bluuebunny/crossref_metadata_2025 huggingface dataset:
The Incidence Of Prescribing Errors In An Eye Hospital
Authors: Mandal K , Fraser SG
Published: March 2005

Background

Relatively little is known about the incidence of prescribing errors and there has been no work on this in a single specialty ophthalmic hospital. Knowing where and when errors are most likely to occur is generally felt to be the first step in trying to prevent these errors. This study is an attempt in, the setting of an eye hospital, to try to identify and attribute these medication errors.

Methods

The study setting was a single specialty eye hospital geographically separated from the main general hospital. Pharmacists prospectively recorded the number of errors of prescribing during a 4 week period at an eye hospital in UK. The errors were categorised as error of prescription writing or drug error. Potential significance of the errors was not addressed.

Results

Overall 144/1952 (8%)prescription sheets had errors. 7% of the total errors were errors of prescription writing while 1% were drug errors. The majority of errors were made by junior doctors and no drug errors were made by senior doctors. The outpatients department had by far the highest prevalence of errors.

Conclusion

Certain areas within the hospital and certain grades of staff are more prone to drug errors. Further study is required to look at the reasons why this is so and what systems can be put in place to reduce these errors.
Further investigation of confirmed urinary tract infection (UTI) in children under five years: a systematic review
Authors: Westwood Marie E , Whiting Penny F , Cooper Julie , Watt Ian S , Kleijnen Jos
Published: March 2005

Background

Further investigation of confirmed UTI in children aims to prevent renal scarring and future complications.

Methods

We conducted a systematic review to determine the most effective approach to the further investigation of confirmed urinary tract infection (UTI) in children under five years of age.

Results

73 studies were included. Many studies had methodological limitations or were poorly reported.

Effectiveness of further investigations: One study found that routine imaging did not lead to a reduction in recurrent UTIs or renal scarring.

Diagnostic accuracy: The studies do not support the use of less invasive tests such as ultrasound as an alternative to renal scintigraphy, either to rule out infection of the upper urinary tract (LR- = 0.57, 95%CI: 0.47, 0.68) and thus to exclude patients from further investigation or to detect renal scarring (LR+ = 3.5, 95% CI: 2.5, 4.8). None of the tests investigated can accurately predict the development of renal scarring. The available evidence supports the consideration of contrast-enhanced ultrasound techniques for detecting vesico-ureteric reflux (VUR), as an alternative to micturating cystourethrography (MCUG) (LR+ = 14.1, 95% CI: 9.5, 20.8; LR- = 0.20, 95%CI: 0.13, 0.29); these techniques have the advantage of not requiring exposure to ionising radiation.

Conclusion

There is no evidence to support the clinical effectiveness of routine investigation of children with confirmed UTI. Primary research on the effectiveness, in terms of improved patient outcome, of testing at all stages in the investigation of confirmed urinary tract infection is urgently required.
Developing optimal search strategies for detecting clinically sound and relevant causation studies in EMBASE
Authors: Haynes R Brian , Kastner Monika , Wilczynski Nancy L ,   the Hedges Team
Published: March 2005

Background

Evaluating the existence and strength of an association between a putative cause and adverse clinical outcome is complex and best done by assessing all available evidence. With the increasing burden of chronic disease, greater time demands on health professionals, and the explosion of information, effective retrieval of best evidence has become both more important and more difficult. Optimal search retrieval can be hampered by a number of obstacles, especially poor search strategies, but using empirically tested methodological search filters can enhance the accuracy of searches for sound evidence concerning etiology. Although such filters have previously been developed for studies of relevance to causation in MEDLINE, no empirically tested search strategy exists for EMBASE.

Methods

An analytic survey was conducted, comparing hand searches of journals with retrievals from EMBASE for candidate search terms and combinations. 6 research assistants read all issues of 55 journals indexed in EMBASE. All articles were rated using purpose and quality indicators and categorized into clinically relevant original studies, review articles, general papers, or case reports. The original and review articles were then categorized as 'pass' or 'fail' for scientific merit according to explicit criteria in the areas of causation (etiology) and other clinical topics. Candidate search strategies were developed for causation, then run in a subset of 55 EMBASE journals, the retrievals being compared with the hand search data. The sensitivity, specificity, precision, and accuracy of the search strategies were calculated.

Results

Of the 1489 studies classified as causation, 14% were methodologically sound. When search terms were combined, sensitivity reached 92%. Compared with the best single-term strategy, the best combination of terms resulted in an absolute increase in sensitivity (19%) and specificity (5.2%). Maximizing specificity for combined terms resulted in an increase of 7.1% compared with the single term but this came at an expense of sensitivity (39% absolute decrease). A search strategy that optimized the trade-off between sensitivity and specificity achieved 81.9% for sensitivity and 81.4% for specificity.

Conclusion

We have discovered search strategies that retrieve high quality studies of causation from EMBASE with high sensitivity, high specificity, or an optimal balance of each.
Complete reannotation of the Arabidopsis genome: methods, tools, protocols and the final release
Authors: Haas Brian J , Wortman Jennifer R , Ronning Catherine M , Hannick Linda I , Smith Roger K , Maiti Rama , Chan Agnes P , Yu Chunhui , Farzad Maryam , Wu Dongying , White Owen , Town Christopher D
Published: March 2005

Background

Since the initial publication of its complete genome sequence, Arabidopsis thaliana has become more important than ever as a model for plant research. However, the initial genome annotation was submitted by multiple centers using inconsistent methods, making the data difficult to use for many applications.

Results

Over the course of three years, TIGR has completed its effort to standardize the structural and functional annotation of the Arabidopsis genome. Using both manual and automated methods, Arabidopsis gene structures were refined and gene products were renamed and assigned to Gene Ontology categories. We present an overview of the methods employed, tools developed, and protocols followed, summarizing the contents of each data release with special emphasis on our final annotation release (version 5).

Conclusion

Over the entire period, several thousand new genes and pseudogenes were added to the annotation. Approximately one third of the originally annotated gene models were significantly refined yielding improved gene structure annotations, and every protein-coding gene was manually inspected and classified using Gene Ontology terms.
Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients: a randomised trial [ISRCTN47583497]
Authors: Breen Des , Karabinis Andreas , Malbrain Manu , Morais Rex , Albrecht Sven , Jarnvig Inge-Lise , Parkinson Pauline , Kirkham Andrew JT
Published: March 2005

Introduction

This randomised, open-label, multicentre study compared the safety and efficacy of an analgesia-based sedation regime using remifentanil with a conventional hypnotic-based sedation regime in critically ill patients requiring prolonged mechanical ventilation for up to 10 days.

Methods

One hundred and five randomised patients received either a remifentanil-based sedation regime (initial dose 6 to 9 μg kg-1 h-1 (0.1 to 0.15 μg kg-1 min-1) titrated to response before the addition of midazolam for further sedation (n = 57), or a midazolam-based sedation regime with fentanyl or morphine added for analgesia (n = 48). Patients were sedated to an optimal Sedation–Agitation Scale (SAS) score of 3 or 4 and a pain intensity (PI) score of 1 or 2.

Results

The remifentanil-based sedation regime significantly reduced the duration of mechanical ventilation by more than 2 days (53.5 hours, P = 0.033), and significantly reduced the time from the start of the weaning process to extubation by more than 1 day (26.6 hours, P < 0.001). There was a trend towards shortening the stay in the intensive care unit (ICU) by 1 day. The median time of optimal SAS and PI was the same in both groups. There was a significant difference in the median time to offset of pharmacodynamic effects when discontinuing study medication in patients not extubated at 10 days (remifentanil 0.250 hour, comparator 1.167 hours; P < 0.001). Of the patients treated with remifentanil, 26% did not receive any midazolam during the study. In those patients that did receive midazolam, the use of remifentanil considerably reduced the total dose of midazolam required. Between days 3 and 10 the weighted mean infusion rate of remifentanil remained constant with no evidence of accumulation or of a development of tolerance to remifentanil. There was no difference between the groups in SAS or PI score in the 24 hours after stopping the study medication. Remifentanil was well tolerated.

Conclusion

Analgesia-based sedation with remifentanil was well tolerated; it reduces the duration of mechanical ventilation and improves the weaning process compared with standard hypnotic-based sedation regimes in ICU patients requiring long-term ventilation for up to 10 days.
Daily enteral feeding practice on the ICU: attainment of goals and interfering factors
Authors: Binnekade JM , Tepaske R , Bruynzeel P , Mathus-Vliegen EMH , de Haan RJ
Published: March 2005

Background

The purpose of this study was to evaluate the daily feeding practice of enterally fed patients in an intensive care unit (ICU) and to study the impact of preset factors in reaching predefined optimal nutritional goals.

Methods

The feeding practice of all ICU patients receiving enteral nutrition for at least 48 hours was recorded during a 1-year period. Actual intake was expressed as the percentage of the prescribed volume of formula (a success is defined as 90% or more). Prescribed volume (optimal intake) was guided by protocol but adjusted to individual patient conditions by the intensivist. The potential barriers to the success of feeding were assessed by multivariate analysis.

Results

Four-hundred-and-three eligible patients had a total of 3,526 records of feeding days. The desired intake was successful in 52% (1,842 of 3,526) of feeding days. The percentage of successful feeding days increased from 39% (124 of 316) on day 1 to 51% (112 of 218) on day 5. Average ideal protein intake was 54% (95% confidence interval (CI) 52 to 55), energy intake was 66% (95% CI 65 to 68) and volume 75% (95% CI 74 to 76). Factors impeding successful nutrition were the use of the feeding tube to deliver contrast, the need for prokinetic drugs, a high Therapeutic Intervention Score System category and elective admissions.

Conclusion

The records revealed an unsatisfactory feeding process. A better use of relative successful volume intake, namely increasing the energy and protein density, could enhance the nutritional yield. Factors such as an improper use of tubes and feeding intolerance were related to failure. Meticulous recording of intake and interfering factors helps to uncover inadequacies in ICU feeding practice.
Procollagen trafficking, processing and fibrillogenesis
Authors: Canty Elizabeth G. , Kadler Karl E.
Published: March 2005

Collagen fibrils in the extracellular matrix allow connective tissues such as tendon, skin and bone to withstand tensile forces. The fibrils are indeterminate in length, insoluble and form elaborate three-dimensional arrays that extend over numerous cell lengths. Studies of the molecular basis of collagen fibrillogenesis have provided insight into the trafficking of procollagen (the precursor of collagen) through the cellular secretory pathway, the conversion of procollagen to collagen by the procollagen metalloproteinases, and the directional deposition of fibrils involving the plasma membrane and late secretory pathway. Fibril-associated molecules are targeted to the surface of collagen fibrils, and these molecules play an important role in regulating the diameter and interactions between the fibrils.
Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal
Authors: Cadieux Jean-Sébastien , Leclerc Patrick , St-Onge Mireille , Dussault Andrée-Anne , Laflamme Cynthia , Picard Serge , Ledent Catherine , Borgeat Pierre , Pouliot Marc
Published: March 2005

Neutrophils, which are often the first to migrate at inflamed sites, can generate leukotriene B4 from the 5-lipoxygenase pathway and prostaglandin E2 through the inducible cyclooxygenase-2 pathway. Adenosine, an endogenous autacoid with several anti-inflammatory properties, blocks the synthesis of leukotriene B4 while it potentiates the cyclooxygenase-2 pathway in fMLP-treated neutrophils, following activation of the A2A receptor. Using the murine air pouch model of inflammation, we observed that inflammatory leukocytes from mice lacking the A2A receptor have less cyclooxygenase-2 induction than wild-type animals. In human leukocytes, A2A receptor activation specifically elicited potentiation of cyclooxygenase-2 in neutrophils, but not in monocytes. Signal transduction studies indicated that the cAMP, ERK1/2, PI-3K and p38K intracellular pathways are implicated both in the direct upregulation of cyclooxygenase-2 and in its potentiation. Together, these results indicate that neutrophils are particularly important mediators of adenosine's effects. Given the uncontrolled inflammatory phenotype observed in knockout mice and in view of the potent inhibitory actions of prostaglandin E2 on inflammatory cells, an increased cyclooxygenase-2 expression resulting from A2A receptor activation, observed particularly in neutrophils, may take part in an early modulatory mechanism promoting anti-inflammatory activities of adenosine.
Myofilin, a protein in the thick filaments of insect muscle
Authors: Qiu Feng , Brendel Sigrun , Cunha Paulo M. F. , Astola Nagore , Song Bauzhen , Furlong Eileen E. M. , Leonard Kevin R. , Bullard Belinda
Published: March 2005

Thick filaments in striated muscle are myosin polymers with a length and diameter that depend on the fibre type. In invertebrates, the length of the thick filaments varies widely in different muscles and additional proteins control filament assembly. Thick filaments in asynchronous insect flight muscle have an extremely regular structure, which is likely to be essential for the oscillatory contraction of these muscles. The factors controlling the assembly of thick filaments in insect flight muscle are not known. We previously identified a thick filament core protein, zeelin 1, in Lethocerus flight and non-flight muscles. This has been sequenced, and the corresponding proteins in Drosophila and Anopheles have been identified. The protein has been re-named myofilin. Zeelin 2, which is on the outside of Lethocerus flight muscle thick filaments, has been sequenced and because of the similarity to Drosophila flightin, is re-named flightin. In Drosophila flight muscle, myofilin has a molecular weight of 20 kDa and is one of five isoforms produced from a single gene. In situ hybridisation of Drosophila embryos showed that myofilin RNA is first expressed late in embryogenesis at stage 15, a little later than myosin. Antibody to myofilin labelled the entire A-band, except for the H-zone, in cryosections of flight and non-flight muscle. The periodicity of myofilin in Drosophila flight muscle thick filaments was found to be 30 nm by measuring the spacing of gold particles in labelled cryosections; this is about twice the 14.5 nm spacing of myosin molecules. The molar ratio of myofilin to myosin in indirect flight muscle is 1:2, which is the same as that of flightin. We propose a model for the association of these proteins in thick filaments, which is consistent with the periodicity and stoichiometry. Myofilin is probably needed for filament assembly in all muscles, and flightin for stability of flight muscle thick filaments in adult flies.
DNA CpG hypomethylation induces heterochromatin reorganization involving the histone variant macroH2A
Authors: Ma Yinghong , Jacobs Stephanie B. , Jackson-Grusby Laurie , Mastrangelo Mary-Ann , Torres-Betancourt José A. , Jaenisch Rudolf , Rasmussen Theodore P.
Published: March 2005

In mammalian heterochromatin, cytosine bases of CpG dinucleotides are symmetrically modified by methylation. Patterns of CpG methylation are maintained by the action of Dnmt1, the mammalian maintenance cytosine methyltransferase enzyme. We genetically manipulated the levels of CpG methylation and found that extensive chromatin alterations occur in pericentric heterochromatin. Homozygous mutations in Dnmt1 cause severe hypomethylation of pericentric heterochromatin and concomitant chromatin reorganization involving the histone variant macroH2A. Demethylation-induced alterations in macroH2A localization occur in both interphase and mitotic embryonic stem (ES) cells. Heterochromatin protein 1 (HP1) marks interphase pericentric heterochromatin (chromocenters). MacroH2A immunostaining in Dnmt1–/– cells becomes coincident with chromocenters detected by HP1 content. MacroH2A, but not HP1, is enriched in nuclease-resistant chromatin fractions extracted from Dnmt1–/– cells. Normal localization of macroH2A was restored upon reintroduction of a Dnmt1 transgene into Dnmt1–/– cells. MacroH2A localization was also affected in T-antigen-transformed fibroblasts subjected to the conditional mutation of Dnmt1. Together, these results suggest that pericentric heterochromatin can be maintained in the absence of CpG methylation, but in a significantly altered configuration.
Influence of Warfarin on Symptoms of Fatigue: Findings of a Randomized Trial
Authors: Kovacs Michael J , Kearon Clive , Julian Jim A , Douketis James D , Demers Christine , Wells Philip S , Turpie Alexander G , Anderson David R , Kahn Susan R , v Nguyen Paul , Green David , Kassis Jeannine , Geerts William , MacKinnon Betsy , Ginsberg Jeffrey S
Published: March 2005

BACKGROUND:

Some patients develop fatigue while taking warfarin, but causality is uncertain.

OBJECTIVE:

To assess whether warfarin use is associated with fatigue.

METHODS:

This investigation was a substudy of a randomized double-blind trial in 13 outpatient thromboembolism clinics. Subjects who had received one month of open-label warfarin therapy for venous thromboembolism due to a transient risk factor were randomly assigned to receive warfarin or placebo for 2 months and followed for another 9 months after stopping the study drug. Fatigue was measured using a Likert scale, and change of fatigue was measured by the patient's global rating.

RESULTS:

In 87 subjects, the overall ratings of fatigue were 0.1 unit lower (95% CI 0.6 units lower to 0.4 units higher) while taking warfarin. Global rating for change in fatigue intensity showed no increase of fatigue with warfarin use.

CONCLUSIONS:

The short-term use of warfarin was not associated with symptoms of fatigue.
Outcomes of Project Dulce: A Culturally Specific Diabetes Management Program
Authors: Gilmer Todd P , Philis-Tsimikas Athena , Walker Chris
Published: March 2005

BACKGROUND:

Diabetes mellitus is a common and costly chronic disease that increasingly affects minority populations; however, there is little evidence regarding the clinical effectiveness and costs of culturally appropriate disease management programs.

OBJECTIVE:

To determine the clinical outcomes and costs of Project Dulce, a combined stepped-care diabetes nurse case management program and culturally oriented peer-led self-empowerment training program.

METHODS:

Pre—post clinical outcome and cost analysis of Project Dulce participants were compared with a cohort of historical controls over a one-year period. Subjects included 348 persons with diabetes with coverage under County Medical Services who were receiving services in community health centers in San Diego, CA. Generalized regression models were used to estimate changes in clinical outcomes (hemoglobin [Hb] A1c, blood pressure, cholesterol level) and costs associated with participation in Project Dulce.

RESULTS:

Project Dulce participants had significant reductions in HbA1c (0.8%; p < 0.001), systolic (5.4 mm Hg; p = 0.001) and diastolic (8.0 mm Hg; p < 0.001) blood pressure, total cholesterol (28.1 mg/dL; p < 0.001), and low-density-lipoprotein cholesterol (15.6 mg/dL; p < 0.001). Expenditures for pharmacy ($3157 Dulce vs $1618 control) and disease management ($507 Dulce) increased. Total costs were higher during the first year of disease management ($5711 Dulce vs $4365 control; p < 0.001).

CONCLUSIONS:

Project Dulce was effective in improving clinical outcomes for control of diabetes and related conditions in a medically indigent, culturally diverse population. Our finding of reduced hospital expenditures, although statistically insignificant, is clinically and economically important and suggests that intervention might provide an immediate benefit to a high-risk population.
Long-Term Prophylaxis of Spontaneous Bacterial Peritonitis in Patients with Cirrhosis
Authors: Frazee Lawrence A , Marinos Antonio E , Rybarczyk Amy M , Fulton Scott A
Published: March 2005

OBJECTIVE:

To review the literature regarding long-term prophylaxis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis.

DATA SOURCES:

A MEDLINE (1967–September 2004) and bibliographic search of the English-language literature was conducted using the search terms spontaneous bacterial peritonitis, cirrhosis, antimicrobial, and prophylaxis.

DATA SYNTHESIS:

Long-term antimicrobial prophylaxis has been shown to decrease recurrent SBP in cirrhotics with a prior episode. Prophylaxis in patients with low ascitic fluid protein has also been shown to reduce the incidence of SBP; however, studies are too in-homogeneous to identify subgroups that benefit the most.

CONCLUSIONS:

Long-term antimicrobial therapy should be considered for secondary prophylaxis of SBP. Studies should be done to confirm this benefit and identify subsets of patients with low ascitic fluid protein who clearly benefit.
The Effects of Strategic Orientations on Technology- and Market-Based Breakthrough Innovations
Authors: Zhou Kevin Zheng , Yim Chi Kin (Bennett) , Tse David K.
Published: March 2005

Does market orientation impede breakthrough innovation? To date, researchers have presented opposing arguments with respect to this important issue. To address this controversy, the authors conceptualize and empirically test a model that links different types of strategic orientations and market forces, through organizational learning, to breakthrough innovations and firm performance. The results show that a market orientation facilitates innovations that use advanced technology and offer greater benefits to mainstream customers (i.e., technology-based innovations) but inhibits innovations that target emerging market segments (i.e., market-based innovations). A technology orientation is beneficial to technology-based innovations but has no impact on market-based innovations, and an entrepreneurial orientation facilitates both types of breakthroughs. Different market forces (demand uncertainty, technology turbulence, and competitive intensity) exert significant influence on technology- and market-based innovations, and these two types of innovations affect firm performance differently. The results have significant implications for firm strategies to facilitate product innovations and achieve competitive advantages.
Critical Assessment of the Standard ASTM E 399
Authors: Wallin KRW
Published: March 2005

The plane-strain fracture toughness, KIC, defined by ASTM E 399, is assumed to represent a size insensitive lower bound value. The interpretation is due to the original work by George Irwin. In this work the consistency of the ASTM KIC plane-strain fracture toughness standard (ASTM E 399) is examined by reassessing the original data used to develop the standard, based on present knowledge about fracture micromechanisms. Originally, the standard was based on continuum mechanics assumptions, which have later been found inadequate to describe the real physical fracture process. The materials used for the development of ASTM E 399 were generally aluminum and titanium alloys or extra high strength steels. The materials had in common that their fracture micro-mechanism was ductile fracture, i.e., the materials showed a rising tearing resistance curve. Therefore, the fracture toughness did not show the expected decreasing trend with increasing specimen size, but generally the opposite trend. The specimen thickness was assumed to be the limiting dimension, even though much of the experimental data indicated that the specimen ligament size, not the thickness, controlled the fracture toughness value.
Comparison of Abscission Spray Application Practices for Mechanical Harvesting of Oranges
Authors: Farooq M , Salyani M , Whitney JD
Published: March 2005

Two air-carrier sprayers were used to investigate the feasibility of applying abscission materials from one side of the tree in a two-row bedded orange grove. One-sided (bed side) and two-sided (both bed and ditch side) applications at 2.4 and 4.8 km/h were compared using each sprayer. Tank mixture contained active ingredient (a.i.) 5-chloro-3-methyl-4-nitro-1-H-pyrazole (CMN-P) at about 350 mg/L a.i., a surfactant, a drift retardant, and a fluorescent tracer. Leaf samples were collected from different locations on the bed and ditch sides, and deposition was determined by fluorometry. The efficacy of abscission application was assessed in terms of fruit detachment force (FDF) and percent fruit removal (PFR) by trunk shakers.

With both sprayers, one-sided applications resulted in comparable depositions to two-sided applications at the far side of the lower canopy level. This result implies that one-sided applications might provide acceptable spray coverage in lightly foliated canopies. Abscission sprays at one-half or full a.i. (526 or 1052 g/ha) rate reduced fruit detachment force significantly. The best results were obtained with two-sided applications at lower ground speed (highest volume/a.i. rate). The air-curtain sprayer at full a.i. rate and the air-blast sprayer at one-half or full a.i. rate resulted in a significant increase in percent fruit removal.
Spinal Synaptic Enhancement with Acute Intermittent Hypoxia Improves Respiratory Function after Chronic Cervical Spinal Cord Injury
Authors: Golder Francis J. , Mitchell Gordon S.
Published: March 2005

Respiratory insufficiency is the leading cause of death after high-cervical spinal cord injuries (SCIs). Although respiratory motor recovery can occur with time after injury, the magnitude of spontaneous recovery is limited. We hypothesized that partial respiratory motor recovery after chronic cervical SCI could be strengthened using a known stimulus for spinal synaptic enhancement, intermittent hypoxia. Phrenic motor output was recorded before and after intermittent hypoxia from anesthetized, vagotomized, and pump-ventilated control and C2 spinally hemisected rats at 2, 4, and 8 weeks after injury. Weak spontaneous phrenic motor recovery was present in all C2-injured rats via crossed spinal synaptic pathways that convey bulbospinal inspiratory premotor drive to phrenic motoneurons on the side of injury. Intermittent hypoxia augmented crossed spinal synaptic pathways [phrenic long-term facilitation; pLTF] for up to 60 min after hypoxia at 8 weeks, but not 2 weeks, after injury. Ketanserin, a serotonin 2A receptor antagonist, administered before intermittent hypoxia at 8 weeks after injury prevented pLTF. Serotonergic innervation near phrenic motoneurons was assessed after injury. The limited magnitude of pLTF at 2 weeks was associated with an injury-induced reduction in serotonin-containing nerve terminals in the vicinity of phrenic motoneurons ipsilateral to C2 hemisection. Thereafter, pLTF magnitude progressively increased with the recovery of serotonergic innervation in the phrenic motor nucleus. Intermittent hypoxia (or pLTF) has intriguing possibilities as a therapeutic tool, because its greatest efficacy may be in patients with chronic SCI, a time when most patients have already achieved maximal spontaneous functional recovery.
Familial Alzheimer's Disease Presenilin 1 Mutations Cause Alterations in the Conformation of Presenilin and Interactions with Amyloid Precursor Protein
Authors: Berezovska Oksana , Lleo Alberto , Herl Lauren D. , Frosch Matthew P. , Stern Edward A. , Bacskai Brian J. , Hyman Bradley T.
Published: March 2005

Presenilin 1 (PS1) is a critical component of the γ-secretase complex, an enzymatic activity that cleaves amyloid β (Aβ) from the amyloid precursor protein (APP). More than 100 mutations spread throughout the PS1 molecule are linked to autosomal dominant familial Alzheimer's disease (FAD). All of these mutations lead to a similar phenotype: an increased ratio of Aβ42to Aβ40, increased plaque deposition, and early age of onset. We use a recently developed microscopy approach, fluorescence lifetime imaging microscopy, to monitor the relative molecular distance between PS1 N and C termini in intact cells. We show that FAD-linked missense mutations located near the N and C termini, in the mid-region of PS1, and the exon 9 deletion mutation all change the spatial relationship between PS1 N and C termini in a similar way, increasing proximity of the two epitopes. This effect is opposite of that observed by treatment with Aβ42-lowering nonsteroidal anti-inflammatory drugs (NSAIDs) (Lleo et al., 2004b). Accordingly, treatment of M146L PS1-overexpressing neurons with high-dose NSAIDs somewhat offsets the conformational change associated with the mutation. Moreover, by monitoring the relative distance between a PS1 loop epitope and the APP C terminus, we demonstrate that the FAD PS1 mutations are also associated with a consistent change in the configuration of the PS1-APP complex. The nonpathogenic E318G PS1 polymorphism had no effect on PS1 N terminus-C terminus proximity or PS1-APP interactions. We propose that the conformational change we observed may therefore provide a shared molecular mechanism for FAD pathogenesis caused by a wide range of PS1 mutations.
When 1+1≠2: making mathematics in central Brazil
Authors: Ferreira Mariana Kawall Leal
Published: March 2005

In this ethnographic account of mathematical activity among the Juruna, Kayabi, and Suya of central Brazil, I show how arithmetic practices are fashioned in a specific social setting. Values and symbolic properties of both the gift exchange and capitalist economics structure arithmetic dilemmas in the Xingu Indian Park. Within a broad social field that transcends the boundaries of the park to include prospecting sites and cattle ranches, economic calculations are extended to all kinds of goods, both material and symbolic. The distribution and circulation of these different forms of capital are discussed in view of the constitution of particular arenas of exchange. Practice theories highlight the ways in which mathematical knowledge is constituted in everyday activities, challenging functional assumptions about cognition and schooling. By articulating principles of the gift with those of capitalist exchange, mathematics is construed by the juruna, Kayabi, and Suyá as a product of social work and symbolic fashioning.
Knowledge and the Scholarly Medical Traditions
Authors: Alter Joseph S.
Published: March 2005

Knowledge and the Scholarly Medical Traditions. DON BATES, ed. Cambridge: Cambridge University Press, 1995. xiv + 369 pp., Illustrations, notes, index.
The Beautiful and the Dangerous: Encounters with the Zuni Indians
Authors: Turner Edith
Published: March 2005

The Beautiful and the Dangerous: Encounters with the Zuni Indians. BARBARA TEDLOCK. New York: Penguin Books, 1992. xiv + 336 pp., notes, bibliography, index.
The Macedonian Conflict: Ethnic Nationalism in a Transnational World
Authors: Arcyrou Vassos
Published: March 2005

The Macedonian Conflict: Ethnic Nationalism in a Transnational World. LORING M. DANFORTH. Princeton, NJ: Princeton University Press, 1995. xviii + 273 pp., Illustrations, maps, notes, bibliography, index.
Fleldwork and Footnotes: Studies In European Anthropology
Authors: Darnell Regna
Published: March 2005

Fleldwork and Footnotes: Studies In European Anthropology. HANS F. VERMEULEN and ARTURO ALVAREZ ROLDÁN, eds. London: Routledge, 1995. xiv + 261 pp., contributors, notes, references, index.
The Nuclear Peninsula
Authors: Custerson Hugh
Published: March 2005

The Nuclear Peninsula. FRANÇOISE ZONABEND. J. A. Underwood, trans. New York: Cambridge University Press, 1993. xii + 138 pp., illustrations, notes, index.
Quest for Conception: Gender, Infertility, and Egyptian Medical Traditions
Authors: Krieger Laurie
Published: March 2005

Quest for Conception: Gender, Infertility, and Egyptian Medical Traditions. MARCIA C. INHORN. Philadelphia: University of Pennsylvania Press, 1994. xxvii + 441 pp., photographs, tables, appendixes, glossary, notes, references, index.
Visible and Invisible Realms: Power, Magic, and Colonial Conquest in Bali
Authors: Fox James J.
Published: March 2005

Visible and Invisible Realms: Power, Magic, and Colonial Conquest in Bali. MARGARET J. WIENER. Chicago: University of Chicago Press, 1995. xiv + 445 pp., figures, appendix, notes, bibliography, index.
Knowledge and Secrecy in an Aboriginal Religion: Yolngu of North‐east Arnhem Land
Authors: Vaarzon‐Morel Petronella
Published: March 2005

Knowledge and Secrecy in an Aboriginal Religion: Yolngu of North‐east Arnhem Land. IAN KEEN. Oxford: Oxford University Press, 1994. xviii + 347 pp., illustrations, maps, tables, glossary, bibliography, index.
Another Impolitic Observation on Absalon, fili mi
Authors: Urquhart Peter
Published: March 2005

The 16th-century motet Absalon, fili mi has long been scrutinized by modern scholars. The current effort to reassign its authorship to Pierre de la Rue, fueled largely by an interest in removing it from Josquin's canon, relies paradoxically upon aspects of the work that were celebrated as evidence of Josquin's genius by earlier scholars. These aspects, however, depend solely on our acceptance of a peculiar reading in an early manuscript version of the piece, a version that is indeed radical and unprecedented in its notation but is also internally inconsistent and marked by signs of scribal intervention. The author speculates on a mechanism by which such a flawed version of the motet could have arisen. If correct, this mechanism points to an original notated version of the motet that was clefless, while the much celebrated "incomparable modulation" of the end turns out to be neither a modulation nor incomparable. In themselves, these observations do not support either side of the authorship debate; however, they do suggest that some of the arguments levied against Josquin's authorship have little meaning if the pitch level and signatures present in the early manuscript source resulted from scribal decisions and not the composer's thought.
The Transmission of Western Chant in the 8th and 9th Centuries: Evaluating Kenneth Levy's Reading of the Evidence
Authors: Hornby Emma
Published: March 2005

Since the 19th century, scholars have been attempting to discover the origins of Gregorian chant and to establish when musical notation began to be widely used in its redaction. For almost 30 years, Kenneth Levy's scholarship on the subject has been hugely influential. He hypothesizes that Gregorian chant was notated in the time of Charlemagne (742-814), or even Pippin (714-768). There are alternative ways of reading the 8th- and 9th-century evidence, however, and largely oral transmission of the Gregorian melodies until the later 9th century cannot be ruled out.
Listening to Machaut's Motets
Authors: Clark Alice V.
Published: March 2005

In a significant number of his motets, Guillaume de Machaut uses melodic repetition to provide audible cues to their talea structure. He further breaks or alters that repetition in order to call attention to final talea statements, thereby providing a sounding clue to the motet's end. The use of this technique in a genre well known for its intellectual complexities seems to show a special concern for the unprepared listener, a concern that is less clearly manifested in the work of other motet composers in 14th-century France. This has implications both for how we see Machaut in relation to his contemporaries and for how we may approach his motets today.
"Reading Musicals": Andrea Most's Making Americans: Jews and the Broadway Musical (Cambridge: Harvard University Press, 2004)
Authors: Block Geoffrey
Published: March 2005

Andrea Most's Making Americans: Jews and the Broadway Musical studies eight musicals (The Jazz Singer, Whoopee, Girl Crazy, Babes in Arms, Oklahoma!, Annie Get Your Gun, South Pacific, and The King and I) in an effort to explore "how first- and second-generation American Jewish writers, composers, and performers used the theater to fashion their own identities as Americans."Most offers imaginative and often insightful sociological readings of musical librettos, lyrics, even stage directions, but virtually ignores music. That music can sometimes elucidate or contradict an exclusively social or literary reading may be seen, for example, in Emile de Becque's immobility at the end of "Some Enchanted Evening." In other cases, when the social assimilation of Jewish characters is revealed to be a musical one as well, music can support Most's argument. The problem exemplified by writings such as Most's-the distortions and misreadings that may result from a social history that does not engage music-may be seen in the broader context of Broadway and opera scholarship. Lessons to be learned from studying the musical Show Boat and the works of Sondheim point to the need for scholars and critics to consider how the music in musicals might convey social meanings, intellectual content, and dramatic ideas beyond words, stories, and stage directions.
"Was will dieses Grau'n bedeuten?": Schumann's "Zwielicht" and Daverio's "Incomprehensibility Topos"
Authors: Ferris David
Published: March 2005

John Daverio has argued that Schumann's music was criticized as incomprehensible by many early listeners because of his fragmentary approach to musical form. He proposed that, rather than shy away from the seemingly incomprehensible moments in Schumann's music and try to "neutralize" them through "analytical sophistry," we should confront them "head-on as constitutive aesthetic qualities of Schumann's oeuvre." In the present paper, I take on Daverio's challenge through an analysis of "Zwielicht," from the Eichendorff Liederkreis. I use Daverio's critical theory of the romantic fragment as a starting point for my discussion, but I explain how my use of the concept as an analytic tool differs from his.
Maskenfreiheit and Schumann's Napoleon-Ballad
Authors: Youens Susan
Published: March 2005

One of the best known compositions from Robert Schumann's "song year" of 1840 is the ballad "Die beiden Grenadiere," op. 49, no. 1, to a poem by Heinrich Heine (1797-1856). Any work about Napoleon, in any genre, was inevitably politically charged, both at the time Heine wrote his poem (perhaps in 1821, after hearing the news of the former emperor's death on 5 May 1821) and the date of its most famous musical setting (at the beginning of the decade when Germany was edging towards revolutionary outbreak). What impelled this 21st-century investigation of the song was curiosity about its confusing initial gesture in the piano, a tonic six-four chord as an anacrusis, leading to unharmonized tonic pitches on the downbeat of measure 1. Speculation about Schumann's intention led to an investigation of both men's attitudes towards Napoleon, especially the aftermath of his downfall. That Heine venerated Napoleon (who emancipated the Jews) cannot be doubted, but Heine, given to paradox and contradiction, was no hagiographer. His poem is as much literary as it is political, with its borrowings from Des Knaben Wunderhorn and Herder's translation of the Scottish ballad "Edward." The First Empire, like all empires, is not merely historical fact but a confabulation of poetic legends. Heine's underlying concern, I would argue, was not Bonapartism per se but rising German nationalism of the sort he found ominous and that Schumann, to some as yet ill-defined degree, supported. But composer and poet both associated Napoleon with the ideals of the French Revolution in the days before it and the emperor succumbed to what is darkest in human nature. In my opinion, Schumann understood Heine's delineation of nationalistic fanaticism and found apt musical gestures for that understanding. Here, I trace the composer's lifelong sense of identification with Napoleon and the compositional decisions that tell of a political point of view in "Die beiden Grenadiere."
Epigenetic analysis of HIC1, CASP8, FLIP, TSP1, DCR1, DCR2, DR4, DR5, KvDMR1, H19 and preferential 11p15.5 maternal-allele loss in von Hippel-Lindau and sporadic phaeochromocytomas
Authors: Margetts C D E , Astuti D , Gentle D C , Cooper W N , Cascon A , Catchpoole D , Robledo M , Neumann H P H , Latif F , Maher E R
Published: March 2005

Phaeochromocytoma is a neural-crest-derived tumour that may be a feature of several familial cancer syndromes including von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1 (NF1) and germline succinate dehydrogenase subunit (SDHB and SDHD) mutations. However the somatic genetic and epigenetic events that occur in phaeochromocytoma tumourigenesis are not well defined. Epigenetic events including de novo promoter methylation of tumour-suppressor genes are frequent in many human neoplasms. As neuroblastoma and phaeochromocytoma are both neural-crest-derived tumours, we postulated that some epigenetic events might be implicated in both tumour types and wished to establish how somatic epigenetic alterations compared in VHL-associated and sporadic phaeochromocytomas. We identified frequent aberrant methylation of HIC1 (82%) and CASP8 (31%) in phaeochromocytoma, but both genes were significantly more methylated in VHL phaeochromocytomas than in sporadic cases. Of four tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors analysed, DR4 was most commonly methylated (41%; compared with DcR2 (26%), DcR1 (23%) and DR5 (10%)). Gene methylation patterns in phaeochromocytoma and neuroblastoma did not differ significantly suggesting overlapping mechanisms of tumourigenesis. We also investigated the role of 11p15.5-imprinted genes in phaeochromocytoma. We found that in 10 sporadic and VHL phaeochromocytomas with 11p15.5 allele loss, the patterns of methylation of 11p15.5-differentially methylated regions were consistent with maternal, rather than, paternal chromosome loss in all cases (P<0.001). This suggests that 11p15.5-imprinted genes may be implicated in the pathogenesis of both familial (germline VHL and SDHD mutations) and sporadic phaeochromocytomas.
Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease
Authors: Berruti A , Mosca A , Tucci M , Terrone C , Torta M , Tarabuzzi R , Russo L , Cracco C , Bollito E , Scarpa R M , Angeli A , Dogliotti L
Published: March 2005

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease.

One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study. Plasma CgA levels and other biochemical parameters, such as serum prostate specific antigen, serum alkaline phosphatase, serum lactate dehydrogenase, serum albumin and hemoglobin concentration, were measured at baseline (i.e. when hormone refractoriness occurred) and their prognostic role was evaluated together with patient performance status, Gleason score (at diagnosis of prostate cancer) and the presence of visceral metastases. Furthermore, plasma CgA was prospectively evaluated in 50 patients undergoing chemotherapy.

At baseline, 45 patients (43.3%) showed elevated CgA values. Plasma CgA negatively correlated with survival, either in univariate analysis (P=0.008) or in multivariate analysis, after adjusting for previously mentioned prognostic parameters (P<0.05). In the patient subset undergoing chemotherapy, median CgA (range) values were 13.3 (3.0–141.0) U/l at baseline, 19.1 (3.0–486.0) U/l after 3 months, 20.8 (3.0–702.0) U/l after 6 months and 39.4 (3.0–414.0) U/l after 9 months (P<0.01). The corresponding supranormal rates were 17/50 (34%), 23/50 (46%), 26/50 (52%) and 34/50 (68%) respectively (P<0.005).

Elevated plasma CgA levels are frequently observed in prostate cancer patients with hormone-refractory disease and correlate with poor prognosis. NE differentiation in hormone-refractory patients is a time-dependent phenomenon and is not influenced by conventional antineoplastic treatments.
In situ androgen producing enzymes in human prostate cancer
Authors: Nakamura Yasuhiro , Suzuki Takashi , Nakabayashi Masao , Endoh Mareyuki , Sakamoto Kazuhiro , Mikami Yoshiki , Moriya Takuya , Ito Akihiro , Takahashi Shoki , Yamada Shogo , Arai Yoichi , Sasano Hironobu
Published: March 2005

Androgens have been proposed to be actively produced in situ in human prostate cancer. These locally produced androgens have also been considered to play important roles in the pathogenesis and development of prostate cancer. Therefore, it is important to examine the status of this in situ androgen metabolism and/or synthesis in detail in order to improve the clinical response to hormonal therapy in patients diagnosed with prostate cancer. Several studies have previously demonstrated the expression of androgen-producing enzymes such as 5α-reductase types 1 and 2, and 17β-hydroxysteroid dehydrogenase type 5 (17β-HSD5), in human prostate carcinoma cells. However, their biological significance has remained largely unknown. In this study, we evaluated the immunoreactivities of these steroidogenic enzymes in human prostate cancer obtained from surgery (n=70), and correlated the findings with clinicopathological features of the patients. 17β-HSD5 immunoreactivity was detected in 54 cases (77%), 5α-reductase type 1 in 51 cases (73%) and 5α-reductase type 2 in 39 cases (56%). 5α-reductase type 2 immunoreactivity was significantly correlated with that of androgen receptor (AR), and 17β-HSD5 positive cases were significantly associated with clinical stage (TNM stage pT3 vs pT2). These data all suggest that androgen-producing enzymes, such as 5α-reductase type 1 and type 2, and 17β-HSD5 are expressed in a majority of prostate cancers, and are involved in the local production and actions of androgens in prostate cancers.
Titelbild: 1D Arrangement of Au Nanoparticles by the Helical Structure of Schizophyllan: A Unique Encounter of a Natural Product with Inorganic Compounds (Angew. Chem. 13/2005)
Authors: Bae Ah‐Hyun , Numata Munenori , Hasegawa Teruaki , Li Chun , Kaneko Kenji , Sakurai Kazuo , Shinkai Seiji
Published: March 2005

Lineare Aggregate von Nanopartikeln entstehen in geeigneten Templaten. Das Titelbild zeigt ein TEM‐Bild einer eindimensionalen Anordnung von hydrophoben Gold‐Nanopartikeln in dem β‐1,3‐Glucan‐Polysaccharid Schizophyllan, das in wässriger Lösung eine Tripelhelix‐Struktur bildet. In der Zuschrift auf S. 2066 ff. beschreiben S. Shinkai et al., wie die Nanopartikel im hydrophoben Inneren der Helix aufgenommen und entlang der Achse ausgerichtet werden.