bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequential genome‐wide association studies for monitoring adverse events in the clinical evaluation of new drugs
Authors: Kelly Patrick , Stallard Nigel , Zhou Yinghui , Whitehead John , Bowman Clive 
Published: January 2006

AbstractPharmacovigilance, the monitoring of adverse events (AEs), is an integral part in the clinical evaluation of a new drug. Until recently, attempts to relate the incidence of AEs to putative causes have been restricted to the evaluation of simple demographic and environmental factors. The advent of large‐scale genotyping, however, provides an opportunity to look for associations between AEs and genetic markers, such as single nucleotides polymorphisms (SNPs). It is envisaged that a very large number of SNPs, possibly over 500 000, will be used in pharmacovigilance in an attempt to identify any genetic difference between patients who have experienced an AE and those who have not.We propose a sequential genome‐wide association test for analysing AEs as they arise, allowing evidence‐based decision‐making at the earliest opportunity. This gives us the capability of quickly establishing whether there is a group of patients at high‐risk of an AE based upon their DNA. Our method provides a valid test which takes account of linkage disequilibrium and allows for the sequential nature of the procedure. The method is more powerful than using a correction, such as Šidák, that assumes that the tests are independent. Copyright © 2006 John Wiley & Sons, Ltd.
An evaluation of the WAsP model at a coastal mountainous site in Norway
Authors: Berge Erik , Nyhammer Finn , Tallhaug Lars , Jacobsen Øystein 
Published: January 2006

AbstractThe prediction errors of WAsP are analysed by use of five 50 m measuring masts and the differences in the RIX‐values in a mountainous site of wind energy development at the Norwegian coast. The RIX‐values range from 13% to 18% thus the terrain is quite complex. High correlation (0.96) is found between the prediction error of WAsP and the differences in the RIX‐values. The inclusion of a coastal background station contributes strongly to this correlation. Predictions errors of 10%–15% are found based on the background coastal site. One should therefore be careful in applying background meteorological stations to wind resource assessment at the coastal mountains. Adjustments of the wind speed predictions based on the present findings are recommended. For the measuring stations within the wind farm area only a rather high correlation (0.76) between prediction errors and differences in the RIX‐values are also encountered. Prediction errors are in the range 0%–6%, which is considered quite low taking the complexity of the terrain into account. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of enriched rotifers on growth, survival, and composition of larval Atlantic cod (Gadus morhua)
Authors: Park Heum Gi , Puvanendran Velmurugu , Kellett Anne , Parrish Christopher C. , Brown Joseph A. 
Published: January 2006

AbstractRecently, the nutritional requirements of marine finfish larvae have received considerable attention, and studies have shown that docosahexaenoic acid (DHA) affects the growth and survival of marine finfish larvae. We investigated the effects of different rotifer diets containing variable amounts of DHA on the growth and survival of larval Atlantic cod (Gadus morhua L.). Four different commercial rotifer enrichment formulations were used: spray-dried whole cells composed of Crypthecodinium sp. (ED1), spray-dried whole cells of Schizochytrium sp. (ED2), an oil emulsion (ED3) and ED1, and dried Chlorella at a 7:3 ratio by weight (ED4). The resultant rotifers contained a similar concentration of DHA (1.1–1.6% DW), but the level of DHA differed in proportion to EPA for each enrichment, and was designated ER1–4. Twelve 30-l aquaria were used with three replicates per treatment. Larvae were fed with rotifers from 3 to 43 days post-hatch (dph) at 4000 prey l−1. At the end of the experiment, no significant differences were found in body length and dry weight between the larvae reared on ER1 and ER2. However, larvae reared on ER3 were significantly smaller (both in length and weight) than larvae reared on ER1 and ER2. Larval survival on the ER2 treatment at 43 dph was significantly higher than on the other three treatments. Our results showed a positive effect of rotifer DHA proportions on growth and survival of cod larvae, and demonstrated that Atlantic cod larvae require a high ratio of dietary DHA to EPA.
Genetic impact of gadoid culture on wild fish populations: predictions, lessons from salmonids, and possibilities for minimizing adverse effects
Authors: Bekkevold Dorte , Hansen Michael M. , Nielsen Einar E. 
Published: January 2006

Abstract
Little is known about the effects of ranched gadoids escaping into wild populations, and plans for substantial up-scaling of gadoid mariculture raise concerns about detrimental effects on local gene pools. Genetic studies from salmonid populations subjected to intentional or unintentional releases of hatchery-produced fish suggest that wild gene pools are affected by introgression, but that the genetic impact can be minor relative to expectations from the often substantial numbers of released hatchery fish. However, even if resilience to introgression is a general trend, wild population fitness is still predicted to be jeopardized by releases. In this paper, we review theoretical genetic effects of escapes of cultivated individuals and the empirical evidence for introgression effects, which are based mainly on salmonid studies. Based on knowledge of gadoid population structure and life history traits, we make predictions for effects of gadoid mariculture on wild populations and discuss approaches for monitoring and minimizing introgression effects.
67‐kDa Laminin Receptor in Human Laryngeal Squamous Cell Carcinoma
Authors: Zhou Liang , Xie Ming , Zhou Jia Qing , Tao Lei 
Published: January 2006

AbstractObjectives/Hypothesis: Abnormal interaction of epithelial cells with laminin component of basement membrane may account for altered biological behavior of cells, influencing proliferation, adhesion, and motility. In the current study, we investigated the role of 67‐kDa laminin receptor (67LR), a high affinity receptor for laminin, in aggressiveness of laryngeal squamous cell carcinoma.Methods: Thirty paraffin‐embedded specimens and 20 fresh tissues of pa‐tients with laryngeal squamous cell carcinoma were analyzed using immunohistologic and reverse‐transcriptase polymerase chain reaction techniques, respectively. Expression of 67LR on the surface of AMC‐HN‐8 cells was examined by flow cytometry. The effect of 67LR monoclonal antibody (MLuC5) on the adhesive and invasive abilities of AMC‐HN‐8 cells was determined by adherence and invasion inhibition assay in vitro.Results: Both at the mRNA and protein level, laryngeal carcinoma cells expressed higher level of 67LR than normal epithelial cells (P < .01). The expression of 67LR correlated inversely with differentiation extent of tumor (P < .05). 67LR level was significantly increased in patients with lymph node metastases than those without lymph node involvement (P < .05). Flow cytometry showed 80.9 ± 0.9% of AMC‐HN‐8 cells expressed 67LR. After 60 minutes and 120 minutes of incubation, MluC5 induced 57.1 ± 3.6% and 63.2 ± 2.8% inhibition of adhesion, respectively. The invasive ability of AMC‐HN‐8 cells to matrigel was reduced by MLuC5.Conclusions: Laryngeal carcinoma cells over‐expressing 67LR have a stronger aggressive potential, which might make 67LR a promising target for the treatment of metastatic tumor.
The Learning Curve in Stapes Surgery and Its Implication to Training
Authors: Yung M. W. , Oates J , Vowler S. L. 
Published: January 2006

AbstractObjective: To identify the stapedotomy learning curve of two U.K. otolaryngologists.Study Design: A retrospective review of the outcome of first 100 stapedotomy operations by each surgeon. Included in the study was a postal survey of the incidence of stapes surgery by U.K. otolaryngologists.Setting: Two tertiary referral centers.Patients: All ears in which primary stapedotomy was performed for otosclerosis. Nonotosclerotic cases and malleus stapedotomy cases were excluded.Intervention: One surgeon used the technique of small fenestra stapedotomy with either a Teflon‐wire or titanium piston but without vein graft interposition, whereas the second used the technique of stapedotomy with vein graft interposition and a Teflon piston.Main Outcome Measures: A moving average with a window of 15 dB was used to plot learning curves for the postoperative air‐bone gaps. Using a postoperative air‐bone gap of 20 dB or better as a definition of ‘success,’ the success rates with the increase in surgical experience of both surgeons were plotted on graphs, the learning curves. The end point of the learning curve was defined as the point where the curve reached its peak, and the results were sustainable.Results: There was no clear‐cut end point in both learning curves, although it appears that there is a landmark point at 60 to 80 cases for both surgeons. Both surgeons also had one “dead ear” in their first 15 cases. The postal survey showed that some trainers only performed small numbers of stapes surgery, whereas some otolaryngologists who performed stapedotomies regularly were not trainers.Conclusions: The study supports a learning curve in stapes surgery. To maximize the training opportunity of trainee surgeons, it may be advisable for learning centers to form network to provide target training for the trainee who has demonstrated the necessary dexterity and temperament of an otologist.
Response to Galvanic Vestibular Stimulation in Patients with Unilateral Vestibular Loss
Authors: Kim Hyun Jik , Choi Jae Young , Son Eun Jin , Lee Won‐Sang 
Published: January 2006

AbstractObjectives: This study sought to characterize various responses to galvanic vestibular stimulation (GVS) by comparing GVS‐induced eye movements in healthy subjects and patients with vestibular function loss. The study also aimed to estimate the clinical significance of GVS tests. Finally, an effort was made to localize the primary excitation site of stimulation in the vestibular system.Materials and Methods: Three parameters of response to GVS, spontaneous nystagmus, galvanic stimulating nystagmus (GSN), and postgalvanic stimulating nystagmus (PGSN), were evaluated in 20 normal subjects and 14 patients with complete unilateral vestibular function loss resulting from labyrinthectomy or vestibular neurectomy using a three‐dimensional video‐electronystagmography technique.Results: In normal subjects, GSN was detected in all subjects and was directed toward the negative electrode. PGSN was also detected but was directed toward the opposite electrode. When the negative electrode was attached to the intact side in unilateral vestibular loss subjects, GSN was always directed toward the negative electrode and PGSN was never observed. When the negative electrode was attached to the lesion side, however, GSN was detected in only one case, and PGSN was observed and directed to the intact side in 13 patients.Conclusions: The response to GVS in vestibular loss patients differed from that in normal subjects, which suggests that GVS could be useful for estimating the extent of vestibular function loss. The fact that the patterns of GVS response differed so significantly suggests that the primary site of excitation is not central but is instead the peripheral vestibular organ.
Hearing Genes and Cisplatin Deafness: A Pilot Study
Authors: Knoll Christine , Smith Richard J. H. , Shores Carol , Blatt Julie 
Published: January 2006

AbstractObjective: Cisplatin commonly is used to treat pediatric solid tumors. A major dose‐limiting toxicity is sensorineural hearing loss. Which patients experience ototoxicity after treatment with cisplatin must reflect individual susceptibility, since it is not seen in all similarly treated patients. We hypothesized that mutations or polymorphisms in hearing genes are more common in patients who experience ototoxicity than in the general population.Study Design: We completed retrospective mutation screening of GJB2 and SLC26A4 and screened for three mtDNA mutations in patients with a history of childhood cancer who developed severe hearing loss at cumulative cisplatin doses of less than 400 mg/M2.Materials and Methods: Patients younger than 21 years of age who experienced severe hearing loss after cisplatin were identified using the Childhood Cancer Survivor Study database. Archival DNA from buccal washes of 11 patients was used for mutation screening and detection.Results: With the exception of one patient (9.1%) who was a carrier for the 35delG mutation, no mutant alleles were found. Given the reported prevalence of the 35delG mutation in the general population of 2.5%, this result is not significant (P = .35).Conclusions: It is not likely that any of the five hearing genes we examined contribute to cisplatin ototoxicity. Further study may be warranted to look at other hearing genes as possible predictors of cisplatin ototoxicity.
Planned Post‐Chemoradiation Neck Dissection: Significance of Radiation Dose
Authors: Stenson Kerstin M. , Huo Dezheng , Blair Elizabeth , Cohen Ezra E.W. , Argiris Athanassios , Haraf Daniel J. , Vokes E Everett 
Published: January 2006

AbstractObjective: The increasing prominence of multimodality therapy for patients with advanced head and neck cancer reflects its high survival and functional preservation rates. We report the pathologic data on patients undergoing neck dissection (ND) after induction chemotherapy followed by concomitant chemoradiotherapy (IC‐CRT) in three similar protocols utilizing decreasing doses of radiation therapy.Materials and Methods: The databases of 221 patients who underwent IC‐CRT between 1999 and 2002 were reviewed. Based on posttreatment residual or pretreatment N2a or greater neck disease, 73 patients without pretreatment neck surgery were eligible for analysis (1 N1, 3 N2a, 26 N2b, 20 N2c, 23 N3). Three additional subgroups were also analyzed with respect to outcome: Undissected patients with less than N2 disease, patients who had neck surgery prior to IC‐CRT, and patients with N2a or greater neck disease who did not have post‐IC‐CRT ND.Study Design: Retrospective analysis.Results: Sixty‐seven patients underwent unilateral or bilateral selective neck dissection. Six patients had modified or radical ND. There were no wound healing complications. Pathologic analysis revealed viable cancer in 15 of 73 patients (20.5%): 1 had N1, 3 had N2b, 4 had N2c, and 7 had N3 neck disease. The incidence of viable cancer in the neck dissection specimen increased as radiation dose decreased. Complete response induction chemotherapy predicted negative pathology (P = .003). In the subgroup analysis, patients who had pretreatment surgery had a lower risk of dying from the primary cancerConclusions: 1) The incidence of positive pathology after IC‐CRT increases as radiation dose decreases. 2) Selective neck dissection after CRT has been demonstrated to be feasible and safe; the complication rate of ND after IC‐CRT is acceptably low. 3) There is viable posttreatment cancer in 20.5% of patients, indicating necessity of ND in these patients.
Local disturbance history and habitat parameters influence the microdistribution of stream invertebrates
Authors: EFFENBERGER MICHAEL , SAILER GABRIELE , TOWNSEND COLIN R. , MATTHAEI CHRISTOPH D. 
Published: January 2006

Summary1. We investigated the effects of local disturbance history and habitat parameters (abiotic and biotic) on the microdistribution of benthic invertebrates during several floods in two streams, the Schmiedlaine in Germany (four events) and the Kye Burn in New Zealand (two events).2. Bed movement patterns were quantified using metal‐link scour chains. Before and after each flood, quantitative invertebrate samples were taken from replicate bed patches that had experienced sediment scour, fill or remained stable.3. Patterns of invertebrate density in the different bed stability types (i.e. scour, fill, stable) varied between floods, sampling dates and streams, but invertebrate density was highest in stable patches in >50% of all the patch type effects detected and lowest in fill patches in 75% of all detected effects. Stable bed patches acted as a refugium for Liponeura spp. and Leuctra spp. in the Schmiedlaine and for Hydracarina and Deleatidium spp. in the Kye Burn.4. Averaged across both streams, only near‐bed current velocity was correlated with invertebrate distribution on the streambed more often than disturbance history. In the Kye Burn, disturbance history and water depth were the most influential habitat parameters.5. Our results suggest that a thorough understanding of the microdistribution of benthic invertebrates requires knowledge of disturbance history, as well as more readily measured habitat parameters such as current velocity or water depth.
Severe malaria in children in areas with low, moderate and high transmission intensity in Uganda
Authors: Idro R. , Aloyo J. , Mayende L. , Bitarakwate E. , John C. C. , Kivumbi G. W. 
Published: January 2006

SummaryObjectives  Age and transmission intensity are known to influence the manifestations of severe falciparum malaria in African children. However, it is unclear how specific clinical features such as seizures, impairment of consciousness, or respiratory distress vary with the parasite load and transmission intensity. We examined how the peripheral parasite load varies with transmission intensity and how this influences the symptoms and manifestations of severe malaria in children under 5 years in three areas with different malaria transmission intensity across Uganda.Methods  We consecutively recruited 617 children with severe malaria presenting to three hospitals in areas with very low (51), moderate (367) and very high (199) transmission intensities and compared the age, admission parasite density and proportions of patients with different manifestations of severe disease.Results  The median age (months) was inversely proportional to transmission intensity and declined with rising transmission (26.4 in very low, 18.0 in moderate and 9.0 under very high transmission). The highest proportion of patients reporting previous malaria admissions came from the area with moderate transmission. The geometric mean parasite density (18 357, 32 508 and 95 433/μl) and the proportion of patients with seizures (13.7%, 36.8% and 45.7%, P < 0.001) from very low, moderate and very high transmission respectively, increased with rising transmission. A linear increase with transmission was also observed in the proportion of those with repeated seizures (9.8%, 13.4% and 30.2%, P < 0.001) or impaired consciousness (7.8%, 12.8% and 18.1%, P = 0.029) but not respiratory distress. The proportion of patients with severe anaemia (19.6%, 24.8% and 37.7%, P = 0.002) mirrored that of patients with seizures.Conclusions  These findings suggest that heavy Plasmodium falciparum parasitaemia may be important in development of seizures, severe malarial anaemia and impaired consciousness in children under 5 years of age but may not be important in the development of respiratory distress.
Cutaneous leishmaniasis: successful treatment with itraconazole
Authors: Consigli Javier , Danielo Cristian , Gallerano Verónica , Papa Mariana , Guidi Andrés 
Published: January 2006

AbstractBackground  Leishmaniasis is a disease produced by several species of protozoa of the Leishmania genus. These protozoa are injected into the human bloodstream by sandflies. The symptomathology, either cutaneous, mucocutaneous or visceral, depends on the infective species and the immune status of the patient. Antimonial drugs are the mainstay treatment for all the clinical forms of the disease. Amphotericin B is the second‐choice drug.Methods  We report two clinical cases of cutaneous leishmaniasis treated with itraconazole. One case was a relapsing form unresponsive to conventional therapy.Results  Both patients achieved fast resolution of their lesions with no secondary effects.Conclusions  Itraconazole may be a valid option for the treatment of cutaneous leishmaniasis, mainly in those cases unresponsive to conventional drugs.
“More is missed by not looking than by not knowing”[Thomas McCrae, 1870–1935]
Authors: Wolf Ronni , Orion Edith , Marcos Batsheva , Matz Hagit 
Published: January 2006

Case 1  A 19‐year‐old woman presented with a black crust on one part of the tattoo on her right leg (Fig. 1) which appeared after laser‐assisted hair removal by an alexandrite laser (755 nm).A depressed black crust with an erythematous halo on the black part of the tattoo in Case 1, 2 weeks after laser hair removalimageCase 2  A 28‐year‐old man underwent laser‐assisted hair removal from his back and shoulders by an alexandrite laser (755 nm), after which he developed a burn on part of the tattoo on his right shoulder and was left with an atrophic scar (Fig. 2).Atrophic, stria‐like scar at the site of the black tattoo in Case 2, 6 months after laser hair removalimage
Pravastatin‐induced lichenoid drug eruption
Authors: Pua Vernon SC , Scolyer Richard A , Barnetson Ross StC 
Published: January 2006

SUMMARYA 64‐year‐old woman presented with diffuse and numerous pigmented macules on her face and upper back. Histopathological examination of a skin punch biopsy of the rash showed a lichenoid dermatitis. The most likely offending drug was pravastatin. Cessation of pravastatin resulted in gradual fading of the pigmentation. 3‐Hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors have previously been reported to cause lichenoid drug eruptions.
Alar anaesthesia: A kinder method
Authors: Stanway Amy , Salmon Paul 
Published: January 2006

SUMMARYLocal infiltration of anaesthetic in the ala of the nose is very uncomfortable for most patients. This is an area frequently operated on by dermatosurgeons under local anaesthesia as it is a common site for non‐melanoma cutaneous malignancies. A simple method is described of providing more pleasant local anaesthesia for patients undergoing alar surgery by using nerve blocks prior to local infiltration.
Butterfly extinctions in European states: do socioeconomic conditions matter more than physical geography?
Authors: Konvicka Martin , Fric Zdenek , Benes Jiri 
Published: January 2006

ABSTRACTAim To distinguish the effects of physical geography and socioeconomic conditions on the extinction of butterflies in European states, and to compare patterns influencing extinctions with patterns influencing species richness.Location Europe.Method Per‐state species richness and extinctions were taken from theRed Data Book of European Butterflies, and their relationships with physical geography and socioeconomic predictors were analysed using regression analysis. Two hypothesis were explored: (1) extinctions are related primarily to identical physical geography factors that influence species richness; and (2) extinctions are influenced primarily by human pressure on natural biotopes and follow correlates of modern land use.Results Extinctions and richness are not correlated. Richness increased towards low latitudes and with biotope and topographic heterogeneity, and decreased in states affected by Quaternary glaciation and on islands. The only socioeconomic correlate was human density, exhibiting a weak negative effect. Extinctions were negatively correlated with area and with biotope and topographic heterogeneity. They peaked in regions with mild climate in central latitudes. The strongest socioeconomic correlate was high density of railways, interpreted as a proxy of early industrialization. Further correlates were human density and urban employment.Main conclusion Topographic and biotope heterogeneity predicts both high species richness and low extinction rates. Losses of butterflies result from a complex interplay of geography and relatively recent economic history, as low topographic heterogeneity and flat relief favoured the early advent of industrialization and intensive land use.