bluuebunny/crossref_metadata_2025 huggingface dataset:
Does training in motivational interviewing for community pharmacists improve outcomes for methadone patients? A cluster randomised controlled trial
Authors: Jaffray Mariesha , Matheson Catriona , Bond Christine M , Lee Amanda J , McLernon David J , Johnstone Allan , Skea Lucy , Davidson Bruce
Published: July 2013

Objectives

Feasibility of pharmacist delivered motivational interviewing (MI) to methadone patients has been demonstrated, but its efficacy is untested. This study aimed to determine whether pharmacists trained in MI techniques can improve methadone outcomes.

Methods

A cluster randomised controlled trial by pharmacy, with community pharmacies across Scotland providing supervised methadone to >10 daily patients, aged >18 years, started on methadone <24 months. Pharmacies were randomised to intervention or control. Intervention pharmacists received MI training and a resource pack. Control pharmacists continued with normal practice. Primary outcome was illicit heroin use. Secondary outcomes were treatment retention, substance use, injecting behaviour, psychological/physical health, treatment satisfaction and patient feedback. Data were collected via structured interviews at baseline and 6 months.

Key findings

Seventy-six pharmacies recruited 542 patients (295 intervention, 247 control), mean age 32 years; 64% male; 91% unemployed; mean treatment length 9 months. No significant difference in outcomes between groups for illicit heroin use (32.4% cf. 31.4%), although within-groups use reduced (P < 0.001); treatment retention was higher in the intervention group but not significantly (88% cf. 81%; P = 0.34); no significant difference between groups in treatment satisfaction, although this improved significantly in intervention (P < 0.05). More intervention than control patients said pharmacists had ‘spoken more,’ which approached statistical significance (P = 0.06), and more intervention patients found this useful (P < 0.05).

Conclusions

Limited intervention delivery may have reduced study power. The intervention did not significantly reduce heroin use, but there are indications of positive benefits from increased communication and treatment satisfaction.
Exploring nurses' and patients' perspectives of limit setting in a forensic mental health setting
Authors: Maguire Tessa , Daffern Michael , Martin Trish
Published: July 2013

Limit setting is an intervention that is frequently used by mental health nurses. However, limit setting is poorly conceptualized, its purpose is unclear, and there are few evidence‐based guidelines to assist nurses to set limits in a safe and effective manner. What is known is that the manner in which nurses set limits influences patients' perceptions of the interactions and their emotional and behavioural responses. In this qualitative study, 12 nurses and 12 patients participated in personal, semistructured interviews that aimed to explore limit setting and to propose principles to guide practice. The findings suggested that: (i) limit setting is important to safety in mental health hospitals; (ii) engaging patients in an empathic manner is necessary when setting limits (when nurses engage in an empathic manner, the therapeutic relationship is more likely to be preserved and the risk of aggressive responses is reduced); and (iii) an authoritative (fair, respectful, consistent, and knowledgeable), rather than authoritarian (controlling and indifferent), limit‐setting style enhances positive outcomes with regards to adherence, reduced likelihood of aggression, and preservation of the therapeutic relationship. In conclusion, a limit‐setting style characterized by empathic responding and an authoritative, rather than authoritarian interpersonal, style is recommended. Elucidating the components of this style is critical for effective training and best practice of mental health nurses, and to reduce aggressive responses from limit setting.
CHANGES IN WAIST CIRCUMFERENCE FOLLOWING HAEMODIALYSIS: A BRIEF REPORT
Authors: Parsons Trisha L. , Rombough Rosemarié E. , King‐VanVlack Cheryl E. , Toffelmire Edwin B.
Published: July 2013

Background

Waist circumference (WC) is a known indicator of cardiovascular disease in the haemodialysis (HD) population. However it is not known if HD results in clinically significant changes in WC.

Objective

The study purpose was to quantify the degree of change in WC induced by HD.

Methods

This was a prospective cohort study with 27 patients on HD. Height, body weight, WC, hip circumference (HC), body mass index (BMI) and waist to hip ratio (WHR) were measured immediately prior to and following HD over three consecutive treatments. Differences between three‐day average pre‐ and post‐HD weight, BMI, WC, HC and WHR were assessed.

Results

Post‐HD WC was significantly lower than that measured pre‐HD. Differences in pre‐post HD body weight, BMI, HC and WHR were also observed.

Conclusions

All of the traditional clinical indicators of body composition (WC, HC, WHR, body weight and BMI) were lower following HD.
Evaluation of passage of fetal erythrocytes into maternal circulation after invasive obstetric procedures
Authors: Meleti Daniela , De Oliveira Leandro Gustavo , Araujo Júnior Edward , Caetano Ana Carolina Rabachini , Boute Tatiane , Nardozza Luciano Marcondes Machado , Moron Antonio Fernandes
Published: July 2013

Aim 

The aim of this study was to evaluate the passage of fetal erythrocytes into the maternal circulation after invasive obstetric procedures, using the Kleihauer–Betke test, flow cytometry and α‐fetoprotein concentration in maternal blood.

Material and Methods

This was a prospective descriptive study on patients who underwent: amniocentesis, cordocentesis, chorionic villus sample, amniotic infusion, bladder drainage and ventricular–amniotic shunt to investigate the karyotype; treatment for hydrocephalus, oligohydramnios, obstructive uropathy and polyhydramnios; and investigation of lung maturity. Maternal blood samples were collected before and 60 min after the invasive obstetric procedure in order to evaluate the passage of fetal erythrocytes using the Kleihauer–Betke test, flow cytometry and α‐fetoprotein concentration.

Results

In total, 43 invasive obstetric procedures were performed. The procedures performed were: 27 cases of amniocentesis (62.7%), seven cases of cordocentesis (16.2%), four chorionic villus samples (9.4%), two amniotic infusions (4.7%), two ventricular–amniotic shunts and one bladder drainage (2.3%). After one case of cordocentesis with two puncture attempts via the placenta, a significant increase in fetal erythrocytes was detected using the three methods. After another cordocentesis with one puncture via the placenta, a significant increase in fetal erythrocytes was detected using flow cytometry and α‐fetoprotein concentration, but not through the Kleihauer–Betke test. The other 41 samples did not show any significant increase in fetal erythrocytes in the maternal blood.

Conclusion

Invasive obstetric procedures performed during prenatal care are safe when performed by experienced professionals with the proper technique, with minimal chance of passage of fetal erythrocytes into the maternal compartment.
Effect of feeding fine maize particles on the reticular pH, milk yield and composition of dairy cows
Authors: De Nardi R. , Marchesini G. , Stefani A.‐L. , Barberio A. , Andrighetto I. , Segato S.
Published: July 2013

The particle size of cereal grains has been found to modulate the rate of passage from the rumen and the digestibility of starch and neutral detergent fibre (NDF), but few studies have examined its impact on reticular pH. The study aimed to evaluate the effect of feeding finely ground maize on the risk of ruminal acidosis, milk yield and composition. Twelve Holstein‐Friesian cows were assigned to one of two experimental groups and fed according to a cross‐over design. Diets were isoenergetic and isonitrogenous and were characterised by the same NDF and ADF, differing only in maize particle size. In the control diet (Ct), the maize meal was ground to 1.0 mm, whereas in the experimental diet, it was finely ground (Fg) to 0.5 mm. The pH and temperature of the reticulum were continuously measured in eight cows throughout the trial using indwelling sensors. Dry matter intake was higher in cows offered Fg diet than in Ct (19.0 vs. 20.3 kg/day; p = 0.067). However, milk yield (p = 0.855) and the 3.5% fat‐corrected milk (FCM) (p = 0.724) did not show any differences between the diets. Casein (2.48 vs. 2.57%; p = 0.035) and crude protein (CP) (3.18 vs. 3.31%; p = 0.021) resulted higher in Fg. Similarly, starch digestibility increased in animals offered Fg diet versus Ct (0.94 vs. 0.98; p = 0.078). Among the reticular parameters, the Fg‐fed cows spent a significantly higher time below the 5.5 pH threshold (15 vs. 61 min/day; p = 0.047) and had an average daily variation in reticular pH characterised by a lower nadir pH (5.95 vs. 5.72; p < 0.001) and a higher pH range (0.79 vs. 0.94; p = 0.003). In this study, grain particle size affected the risk of the onset of ruminal acidosis. Therefore, it should be carefully considered when formulating rations.
Phylogenetic distribution of compatible solute synthesis genes support a freshwater origin for cyanobacteria
Authors: Blank Carrine E.
Published: July 2013

Previous work using ancestral state reconstruction of habitat salinity preference proposed that the early cyanobacteria likely lived in a freshwater environment. The aim of this study was to test that hypothesis by performing phylogenetic analyses of the genes underlying salinity preferences in the cyanobacteria. Phylogenetic analysis of compatible solute genes shows that sucrose synthesis genes were likely ancestral in the cyanobacteria, and were also likely inherited during the cyanobacterial endosymbiosis and into the photosynthetic algae and land plants. In addition, the genes for the synthesis of compatible solutes that are necessary for survival in marine and hypersaline environments (such as glucosylglycerol, glucosylglycerate, and glycine betaine) were likely acquired independently high up (i.e., more recently) in the cyanobacterial tree. Because sucrose synthesis is strongly associated with growth in a low salinity environment, this independently supports a freshwater origin for the cyanobacteria. It is also consistent with geologic evidence showing that the early oceans were much warmer and saltier than modern oceans—sucrose synthesis alone would have been insufficient for early cyanobacteria to have colonized early Precambrian oceans that had a higher ionic strength. Indeed, the acquisition of an expanded set of new compatible solute genes may have enabled the historical colonization of marine and hypersaline environments by cyanobacteria, midway through their evolutionary history.
Plant sexual systems correlated with morphological traits: Reflecting reproductive strategies of alpine plants
Authors: PENG De‐Li , OU Xiao‐Kun , XU Bo , ZHANG Zhi‐Qiang , NIU Yang , LI Zhi‐Min , SUN Hang
Published: July 2013

Plant sexual systems can be affected by various environmental factors, and thus show a range of morphological differences. The associations between plant sexual systems and morphology are unique, for example, the subnival belt of the Hengduan Mountains has harsh climatic conditions, but hosts remarkable biodiversity. However, these associations have received surprisingly little attention. We analyzed the associations in this region, and compared the pattern of sexual systems with that of other floras, and we also reviewed the breeding system of 36 alpine species. Information on plant sexual systems and these traits were mainly based on published information, herbarium collections, and field observations. The results showed that there was a high proportion of hermaphroditic species and a low proportion of dioecious and monoecious species. Hermaphroditism was strongly associated with showy floral displays, specialist entomophily, and perennial forbs. Dioecy was strongly associated with inconspicuous, pale‐colored flowers, anemophily, and shrubs, whereas monoecy was strongly associated with inconspicuous, pale‐colored flowers, generalist entomophily, and perennial grasses. Although no association was found between sexual systems and fruit type, plants with dry fruits (98.1%) were predominant in our study region. With respect to the plant breeding systems in the alpine region of southwest China, we predicted that pollination service might be particularly low; most of the plants lacked enough outcrossing pollinators. Our data revealed that 97.1% of the hermaphroditic species were self‐compatible, and 88.2% of them showed autonomous or facilitated selfing. The plant sexual systems identified might serve to optimize the probability of pollination and thus ensure reproductive success.
Concept analysis of concussion
Authors: Snedden Traci R.
Published: July 2013

Purpose

Concussion has been estimated to occur in 1.6–3.8 million adolescent athletes in the United States each year. However, because of conceptual ambiguity regarding its definition, the true incidence is estimated to be significantly higher. This article seeks to identify and support a single definition for the term concussion.

Conclusions

Defining attributes, antecedents, and consequences of concussion allow for a better understanding of this concept. Sample cases from pediatric clinical practice further clarify the concept as it applies to pediatric nursing.

Practice Implications

A clear definition has the potential to increase knowledge and recognition of concussion injury, leading to strategies that would decrease the risk of long‐term effects and devastating outcomes.
Labour Market Effects of Eastern European Migration in Wales
Authors: Lemos Sara
Published: July 2013

The enlargement of the European Union in May 2004 triggered a relatively large and rapid migration inflow into Wales which was concentrated into narrow districts and occupations. We found little evidence that the inflow of migrants contributed to a fall in wages or a rise in claimant unemployment in Wales between 2004 and 2006. In particular, we found no evidence of an adverse impact on young, female or low‐skilled claimant unemployment and no evidence of an adverse impact on the wages of the low‐paid.
Twin‐arginine translocation system (tat) mutants of Salmonella are attenuated due to envelope defects, not respiratory defects
Authors: Craig Maureen , Sadik Adam Y. , Golubeva Yekaterina A. , Tidhar Avital , Slauch James M.
Published: July 2013

The twin‐arginine translocation system (Tat) transports folded proteins across the cytoplasmic membrane and is critical to virulence in Salmonella and other pathogens. Experimental and bioinformatic data indicate that 30 proteins are exported via Tat in Salmonella Typhimurium. However, there are no data linking specific Tat substrates with virulence. We inactivated every Tat‐exported protein and determined the virulence phenotype of mutant strains. Although a tat mutant is highly attenuated, no single Tat‐exported substrate accounts for this virulence phenotype. Rather, the attenuation is due primarily to envelope defects caused by failure to translocate three Tat substrates, the N‐acetylmuramoyl‐l‐alanine amidases, AmiA and AmiC, and the cell division protein, SufI. Strikingly, neither the amiA amiC nor the sufI mutations alone conferred any virulence defect. Although AmiC and SufI have previously been localized to the divisome, the synthetic phenotypes observed are the first to suggest functional overlap. Many Tat substrates are involved in anaerobic respiration, but we show that a mutant completely deficient in anaerobic respiration retains full virulence in both the oral and systemic phases of infection. Similarly, an obligately aerobic mutant is fully virulent. These results suggest that in the classic mouse model of infection, S. Typhimurium is replicating only in aerobic environments.
High temperature causes negative whole‐plant carbon balance under mild drought
Authors: Zhao Junbin , Hartmann Henrik , Trumbore Susan , Ziegler Waldemar , Zhang Yiping
Published: July 2013

Theoretically, progressive drought can force trees into negative carbon (C) balance by reducing stomatal conductance to prevent water loss, which also decreases C assimilation. At higher temperatures, negative C balance should be initiated at higher soil moisture because of increased respiratory demand and earlier stomatal closure. Few data are available on how these theoretical relationships integrate over the whole plant.

We exposed Thuja occidentalis to progressive drought under three temperature conditions (15, 25, and 35°C), and measured C and water fluxes using a whole‐tree chamber design.

High transpiration rates at higher temperatures led to a rapid decline in soil moisture. During the progressive drought, soil moisture‐driven changes in photosynthesis had a greater impact on the whole‐plant C balance than respiration. The soil moisture content at which whole‐plant C balance became negative increased with temperature, mainly as a result of higher respiration rates and an earlier onset of stomatal closure under a warmer condition.

Our results suggest that the effect of drought on whole‐plant C balance is highly temperature‐dependent. High temperature causes a negative C balance even under mild drought and may increase the risk of C starvation.
Cardiac Device Complications in the Cognitively Impaired
Authors: JAMA ABDI , RABINSTEIN ALEJANDRO , HODGE DAVID , HERGES REGINA , ASIRVATHAM SAMUEL , CHA YONG‐MEI , POWELL BRIAN , REA ROBERT F. , FRIEDMAN PAUL
Published: July 2013

Background

Patients with preexisting mild cognitive impairment or dementia may be at increased risk for developing cardiac device complications due to an impaired ability to follow postimplant care instructions. We sought to determine whether rates of infection, lead dislodgement, or appropriate or inappropriate implantable cardioverter defibrillator (ICD) shocks are increased in this population.

Methods

Medical charts of 561 patients with mild cognitive impairment or dementia who underwent pacemaker (PM) or ICD implantation between January 2002 and October 2009 at Mayo Clinic were identified. A total of 134 patients who were diagnosed with cognitive impairment or dementia before device implantation or within 1 year of implantation were compared with 134 matched controls. Information was collected on patient characteristics, comorbid medical conditions, ejection fraction, complications, device type, device therapy, and mortality. Device information was prospectively entered into a database and retrospectively reviewed.

Results

Of the 134 patients with mild cognitive impairment and dementia, 99 underwent PM implantation and 35 underwent ICD implantation. Compared to controls, there was no difference in patient characteristics, ejection fraction, or comorbidities except for diabetes, which was more prevalent in the cognitively impaired and demented group (18.7% vs 30.6%, P = 0.02). There was no difference in device therapy and complications (14.4% vs 5.8%, P = 0.268). However, there was a decreased survival in patients with cognitive impairment and dementia when compared to the control group (42% vs 67% at 5 years, P = 0.007).

Conclusion

Patients with cognitive impairment and standard device indications are not at increased risk for device complications and therapy but their survival is much lower than in matched controls. The cause of this lower survival is unknown but may be related to the underlying neurological disease. Presence of cognitive impairment should therefore be considered when contemplating implantation of a cardiac device.
The Economic Security Index: A New Measure for Research and Policy Analysis
Authors: Hacker Jacob S. , Huber Gregory A. , Nichols Austin , Rehm Philipp , Schlesinger Mark , Valletta Rob , Craig Stuart
Published: July 2013

This article presents the Economic Security Index (ESI), a new measure of economic insecurity. TheESIassesses the individual‐level occurrence of substantial year‐to‐year declines in available household resources, accounting for fluctuations not only in income but also in out‐of‐pocket medical expenses. It also assesses whether those experiencing such declines have sufficient liquid financial wealth to buffer against these shocks. We find that insecurity—the share of individuals experiencing substantial resource declines without adequate financial buffers—has risen steadily since the mid‐1980s for virtually all subgroups ofAmericans, albeit with cyclical fluctuation. At the same time, we find that there is substantial disparity in the degree to which different subgroups are exposed to economic risk. As theESIderives from a data‐independent conceptual foundation, it can be measured using different panel datasets. We find that the degree and disparity by which insecurity has risen is robust across the best available sources.
Assessing the susceptibility of alpine soils to erosion using soil physical and site indicators
Authors: Stanchi S. , Freppaz M. , Godone D. , Zanini E.
Published: July 2013

Soil erosion in mountainous regions is a key issue in land use planning, and this is particularly true in the Alps where intense anthropogenic influences at low elevations and abandonment in higher regions often coexist to affect soils. Natural hazard and risk assessment are essential given the density of settlements and associated facilities. Soil loss due to water erosion is very common and is becoming more frequent as a consequence of climate change which affects precipitation regimes, frequency of extreme meteorological events, snow melt and vegetation. In this study, we describe the production of a map showing susceptibility to soil erosion in the Aosta Valley (northwest Italian Alps). Most research on slope instability has focused on rock failures, but we investigated upper soil horizons by analysing chemical and physical properties, which could contribute to slope instability. The steps involved in creating the map are explained, and these involved GIS overlay, sampling, soil description, selection of relevant chemical and physical indicators of soil susceptibility to erosion, and overall erosion susceptibility assessment. The resultant indicator values correspond well with field observations to thus validate the methodology and demonstrate its usefulness in land use planning and management in Alpine areas.
HCCI Operability Limits: The Impact of Refinery Stream Gasoline Property Variation
Authors: Lacey Joshua S. , Filipi Zoran S. , Sathasivam Sakthish R. , Cannella William J. , Fuentes-Afflick Peter A.
Published: July 2013

Homogeneous charge compression ignition (HCCI) combustion is highly dependent on in-cylinder thermal conditions favorable to autoignition, for a given fuel. Fuels available at the pump can differ considerably in composition and autoignition chemistry; hence strategies intended to bring HCCI to market must account for the fuel variability. To this end, a test matrix consisting of eight gasoline fuels composed of blends made solely from refinery streams was investigated in an experimental, single cylinder HCCI engine. The base compositions were largely representative of gasoline one would expect to find across the United States, although some of the fuels had slightly lower average octane values than the ASTM minimum specification of 87. All fuels had 10% ethanol by volume included in the blend. The properties of the fuels were varied according to research octane number (RON), sensitivity (S=RON-MON) and the volumetric fractions of aromatics and olefins. For each fuel, a sweep of the fuelling was carried out at each speed from the level of instability to excessive ringing to determine the limits of HCCI operation. This was repeated for a range of speeds to determine the overall operability zone. The fuels were kept at a constant intake air temperature during these tests. The variation of fuel properties brought about changes in the overall operating range of each fuel, as some fuels had more favorable low load limits, whereas others enabled more benefit at the high load limit. The extent to which the combustion event changed from the low load limit to the high load limit was examined as well, to provide a relative criterion indicating the sensitivity of HCCI range to particular fuel properties.
Evaluation of Single-Use Radio Attenuating Gloves: From Technical Data to Clinical Practice
Authors: Nguyen-Kim L. , Beaussier H. , Fargeot C. , Payen S. , Chiras J.
Published: July 2013

Single-use radio-attenuating gloves are devices protecting the operator's hand by reducing the exposition to scattered radiations during radiological-guided intervention. Expensive, these devices are important, as they contribute to lessen the annual dose to which personals are exposed to. However, inconsistencies in their protection value have been reported between theoretical and clinical practice. In this study, we aim to highlight the normative bias existing in standard norms for radioprotective assessments. Using thermoluminescent captors positioned inside and outside the glove, we designed an EN1331-1 norm-inspired bench test with five brands of radio-attenuating gloves. At 100 keV and 56 cm away from the source, we measured indirect beam and attenuated doses in a clinical setting. From the attenuation index measured, we deduced attenuation rates. We then compared our results to their commercial technical data sheets. The assessed attenuating rates of the tested references were 20%, 30%, 32%, 15%, and 25%. Theoretical rates are, respectively, 38%, 43%, 30%, 26%, and 35%. Only one reference showed no difference between commercial and technical attenuating values (p = 0.12). The inconsistencies between observed and theoretical attenuation value show the importance of the conditions in which protection is assessed. Without complete information, the choice of a protective device as simple as a glove is biased, and this may lead to inappropriate protection of the operator, which should raise concern, as interventional radiology is now widespread in routine practice.
Response Probability Analysis of Random Acoustic Field Based on Perturbation Stochastic Method and Change-of-Variable Technique
Authors: Xia Baizhan , Yu Dejie
Published: July 2013

To calculate the probability density function of the response of a random acoustic field, a change-of-variable perturbation stochastic finite element method (CVPSFEM), which integrates the perturbation stochastic finite element method (PSFEM) and the change-of-variable technique in a unified form, is proposed. In the proposed method, the response of a random acoustic field is approximated as a linear function of the random variables based on a first order stochastic perturbation analysis. According to the linear relationship between the response and the random variables, the formal expression of the probability density function of the response of a random acoustic field is obtained by the change-of-variable technique. The numerical examples on a two-dimensional (2D) acoustic tube and a three-dimensional (3D) acoustic cavity of an automobile cabin verify the accuracy and efficiency of the proposed method. Hence, the proposed method can be considered as an effective method to quantify the effects of the parametric randomness of a random acoustic field on the sound pressure response.
Modeling of Direct Methanol Fuel Cell Using the Artificial Neural Network
Authors: Tafazoli Mehdi , Baseri Hamid , Alizadeh Ebrahim , Shakeri Mohsen
Published: July 2013

The performance of a direct methanol fuel cell (DMFC) has complex nonlinear characteristics. In this paper, the performance of a DMFC has been modeled using a neural network approach. The input parameters of the DMFC model include cell geometrical and operational parameters such as the cell temperature, oxygen flow rate, channel depth of the bipolar plate, methanol concentration, cathode back pressure, and current density and the output parameter is the cell voltage. In order to predict the performance of a DMFC single cell, two types of artificial neural network (ANN) have been developed to correlate the input parameters of the DMFC to the cell voltage. The performance of the networks was investigated by varying the number of neurons, number of layers, and transfer function of the ANNs and the best one is selected based on the mean square error. The results indicated that the neural network models can predict the cell voltage with an acceptable accuracy.
Signatures of Cool Gas Fueling a Star-Forming Galaxy at Redshift 2.3
Authors: Bouché N. , Murphy M. T. , Kacprzak G. G. , Péroux C. , Contini T. , Martin C. L. , Dessauges-Zavadsky M.
Published: July 2013

Cool Accretion

Numerical models predict that in order to keep forming stars, galaxies should be continuously replenished with gas from the intergalactic medium. Using data from the Very Large Telescope in Chile,

Bouché
et al.

(p.
50
) report observations that are consistent with accretion of cold, chemically pristine gas onto a star-forming galaxy at a time when the cosmic star-formation activity was at its peak.
Radio Bursts, Origin Unknown
Authors: Cordes James M.
Published: July 2013

Observations of radio bursts that appear to originate from outside the Milky Way may suggest the existence of a large and exotic source population.

[Also see Report by

Thornton
et al.

]
Building Better Institutions
Authors: Nurse Paul , Treisman Richard , Smith Jim
Published: July 2013

What is the best way to promote innovative research? How can we build research institutions of the future that will promote cross-disciplinary interactions among young creative minds? Despite the recent growth in scientific knowledge, conventional disciplinebased methods have not been sufficiently effective at developing new understanding and treatments. Researchers need to be encouraged to identify important questions and tackle them with multidisciplinary approaches. Contemporary biomedical research has to integrate biological, nonbiological, and clinical disciplines, and its application requires interactions with hospital and commercial partners. This can be facilitated by research institutions with an environment that supports strong interdisciplinary interactions between scientists: a place where laboratory biologists are encouraged to collaborate with clinical researchers to understand the medical implications of their work, with pharmaceutical companies for the translation of discoveries into treatments, and with physical scientists to expand their thinking and repertoire of experimental approaches. Such an institution must be continually open to new ideas and permeable to interactions with outside researchers and organizations.
New Law Would Dilute and Diminish Science Academy
Authors: Pokrovsky Vladimir
Published: July 2013

Last week, Russia's science minister unveiled a draft law that would merge the Russian Academy of Sciences with two other science academies, strip it of control of its extensive real estate holdings, and abolish any distinction between full-fledged academicians and members of a lower rank.
At Long Last, Europe's Mega R&D Program Comes Into Focus
Authors: Rabesandratana Tania , Vogel Gretchen
Published: July 2013

Last week, leaders of the European Union agreed on a budget and rules for the next continent-wide R&D program, Horizon 2020, slated to get €70.2 billion from 2014 to 2020.
Solution to Vaccine Mystery Starts to Crystallize
Authors: Leslie Mitch
Published: July 2013

For 80 years, people have received injections of alum as part of vaccines, but only recently have researchers begun to explain how the compound helps stimulate immunity
Mitogen-Activated Protein Kinase Phosphatase 1 Disrupts Proinflammatory Protein Synthesis in Endotoxin-Adapted Monocytes
Authors: Brudecki Laura , Ferguson Donald A. , McCall Charles E. , El Gazzar Mohamed
Published: July 2013

Autotoxic production of proinflammatory mediators during early sepsis induces excessive inflammation, and their later suppression may limit the immune response. We previously reported that sepsis differentially represses transcription and translation of tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) to reprogram sepsis inflammation. This switch is gene specific and plays a crucial role in the clinically relevant syndrome of endotoxin adaptation/tolerance, multiorgan failure, and poor sepsis outcome. To further define the mechanisms responsible for translation disruption that follows inflammation induction, we used THP-1 human promonocytes as a model of Toll-like receptor 4 (TLR4) responses found in sepsis. We showed that phosphorylation-dependent activation of p38 mitogen-activated protein kinase (MAPK) and translation disruption of TNF-α and IL-6 follow increased MAPK phosphatase 1 (MKP-1) expression and that MKP-1 knockdown rephosphorylates p38 and restores the capacity to translate TNF-α and IL-6 mRNAs. We also observed that the RNA-binding protein motif 4 (RBM4), a p38 MAPK target, accumulates in an unphosphorylated form in the cytosol in endotoxin-adapted cells, suggesting that dephosphorylated RBM4 may function as a translational repressor. Moreover, MKP-1 knockdown promotes RBM4 phosphorylation, blocks its transfer from the nucleus to the cytosol, and reverses translation repression. We also found that microRNA 146a (miR-146a) knockdown prevents and miR-146a transfection induces MKP-1 expression, which lead to increases or decreases in TNF-α and IL-6 translation, respectively. We conclude that a TLR4-, miR-146a-, p38 MAPK-, and MKP-1-dependent autoregulatory pathway regulates the translation of proinflammatory genes during the acute inflammatory response by spatially and temporally modifying the phosphorylation state of RBM4 translational repressor protein.
Cks1 Enhances Transcription Efficiency at the
GAL1
Locus by Linking the Paf1 Complex to the 19S Proteasome
Authors: Pan Yen-Ru , Sun Michael , Wohlschlegel James , Reed Steven I.
Published: July 2013

Cks1 was originally identified based on genetic interactions with
CDC28
, the gene that encodes Cdk1 in the budding yeast
Saccharomyces cerevisiae
. Subsequent work has shown that Cks1 binds Cdc28 and modulates its activity against certain substrates. However, the Cks1/Cdc28 complex also has a role in transcriptional chromatin remodeling not related to kinase activity. In order to elucidate protein networks associated with Cks1 transcriptional functions, proteomic analysis was performed on immunoaffinity-purified Cks1, identifying a physical interaction with the Paf1 complex. Specifically, we found that the Paf1 complex component Rtf1 interacts directly with Cks1 and that this interaction is essential for efficient recruitment of Cks1 to chromatin in the context of
GAL1
gene induction. We further found that Cks1 in this capacity serves as an adaptor allowing Rtf1 to recruit 19S proteasome particles, shown to be required for efficient RNA production from some rapidly inducible genes such as
GAL1
.
A Literature Review of Laboratory-Acquired Brucellosis
Authors: Traxler Rita M. , Lehman Mark W. , Bosserman Elizabeth A. , Guerra Marta A. , Smith Theresa L.
Published: July 2013

Brucellosis is a bacterial zoonotic disease which has been associated with laboratory-acquired infections. No recent reviews have addressed the characteristics of laboratory-acquired brucellosis (LAB). English-language literature was reviewed to identify reports of laboratory exposures toBrucellaspp. and LAB cases between 1982 and 2007. Evaluation of 28 case reports identified 167 potentially exposed laboratory workers, of whom 71 had LAB. Nine reports were identified that summarized an additional 186 cases of LAB. Only 18 (11%) exposures were due to laboratory accidents, 147 (88%) exposures were due to aerosolization of organisms during routine identification activities, and the circumstances of 2 (1%) exposures were unknown.Brucella melitensiswas the causative agent in 80% (135/167) of the exposures. Workers with high-risk exposures were 9.3 times more likely to develop LAB than workers with low-risk exposures (95% confidence interval [CI], 3.0 to 38.6;P< 0.0001); they were also 0.009 times likelier to develop LAB if they took antimicrobial PEP than if they did not (95% CI, 0 to 0.042;P< 0.0001). The median incubation period in case and summary reports was 8 weeks (range 1 to 40 weeks). Antimicrobial PEP is effective in preventing LAB. The incubation period may be used to identify appropriate serological and symptom surveillance time frames for exposed laboratory workers.
Review of Brucellosis Cases from Laboratory Exposures in the United States in 2008 to 2011 and Improved Strategies for Disease Prevention
Authors: Traxler R. M. , Guerra M. A. , Morrow M. G. , Haupt T. , Morrison J. , Saah J. R. , Smith C. G. , Williams C. , Fleischauer A. T. , Lee P. A. , Stanek D. , Trevino-Garrison I. , Franklin P. , Oakes P. , Hand S. , Shadomy S. V. , Blaney D. D. , Lehman M. W. , Benoit T. J. , Stoddard R. A. , Tiller R. V. , De B. K. , Bower W. , Smith T. L.
Published: July 2013

Five laboratory-acquired brucellosis (LAB) cases that occurred in the United States between 2008 and 2011 are presented. The Centers for Disease Control and Prevention (CDC) reviewed the recommendations published in 2008 and the published literature to identify strategies to further prevent LAB. The improved prevention strategies are described.
Flaviviruses Are Sensitive to Inhibition of Thymidine Synthesis Pathways
Authors: Fischer Matthew A. , Smith Jessica L. , Shum David , Stein David A. , Parkins Christopher , Bhinder Bhavneet , Radu Constantin , Hirsch Alec J. , Djaballah Hakim , Nelson Jay A. , Früh Klaus
Published: July 2013

Dengue virus has emerged as a global health threat to over one-third of humankind. As a positive-strand RNA virus, dengue virus relies on the host cell metabolism for its translation, replication, and egress. Therefore, a better understanding of the host cell metabolic pathways required for dengue virus infection offers the opportunity to develop new approaches for therapeutic intervention. In a recently described screen of known drugs and bioactive molecules, we observed that methotrexate and floxuridine inhibited dengue virus infections at low micromolar concentrations. Here, we demonstrate that all serotypes of dengue virus, as well as West Nile virus, are highly sensitive to both methotrexate and floxuridine, whereas other RNA viruses (Sindbis virus and vesicular stomatitis virus) are not. Interestingly, flavivirus replication was restored by folinic acid, a thymidine precursor, in the presence of methotrexate and by thymidine in the presence of floxuridine, suggesting an unexpected role for thymidine in flavivirus replication. Since thymidine is not incorporated into RNA genomes, it is likely that increased thymidine production is indirectly involved in flavivirus replication. A possible mechanism is suggested by the finding that p53 inhibition restored dengue virus replication in the presence of floxuridine, consistent with thymidine-less stress triggering p53-mediated antiflavivirus effects in infected cells. Our data reveal thymidine synthesis pathways as new and unexpected therapeutic targets for antiflaviviral drug development.
CD8
+
T-Cell Epitope Mapping for Pneumonia Virus of Mice in H-2
b
Mice
Authors: Walsh Kevin B. , Sidney John , Welch Megan , Fremgen Daniel M. , Sette Alessandro , Oldstone Michael B. A.
Published: July 2013

The paramyxovirus pneumonia virus of mice (PVM) is a rodent model of human respiratory syncytial virus (hRSV) pathogenesis. Here we characterized the PVM-specific CD8
+
T-cell repertoire in susceptible C57BL/6 mice. In total, 15 PVM-specific CD8
+
T-cell epitopes restricted by H-2D
b
and/or H-2K
b
were identified. These data open the door for using widely profiled, genetically manipulated C57BL/6 mice to study the contribution of epitope-specific CD8
+
T cells to PVM pathogenesis.
Epstein-Barr Virus-Encoded BARF1 Promotes Proliferation of Gastric Carcinoma Cells through Regulation of NF-κB
Authors: Chang Mee Soo , Kim Dong Ha , Roh Jin Kyung , Middeldorp Jaap M. , Kim Yang Soo , Kim Sunghan , Han Seungbong , Kim Chul Woo , Lee Byung Lan , Kim Woo Ho , Woo Jun Hee
Published: July 2013

In Epstein-Barr virus (EBV)-infected gastric carcinoma, EBV-encoded BARF1 has been hypothesized to function as an oncogene. To evaluate cellular changes induced by BARF1, we isolated the full-length
BARF1
gene from gastric carcinoma cells that were naturally infected with EBV and transfected
BARF1
into EBV-negative gastric carcinoma cells. BARF1 protein was primarily secreted into culture supernatant and only marginally detectable within cells. Compared with gastric carcinoma cells containing empty vector, BARF1-expressing gastric carcinoma cells exhibited increased cell proliferation (
P
< 0.05). There were no significant differences in apoptosis, invasion, or migration between BARF1-expressing gastric carcinoma cells and empty vector-transfected cells. BARF1-expressing gastric carcinoma cells demonstrated increased nuclear expression of nuclear factor kappa B (NF-κB) RelA protein and increased NF-κB-dependent cyclin D1. The expression of p21
WAF1
was diminished by BARF1 transfection and increased by NF-κB inhibition. Proliferation of naturally EBV-infected gastric carcinoma cells was suppressed by BARF1 small interfering RNA (siRNA) (
P
< 0.05). Immunohistochemical analysis of 120 human gastric carcinoma tissues demonstrated increased expression of cyclin D1 and reduced expression of p21
WAF1
in EBV-positive samples versus EBV-negative gastric carcinomas (
P
< 0.05). In conclusion, the secreted BARF1 may stimulate proliferation of EBV-infected gastric carcinoma cells via upregulation of NF-κB/cyclin D1 and reduction of the cell cycle inhibitor p21
WAF1
, thereby facilitating EBV-induced cancer progression.
High Production Rates Sustain
In Vivo
Levels of PD-1
high
Simian Immunodeficiency Virus-Specific CD8 T Cells in the Face of Rapid Clearance
Authors: Petrovas Constantinos , Yamamoto Takuya , Price David A. , Rao Srinivas S. , Klatt Nichole R. , Brenchley Jason M. , Douek Daniel C. , Gostick Emma , Angermann Bastian R. , Grossman Zvi , Macallan Derek C. , Meier-Schellersheim Martin , Koup Richard A.
Published: July 2013

Programmed Death 1 (PD-1) expression by human/simian immunodeficiency virus (HIV/SIV)-specific CD8 T cells has been associated with defective cytokine production and reduced
in vitro
proliferation capacity. However, the cellular mechanisms that sustain PD-1
high
virus-specific CD8 T cell responses during chronic infection are unknown. Here, we show that the PD-1
high
phenotype is associated with accelerated
in vivo
CD8 T cell turnover in SIV-infected rhesus macaques, especially within the SIV-specific CD8 T cell pool. Mathematical modeling of 5-bromo-2′ deoxyuridine (BrdU) labeling dynamics demonstrated a significantly increased generation rate of PD-1
high
compared to PD-1
low
CD8 T cells in all memory compartments. Simultaneous analysis of Ki67 and BrdU kinetics revealed a complex
in vivo
turnover profile whereby only a small fraction of PD-1
high
cells, but virtually all PD-1
low
cells, returned to rest after activation. Similar kinetics operated in both chronic and acute SIV infection. Our data suggest that the persistence of PD-1
high
SIV-specific CD8 T cells in chronic infection is maintained
in vivo
by a mechanism involving high production coupled with a high disappearance rate.
Efficacy in Pigs of Inactivated and Live Attenuated Influenza Virus Vaccines against Infection and Transmission of an Emerging H3N2 Similar to the 2011-2012 H3N2v
Authors: Loving Crystal L. , Lager Kelly M. , Vincent Amy L. , Brockmeier Susan L. , Gauger Phillip C. , Anderson Tavis K. , Kitikoon Pravina , Perez Daniel R. , Kehrli Marcus E.
Published: July 2013

Vaccines provide a primary means to limit disease but may not be effective at blocking infection and pathogen transmission. The objective of the present study was to evaluate the efficacy of commercial inactivated swine influenza A virus (IAV) vaccines and experimental live attenuated influenza virus (LAIV) vaccines against infection with H3N2 virus and subsequent indirect transmission to naive pigs. The H3N2 virus evaluated was similar to the H3N2v detected in humans during 2011-2012, which was associated with swine contact at agricultural fairs. One commercial vaccine provided partial protection measured by reduced nasal shedding; however, indirect contacts became infected, indicating that the reduction in nasal shedding did not prevent aerosol transmission. One LAIV vaccine provided complete protection, and none of the indirect-contact pigs became infected. Clinical disease was not observed in any group, including nonvaccinated animals, a consistent observation in pigs infected with contemporary reassortant H3N2 swine viruses. Serum hemagglutination inhibition antibody titers against the challenge virus were not predictive of efficacy; titers following vaccination with a LAIV that provided sterilizing immunity were below the level considered protective, yet titers in a commercial vaccine group that was not protected were above that level. While vaccination with currently approved commercial inactivated products did not fully prevent transmission, certain vaccines may provide a benefit by limitating shedding, transmission, and zoonotic spillover of antigenically similar H3N2 viruses at agriculture fairs when administered appropriately and used in conjunction with additional control measures.
Structural Characterization of Cleaved, Soluble HIV-1 Envelope Glycoprotein Trimers
Authors: Khayat Reza , Lee Jeong Hyun , Julien Jean-Philippe , Cupo Albert , Klasse Per Johan , Sanders Rogier W. , Moore John P. , Wilson Ian A. , Ward Andrew B.
Published: July 2013

Human immunodeficiency virus type 1 (HIV-1) infection is a significant global public health problem for which development of an effective prophylactic vaccine remains a high scientific priority. Many concepts for a vaccine are focused on induction of appropriate titers of broadly neutralizing antibodies (bNAbs) against the viral envelope (Env) glycoproteins gp120 and gp41, but no immunogen has yet accomplished this goal in animals or humans. One approach to induction of bNAbs is to design soluble, trimeric mimics of the native viral Env trimer. Here, we describe structural studies by negative-stain electron microscopy of several variants of soluble Env trimers based on the KNH1144 subtype A sequence. These Env trimers are fully cleaved between the gp120 and gp41 components and stabilized by specific amino acid substitutions. We also illustrate the structural consequences of deletion of the V1/V2 and V3 variable loops from gp120 and the membrane-proximal external region (MPER) from gp41. All of these variants adopt a trimeric configuration that appropriately mimics native Env spikes, including the CD4 receptor-binding site and the epitope for the VRC PG04 bNAb. These cleaved, soluble trimer designs can be adapted for use with multiple different
env
genes for both vaccine and structural studies.
Identification of a Novel Subgroup of Koala Retrovirus from Koalas in Japanese Zoos
Authors: Shojima Takayuki , Yoshikawa Rokusuke , Hoshino Shigeki , Shimode Sayumi , Nakagawa So , Ohata Takuji , Nakaoka Rie , Miyazawa Takayuki
Published: July 2013

We identified a new subgroup of koala retrovirus (KoRV), named KoRV-J, which utilizes thiamine transport protein 1 as a receptor instead of the Pit-1 receptor used by KoRV (KoRV-A). By subgroup-specific PCR, KoRV-J and KoRV-A were detected in 67.5 and 100% of koalas originating from koalas from northern Australia, respectively. Altogether, our results indicate that the invasion of the koala population by KoRV-J may have occurred more recently than invasion by KoRV-A.