linked immunosorbent assay for hSOD1 further demonstrated that SOD1:TTC‐infused mice had higher levels of immunoreactive hSOD1 in CNS tissue extracts than hSOD1‐infused mice. Following 24 h of drug washout, tissue extracts from SOD1:TTC‐treated mice still contained substantial amounts of hSOD1, while extracts from hSOD1‐treated mice lacked detectable hSOD1. Immunoprecipitation of SOD1:TTC from these extracts using anti‐TTC antibody revealed that the recovered fusion protein was structurally intact and enzymatically active. These results indicate that TTC may serve as a useful prototype for development as a non‐viral vehicle for improving delivery of therapeutic proteins to the CNS.
Influence of landiolol on the dose requirement of propofol for induction of anesthesia
Authors: Takizawa Daisuke , Saito Shigeru , Sato Eri , Hiraoka Haruhiko , Kunimoto Fumio , Goto Fumio
Published: September 2005

It was reported that the pharmacokinetics of propofol was influenced by cardiac output (CO). The purpose of this study was to evaluate the effect of landiolol (short‐acting beta‐1‐adrenergic blocker) on the dose requirement of propofol for induction of anesthesia. Forty patients were randomly allocated to the control and landiolol group. Induction of anesthesia commenced 10 min after the infusion of 0.9% saline or landiolol, using a Diprifusor set to achieve propofol plasma concentration of 6.0 μg/mL. Induction of anesthesia was defined as the first lack of response to command. Propofol dose was 2.22 ± 0.21 mg/kg for the control group and 1.79 ± 0.28 mg/kg for the landiolol group (P < 0.0001). The quantity of propofol required for the induction of anesthesia was reduced by the administration of landiolol.
Impact of a misspecification of the response rate under standard treatment in sequential clinical trials
Authors: Sébille Véronique , Bellissant Eric
Published: September 2005

Phase III trials are aimed at assessing whether new treatments have superior efficacy than standards. Sequential methods, such as the single triangular test (STT) and the double triangular test (DTT), allow for early stopping of such trials. They use stopping boundaries which depend, for a binary endpoint, on π0 and π1 (response rates under standard and new treatment, respectively) and α and β (type I and II errors, respectively). Thus, a wrong estimation of π0 at planning phase might have an influence on their statistical properties. We assessed the extent of this influence by simulations regarding α, 1 − β, and average sample number (ASN) and compared the two methods with the one‐sided and two‐sided single‐stage designs (SSD). There was no influence on α for any test and the power achieved by the one‐sided or two‐sided SSD was moderately affected by a wrong estimation of π0. However, important drifts (whose magnitude depended on chosen design) were observed for sequential methods concerning power and ASN in case of moderate under‐ or overestimation of π0 (±20% compared with its ‘true’ value). For example, when ‘true’ values of π0 and π1 are 0.30 and 0.40, respectively, using design values of 0.10 and 0.20, the power is 0.57 and 0.50 for the STT and DTT, respectively, instead of 0.95. When ‘true’ values of π0 and π1 are 0.10 and 0.20, respectively, using design values of 0.30 and 0.40, the ASN under H0 is 1309 and 2019 for the STT and DTT, respectively, instead of 392 and 601, respectively, using the right design. Using sequential methods in comparative clinical trials with binary responses requires a precise knowledge of the response rate under standard treatment to avoid losses in power or inappropriate increases in sample size.
Return and Maturity Relationships for Treasury Auctions: Evidence from Turkey
Authors: Berument Hakan , Yucel Eray M.
Published: September 2005

The relationship between the interest rate and the maturity of newly issued bonds provides information on the debt dynamics of an economy as well as on the sustainability of its debt. Such information is crucial especially for countries that have debt‐rollover concerns due to financial stress and/or macroeconomic instability. This study investigates the relationship between treasury auction maturity, which also dictates the debt maturity, and auction interest rates. When the Turkish treasury auction data from 1988 to 2004 are analysed, a reciprocal linkage between auction interest rates and maturities can be observed, especially for the 1995–2000 period, when there were chronic high inflation, high political uncertainty, high public deficits and unsuccessful attempts at stabilisation. This suggests that under an adverse shock, the Treasury decreases the auction maturity in order not to increase interest rates too much. A change in this reciprocal relationship is also reported for the post‐2001 era, which is characterised by decreasing inflation, higher political stability, lower public deficits and successful stabilisation attempts.
Measurement in Veterans Affairs Health Services Research: Veterans as a Special Population
Authors: Morgan Robert O. , Teal Cayla R. , Reddy Siddharta G. , Ford Marvella E. , Ashton Carol M.
Published: September 2005

Objective. To introduce this supplemental issue on measurement within health services research by using the population of U.S. veterans as an illustrative example of population and system influences on measurement quality.

Principal Findings. Measurement quality may be affected by differences in demographic characteristics, illness burden, psychological health, cultural identity, or health care setting. The U.S. veteran population and the VA health system represent a microcosm in which a broad range of measurement issues can be assessed.

Conclusions. Measurement is the foundation on which health decisions are made. Poor measurement quality can affect both the quality of health care decisions and decisions about health care policy. The accompanying articles in this issue highlight a subset of measurement issues that have applicability to the broad community of health services research. It is our hope that they stimulate a broad discussion of the measurement challenges posed by conducting “state‐of‐the‐art” health services research.
Overcoming Bias in Estimating the Volume–Outcome Relationship
Authors: Tsai Alexander C. , Votruba Mark , Bridges John F. P. , Cebul Randall D.
Published: September 2005

Objective. To examine the effect of hospital volume on 30‐day mortality for patients with congestive heart failure (CHF) using administrative and clinical data in conventional regression and instrumental variables (IV) estimation models.

Data Sources. The primary data consisted of longitudinal information on comorbid conditions, vital signs, clinical status, and laboratory test results for 21,555 Medicare‐insured patients aged 65 years and older hospitalized for CHF in northeast Ohio in 1991–1997.

Study Design. The patient was the primary unit of analysis. We fit a linear probability model to the data to assess the effects of hospital volume on patient mortality within 30 days of admission. Both administrative and clinical data elements were included for risk adjustment. Linear distances between patients and hospitals were used to construct the instrument, which was then used to assess the endogeneity of hospital volume.

Principal Findings. When only administrative data elements were included in the risk adjustment model, the estimated volume–outcome effect was statistically significant (p=.029) but small in magnitude. The estimate was markedly attenuated in magnitude and statistical significance when clinical data were added to the model as risk adjusters (p=.39). IV estimation shifted the estimate in a direction consistent with selective referral, but we were unable to reject the consistency of the linear probability estimates.

Conclusions. Use of only administrative data for volume–outcomes research may generate spurious findings. The IV analysis further suggests that conventional estimates of the volume–outcome relationship may be contaminated by selective referral effects. Taken together, our results suggest that efforts to concentrate hospital‐based CHF care in high‐volume hospitals may not reduce mortality among elderly patients.
Prediction of small for gestational age by logistic regression in twins
Authors: WEN Shi Wu , TAN Hongzhuan , YANG Qiuying , WALKER Mark
Published: September 2005

Background:  Small for gestational age (SGA) is one of the major determinants of perinatal mortality and morbidity, and may relate in adult diseases. Early prediction of SGA could be helpful for health care providers and public health workers in guiding antenatal management and prevention. The reported methods of SGA prediction are not satisfactory because the diagnostic performance is poor and the interval between prediction and delivery is too short.

Aims:  To establish a SGA prediction model for twin pregnancies based on variables obtainable in early gestation.

Methods:  We used a large twin registry United States data (1995–1997). The study subjects were randomly divided into two groups: group 1 to establish the prediction model by logistic regression and group 2 to validate the prediction model. SGA was defined as birth weight for gestational age z scores less than 10th percentiles. Pair of twin was the unit of analysis. Two sets of multiple logistic regression analyses with different outcome measures – one or both twins SGAs and both twins SGAs – were used to establish the prediction model.

Results:  The sensitivity, specificity, and positive predictive value were 52.3, 62.5, and 21.5%, respectively, at the cutoff value 0.16 in a SGA prediction model based on maternal race, education, marital status, parity, prenatal care visit initiation, cigarette smoking, and paternal race.

Conclusions:  A prediction model based on determinants that can be obtained at early gestation might be useful in the management of pregnancies with high risk of SGA in twins.
Comparison of cerebral magnetic resonance and electroencephalogram findings in pre‐eclamptic and eclamptic women
Authors: OSMANAĞAOĞLU Mehmet A. , DINÇ Gülseren , OSMANAĞAOĞLU Selen , DINÇ Hasan , BOZKAYA Hasan
Published: September 2005

Objective:  To compare the cerebral magnetic resonance (MR) and electroencephalogram (EEG) findings in pre‐eclamptic and eclamptic pregnant women.

Methods:  A total of 38 pregnant women with mild pre‐eclampsia (n = 15), severe pre‐eclampsia (n = 11) and eclampsia (n = 12) were included in this study. Cranial MR without contrast and EEG were performed in these women on admission or within 3 days of onset. Follow‐up control MR or EEG evaluations were performed 4–6 weeks postpartum in women with MR or EEG abnormalities in the initial examination. To compare differences, X2 test, Fisher exact or Mann–Whitney U‐tests were used.

Results:  Abnormal cranial MR findings were found in one (6%) pre‐eclamptic woman, in four (36%) severe pre‐eclamptic women, and in 11 (92%) eclamptic women. Cranial MR findings were consistent with ischaemia in 15 (39%) patients and haemorrhage in one (3%) case. Two (5%) severe pre‐eclamptic women showed cerebral infarction during the follow‐up period. MR and EEG abnormalities were totally resolved in 88% of cases. The MR findings of 12 (71%) patients were located in the occipital lobes followed by the parietal lobes in six (40%) cases. Three (20%) mild pre‐eclamptic women, four (36%) severe pre‐eclamptic women and 10 (83%) eclamptic women had abnormal EEGs. The EEG changes were totally resolved in 13 of 14 (93%) patients after the first month. In one patient with cerebral haemorrhage, the EEG changes lasted for a duration of 6 months.

Conclusions:  A correlation between EEG abnormalities and MR findings was found in this study. The combined use of MR and EEG may help to determine the prognosis for these patients, but the interictal EEG findings recorded in eclampsia were non‐specific.
Human papilloma virus is detectable by the Hybrid Capture 2 test in cervical smear samples from women over 40 years of age with high‐grade squamous intraepithelial lesions
Authors: SYKES Peter , JENNINGS Lance , HARKER Dianne , BEYNON Kirsten
Published: September 2005

To establish that in Canterbury, New Zealand, women over the age of 40 with biopsy confirmed high grade squamous intraepithelial lesions (HSIL) have human papilloma virus (HPV) detectable by the Hybrid Capture 2 (HC2) test. Fifty‐two women with abnormal cytology under going colposcopy had HC2 performed. HPV status, cytology and histology were compared. HC2 was positive in 30/31 with grade 2 cervical intraepithelial neoplasia (CIN2) or worse, 5/6 with HPV changes or CIN1, and 10/15 with no demonstrated abnormality.
Vested Interest and Biased Price Estimates: Evidence from an Auction Market
Authors: MEI JIANPING , MOSES MICHAEL
Published: September 2005

This study employs a new data set from art auctions to examine the relationship between auctioneer presale price estimates and the long‐term performance of artworks. We find that the price estimates for expensive paintings have a consistent upward bias over a long period of 30 years. High estimates at the time of purchase are associated with adverse subsequent abnormal returns. Moreover, the estimation error for individual paintings tends to persist over time. These results are consistent with the view that auction house price estimates are affected by agency problems and that some investors are credulous.
Arbitraging Arbitrageurs
Authors: ATTARI MUKARRAM , MELLO ANTONIO S. , RUCKES MARTIN E.
Published: September 2005

This paper develops a theory of strategic trading in markets with large arbitrageurs. If arbitrageurs are not well capitalized, capital constraints make their trades predictable. Other market participants can exploit this by trading against them. Competitors may find it optimal to lend to arbitrageurs that are financially fragile; additional capital makes the arbitrageurs more viable, and lenders can reap profits from trading against them for a longer time. The strategic behavior of these market participants has implications for the functioning of financial markets. Strategic trading may produce significant price distortions, increase price manipulation, and trigger forced liquidations of large traders.
Relationship Between Dominant Prolongation of the Filtered QRS Duration in the Right Precordial Leads and Clinical Characteristics in Brugada Syndrome
Authors: FURUSHIMA HIROSHI , CHINUSHI MASAOMI , HIRONO TAKASHI , SUGIURA HIROTAKA , WATANABE HIROSHI , KOMURA SATORU , WASHIZUKA TAKASHI , AIZAWA YOSHIFUSA
Published: September 2005

Background: Electrical abnormalities in the RVOT may be involved in Brugada syndrome.

Objectives: We investigated the relationship between the signal‐averaged ECG (SAECG) and electrophysiologic study (EPS), especially focusing on conduction delay in the outflow tract of the right ventricle (RVOT) and its contribution to clinical characteristics.

Methods: Twenty‐four patients with Brugada syndrome (23 men and 1 woman; 61 ± 16 years old) were studied. We assessed the presence of late potential (LP) in SAECG and the filtered QRS duration in the right precordial leads (V1 or V2; RfQRS) and in the left precordial leads (V5 or V6; LfQRS) and the difference between them. In 18 patients, SAECG was evaluated for an LP on three separate occasions.

Results: SAECG was positive for LP in 15 patients at least once; and in 7 patients, SAECG was positive for an LP on multiple occasions, and 6 of 7 patients (86%) had a history of cardiac arrest. The difference between RfQRS and LfQRS was significantly greater in patients with cardiac arrest than in patients with syncope or in asymptomatic patients; 29 ± 10, 14 ± 11 (P < 0.01), and 7 ± 5 msec (P < 0.001), respectively. All patients were alive and one patient with cardiac arrest had an appropriate VF therapy delivered by the ICD.

Conclusions: The dominant prolongation of the filtered QRS duration in the right precordial leads may be related to the risk of arrhythmic event in Brugada syndrome.
Effect of three distinct treatments of titanium surface on osteoblast attachment, proliferation, and differentiation
Authors: Sader Márcia Soares , Balduino Alex , De Almeida Soares Glória , Borojevic Radovan
Published: September 2005

Abstract: Cell–titanium interactions are crucial to the clinical success of bone and dental implants. The physico‐chemical characteristics of the substrates surface influence osteoblast proliferation, differentiation, and activity as well. The osteoblast behavior was analyzed on three different titanium surfaces: ground with an abrasive 600 grit SiC paper, blasted with alumina particles (65 μm diameter) and alumina blasted followed by a double chemical etch (4% HF+4% HF/8% H2O2). Scanning electron microscopy (SEM) and profilometry showed distinct microtopographies. Ground samples showed parallel‐groove orientation. The Al2O3‐blasted surface presented the roughest microtopography with aluminum‐rich particles incrusted in the titanium surface. Osteoblasts cells from femora of Balb/c mice were seeded onto the substrates tested. Cell morphology and initial attachment were evaluated by SEM. Osteoblasts adhered to and spread on all samples tested. However, on rough surfaces, osteoblasts did not spread completely and acquired a polygonal morphology. Besides, the cell proliferation rate was diminished at the beginning of incubation on rough surfaces. Our results suggest a delay, rather than an impairment, in osteoblast viability and alkaline phosphatase activity when cells are cultured on rough surfaces, inducing a distinct osteoblast phenotype, rather than blocking its activity. At least in the culture conditions used in this work, alumina particles did not affect osteoblast behavior.