bluuebunny/crossref_metadata_2025 huggingface dataset:
Polarized Light Emission from Nonpolar InGaN Light-Emitting Diodes Grown on a Bulk m-Plane GaN Substrate
Authors: Masui Hisashi , Chakraborty Arpan , Haskell Benjamin A. , Mishra Umesh K. , Speck James S. , Nakamura Shuji , DenBaars Steven P.
Published: October 2005

Polarized light emission from (1010) m-plane InGaN/GaN light-emitting diodes has been observed and analyzed in relation to the valence band structure in nonpolar InGaN/GaN quantum wells. Electroluminescence along the <1100> direction out of the m-plane was partially polarized in the <1120> direction, with a polarization ratio of 0.17. This polarized light emission exhibited a spectral peak at 2.69 eV, which has been attributed to the transition between the conduction band and the heavy hole subband with p
x atomic orbital-like character due to the inhomogeneous biaxial strain in the device structure. Weak polarized emission in the <0001> direction was also observed, with a spectral peak at the higher energy of 2.78 eV. The transition between the conduction band and the crystal-field split-off subband is believed to be responsible for the <0001> polarized light emission.
Recent evolution of a Mediterranean deltaic coastal zone: human impacts on the Inner Thermaikos Gulf, NW Aegean Sea
Authors: Kapsimalis Vasilios , Poulos Serafim E. , Karageorgis Aristomenis P. , Pavlakis Petros , Collins Michael
Published: October 2005

The Inner Thermaikos Gulf is located in the northwestern Aegean Sea, receiving water and sediment fluxes from the Axios, Aliakmon, Gallikos and Loudias Rivers. The geomorphological and sedimentological evolution of the system is reconstructed for the last 150 years (1850–2000), on the basis of detailed analysis of historical bathymetric charts. Late Holocene history is considered within the context of changing riverine sediment supply and human activities. Three evolutionary stages are identified. Stage I (1850–1916) corresponds to a natural phase of rapid deltaic progradation and sea-floor deposition, with an average sediment accumulation rate of 6.5 × 10
6
m
3
a
−1
. During Stage II (1916–1956), human interference (e.g. artificial changes in river delta plains, realignment of channels and land reclamation schemes) to the deltaic system increased sediment delivery to the coastal waters by a factor of three; this, in turn, enhanced the progradation of the active river mouth areas. In contrast, Stage III (1956–2000) is characterized by significant coastline (deltaic) retreat and erosion of the adjacent sea floor (net loss of 2.5 × 10
6
m
3
a
−1
); this was as a result of extensive river damming, which trapped a significant part of the sediment moving seaward. Furthermore, these human impacts have affected the character of the surficial sea-bed sediments of the Gulf, by reducing the proportion of mud. The response of the deltaic margin of the Inner Thermaikos Gulf to various anthropogenic interventions seems to be analogous to that of other deltas in the Mediterranean region where large drainage projects, the development of irrigation networks and dam construction have taken place within their river basins.
The orthogneisses of the Orlica–Śniez2nik complex (West Sudetes, Poland): geochemical characteristics, the importance of pre-Variscan migmatization and constraints on the cooling history
Authors: Lange Ulrich , Bröcker Michael , Armstrong Richard , Zelaźniewicz Andrzej , Trapp Endres , Mezger Klaus
Published: October 2005

Geochemical analyses in combination with Rb–Sr (whole-rock, phengite, biotite) and U–Pb zircon ages provide important constraints on the magmatic, metamorphic and structural evolution of the Śniez2nik and Gierałtów gneisses from the Orlica–Śniez2nik complex (West Sudetes). These two gneisses have been considered to represent distinct petrogenetic units; however, their major and trace element compositions as well as their Sr–Nd isotope characteristics show no systematic differences that are indicative for different protoliths. This striking similarity leads to the conclusion that the petrographic variability is caused by modifications superimposed during deformation and migmatization. Most εNd
500
values are in the range between −3.3 and −5.7 and suggest derivation of the protoliths from pre-existing continental crust. Two-stage
T
DM
model ages mostly fall in the range between 1.4 and 1.6 Ga and closely correspond to other orthogneiss occurrences in the Bohemian Massif. The Rb–Sr whole-rock system is disturbed on a regional scale, to variable degrees, resulting in dates (
c
. 450 Ma and
c
. 395 Ma) considerably younger than the time of magmatic crystallization (
c
. 500 Ma). Secondary ionization mass spectrometry (SIMS) U–Pb analyses provide two groups of
206
Pb/
238
U ages (364–341 Ma and 527–472 Ma), which largely correlate with previously established ages for protolith formation and Variscan high-temperature metamorphism. No geochronological evidence for pre-Variscan (‘Caledonian’) events was found. For phengite and biotite, the Rb–Sr system yields ages of
c
. 340–320 Ma, which provide further constraints on the regional cooling history.
Glomerular Cytochrome P-450 and Cyclooxygenase Metabolites Regulate Efferent Arteriole Resistance
Authors: Wang Hong , Garvin Jeffrey L. , Falck John R. , Ren YiLin , Sankey Steadman S. , Carretero Oscar A.
Published: October 2005

Bradykinin dilates efferent arterioles via release of efferent arteriole epoxyeicosatrienoic acids when perfused retrograde (no glomerular autacoids). However, when efferent arterioles are perfused orthograde through the glomerulus, bradykinin-induced dilatation is caused by a balance between: (1) the glomerular vasoconstrictor 20-hydroxyeicosatetraenoic acid and vasodilator prostaglandins, and (2) epoxyeicosatrienoic acids from the efferent arteriole and possibly the glomerulus. However, the role of 20-hydroxyeicosatetraenoic acid has only been studied with a cyclooxygenase inhibitor, which may artificially enhance its production by shunting arachidonic acid into the cytochrome P450 pathway. We hypothesized that in the absence of cyclooxygenase inhibition, bradykinin induces release of 20-hydroxyeicosatetraenoic acid from the glomerulus, which blunts the vasodilator effect of bradykinin; and that prostaglandins released from glomeruli in response to bradykinin are generated by cyclooxygenase-1. Rabbit efferent arterioles preconstricted with norepinephrine were perfused orthograde from the end of the afferent arteriole. Bradykinin was added to the perfusate with or without a 20-hydroxyeicosatetraenoic acid antagonist (20-HEDE), epoxyeicosatrienoic acid synthesis inhibitor (MS-PPOH), and/or cyclooxygenase-1 (SC-58560) or cyclooxygenase-2 inhibitor (NS-398). Bradykinin-dependent dilatation was enhanced by 20-HEDE but blunted by MS-PPOH. When the inhibitors were present, bradykinin-induced dilatation was abolished by blockade of cyclooxygenase-1 but not cyclooxygenase-2. We concluded that: (1) in the absence of cyclooxygenase inhibitors, bradykinin causes the release of a glomerular vasoconstrictor (20-hydroxyeicosatetraenoic acid) that antagonizes the vasodilator effect of epoxyeicosatrienoic acids released from the efferent arteriole and perhaps from the glomerulus, and (2) bradykinin-induced vasodilatation is caused by the release of epoxyeicosatrienoic acids from the efferent arteriole and glomerular metabolites of cyclooxygenase-1.
Circulating Angiogenic Factors in the Pathogenesis and Prediction of Preeclampsia
Authors: Lam Chun , Lim Kee-Hak , Karumanchi S. Ananth
Published: October 2005

Preeclampsia is a major cause of maternal, fetal, and neonatal mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, high blood pressure and proteinuria, are due in part to excess circulating soluble fms-like tyrosine kinase-1 concentrations. Soluble fms-like tyrosine kinase-1 is an endogenous antiangiogenic protein that is made by the placenta and acts by neutralizing the proangiogenic proteins vascular endothelial growth factor and placental growth factor. High serum soluble fms-like tyrosine kinase-1 and low serum free placental growth factor and free vascular endothelial growth factor have been observed in preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia but also antedate clinical symptoms by several weeks. Therefore, this raises the possibility of measuring circulating angiogenic proteins in the blood and the urine as a diagnostic and screening tool for preeclampsia. The availability of a test to predict preeclampsia would be a powerful tool in preventing preeclampsia-induced mortality, especially in developing nations, where high-risk specialists are limited. This review will summarize our current understanding of the role of circulating angiogenic proteins in the pathogenesis and clinical diagnosis/prediction of preeclampsia.
Ghurid monuments and Muslim identities
Authors: Flood Finbarr Barry
Published: October 2005

The eastward expansion of the Shansabanid sultanate of Ghur in the late twelfth century has usually been depicted as a confrontation between a unitary Muslim self and its Hindu ‘other’. The reification of heterogeneous and protean categories of belief implicit in this paradigm is particularly ill suited to represent the dynamic religious life of mediaeval Ghur. This was characterised by shifting patterns of royal patronage that reflect intense competition between the Karramiya, a popular pietistic sect, and the orthodox Sunni madhhabs. Drawing on Ghurid architectural and numismatic inscriptions, this article examines the ways in which contem–porary doctrinal disputes inflected elite cultural production during the period. Based on the content and context of Qur'anic citations, it suggests that a rhetorical emphasis on idolatry and unbelief in Ghurid epigraphy was part of a contemporary intra–Sunni polemic, and not primarily an address to those who were literally outside the fold of Islam. The deployment of scripture in the service of sectarian rivalry has significant implications for the inter–pretation of Qur'anic epigraphy in Indo–Ghurid mosques such as the Quwwat al–Islam Mosque in Delhi.
Britain's other civilising mission
Authors: Fischer–Tiné Harald
Published: October 2005

This article reconsiders the policies applied by the colonial state with regard to European ‘loafers’ or vagrants in colonial India, thereby raising a number of questions about the relationship between the categories of ‘race’ and ‘class’ in colonial settings. It starts with a discussion of the intellectual roots of the class prejudices towards working–class Europeans dating back to the Company era, and offers a brief survey of the economic and demographic developments in mid–nineteenth century which brought the issue of ‘white poverty’ to the foreground. The article then focuses on the workhouse system introduced in the 1870s. The main argument brought forward here is that the ‘reclamation’ of European loafers can be regarded as an ‘internal’ civilising mission which shared many features with the ‘external’ mission civilisatrice directed at the Indian population. It is demonstrated that the colonial government's vagrancy policy was largely designed to protect the bluff of ‘colonial difference’ underlying the ‘external’ imperial civilising project. However, it also becomes clear that here, again, the colonial state could never fully realise its ‘civilising’ fantasies, both due to financial constraints and the white subalterns’ strong will to resist.
Methods for controlling amount of talk: Difficulties, considerations and recommendations
Authors: Hutchins Tiffany L. , Brannick Michael , Bryant Judith B. , Silliman Elaine R.
Published: October 2005

The aim of this article is to focus researchers’ attention on some central methodological issues involving control of amount of talk (AOT). First, appropriate methods for standardizing the size of language samples are considered. Second, the common practice of deriving linguistic rates by dividing the frequency of some linguistic variable of interest by a frequency tapping AOT is challenged. This operation does not adequately control for AOT and may result in spurious findings. Third, appropriate contexts for achieving control of AOT through statistical partialling are discussed. Some recommendations for research are offered.
A comparative study between mean length of utterance in morphemes (MLUm) and mean length of utterance in words (MLUw)
Authors: Parker Matthew D. , Brorson Kent
Published: October 2005

Prior to Brown’s (1973) introduction of mean length of utterance in morphemes (MLUm), child language researchers and speech-language pathologists used mean length of utterance in words (MLUw) as a measurement of a child’s gross language development. After Brown (1973) and others documented MLUm to be a measure which was correlated with the development of morphological and syntactic skills in young children, the practice of counting MLUm became more widely used and accepted. In the present study, MLUw and MLUm scores of 40 language transcripts from typically-developing, English-speaking children between the ages of 3;0 and 3;10 were compared. Results indicated that MLUm and MLUw are almost perfectly correlated. This finding suggests that MLUw can be used as effectively as MLUm as a measurement of a child’s gross language development.
‘All that is Rare, Characteristic or Beautiful’
Authors: McGowan Abigail S.
Published: October 2005

In the 1880s and 1890s, British officials worried that traditional Indian design was disappearing in the face of rapid westernization. But their idea of what constituted ‘traditional’ design was itself new, forged first at international exhibitions and then in the context of Indian artisanal and consumer experimentation with novel combinations of foreign styles and objects. Indeed, it was the latter which prompted British art officials in India to call for a return to tradition. But traditionalism in design was not just in reaction to Indian cosmopolitan tendencies; it tried to achieve its own, slightly different cosmopolitanism by Indianizing western forms with the application of pure Indian ornament. I argue that it was in the intersection of these competing visions - Indian and British, metropolitan and colonial - of how to use and fill homes with new goods that a new definition of Indian traditional design emerged in this period.
Identifiability, Performance Feedback and the Köhler Effect
Authors: Kerr Norbert L. , Messé Lawrence A. , Park Ernest S. , Sambolec Eric J.
Published: October 2005

Research, starting with Köhler (1926), has demonstrated a type of group motivation gain, wherein the less capable member of a dyad working conjunctively at a persistence task works harder than comparable individuals. To explore possible boundary conditions of this effect, the current experiment systematically varied the amount and timing of performance feedback group members received. Results showed: (a) continuous feedback of both members’ performance was not necessary for producing the effect; (b) the effect was attenuated, but not eliminated by delaying and restricting feedback, such that group members only learned which of them was the less capable worker (but not how long s/he persisted) sometime after the task trial was completed; and (c) the motivation gain was eliminated in the absence of any performance feedback (i.e. when neither worker could tell who quit first nor how long either had persisted). Some implications of these results for currently viable explanations of the Köhler effect are discussed. It is concluded that the effect is likely to result from several distinct processes.
Death Concerns and Other Adaptive Challenges: The Effects of Coalition-Relevant Challenges on Worldview Defense in the US and Costa Rica
Authors: Navarrete Carlos David
Published: October 2005

A relational approach to the psychology of coalitions suggests that certain stimuli that index adaptive problems for which marshaling coalitional support is a reliably adaptive response should elicit increased support of ingroup ideology. Studies from two cultures produced results consistent with this perspective. In Study 1, Costa Rican participants contemplating coalition-relevant scenarios (i.e. social isolation or the need to enlist the help of others in a cooperative task) increased support of ingroup ideology, but that participants contemplating a mortality-salient prime did not. Study 2 replicated these results in an American sample, and explored the moderating effects of individual variation in interdependence and chronic dangerous world beliefs on normative bias. These results suggest that the determining factor cross-culturally in the elicitation of worldview defense may not be mortality concerns per se, but rather the need for coalitional support.
The Development of Group Stereotypes from Descriptions of Group Members: An Individual Difference Approach
Authors: Clow Kimberley A. , Esses Victoria M.
Published: October 2005

This research examined the effects of Personal Need for Structure, Need for Closure, and Personal Fear of Invalidity on information processing during the development of stereotypes. In Study 1, participants read as many group member descriptions as they wanted before expressing group stereotypes. Participants higher in Personal Fear of Invalidity sought more information; they also developed more detailed stereotypes when they received more information, whereas participants lower in Personal Fear of Invalidity did not. There was a tendency for participants higher in Need for Structure & Closure to develop less accurate stereotypes. Finally, participants higher in Need for Structure & Closure or Personal Fear of Invalidity were less confident about their stereotypes when they received more information, whereas participants lower in Need for Structure & Closure or Personal Fear of Invalidity were more confident. In Study 2, participants were presented with two, four, or eight descriptions of group members before expressing stereotypes. Participants lower in Personal Fear of Invalidity developed more detailed stereotypes when they received more information, whereas participants higher in Personal Fear of Invalidity did not. When two or eight group member descriptions were presented (fewer or more than participants probably would have chosen themselves), participants higher in Personal Fear of Invalidity and lower in Need for Structure & Closure generated the most accurate stereotypes. Finally, participants higher in Need for Structure & Closure did not differ in stereotype confidence as a function of how much information they received, whereas participants lower in Need for Structure & Closure were more confident when they received more information. These results indicate that cognitive style plays a role in the development of group stereotypes.
The Structure of Attitudes Toward Non-Western Immigrant Groups: Second-Order Factor Analysis of Attitudes among Norwegian Adolescents
Authors: Bratt Christopher
Published: October 2005

The study investigated the structure of outgroup attitudes among adolescents from the majority group in Norway ( N > 1100), using confirmatory factor analysis. Five non-Western immigrant groups were used as attitude objects. The analysis found that attitudes toward the five outgroups could be seen as dependent on two strongly correlated second-order factors. Two alternative models of second-order factors gained support, while the structure of outgroup attitudes appeared more stable across subsamples than anticipated. The discussion concludes that attitudes toward different ethnic outgroups will tend to be interrelated; probably dependent on both higher-order categories of outgroups as well as complex effects of intergroup contact. The paper addresses several hypotheses that may be investigated in future research.
Evolutionary, structural and functional relationships revealed by comparative analysis of syntenic genes in Rhizobiales
Authors: Guerrero Gabriela , Peralta Humberto , Aguilar Alejandro , Díaz Rafael , Villalobos Miguel Angel , Medrano-Soto Arturo , Mora Jaime
Published: October 2005

Background

Comparative genomics has provided valuable insights into the nature of gene sequence variation and chromosomal organization of closely related bacterial species. However, questions about the biological significance of gene order conservation, or synteny, remain open. Moreover, few comprehensive studies have been reported for rhizobial genomes.

Results

We analyzed the genomic sequences of four fast growing Rhizobiales (Sinorhizobium meliloti,Agrobacterium tumefaciens,Mesorhizobium lotiandBrucella melitensis). We made a comprehensive gene classification to define chromosomal orthologs, genes with homologs in other replicons such as plasmids, and those which were species-specific. About two thousand genes were predicted to be orthologs in each chromosome and about 80% of these were syntenic. A striking gene colinearity was found in pairs of organisms and a large fraction of the microsyntenic regions and operons were similar. Syntenic products showed higher identity levels than non-syntenic ones, suggesting a resistance to sequence variation due to functional constraints; also, an unusually high fraction of syntenic products contained membranal segments. Syntenic genes encode a high proportion of essential cell functions, presented a high level of functional relationships and a very low horizontal gene transfer rate. The sequence variability of the proteins can be considered the species signature in response to specific niche adaptation. Comparatively, an analysis with genomes of Enterobacteriales showed a different gene organization but gave similar results in the synteny conservation, essential role of syntenic genes and higher functional linkage among the genes of the microsyntenic regions.

Conclusion

Syntenic bacterial genes represent a commonly evolved group. They not only reveal the core chromosomal segments present in the last common ancestor and determine the metabolic characteristics shared by these microorganisms, but also show resistance to sequence variation and rearrangement, possibly due to their essential character. In Rhizobiales and Enterobacteriales, syntenic genes encode a high proportion of essential cell functions and presented a high level of functional relationships.
M protein typing of Thai group A streptococcal isolates by PCR-Restriction fragment length polymorphism analysis
Authors: Yoonim Nonglak , Olive Colleen , Pruksachatkunakorn Chulabhorn , Good Michael F , Pruksakorn Sumalee
Published: October 2005

Background

Group A streptococcal (GAS) infections can lead to the development of severe post-infectious sequelae, such as rheumatic fever (RF) and rheumatic heart disease (RHD). RF and RHD are a major health concern in developing countries, and in indigenous populations of developed nations. The majority of GAS isolates are M protein-nontypeable (MNT) by standard serotyping. However, GAS typing is a necessary tool in the epidemiologically analysis of GAS and provides useful information for vaccine development. Although DNA sequencing is the most conclusive method for M protein typing, this is not a feasible approach especially in developing countries. To overcome this problem, we have developed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assay for molecular typing the M protein gene (emm) of GAS.

Results

Using one pair of primers, 13 known GAS M types showed one to four bands of PCR products and after digestion with Alu I, they gave different RFLP patterns. Of 106 GAS isolates examined from the normal Thai population and from patients with GAS-associated complications including RHD, 95 isolates gave RFLP patterns that corresponded to the 13 known M types. Only 11 isolates gave RFLP patterns that differed from the 13 known M types. These were then analyzed by DNA sequencing and six additional M types were identified. In addition, we found that M93 GAS was the most common M type in the population studied, and is consistent with a previous study of Thai GAS isolates.

Conclusion

PCR-RFLP analysis has the potential for the rapid screening of different GAS M types and is therefore considerably advantageous as an alternative M typing approach in developing countries in which GAS is endemic.
Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans
Authors: Karim Mohammad A , Wang Xiaoqin , Hale Terri C , Elbein Steven C
Published: October 2005

Background

Defective insulin secretion is a key defect in the pathogenesis of type 2 diabetes (T2DM). The β-cell specific transcription factor, insulin promoter factor 1 gene (IPF1), is essential to pancreatic development and the maintenance of β-cell mass. We hypothesized that regulatory or coding variants in IPF1 contribute to defective insulin secretion and thus T2DM.

Methods

We screened 71 Caucasian and 69 African American individuals for genetic variants in the promoter region, three highly conserved upstream regulatory sequences (PH1, PH2 and PH3), the human β-cell specific enhancer, and the two exons with adjacent introns. We tested for an association of each variant with T2DM Caucasians (192 cases and 192 controls) and African Americans (341 cases and 186 controls).

Results

We identified 8 variants in the two populations, including a 3 bp insertion in exon 2 (InsCCG243) in African Americans that resulted in an in-frame proline insertion in the transactivation domain. No variant was associated with T2DM in Caucasians, but polymorphisms at -3766 in the human β-cell enhancer, at -2877 bp in the PH1 domain, and at -108 bp in the promoter region were associated with T2DM in African American subjects (p < 0.01), both individually and as haplotypes (p = 0.01 correcting by permutation test). No SNP altered a binding site for the expected β-cell transcription factors. The rare alleles of InsCCG243 in exon 2 showed a trend to over-representation among African American diabetic subjects (p < 0.1), but this trend was not significant on permutation test.

Conculsion

The common alleles of regulatory variants in the 5' enhancer and promoter regions of the IPF1 gene increase susceptibility to type 2 diabetes among African American individuals, likely as a result of gene-gene or gene-environment interactions. In contrast, IPF1 is not a cause of type 2 diabetes in Caucasians. A previously described InsCCG243 variant may contribute to diabetes susceptibility in African American individuals, but is of low penetrance.
TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival
Authors: Kringen Pedro , Wang Yun , Dumeaux Vanessa , Nesland Jahn M , Kristensen Gunnar , Borresen-Dale Anne-Lise , Dorum Anne
Published: October 2005

Background

Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive.

Methods

DNA was extracted from paraffin embedded formalin fixed tissues for the familial cases, and from fresh frozen specimen from the sporadic cases. All cases were treated at our hospital according to protocol. Mutation analyses of exon 2 – 11 were performed using TTGE, followed by sequencing.

Results

Survival rates for BRCA1-familial cases with TP53 mutations were not significantly lower than for familial cases without TP53 mutations (p = 0.25, RR = 1.64, 95% CI [0.71–3.78]). Median age at diagnosis for sporadic (59 years) and familial (49 years) cases differed significantly (p < 0.001) with or without TP53 mutations. Age at diagnosis between the two types of familial carriers were not significantly different, with median age of 47 for 1675delA and 52.5 for 1135insA carriers (p = 0.245). For cases ≥50 years at diagnosis, a trend toward longer survival for sporadic over familial cases was observed (p = 0.08). The opposite trend was observed for cases <50 years at diagnosis.

Conclusion

There do not seem to be a protective advantage for familial BRCA1 carriers without TP53 mutations over familial cases with TP53 mutations. However, there seem to be a trend towards initial advantage in survival for familial cases compared to sporadic cases diagnosed before the age of 50 both with and without TP53 mutations. However, this trend diminishes over time and for cases diagnosed ≥50 years the sporadic cases show a trend towards an advantage in survival over familial cases. Although this data set is small, if confirmed, this may be a link in the evidence that the differences in ovarian cancer survival reported, are not due to the type of BRCA1 mutation, but may be secondary to genetic factors shared. This may have clinical implications for follow-up such as prophylactic surgery within carriers of the two most frequent Norwegian BRCA1 founder mutations.
Are patient falls in the hospital associated with lunar cycles? A retrospective observational study
Authors: Schwendimann René , Joos Franco , Geest Sabina De , Milisen Koen
Published: October 2005

Background

Falls and associated negative outcomes in hospitalized patients are of significant concerns. The etiology of hospital inpatient falls is multifactorial, including both intrinsic and extrinsic factors. Anecdotes from clinical practice exist in which health care professionals express the idea that the number of patient falls increases during times of full moon. The aim of this study was to examine in-hospital patient fall rates and their associations with days of the week, months, seasons and lunar cycles.

Methods

3,842 fall incident reports of adult in-patients who fell while hospitalized in a 300-bed urban public hospital in Zurich, Switzerland were included. Adjusted fall rates per 1'000 patient days were compared with days of the week, months, and 62 complete lunar cycles from 1999 to 2003.

Results

The fall rate per 1000 patient days fluctuated slightly over the entire observation time, ranging from 8.4 falls to 9.7 falls per month (P = 0.757), and from 8.3 falls on Mondays to 9.3 falls on Saturdays (P = 0.587). The fall rate per 1000 patient days within the lunar days ranged from 7.2 falls on lunar day 17 to 10.6 falls on lunar day 20 (P = 0.575).

Conclusion

The inpatient fall rates in this hospital were neither associated with days of the week, months, or seasons nor with lunar cycles such as full moon or new moon. Preventive strategies should be focused on patients' modifiable fall risk factors and the provision of organizational conditions which support a safe hospital environment.
Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials
Authors: Adams Clive Elliott , Rathbone John , Thornley Ben , Clarke Mike , Borrill Jo , Wahlbeck Kristian , Awad A George
Published: October 2005

Background

Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo.

Methods

We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated.

Results

Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth.

Conclusion

It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations.
Phase III Study Comparing Standard Radiotherapy With or Without Weekly Oxaliplatin in Treatment of Locoregionally Advanced Nasopharyngeal Carcinoma: Preliminary Results
Authors: Zhang Li , Zhao Chong , Peng Pei-Jian , Lu Li-Xia , Huang Pei-Yu , Han Fei , Wu Shao-Xiong
Published: October 2005

Purpose

A prospective, randomized, phase III study was performed to evaluate the feasibility and efficacy of concurrent weekly oxaliplatin with radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).

Patients and Methods

From January 2001 to January 2003, 115 patients with locoregionally advanced NPC were randomly assigned to either radiotherapy (RT) alone (56 patients) or concurrent chemoradiotherapy (CCRT; 59 patients). All patient characteristics were well balanced in both arms. CCRT with oxaliplatin 70 mg/m2 weekly was administered for six doses from the first day of RT.

Results

All patients were eligible for toxicity and response analysis. Compliance with the protocol treatment was excellent, with 97% of patients completing all planned doses of oxaliplatin, and a lack of high-grade toxicity was observed. After a median follow-up time of 24 months, there was a significant difference in overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) in favor of the CCRT arm. The 2-year OS rates were 100% for the CCRT arm and 77% for the RT arm (P = .01). The 2-year MFS rates were 92% for the CCRT arm and 80% for the RT arm (P = .02). The 2-year RFS rates were 96% for the CCRT arm and 83% for the RT arm (P = .02).

Conclusion

CCRT with weekly oxaliplatin is feasible and improves OS, MFS, and RFS rates in patients with locoregionally advanced NPC. Therefore, further randomized trials including oxaliplatin are warranted.
Feasibility of Withholding Antibiotics in Selected Febrile Neutropenic Cancer Patients
Authors: Nijhuis Claudi Oude , Kamps Willem A. , Daenen Simon M.G. , Gietema Jourik A. , van der Graaf Winette T.A. , Groen Harrie J.M. , Vellenga Edo , ten Vergert Els M. , Vermeulen Karin M. , de Vries-Hospers Hillie G. , de Bont Eveline S.J.M.
Published: October 2005

Purpose

To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model.

Patients and Methods

Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol.

Results

Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of €471 (US $572) for every potentially low-risk patient.

Conclusion

This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.
Extending the Frontiers of Surgical Therapy for Hepatic Colorectal Metastases: Is There a Limit?
Authors: Khatri Vijay P. , Petrelli Nicholas J. , Belghiti Jacques
Published: October 2005

Hepatic resection for colorectal metastases, limited to the liver, has become the standard of care, and currently remains the only potentially curative therapy. Numerous single institutional reports have demonstrated long-term survival, and there are no other treatment options that have shown a survival plateau. However, curative resection is possible in less than 25% of patients with disease limited to the liver, which consequently translates into only 5% to 10% of the original group developing colorectal cancer. To increase the number of patients who could benefit from hepatic resection, the last decade has seen considerable effort directed towards the following areas, (1) refining prognostic factors that would improve patient selection, (2) advancements in surgical technique such as, use of intraoperative ultrasonography, controlling hemorrhage through use of vascular clamping techniques supplemented with low central venous pressure anesthesia, availability of novel devices for parenchymal transection, and controlled anatomic hepatectomy with Glissonian technique, and (3) novel approaches to permit curative hepatic resection such as, preoperative portal vein embolization for hypertrophy of future liver remnant and staged hepatic resection. This article reviews development of these innovative multidisciplinary modalities and the aggressive surgical approach that has been adopted to extend the frontiers of surgical therapy for colorectal hepatic metastases.
Sustained Complete Molecular Remissions After Treatment With Imatinib-Mesylate in Patients With Failure After Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia: Results of a Prospective Phase II Open-Label Multicenter Study
Authors: Hess Georg , Bunjes Donald , Siegert Wolfgang , Schwerdtfeger Rainer , Ledderose Georg , Wassmann Barbara , Kobbe Guido , Bornhäuser Martin , Hochhaus Andreas , Ullmann Andrew J. , Kindler Thomas , Haus Ulrike , Gschaidmeier Harald , Huber Christoph , Fischer Thomas
Published: October 2005

Purpose

In the era of molecular therapy of chronic myelogenous leukemia (CML) applying BCR-ABL tyrosine kinase inhibitors, the usefulness of molecular end points, in particular, quantitative polymerase chain reaction (PCR) for BCR-ABL in monitoring responses has been broadly accepted. Therefore, we have designed a prospective phase II trial in CML, which, for the first time, evaluated the feasibility and safety of molecular end points as surrogate markers to guide through a stratified treatment algorithm within a multicenter trial.

Patients and Methods

As a clinical model, we adopted minimal residual disease (MRD) found in relapse after allogeneic stem cell transplantation (SCT) in CML. Forty-four patients were enrolled and received the BCR-ABL tyrosine kinase inhibitor imatinib (IM) at a starting dose of 400 mg/d. The quality of molecular responses achieved then decided on discontinuation of IM or dose escalation up to 800 mg/d, and finally, on application of donor lymphocyte infusions.

Results

Seventy percent of patients achieved a complete molecular response (CMR), defined as nested PCR-negativity for BCR-ABL in three consecutive samples. Interestingly, in four out of 10 patients who discontinued IM, CMR was durable even after cessation of IM with a median follow-up of 494 days. This suggests the possibility of long-term tumor control in a subset of patients.

Conclusion

The treatment strategy showed that IM treatment was well-tolerated and highly efficacious in MRD after allogeneic SCT. Moreover, this study demonstrated that evaluation of a molecular end point within a multicenter trial can be a safe and effective tool for clinical decision making.
Treatment With All-Trans Retinoic Acid and Anthracycline Monochemotherapy for Children With Acute Promyelocytic Leukemia: A Multicenter Study by the PETHEMA Group
Authors: Ortega Juan J. , Madero Luis , Martín Guillermo , Verdeguer Amparo , García Purificación , Parody Ricardo , Fuster José , Molines Antonio , Novo Andrés , Debén Guillermo , Rodríguez Antonia , Conde Eulogio , de la Serna Javier , Allegue María J. , Capote Francisco J. , González José D. , Bolufer Pascual , González Marcos , Sanz Miguel A.
Published: October 2005

Purpose

To analyze the simultaneous combination of all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for children with acute promyelocytic leukemia (APL).

Patients and Methods

Since November 1996, 66 children (younger than 18 years) with genetically proven APL received induction therapy with ATRA and idarubicin. Consolidation therapy consisted of three courses of anthracycline monochemotherapy. After November 1999, patients with intermediate and high risk of relapse received consolidation therapy with ATRA and slightly reinforced doses of idarubicin. Maintenance therapy consisted of ATRA and low-dose mercaptopurine and methotrexate.

Results

Thirty-nine girls (59%) and 27 boys (41%) were included in this study. The WBC count at presentation was more than 10 × 109/L in 26 patients (39%). Sixty-one children (92%) achieved complete remission (CR). Early deaths from hemorrhage and retinoic acid syndrome occurred in three patients and two patients, respectively. Toxicity was manageable during consolidation and maintenance therapy. No deaths in CR, clinical cardiomyotoxicity, or secondary malignancy occurred. Two patients had molecular persistence at the end of consolidation. Three clinical relapses and two molecular relapses were also observed. Apart from one molecular relapse, all these events occurred among children with hyperleukocytosis. The 5-year cumulative incidence of relapse was 17%, whereas disease-free and overall survival rates were 82% and 87%, respectively.

Conclusion

A high incidence of hyperleukocytosis in children with APL was confirmed. Besides low toxicity and a high degree of compliance, a risk-adapted therapy combining ATRA and anthracycline monochemotherapy showed an antileukemic efficacy comparable to those previously reported with other chemotherapy combinations in children.
Retrospective Analysis of Time to Recurrence in the ATAC Trial According to Hormone Receptor Status: An Hypothesis-Generating Study
Authors: Dowsett Mitch , Cuzick Jack , Wale Chris , Howell Tony , Houghton Joan , Baum Michael
Published: October 2005

Purpose

Arimidex, tamoxifen alone, or in combination (ATAC) trial of anastrozole (Arimidex) versus tamoxifen or a combination of the two in 9,366 postmenopausal patients with primary breast cancer found a significant improvement in disease-free survival and time to recurrence (TTR) for anastrozole compared with tamoxifen, that was restricted to patients with hormone receptor-positive (ie, estrogen receptor–positive [ER+] and/or progesterone receptor-positive [PgR+]) disease, the target population for these therapies. We retrospectively tested the hypothesis that this benefit might differ according to PgR status.

Patients and Methods

TTR was compared between the three treatment groups for subgroups defined by ER and PgR status using Cox's proportional hazards model, with and without adjustment for baseline variables.

Results

The unadjusted hazard ratio (HR) for anastrozole versus tamoxifen for TTR was 0.74 (95% CI, 0.64 to 0.87) for women with either ER+ or PgR+ tumors. In the ER+/PgR+ subgroup (n = 3,834) the HR was 0.84 (95% CI, 0.69 to 1.02) compared with 0.43 (95% CI, 0.31 to 0.61) in the ER+/PgR-negative (PgR–) subgroup (n = 880). In the adjusted model the HRs were 0.83 and 0.45, respectively.

Conclusion

Time to recurrence was longer for anastrozole- than tamoxifen-treated patients in both ER+/PgR+ and ER+/PgR– subgroups, but the benefit was substantially greater in the PgR– subgroup. As this was an “exploratory” analysis, this effect should be considered as hypothesis generating and assessed prospectively in other trials comparing the adjuvant use of an aromatase inhibitor with tamoxifen.
Retrospective Analysis of Topoisomerase IIa Amplifications and Deletions As Predictive Markers in Primary Breast Cancer Patients Randomly Assigned to Cyclophosphamide, Methotrexate, and Fluorouracil or Cyclophosphamide, Epirubicin, and Fluorouracil: Danish Breast Cancer Cooperative Group
Authors: Knoop Ann S. , Knudsen Helle , Balslev Eva , Rasmussen Birgitte B. , Overgaard Jens , Nielsen Kirsten V. , Schonau Andreas , Gunnarsdóttir Katrín , Olsen Karen E. , Mouridsen Henning , Ejlertsen Bent
Published: October 2005

Purpose

The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIα gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients.

Patients and Methods

In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions.

Results

HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17).

Conclusion

TOP2A amplification—and possibly deletion—seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.