bluuebunny/crossref_metadata_2025 huggingface dataset:
Histidine-mediated RNA transfer to GDP for unique mRNA capping by vesicular stomatitis virus RNA polymerase
Authors: Ogino Tomoaki , Yadav Satya P. , Banerjee Amiya K.
Published: February 2010

The RNA-dependent RNA polymerase L protein of vesicular stomatitis virus, a prototype of nonsegmented negative-strand (NNS) RNA viruses, forms a covalent complex with a 5′-phosphorylated viral mRNA-start sequence (L-pRNA), a putative intermediate in the unconventional mRNA capping reaction catalyzed by the RNA:GDP polyribonucleotidyltransferase (PRNTase) activity. Here, we directly demonstrate that the purified L-pRNA complex transfers pRNA to GDP to produce the capped RNA (Gpp-pRNA), indicating that the complex is a bona fide intermediate in the RNA transfer reaction. To locate the active site of the PRNTase domain in the L protein, the covalent RNA attachment site was mapped. We found that the 5′-monophosphate end of the RNA is linked to the histidine residue at position 1,227 (H1227) of the L protein through a phosphoamide bond. Interestingly, H1227 is part of the histidine-arginine (HR) motif, which is conserved within the L proteins of the NNS RNA viruses including rabies, measles, Ebola, and Borna disease viruses. Mutagenesis analyses revealed that the HR motif is required for the PRNTase activity at the step of the enzyme-pRNA intermediate formation. Thus, our findings suggest that an ancient NNS RNA viral polymerase has acquired the PRNTase domain independently of the eukaryotic mRNA capping enzyme during evolution and PRNTase becomes a rational target for designing antiviral agents.
Retroviral infection in vivo requires an immune escape virulence factor encrypted in the envelope protein of oncoretroviruses
Authors: Schlecht-Louf Géraldine , Renard Martial , Mangeney Marianne , Letzelter Claire , Richaud Aurélien , Ducos Bertrand , Bouallaga Isabelle , Heidmann Thierry
Published: February 2010

We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins (Envs). The envelope-mediated immunosuppression was manifested by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation specifically abolishes IS activity without affecting the “mechanical” fusogenic function of the entire envelope. Here, we genetically “switched off’ the envelope-mediated immunosuppression of an infectious retrovirus, the Friend murine leukemia virus, while preserving mutant envelope infectivity both ex vivo and in vivo, thus allowing us to test the functional importance of envelope-mediated immunosuppression in retrovirus physiology. Remarkably, we show, in vivo, that the non-IS mutant virus displays the same propagation kinetics as its WT counterpart in irradiated immunocompromised mice but that it is rapidly and totally cleared from normal immunocompetent mice, which become fully protected against a challenge with the WT retrovirus. Using cell depletion strategies, we further establish that envelope-mediated immunosuppression enables the retrovirus to escape innate (natural killer cells) and adaptive (CD8 T cells) antiviral effectors. Finally, we show that inactivated mutant virions induce higher humoral and cellular responses than their WT counterparts. In conclusion, our work demonstrates the critical role of Env-induced immunosuppression for retrovirus propagation in vivo and identifies a unique definite target for antiretroviral therapies and vaccine strategies, also characterized in the human T-cell leukemia virus (HTLV) and xenotropic murine leukemia virus-related virus (XMRV) retroviruses, opening unprecedented prospects for the treatment of retroviral diseases.
Redox potential of pheophytin
a
in photosystem II of two cyanobacteria having the different special pair chlorophylls
Authors: Allakhverdiev Suleyman I. , Tomo Tatsuya , Shimada Yuichiro , Kindo Hayato , Nagao Ryo , Klimov Vyacheslav V. , Mimuro Mamoru
Published: February 2010

Water oxidation by photosystem (PS) II in oxygenic photosynthetic organisms is a major source of energy on the earth, leading to the production of a stable reductant. Mechanisms generating a high oxidation potential for water oxidation have been a major focus of photosynthesis research. This potential has not been estimated directly but has been measured by the redox potential of the primary electron acceptor, pheophytin (Phe)
a
. However, the reported values for Phe
a
are still controversial. Here, we measured the redox potential of Phe
a
under physiological conditions (pH 7.0; 25 °C) in two cyanobacteria with different special pair chlorophylls (Chls):
Synechocystis
sp. PCC 6803, whose special pair for PS II consists of Chl
a
, and
Acaryochloris marina
MBIC 11017, whose special pair for PS II consists of Chl
d
. We obtained redox potentials of −536 ± 8 mV for
Synechocystis
sp. PCC 6803 and −478 ± 24 mV for
A. marina
on PS II complexes in the presence of 1.0 M betaine. The difference in the redox potential of Phe
a
between the two species closely corresponded with the difference in the light energy absorbed by Chl
a
versus Chl
d
. We estimated the potentials of the special pair of PS II to be 1.20 V and 1.18 V for
Synechocystis
sp. PCC 6803 (P680) and
A. marina
(P713), respectively. This clearly indicates conservation in the properties of water-oxidation systems in oxygenic photosynthetic organisms, irrespective of the special-pair chlorophylls.
An expedient route to substituted furans via olefin cross-metathesis
Authors: Donohoe Timothy J. , Bower John F.
Published: February 2010

The olefin cross-metathesis (CM) reaction is used extensively in organic chemistry and represents a powerful method for the selective synthesis of differentially substituted alkene products. Surprisingly, efforts to integrate this remarkable process into strategies for aromatic and heteroaromatic construction have not been reported. Such structures represent key elements of the majority of small molecule drug compounds; methods for the controlled preparation of highly substituted derivatives are essential to medicinal chemistry. Here we show that the olefin CM reaction, in combination with an acid cocatalyst or subsequent Heck arylation, provides a concise and flexible entry to 2,5-di- or 2,3,5-tri-substituted furans. These cascade processes portend further opportunities for the regiocontrolled preparation of other highly substituted aromatic and heteroaromatic classes.
Repositioning of an existing drug for the neglected tropical disease Onchocerciasis
Authors: Gloeckner Christian , Garner Amanda L. , Mersha Fana , Oksov Yelena , Tricoche Nancy , Eubanks Lisa M. , Lustigman Sara , Kaufmann Gunnar F. , Janda Kim D.
Published: February 2010

Onchocerciasis, or river blindness, is a neglected tropical disease caused by the filarial nematode
Onchocerca volvulus
that affects more than 37 million people, mainly in third world countries. Currently, the only approved drug available for mass treatment is ivermectin, however, drug resistance is beginning to emerge, thus, new therapeutic targets and agents are desperately needed to treat and cure this devastating disease. Chitin metabolism plays a central role in invertebrate biology due to the critical structural function of chitin for the organism. Taken together with its absence in mammals, targeting chitin is an appealing therapeutic avenue. Importantly, the chitinase OvCHT1 from
O. volvulus
was recently discovered, however, its exact role in the worm’s metabolism remains unknown. A screening effort against OvCHT1 was conducted using the Johns Hopkins Clinical Compound Library that contains over 1,500 existing drugs. Closantel, a veterinary anthelmintic with known proton ionophore activities, was identified as a potent and specific inhibitor of filarial chitinases, an activity not previously reported for this compound. Notably, closantel was found also to completely inhibit molting of
O. volvulus
infective L3 stage larvae. Closantel appears to target two important biochemical processes essential to filarial parasites. To begin to unravel closantel’s effects, a retro-fragment-based study was used to define structural elements critical for closantel’s chitinase inhibitor function. As resources towards the development of new agents that target neglected tropical diseases are scant, the finding of an existing drug with impact against
O. volvulus
provides promise in the hunt for new therapies against river blindness.
The Lucretian swerve: The biological basis of human behavior and the criminal justice system
Authors: Cashmore Anthony R.
Published: February 2010

It is widely believed, at least in scientific circles, that living systems, including mankind, obey the natural physical laws. However, it is also commonly accepted that man has the capacity to make “free” conscious decisions that do not simply reflect the chemical makeup of the individual at the time of decision—this chemical makeup reflecting both the genetic and environmental history and a degree of stochasticism. Whereas philosophers have discussed for centuries the apparent lack of a causal component for free will, many biologists still seem to be remarkably at ease with this notion of free will; and furthermore, our judicial system is based on such a belief. It is the author’s contention that a belief in free will is nothing other than a continuing belief in vitalism—something biologists proudly believe they discarded well over 100 years ago.
Molecular MRI for sensitive and specific detection of lung metastases
Authors: Branca Rosa T. , Cleveland Zackary I. , Fubara Boma , Kumar Challa S. S. R. , Maronpot Robert R. , Leuschner Carola , Warren Warren S. , Driehuys Bastiaan
Published: February 2010

Early and specific detection of metastatic cancer cells in the lung (the most common organ targeted by metastases) could significantly improve cancer treatment outcomes. However, the most widespread lung imaging methods use ionizing radiation and have low sensitivity and/or low specificity for cancer cells. Here we address this problem with an imaging method to detect submillimeter-sized metastases with molecular specificity. Cancer cells are targeted by iron oxide nanoparticles functionalized with cancer-binding ligands, then imaged by high-resolution hyperpolarized
3
He MRI. We demonstrate in vivo detection of pulmonary micrometastates in mice injected with breast adenocarcinoma cells. The method not only holds promise for cancer imaging but more generally suggests a fundamentally unique approach to molecular imaging in the lungs.
IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses
Authors: Linterman Michelle A. , Beaton Laura , Yu Di , Ramiscal Roybel R. , Srivastava Monika , Hogan Jennifer J. , Verma Naresh K. , Smyth Mark J. , Rigby Robert J. , Vinuesa Carola G.
Published: February 2010

During T cell–dependent responses, B cells can either differentiate extrafollicularly into short-lived plasma cells or enter follicles to form germinal centers (GCs). Interactions with T follicular helper (Tfh) cells are required for GC formation and for selection of somatically mutated GC B cells. Interleukin (IL)-21 has been reported to play a role in Tfh cell formation and in B cell growth, survival, and isotype switching. To date, it is unclear whether the effect of IL-21 on GC formation is predominantly a consequence of this cytokine acting directly on the Tfh cells or if IL-21 directly influences GC B cells. We show that IL-21 acts in a B cell–intrinsic fashion to control GC B cell formation. Mixed bone marrow chimeras identified a significant B cell–autonomous effect of IL-21 receptor (R) signaling throughout all stages of the GC response. IL-21 deficiency profoundly impaired affinity maturation and reduced the proportion of IgG1+ GC B cells but did not affect formation of early memory B cells. IL-21R was required on GC B cells for maximal expression of Bcl-6. In contrast to the requirement for IL-21 in the follicular response to sheep red blood cells, a purely extrafollicular antibody response to Salmonella dominated by IgG2a was intact in the absence of IL-21.
IL-21 regulates germinal center B cell differentiation and proliferation through a B cell–intrinsic mechanism
Authors: Zotos Dimitra , Coquet Jonathan M. , Zhang Yang , Light Amanda , D'Costa Kathy , Kallies Axel , Corcoran Lynn M. , Godfrey Dale I. , Toellner Kai-Michael , Smyth Mark J. , Nutt Stephen L. , Tarlinton David M.
Published: February 2010

Germinal centers (GCs) are sites of B cell proliferation, somatic hypermutation, and selection of variants with improved affinity for antigen. Long-lived memory B cells and plasma cells are also generated in GCs, although how B cell differentiation in GCs is regulated is unclear. IL-21, secreted by T follicular helper cells, is important for adaptive immune responses, although there are conflicting reports on its target cells and mode of action in vivo. We show that the absence of IL-21 signaling profoundly affects the B cell response to protein antigen, reducing splenic and bone marrow plasma cell formation and GC persistence and function, influencing their proliferation, transition into memory B cells, and affinity maturation. Using bone marrow chimeras, we show that these activities are primarily a result of CD3-expressing cells producing IL-21 that acts directly on B cells. Molecularly, IL-21 maintains expression of Bcl-6 in GC B cells. The absence of IL-21 or IL-21 receptor does not abrogate the appearance of T cells in GCs or the appearance of CD4 T cells with a follicular helper phenotype. IL-21 thus controls fate choices of GC B cells directly.
Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations
Authors: Gross Stefan , Cairns Rob A. , Minden Mark D. , Driggers Edward M. , Bittinger Mark A. , Jang Hyun Gyung , Sasaki Masato , Jin Shengfang , Schenkein David P. , Su Shinsan M. , Dang Lenny , Fantin Valeria R. , Mak Tak W.
Published: February 2010

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present in most gliomas and secondary glioblastomas, but are rare in other neoplasms. IDH1/2 mutations are heterozygous, and affect a single arginine residue. Recently, IDH1 mutations were identified in 8% of acute myelogenous leukemia (AML) patients. A glioma study revealed that IDH1 mutations cause a gain-of-function, resulting in the production and accumulation of 2-hydroxyglutarate (2-HG). Genotyping of 145 AML biopsies identified 11 IDH1 R132 mutant samples. Liquid chromatography-mass spectrometry metabolite screening revealed increased 2-HG levels in IDH1 R132 mutant cells and sera, and uncovered two IDH2 R172K mutations. IDH1/2 mutations were associated with normal karyotypes. Recombinant IDH1 R132C and IDH2 R172K proteins catalyze the novel nicotinamide adenine dinucleotide phosphate (NADPH)–dependent reduction of α-ketoglutarate (α-KG) to 2-HG. The IDH1 R132C mutation commonly found in AML reduces the affinity for isocitrate, and increases the affinity for NADPH and α-KG. This prevents the oxidative decarboxylation of isocitrate to α-KG, and facilitates the conversion of α-KG to 2-HG. IDH1/2 mutations confer an enzymatic gain of function that dramatically increases 2-HG in AML. This provides an explanation for the heterozygous acquisition of these mutations during tumorigenesis. 2-HG is a tractable metabolic biomarker of mutant IDH1/2 enzyme activity.
Natural killer receptors: the burden of a name
Authors: Veiga-Fernandes Henrique , Kioussis Dimitris , Coles Mark
Published: February 2010

A population of cells that expresses the NK cell receptor NKp46 and produces interleukin (IL)-22 have recently attracted considerable attention. The identity of these cells is still the subject of speculation, being variably defined as a novel NK cell subset or as a population containing conventional NK (cNK) cell precursors. In this issue, two studies shed light on this conundrum, demonstrating that NKp46+ IL-22+ cells and cNK cells belong to distinct lineages.
Regulation of conductance by the number of fixed positive charges in the intracellular vestibule of the CFTR chloride channel pore
Authors: Zhou Jing-Jun , Li Man-Song , Qi Jiansong , Linsdell Paul
Published: February 2010

Rapid chloride permeation through the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is dependent on the presence of fixed positive charges in the permeation pathway. Here, we use site-directed mutagenesis and patch clamp recording to show that the functional role played by one such positive charge (K95) in the inner vestibule of the pore can be “transplanted” to a residue in a different transmembrane (TM) region (S1141). Thus, the mutant channel K95S/S1141K showed Cl− conductance and open-channel blocker interactions similar to those of wild-type CFTR, thereby “rescuing” the effects of the charge-neutralizing K95S mutation. Furthermore, the function of K95C/S1141C, but not K95C or S1141C, was inhibited by the oxidizing agent copper(II)-o-phenanthroline, and this inhibition was reversed by the reducing agent dithiothreitol, suggesting disulfide bond formation between these two introduced cysteine side chains. These results suggest that the amino acid side chains of K95 (in TM1) and S1141 (in TM12) are functionally interchangeable and located closely together in the inner vestibule of the pore. This allowed us to investigate the functional effects of increasing the number of fixed positive charges in this vestibule from one (in wild type) to two (in the S1141K mutant). The S1141K mutant had similar Cl− conductance as wild type, but increased susceptibility to channel block by cytoplasmic anions including adenosine triphosphate, pyrophosphate, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and Pt(NO2)42− in inside-out membrane patches. Furthermore, in cell-attached patch recordings, apparent voltage-dependent channel block by cytosolic anions was strengthened by the S1141K mutation. Thus, the Cl− channel function of CFTR is maximal with a single fixed positive charge in this part of the inner vestibule of the pore, and increasing the number of such charges to two causes a net decrease in overall Cl− transport through a combination of failure to increase Cl− conductance and increased susceptibility to channel block by cytosolic substances.
Small Sounds, Big Deals: Phonetic Symbolism Effects in Pricing
Authors: Coulter Keith S. , Coulter Robin A.
Published: February 2010

Studies suggest that certain vowel and consonant sounds (or phonemes) can be associated with perceptions of large and small size. Mental rehearsal of prices containing numbers with small phonemes results in overestimation of price discounts, whereas mental rehearsal of prices containing numbers with large phonemes results in underestimation. Mental rehearsal of the same sale prices characterized by small phonemes in one language and large phonemes in another language can yield differential effects. For example, when sale prices are rehearsed in English, an $\$ 11.00-\$ 7.88$ (28.4%) discount is perceived as greater than a $\$ 10.00-\$ 7.01$ (29.9%) discount; however, when these same prices are rehearsed in Chinese, the latter discount is perceived as greater. Non-price-related phonemes do not yield these same discount distortions. Collectively, findings indicate that the mere sounds of numbers can nonconsciously affect and distort numerical magnitude perceptions.
Quantum algebras and symplectic reflection algebras for wreath products
Authors: Guay Nicolas
Published: February 2010

To a finite subgroup

Γ
\Gamma

of

S

L
2

(

C

)

SL_2(\mathbb {C})

, we associate a new family of quantum algebras which are related to symplectic reflection algebras for wreath products

S
l

≀
Γ

S_l\wr \Gamma

via a functor of Schur-Weyl type. We explain that they are deformations of matrix algebras over rank-one symplectic reflection algebras for

Γ
\Gamma

and construct for them a PBW basis. When

Γ
\Gamma

is a cyclic group, we are able to give more information about their structure and to relate them to Yangians.
The impact of a supervised injecting facility on ambulance call‐outs in Sydney, Australia
Authors: Salmon Allison M. , Van Beek Ingrid , Amin Janaki , Kaldor John , Maher Lisa
Published: February 2010

Aims  Supervised injecting facilities (SIFs) are effective in reducing the harms associated with injecting drug use among their clientele, but do SIFs ease the burden on ambulance services of attending to overdoses in the community? This study addresses this question, which is yet to be answered, in the growing body of international evidence supporting SIFs efficacy.

Design  Ecological study of patterns in ambulance attendances at opioid‐related overdoses, before and after the opening of a SIF in Sydney, Australia.

Setting  A SIF opened as a pilot in Sydney's ‘red light’ district with the aim of accommodating a high throughput of injecting drug users (IDUs) for supervised injecting episodes, recovery and the management of overdoses.

Measurements  A total of 20 409 ambulance attendances at opioid‐related overdoses before and after the opening of the Sydney SIF. Average monthly ambulance attendances at suspected opioid‐related overdoses, before (36 months) and after (60 months) the opening of the Sydney Medically Supervised Injecting Centre (MSIC), in the vicinity of the centre and in the rest of New South Wales (NSW).

Results  The burden on ambulance services of attending to opioid‐related overdoses declined significantly in the vicinity of the Sydney SIF after it opened, compared to the rest of NSW. This effect was greatest during operating hours and in the immediate MSIC area, suggesting that SIFs may be most effective in reducing the impact of opioid‐related overdose in their immediate vicinity.

Conclusions  By providing environments in which IDUs receive supervised injection and overdose management and education SIF can reduce the demand for ambulance services, thereby freeing them to attend other medical emergencies within the community.
How much alcohol do you buy? A comparison of self‐reported alcohol purchases with actual sales
Authors: Ramstedt Mats
Published: February 2010

Background  Unrecorded alcohol has increased in the Nordic countries during recent years, above all in terms of cross‐border trade. This implies that trends and levels of per capita consumption would look different without estimates of this source of alcohol, estimates that in Sweden and other countries are made through surveys.

Aim  The overall aim is to analyse the validity of Swedish survey estimates of alcohol bought in the cross‐border trade and possibly to develop weights that can be applied to such estimates.

Data and method  The analysis consists of comparing self‐reported purchases of spirits, wine, cider/alcopops and beer at retail monopoly (Systembolaget) during 2008 (n = 18 000) with actual sales during the same period overall and monthly.

Findings  Of the recorded amount of purchases at Systembolaget, 87% was reported in the survey, compared with the 40–60% usually found for self‐reported consumption. Significant differences across beverages were revealed, showing a lower coverage rate for beer and spirits and a higher coverage rate for wine and cider. Changes in purchases of all beverages were captured fairly well, at least changes taking place from one month to another.

Conclusions  Self‐reported alcohol purchases achieve a higher coverage rate than found typically in studies based on self‐reported use of alcohol. If adjustments are to be made to correct for underreporting in self‐reported data on alcohol purchases, different weights should be applied to different beverages. Furthermore, at least major changes in how much alcohol is purchased in the population can be monitored using well‐designed population surveys.
How ideology shapes the evidence and the policy: what do we know about cannabis use and what should we do?
Authors: Macleod John , Hickman Matthew
Published: February 2010

In the United Kingdom, as in many places, cannabis use is considered substantially within a criminal justice rather than a public health paradigm with prevention policy embodied in the Misuse of Drugs Act. In 2002 the maximum custodial sentence tariff for cannabis possession under the Act was reduced from 5 to 2 years. Vigorous and vociferous public debate followed this decision, centred principally on the question of whether cannabis use caused schizophrenia. It was suggested that new and compelling evidence supporting this hypothesis had emerged since the re‐classification decision was made, meaning that the decision should be reconsidered. The re‐classification decision was reversed in 2008. We consider whether the strength of evidence on the psychological harms of cannabis has changed substantially and discuss the factors that may have influenced recent public discourse and policy decisions. We also consider evidence for other harms of cannabis use and public health implications of preventing cannabis use. We conclude that the strongest evidence of a possible causal relation between cannabis use and schizophrenia emerged more than 20 years ago and that the strength of more recent evidence may have been overstated—for a number of possible reasons. We also conclude that cannabis use is almost certainly harmful, mainly because of its intimate relation to tobacco use. The most rational policy on cannabis from a public health perspective would seem to be one able to achieve the benefit of reduced use in the population while minimizing social and other costs of the policy itself. Prohibition, whatever the sentence tariff associated with it, seems unlikely to fulfil these criteria.
Symptoms of nicotine dependence in a cohort of Swedish youths: a comparison between smokers, smokeless tobacco users and dual tobacco users
Authors: Post Ann , Gilljam Hans , Rosendahl Ingvar , Bremberg Sven , Rosaria Galanti Maria
Published: February 2010

Aims  To determine whether symptoms of nicotine dependence, addiction and withdrawal symptoms differ between exclusive smokers, exclusive snus (moist snuff) users and dual users.

Design  A cross‐sectional survey of a cohort subsample.

Setting  County of Stockholm, Sweden.

Participants  Current exclusive smokers (n = 466), exclusive snus users (n = 209) and dual users (n = 144), mean age 17.6 years.

Measurements  Self‐reported life‐time experience of nicotine dependence and withdrawal symptoms in periods of discontinued tobacco use. Selected items from the modified Fagerstöm Tolerance Questionnaire (mFTQ), the Hooked on Nicotine Checklist (HONC) and the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV).

Findings  The odds ratio of endorsing each of four mFTQ items as well as the HONC item investigating the risk of feeling addicted to tobacco was two to five‐fold higher for exclusive snus users and for dual users compared to exclusive smokers. One DSM‐IV item (difficult to refrain from use) was elevated among dual users compared to smokers. Dual users reported the highest prevalence of any withdrawal symptom in contrast to exclusive snus users, who reported a lower risk of withdrawal symptoms compared to exclusive smokers.

Conclusions  Smokeless tobacco users show symptoms of nicotine dependence at least as frequently as cigarette smokers. Symptoms of nicotine dependence and of withdrawal during quit attempts are particularly frequent in the subgroup of users who combine smokeless tobacco with smoking.
Characteristics and comorbidity of drug and alcohol‐related emergency department presentations detected by nursing triage text
Authors: Indig Devon , Copeland Jan , Conigrave Katherine M. , Arcuri Anthony
Published: February 2010

Introduction  This study used nursing triage text to detect drug‐ and alcohol‐related emergency department (ED) presentations and describe their patient and service delivery characteristics.

Methods  Data were reviewed for all ED presentations from 2004 to 2006 (n = 263 937) from two hospitals in Sydney, Australia. Each record included two nursing triage free‐text fields, which were searched for more than 100 drug‐related and more than 60 alcohol‐related terms. Adjusted odds ratios were used to compare the characteristics of drug and alcohol‐related ED presentations with all other ED presentation types.

Results  Just over 5% of ED presentations were identified as alcohol‐related and 2% as drug‐related. The most prevalent drug‐related ED presentations specified were related to amphetamines (18%), heroin (14%), cannabis (14%) and ecstasy (12%), while nearly half (43%) were drug unspecified. Polydrug use was mentioned in 25% of drug‐related and 9% of alcohol‐related ED presentations, with the highest rate of polydrug use among ecstasy‐related (68%) presentations. Drug‐ and alcohol‐related ED presentations were significantly more likely than other ED presentations to have a mental health diagnosis, with the highest rates found among cannabis‐related (OR = 7.6) or amphetamine‐related (OR = 7.5) presentations.

Conclusion  The ED provides an opportunity for early intervention for patients presenting with comorbid drug and alcohol and mental health problems. Further research is needed to assess the prevalence of drug and alcohol problems in ED patients with mental health problems and to develop effective interventions in that setting.
Human sex differences in d‐amphetamine self‐administration
Authors: Vansickel Andrea R. , Stoops William W. , Rush Craig R.
Published: February 2010

Women and men may respond differently to the effects of stimulants such as amphetamine and cocaine.

Aim  In order to assess potential sex differences in the reinforcing effects of d‐amphetamine, a retrospective‐analysis was conducted on data collected from three studies that employed similar d‐amphetamine self‐administration procedures and used identical subject‐rated drug‐effect measures.

Methods  Data from 10 women and 15 men were included in the analysis. In all studies, participants sampled placebo, low (8–10 mg) or high (16–20 mg) dose oral d‐amphetamine. Following sampling sessions, participants worked for capsules containing one eighth of the previously sampled dose on a modified progressive‐ratio schedule of reinforcement. We hypothesized that women and men would be differentially sensitive to the reinforcing effects of d‐amphetamine. A two‐way mixed‐model analysis of variance (sex and dose) and planned comparisons were used in the statistical analyses.

Results  The low dose of d‐amphetamine functioned as a reinforcer in women, but not men, whereas the high dose of d‐amphetamine functioned as a reinforcer in men, but not women. Men self‐administered significantly more capsules under the high dose condition than women.

Conclusion  The results of this study suggest that men are more sensitive to the reinforcing effects of a high dose of d‐amphetamine than women. Future research is needed that determines prospectively the reinforcing effects of weight‐adjusted doses of d‐amphetamine in women and men while controlling for menstrual cycle phase.
The effect of image complexity on attentional bias towards alcohol‐related images in adult drinkers
Authors: Miller Melissa A. , Fillmore Mark T.
Published: February 2010

Aim Visual probe tasks are often used to measure attentional bias (AB) towards alcohol‐related images in drinkers, but little is known about the effect of the properties of the images used in this task: specifically, image complexity.

Methods AB was examined in a group of adult drinkers (n = 25). Two measures of attentional bias were obtained from a modified visual probe task. First, a traditional dot probe detection task measured attentional bias in drinkers based on their reaction times to probes replacing neutral and alcohol‐related images. Secondly, an eye‐tracking measure was applied to this task to directly assess the drinkers' eye gazes to the alcohol‐related and neutral images. The effect of image complexity was examined by comparing AB towards images classified as simple and complex.

Findings Results showed that drinkers displayed AB only towards simple alcohol‐related images as measured by both probe RT and fixation times.

Conclusion These findings suggest that complex alcohol‐related images might be less effective at capturing drinkers' attention and could result in less attentional bias when used in visual probe tasks.
Sweet preferences and analgesia during childhood: effects of family history of alcoholism and depression
Authors: Mennella Julie A. , Pepino M. Yanina , Lehmann‐Castor Sara M. , Yourshaw Lauren M.
Published: February 2010

Aim  To determine whether depression and family history of alcoholism are associated with heightened sweet preferences in children, before they have experienced alcohol or tobacco and at a time during the life‐span when sweets are particularly salient.

Design  Between‐ and within‐subject experimental study.

Participants  Children, 5–12 years old (n = 300), formed four groups based on family history of alcohol dependence up to second‐degree relatives [positive (FHP) versus negative (FHN)] and depressive symptoms as determined by the Pictorial Depression Scale [depressed (PDEP) versus non‐depressed (NDEP)].

Measurements  Children were tested individually to measure sucrose preferences, sweet food liking and, for a subset of the children, the analgesic properties of sucrose versus water during the cold pressor test.

Findings  The co‐occurrence of having a family history of alcoholism and self‐reports of depressive symptomatology was associated significantly with a preference for a more concentrated sucrose solution, while depressive symptomatology alone was associated with greater liking for sweet‐tasting foods and candies and increased pain sensitivity. Depression antagonized the analgesic properties of sucrose.

Conclusions  While children as a group innately like sweets and feel better after eating them, the present study reveals significant contributions of family history of alcoholism and depression to this effect. Whether the heightened sweet preference and the use of sweets to alleviate depression are markers for developing alcohol‐related problems or responses that are protective are important areas for future research.
Modeling missing binary outcome data in a successful web‐based smokeless tobacco cessation program
Authors: Smolkowski Keith , Danaher Brian G. , Seeley John R. , Kosty Derek B. , Severson Herbert H.
Published: February 2010

AimTo examine various methods to impute missing binary outcome from a web‐based tobacco cessation intervention.

DesignThe ChewFree randomized controlled trial used a two‐arm design to compare tobacco abstinence at both the 3‐ and 6‐month follow‐up for participants randomized to either an enhanced web‐based intervention condition or a basic information‐only control condition.

SettingInternet in the United States and Canada.

ParticipantsSecondary analyses focused upon 2523 participants in the ChewFree trial.

MeasurementsPoint‐prevalence tobacco abstinence measured at 3‐ and 6‐month follow‐up.

FindingsThe results of this study confirmed the findings for the original ChewFree trial and highlighted the use of different missing‐data approaches to achieve intent‐to‐treat analyses when confronted with substantial attrition. The use of different imputation methods yielded results that differed in both the size of the estimated treatment effect and the standard errors.

ConclusionsThe choice of imputation model used to analyze missing binary outcome data can affect substantially the size and statistical significance of the treatment effect. Without additional information about the missing cases, they can overestimate the effect of treatment. Multiple imputation methods are recommended, especially those that permit a sensitivity analysis of their impact.
Venous thrombosis prevention – more than just guidelines
Authors: Clark Peter , Wu Olivia , Greer Ian A. , Lowe Gordon D. O.
Published: February 2010

Hospital‐associated venous thromboembolism remains a major international cause of avoidable mortality and morbidity. Although the publication of national guidelines does increase the use of thromboprophylaxis, we present the results of a recent audit of thrombosis prevention in UK hospitals which, despite published guidelines, shows continuing significant variations in guideline implementation and practice. The results of this audit are paralleled with UK and international data on hospital‐acquired thrombosis prevention and the potential solutions to these problems, particularly the lessons which can be learned from other areas of clinical practice, are discussed.
The genotype nucleophosmin mutated and FLT3‐ITD negative is characterized by high bax/bcl‐2 ratio and favourable outcome in acute myeloid leukaemia
Authors: Del Poeta Giovanni , Ammatuna Emanuele , Lavorgna Serena , Capelli Giovanni , Zaza Serena , Luciano Fabrizio , Ottone Tiziana , Del Principe Maria Ilaria , Buccisano Francesco , Maurillo Luca , Panetta Paola , De Fabritiis Paolo , Stasi Roberto , Venditti Adriano , Amadori Sergio , Lo Coco Francesco
Published: February 2010

Nucleophosmin gene (NPM1) mutations characterize acute myeloid leukaemia (AML) with normal karyotype and frequently co‐exist with FLT3 internal tandem duplications (ITD). We evaluated bcl‐2, bax, NPM1 and FLT3‐ITD in 222 AML patients. Bax/bcl‐2 ratio >0·35 and NPM1 without FLT3‐ITD were significantly associated (P = 0·0001). NPM1‐mutated (mt)/FLT3‐ITD negative patients showed a higher complete remission (CR) rate (90%, P = 0·0002) and a longer overall survival (OS, P = 0·00007). NPM1‐mt/FLT3‐ITD negative plus bax/bcl‐2 > 0·35 subset showed a very high CR rate (96%), very long OS (P = 0·00005) and disease‐free survival (P = 0·004). The favourable prognosis of NPM1‐mt/FLT3‐ITD negative patients might be explained by a higher bax/bcl‐2 ratio.
A curriculum for nurses in Germany undertaking medically‐delegated tasks in primary care
Authors: Dreier Adina , Rogalski Hagen , Oppermann Roman Frank , Terschüren Claudia , Van Den Berg Neeltje , Hoffmann Wolfgang
Published: February 2010

dreier a., rogalski h., oppermann r.f., terschüren c., van den berg n. & hoffmann w. (2010) A curriculum for nurses in Germany undertaking medically‐delegated tasks in primary care. Journal of Advanced Nursing66(3), 635–644.

Aim.  This paper is a report of a study conducted to develop a qualification for nurses in primary care based on the delegation of medical tasks in order to relieve general practitioners and to supply the population in rural regions today and in the future.

Background.  Age‐demographic changes will cause medical care supply problems, especially for older people, motivating a re‐evaluation of the nursing role in ambulatory medical care.

Methods.  An intervention study was conducted in Germany between 1 January 2006 and 31 December 2007, comprising a theoretical and practical phase evaluated by participants, general practitioners and patients through questionnaires, reflection rounds and structured interviews during and after the practice phase.

Findings.  Participants and general practitioners rated the curriculum as relevant and useful. Nurses were motivated by the ability to be self‐employed and the expansion of their scope of professional work general practitioners regarded medical duty delegation as workload relief. Patients positively evaluated nurse visits, comparing medical competence and conduct to that of a general practitioner’s.

Conclusion.  The qualification is a promising approach to compensate for the imminent undersupply of primary care and allows maintenance a high standard of healthcare quality for rural areas of Germany and countries with similar structures. It supports doctors through task delegation, and offers an option for an advanced training for nurses.
Leaving the organization or the profession – a multilevel analysis of nurses’ intentions
Authors: Simon Michael , Müller Bernd Hans , Hasselhorn Hans Martin
Published: February 2010

simon m., müller b.h. & hasselhorn h.m. (2010) Leaving the organization or the profession – a multilevel analysis of nurses’ intentions. Journal of Advanced Nursing66(3), 616–626.

Aim.  This paper is a report of a study of (i) which variables are associated with the intention to leave the profession (ii) which variables are associated with the intention to leave the organization; and (iii) how the related variables differ between intentions in a secondary analysis of data of the German part of the European Nurses’ Early Exit Study.

Background.  Nursing turnover research so far rarely differentiates between leaving the profession or the organization. The identification of specific correlates for different leaving intentions would support better understanding of the turnover process and the development of targeted measures to reduce turnover.

Methods.  A secondary data analysis of the German sample of the European Nurses’ Early Exit‐Study was performed, using a generalized linear mixed model approach.

Results.  Data from 2119 Registered Nurses in 71 departments of 16 hospitals from 2003 were analysed. Models for intentions to leave the profession explained more of the variance (r2 = 0·46) than models for intentions to leave the organization (r2 = 0·28). Both leaving intentions were associated with age, professional commitment and job satisfaction. Intentions to leave the profession were strongly associated with variables related to the personal background and the work/home interface whereas intentions to leave the organization were related to organizational leadership and the local context.

Conclusion.  Retention initiatives should address the work‐home interface. Surveys assessing nursing turnover should be based on comprehensive turnover definitions, including different leaving directions.
The nurse practitioner role in pain management in long‐term care
Authors: Kaasalainen Sharon , Martin‐Misener Ruth , Carter Nancy , DiCenso Alba , Donald Faith , Baxter Pamela
Published: February 2010

kaasalainen s., martin‐misener r., carter n., dicenso a., donald f. & baxter p. (2010) The nurse practitioner role in pain management in long‐term care. Journal of Advanced Nursing66(3), 542–551.

Aim.  This paper is a report of a study exploring the perceptions of long‐term care team members and nurse managers about barriers and facilitators to optimal use of nurse practitioners to manage residents’ pain in long‐term care settings.

Background.  Considering the high rates of pain in long‐term care, research is needed to explore innovations in health‐services delivery, including the emerging nurse practitioner role.

Methods.  For this study, an exploratory descriptive design was used to collect data in spring 2007 from five focus groups of nurses and 14 individual interviews with other healthcare team members and nurse managers. Data were analysed using thematic content analysis.

Findings.  Five pain management activities performed by nurse practitioners were identified, including assessing pain, prescribing pain medications, monitoring pain levels and side effects of pain medications, consulting and advocating for staff and patients, and leading and educating staff related to pain management. Factors that influenced the implementation of the nurse practitioner role included the availability of the nurse practitioner, scope of practice, role clarity, perceived added value of nurse practitioner role, terms of employment, nurse practitioner–physician relationship. Perceived outcomes of the nurse practitioner role were also described.

Conclusions.  The findings from this study contribute to our understanding of how the nurse practitioner role is perceived by other healthcare professionals, particularly in pain management. Stronger interprofessional collaborative relationships need to be facilitated within a model of care that includes a nurse practitioner, with the ultimate goal of improving pain management services in long‐term care.
Keeping Vigil over the Patient: a grounded theory of nurse anaesthesia practice
Authors: Schreiber Rita , MacDonald Marjorie
Published: February 2010

schreiber r. & macdonald m. (2010) Keeping Vigil over the Patient: a grounded theory of nurse anaesthesia practice. Journal of Advanced Nursing66(3), 552–561.

Aim.  This paper is a report of a study exploring the role and practice of nurse anaesthetists, with particular attention to describing how it is ‘nursing’.

Background.  In many countries, there is no nurse anaesthetist role. Recent events suggest that hesitancy about the role may be changing in Canada. Yet, there is limited understanding in Canada about nurse anaesthesia, and many nurses do not believe it is nursing.

Method.  This grounded theory study involved theoretical and purposive sampling to gather data through: (i) participant observation and face‐to‐face interviews at the 75th annual American Association of Nurse Anesthetists convention in August, 2006, (ii) follow‐up telephone interviews and (iii) a 4‐day site visit to a small city in the west of the United States to observe anaesthetists in practice and working with students, visit an educational program, and conduct further interviews. Data collection and analysis were iterative and continued until saturation was reached in December, 2007.

Findings.  A basic social process of how nurse anaesthetists practise, Keeping Vigil over the Patient, was identified. Keeping Vigil over the Patient is comprised of four categories: Engaging with the Patient, Finessing the Human–Technology Interface, Massaging the Message and Foregrounding Nursing.

Conclusion.  Nursing was clearly evident in anaesthesia practice, reflecting a seamless integration of divergent ontological perspectives. Based on this examination, this role has considerable potential as a new advanced practice nursing role in countries where it has not yet been adopted.
The Disaster Preparedness Evaluation Tool©: psychometric testing of the Classical Arabic version
Authors: Al Khalaileh Murad A.A. , Bond A. Elaine , Beckstrand Renea L. , Al‐Talafha Abbas
Published: February 2010

al khalaileh m.a.a., bond a.e., beckstrand r.l. & al‐talafha a. (2010) The Disaster Preparedness Evaluation Tool©: psychometric testing of the Classical Arabic version. Journal of Advanced Nursing66(3), 664–672.

Aim.  This paper is a report of a study conducted to translate the Disaster Preparedness Evaluation Tool© into Arabic and to determine its psychometric properties, including reliability, validity and factorial structure.

Background.  Worldwide numbers of natural and man‐made disasters have greatly increased in recent years. Since disaster strikes without warning, all healthcare providers, especially nurses, must be prepared with appropriate skills and resources for disaster procedures and management during the three phases of disaster: pre disaster, during disaster and post disaster. Knowledge levels need to be evaluated to plan effective educational programmes.

Methods.  The Disaster Preparedness Evaluation Tool© was translated into Classical Arabic using Beaton’s guideline for translation and validated by experts and a pilot study with 20 Registered Nurses from the target population. Data were collected in 2008 using self‐administered questionnaires from 474 (79% return rate) Jordanian Registered Nurses who worked in randomly selected Ministry of Health hospitals and two university hospitals.

Results.  Principal component analysis (Promax rotation with Kaiser Normalization procedure, SPSS© version 15) was used to determined construct validity, and three factors explained 64% of the variance: knowledge, skills and post disaster management. Cronbach’s alpha was 0·90, which demonstrated internal consistency.

Conclusion.  These results support the reliability and validity of the Disaster Preparedness Evaluation Tool© as a measure of knowledge, skills and post disaster management. It can be used with confidence with an Arabic‐speaking nursing population to measure their preparedness for disasters. Based on the results of such studies, effective disaster preparedness programmes could be developed to enhance nurses’ disaster preparedness.