bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SummaryObjectives  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

Summary1. 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.
Treatment recommendations in patients diagnosed with high‐risk cutaneous squamous cell carcinoma
Authors: Veness MJ 
Published: September 2005

SummaryNon‐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.
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

AbstractHigh‐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

AbstractSupraspinal 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

AbstractDrug‐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

AbstractIn 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

AbstractThe 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.
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

AbstractTo 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

AbstractIt 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

AbstractPhase 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

AbstractThe 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.