bluuebunny/crossref_metadata_2025 huggingface dataset:
Aggregation Interplay between Variants of the RepA-WH1 Prionoid in Escherichia coli
Authors: Molina-García Laura , Giraldo Rafael
Published: May 2014

The N-terminal domain (winged-helix domain, or WH1) of the
Pseudomonas
pPS10 plasmid DNA replication protein RepA can assemble into amyloid fibers
in vitro
and, when expressed in
Escherichia coli
, leads to a unique intracellular amyloid proteinopathy by hampering bacterial proliferation. RepA-WH1 amyloidosis propagates along generations through the transmission of aggregated particles across the progeny, but it is unable to propagate horizontally as an infectious agent and is thus the first synthetic bacterial prionoid. RepA-WH1 amyloidosis is promoted by binding to double-stranded DNA (dsDNA)
in vitro
, and it is modulated by the Hsp70 chaperone DnaK
in vivo
. Different mutations in the
repA
-WH1 gene result in variants of the protein with distinct amyloidogenic properties. Here, we report that intracellular aggregates of the hyperamyloidogenic RepA with an A31V change in WH1 [RepA-WH1(A31V)] are able to induce and enhance the growth
in vivo
of new amyloid particles from molecules of wild-type RepA-WH1 [RepA-WH1(WT)], which otherwise would remain soluble in the cytoplasm. In contrast, RepA-WH1(ΔN37), a variant lacking a clear amyloidogenic sequence stretch that aggregates as conventional inclusion bodies (IBs), can drive the aggregation of the soluble protein into IBs only if expressed at high molar ratios over RepA-WH1(WT). The cytotoxic bacterial intracellular prionoid RepA-WH1 thus exhibits a hallmark feature of amyloids, as characterized in eukaryotes: cross-aggregation between variants of the same protein.
Effects of (p)ppGpp on the Progression of the Cell Cycle of Caulobacter crescentus
Authors: Gonzalez Diego , Collier Justine
Published: May 2014

Bacteria must control the progression of their cell cycle in response to nutrient availability. This regulation can be mediated by guanosine tetra- or pentaphosphate [(p)ppGpp], which are synthesized by enzymes of the RelA/SpoT homologue (Rsh) family, particularly under starvation conditions. Here, we study the effects of (p)ppGpp on the cell cycle of
Caulobacter crescentus
, an oligotrophic bacterium with a dimorphic life cycle.
C. crescentus
divides asymmetrically, producing a motile swarmer cell that cannot replicate its chromosome and a sessile stalked cell that is replication competent. The swarmer cell rapidly differentiates into a stalked cell in appropriate conditions. An artificial increase in the levels of (p)ppGpp in nonstarved
C. crescentus
cells was achieved by expressing a truncated
relA
gene from
Escherichia coli
, encoding a constitutively active (p)ppGpp synthetase. By combining single-cell microscopy, flow cytometry approaches, and swarming assays, we show that an increase in the intracellular concentration of (p)ppGpp is sufficient to slow down the swarmer-to-stalked cell differentiation process and to delay the initiation of chromosome replication. We also present evidence that the intracellular levels of two master regulators of the cell cycle of
C. crescentus
, DnaA and CtrA, are modulated in response to (p)ppGpp accumulation, even in the absence of actual starvation. CtrA proteolysis and DnaA synthesis seem indirectly inhibited by (p)ppGpp accumulation. By extending the life span of the motile nonreproductive swarmer cell and thus promoting dispersal and foraging functions over multiplication under starvation conditions, (p)ppGpp may play a central role in the ecological adaptation of
C. crescentus
to nutritional stresses.
Expression of Each Cistron in the
gal
Operon Can Be Regulated by Transcription Termination and Generation of a
galK
-Specific mRNA, mK2
Authors: Wang Xun , Ji Sang Chun , Yun Sang Hoon , Jeon Heung Jin , Kim Si Wouk , Lim Heon M.
Published: May 2014

The
gal
operon of
Escherichia coli
has 4 cistrons,
galE
,
galT
,
galK
, and
galM
. In our previous report (H. J. Lee, H. J. Jeon, S. C. Ji, S. H. Yun, H. M. Lim, J. Mol. Biol.
378:
318–327, 2008), we identified 6 different mRNA species, mE1, mE2, mT1, mK1, mK2, and mM1, in the
gal
operon and mapped these mRNAs. The mRNA map suggests a gradient of gene expression known as natural polarity. In this study, we investigated how the mRNAs are generated to understand the cause of natural polarity. Results indicated that mE1, mT1, mK1, and mM1, whose 3′ ends are located at the end of each cistron, are generated by transcription termination. Since each transcription termination is operating with a certain frequency and those 4 mRNAs have 5′ ends at the transcription initiation site(s), these transcription terminations are the basic cause of natural polarity. Transcription terminations at
galE-galT
and
galT-galK
junctions, making mE1 and mT1, are Rho dependent. However, the terminations to make mK1 and mM1 are partially Rho dependent. The 5′ ends of mK2 are generated by an endonucleolytic cleavage of a pre-mK2 by RNase P, and the 3′ ends are generated by Rho termination 260 nucleotides before the end of the operon. The 5′ portion of pre-mK2 is likely to become mE2. These results also suggested that
galK
expression could be regulated through mK2 production independent from natural polarity.
Streptococcus pyogenes Polymyxin B-Resistant Mutants Display Enhanced ExPortal Integrity
Authors: Port Gary C. , Vega Luis A. , Nylander Andrew B. , Caparon Michael G.
Published: May 2014

The ExPortal protein secretion organelle in
Streptococcus pyogenes
is an anionic phospholipid-containing membrane microdomain enriched in Sec translocons and postsecretion protein biogenesis factors. Polymyxin B binds to and disrupts ExPortal integrity, resulting in defective secretion of several toxins. To gain insight into factors that influence ExPortal organization, a genetic screen was conducted to select for spontaneous polymyxin B-resistant mutants displaying enhanced ExPortal integrity. Whole-genome resequencing of 25 resistant mutants revealed from one to four mutations per mutant genome clustered primarily within a core set of 10 gene groups. Construction of mutants with individual deletions or insertions demonstrated that 7 core genes confer resistance and enhanced ExPortal integrity through loss of function, while 3 were likely due to gain of function and/or combinatorial effects. Core resistance genes include a transcriptional regulator of lipid biosynthesis, several genes involved in nutrient acquisition, and a variety of genes involved in stress responses. Two members of the latter class also function as novel regulators of the secreted SpeB cysteine protease. Analysis of the most frequently isolated mutation, a single nucleotide deletion in a track of 9 consecutive adenine residues in
pstS
, encoding a component of a high-affinity P
i
transporter, suggests that this sequence functions as a molecular switch to facilitate stress adaptation. Together, these data suggest the existence of a membrane stress response that promotes enhanced ExPortal integrity and resistance to cationic antimicrobial peptides.
NtrBC and Nac Contribute to Efficient Shigella flexneri Intracellular Replication
Authors: Waddell Chelsea D. , Walter Thomas J. , Pacheco Sophia A. , Purdy Georgiana E. , Runyen-Janecky Laura J.
Published: May 2014

Shigella flexneritwo-component regulatory systems (TCRS) are responsible for sensing changes in environmental conditions and regulating gene expression accordingly. We examined 12 TCRS that were previously uncharacterized for potential roles inS. flexnerigrowth within the eukaryotic intracellular environment. We demonstrate that the TCRS EvgSA, NtrBC, and RstBA systems are required for wild-type plaque formation in cultured epithelial cells. The phenotype of the NtrBC mutant depended in part on the Nac transcriptional regulator. Microarray analysis was performed to identifyS. flexnerigenes differentially regulated by the NtrBC system or Nac in the intracellular environment. This study contributes to our understanding of the transcriptional regulation necessary forShigellato effectively adapt to the mammalian host cell.
A Putative Bifunctional Histidine Kinase/Phosphatase of the HWE Family Exerts Positive and Negative Control on the Sinorhizobium meliloti General Stress Response
Authors: Sauviac Laurent , Bruand Claude
Published: May 2014

The EcfG-type sigma factor RpoE2 is the regulator of the general stress response in
Sinorhizobium meliloti
. RpoE2 activity is negatively regulated by two NepR-type anti-sigma factors (RsiA1/A2), themselves under the control of two anti-anti-sigma factors (RsiB1/B2) belonging to the PhyR family of response regulators. The current model of RpoE2 activation suggests that in response to stress, RsiB1/B2 are activated by phosphorylation of an aspartate residue in their receiver domain. Once activated, RsiB1/B2 become able to interact with the anti-sigma factors and release RpoE2, which can then associate with the RNA polymerase to transcribe its target genes. The purpose of this work was to identify and characterize proteins involved in controlling the phosphorylation status of RsiB1/B2. Using
in vivo
approaches, we show that the putative histidine kinase encoded by the
rsiC
gene (SMc01507), located downstream from
rpoE2
, is able to both positively and negatively regulate the general stress response. In addition, our data suggest that the negative action of RsiC results from inhibition of RsiB1/B2 phosphorylation. From these observations, we propose that RsiC is a bifunctional histidine kinase/phosphatase responsible for RsiB1/B2 phosphorylation or dephosphorylation in the presence or absence of stress, respectively. Two proteins were previously proposed to control PhyR phosphorylation in
Caulobacter crescentus
and
Sphingomonas
sp. strain FR1. However, these proteins contain a Pfam:HisKA_2 domain of dimerization and histidine phosphotransfer, whereas
S. meliloti
RsiC harbors a Pfam:HWE_HK domain instead. Therefore, this is the first report of an HWE_HK-containing protein controlling the general stress response in
Alphaproteobacteria
.
The Terminal Oxidase
cbb
3
Functions in Redox Control of Magnetite Biomineralization in Magnetospirillum gryphiswaldense
Authors: Li Yingjie , Raschdorf Oliver , Silva Karen T. , Schüler Dirk
Published: May 2014

The biomineralization of magnetosomes in
Magnetospirillum gryphiswaldense
and other magnetotactic bacteria occurs only under suboxic conditions. However, the mechanism of oxygen regulation and redox control of biosynthesis of the mixed-valence iron oxide magnetite [FeII(FeIII)
2
O
4
] is still unclear. Here, we set out to investigate the role of aerobic respiration in both energy metabolism and magnetite biomineralization of
M. gryphiswaldense
. Although three operons encoding putative terminal
cbb
3
-type,
aa
3
-type, and
bd
-type oxidases were identified in the genome assembly of
M. gryphiswaldense
, genetic and biochemical analyses revealed that only
cbb
3
and
bd
are required for oxygen respiration, whereas
aa
3
had no physiological significance under the tested conditions. While the loss of
bd
had no effects on growth and magnetosome synthesis, inactivation of
cbb
3
caused pleiotropic effects under microaerobic conditions in the presence of nitrate. In addition to their incapability of simultaneous nitrate and oxygen reduction,
cbb
3
-deficient cells had complex magnetosome phenotypes and aberrant morphologies, probably by disturbing the redox balance required for proper growth and magnetite biomineralization. Altogether, besides being the primary terminal oxidase for aerobic respiration,
cbb
3
oxidase may serve as an oxygen sensor and have a further role in poising proper redox conditions required for magnetite biomineralization.
Novel MntR-Independent Mechanism of Manganese Homeostasis in Escherichia coli by the Ribosome-Associated Protein HflX
Authors: Kaur Gursharan , Sengupta Sandeepan , Kumar Vineet , Kumari Aruna , Ghosh Aditi , Parrack Pradeep , Dutta Dipak
Published: May 2014

Manganese is a micronutrient required for activities of several important enzymes under conditions of oxidative stress and iron starvation. In
Escherichia coli
, the manganese homeostasis network primarily constitutes a manganese importer (MntH) and an exporter (MntP), which are regulated by the MntR dual regulator. In this study, we find that deletion of
E. coli
hflX
, which encodes a ribosome-associated GTPase with unknown function, renders extreme manganese sensitivity characterized by arrested cell growth, filamentation, lower rate of replication, and DNA damage. We demonstrate that perturbation by manganese induces unprecedented influx of manganese in Δ
hflX
cells compared to that in the wild-type
E. coli
strain. Interestingly, our study indicates that the imbalance in manganese homeostasis in the Δ
hflX
strain is independent of the MntR regulon. Moreover, the influx of manganese leads to a simultaneous influx of zinc and inhibition of iron import in Δ
hflX
cells. In order to review a possible link of HflX with the λ phage life cycle, we performed a lysis-lysogeny assay to show that the Mn-perturbed Δ
hflX
strain reduces the frequency of lysogenization of the phage. This observation raises the possibility that the induced zinc influx in the manganese-perturbed Δ
hflX
strain stimulates the activity of the zinc-metalloprotease HflB, the key determinant of the lysis-lysogeny switch. Finally, we propose that manganese-mediated autophosphorylation of HflX plays a central role in manganese, zinc, and iron homeostasis in
E. coli
cells.
Risk factors for groin/hip injuries in field-based sports: a systematic review
Authors: Ryan Julianne , DeBurca Neasa , Mc Creesh Karen
Published: May 2014

Background

Groin/hip injuries are common in the athletic population, particularly in sports requiring kicking, twisting, turning and rapid acceleration and deceleration. Chronic hip, buttock and groin pain account for 10% of all attendances to sports medicine centres. Understanding risk factors for field-based sports (FBS) players is important in developing preventive measures for injury.

Objective

This systematic review aims to identify and examine the evidence for groin/hip injury risk factors in FBS.

Methods

14 electronic databases were searched using keywords. Studies were included if they met the inclusion criteria and investigated one or more risk factors with relation to the incidence of groin/hip injuries in FBS. Studies were accumulated and independently analysed by two reviewers under a 12-point quality assessment scale (modified CASP (for cohort study design) assessment scale). Owing to the heterogeneity of studies and measures used, a meta-analysis could not be conducted. As a result risk factors were pooled for analysis and discussion.

Results

Of the 5842 potentially relevant studies, 7 high-quality studies were included in this review. Results demonstrated that previous groin/hip injury was the most prominent risk factor, identified across four studies (OR range from 2.6 (95% CI 1.1 to 6.11) to 7.3, (p=0.001)), followed by older age (OR 0.9, p=0.05) and weak adductor muscles (OR 4.28, 95% CI 1.31 to 14.0, p=0.02) each identified in two studies. Eight other significant risk factors were identified once across the included studies.

Conclusions

11 significant risk factors for groin/hip injury for FBS players were identified. The most prominent risk factor identified was previous groin/hip injury. Future research should include a prospective study of a group of FBS players to confirm a relationship between the risk factors identified and development of groin/hip injuries.
The use and impact of cancer medicines in routine clinical care: methods and observations in a cohort of elderly Australians
Authors: Pearson Sallie-Anne , Schaffer Andrea
Published: May 2014

Introduction

After medicines have been subsidised in Australia we know little about their use in routine clinical practice, impact on resource utilisation, effectiveness or safety. Routinely collected administrative health data are available to address these issues in large population-based pharmacoepidemiological studies. By bringing together cross-jurisdictional data collections that link drug exposure to real-world outcomes, this research programme aims to evaluate the use and impact of cancer medicines in a subset of elderly Australians in the real-world clinical setting.

Methods and analysis

This ongoing research programme involves a series of retrospective cohort studies of Australian Government Department of Veterans’ Affairs (DVA) clients. The study population includes 104 635 veterans who reside in New South Wales, Australia, and were aged 65 years and over as of 1 July 2004. We will investigate trends in cancer medicines use according to cancer type and other sociodemographic characteristics as well as predictors of the initiation of cancer medicines and other treatment modalities, survival and adverse outcomes among patients with cancer. The programme is underpinned by the linkage of eight health administrative databases under the custodianship of the DVA and the New South Wales Ministry of Health, including cancer notifications, medicines dispensing data, hospitalisation data and health services data. The cancer notifications database is available from 1994 with all other databases available from 2005 onwards.

Ethics and dissemination

Ethics approval has been granted by the DVA and New South Wales Population and Health Service Research Ethics Committees.

Results

Results will be reported in peer-reviewed publications, conference presentations and policy forums. The programme has high translational potential, providing invaluable evidence about cancer medicines in an elderly population who are under-represented in clinical trials.
Age, occupational class and sickness absence during pregnancy: a retrospective analysis study of the Norwegian population registry
Authors: Ariansen Anja M S
Published: May 2014

Objective

Western women increasingly delay having children to advance their career, and pregnancy is considered to be riskier among older women. In Norway, this development surprisingly coincides with increased sickness absence among young pregnant women, rather than their older counterparts. This paper tests the hypothesis that young pregnant women have a higher number of sick days because this age group includes a higher proportion of working class women, who are more prone to sickness absence.

Design

A zero-inflated Poisson regression was conducted on the Norwegian population registry.

Participants

All pregnant employees giving birth in 2004–2008 were included in the study. A total number of 216 541 pregnancies were observed among 180 483 women.

Outcome measure

Number of sick days.

Results

Although the association between age and number of sick days was U-shaped, pregnant women in their early 20s had a higher number of sick days than those in their mid-40s. This was particularly the case for pregnant women with previous births. In this group, 20-year-olds had 12.6 more sick days than 45-year-olds; this age difference was reduced to 6.3 after control for class. Among women undergoing their first pregnancy, 20-year-olds initially had 1.2 more sick days than 45-year-olds, but control for class altered this age difference. After control for class, 45-year-old first-time pregnant women had 2.9 more sick days than 20-year-olds with corresponding characteristics.

Conclusions

The negative association between age and sickness absence was partly due to younger age groups including more working class women, who were more prone to sickness absence. Young pregnant women's needs for job adjustments should not be underestimated.
Should vitamin B12tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12maintenance therapy for Alberta seniors
Authors: Houle Sherilyn K D , Kolber Michael R , Chuck Anderson W
Published: May 2014

Objective

The aim of this study was to estimate the cost-savings attainable if all patients aged ≥65 years in Alberta, Canada, currently on intramuscular therapy were switched to oral therapy, from the perspective of a provincial ministry of health.

Setting

Primary care setting in Alberta, Canada.

Participants

Seniors of age 65 years and older currently receiving intramuscular vitamin B12therapy.

Intervention

Oral vitamin B12therapy at 1000 μg/day versus intramuscular therapy at 1000 μg/month.

Primary and secondary outcome measures

Cost saving from oral therapy over intramuscular therapy, from the perspective of the Alberta Ministry of Health, including drug costs, dispensing fees, injection administration fees, additional laboratory monitoring and physician visit fees.

Results

Over 5 years, if all Albertans aged 65 years and older who currently receive intramuscular B12are switched to oral therapy, our model found that $C13 975 883 can be saved. Even if no additional physician visits are billed for among patients receiving intramuscular therapy, $C8 444 346 could be saved from reduced administration costs alone.

Conclusions

Oral B12therapy has been shown to be an effective therapeutic option for patients with vitamin B12deficiency, yet only three provinces and the Non-Insured Health Benefits program include oral tablets on their formulary rather than the parenteral preparation. To ensure judicious use of limited health resources, clinicians and formulary committees are encouraged to adopt oral B12therapy as a clinically and cost-effective first-line therapy for vitamin B12deficiency.
Risk factors for exposure of glaucoma drainage devices: a retrospective observational study
Authors: Muir Kelly W , Lim Annie , Stinnett Sandra , Kuo Anthony , Tseng Henry , Walsh Molly M
Published: May 2014

Objectives

The purpose of this study was to identify risk factors for exposure of glaucoma drainage devices (GDD).

Setting

This retrospective, observational study was conducted in the eye clinic of an academic medical centre.

Participants

Participants included 1073 consecutive adults who underwent GDD surgery between 1 January 2005 and 1 January 2011. Participants were included if chart review indicated GDD surgery during the study period and excluded if at least 12 months of clinical follow-up was not available in the medical record.

Primary outcome measure

The primary outcome measure was exposure of the GDD occurring at least 1 month after implant surgery. The characteristics of participants who experienced exposure of the implant were compared to the characteristics of participants who did not experience exposure.

Results

Of the 1073 participants having undergone GDD surgery, 67 experienced exposure of the device. Neither the type of GDD, type of patch graft (eye bank sclera, Tutoplast sclera and Tutoplast pericardium), surgeon, location of GDD, number of GDD previously implanted into the eye, nor history of diabetes or uveitis were associated with likelihood of exposure. Women were more likely than men to experience exposure of the GDD (OR 2.004 (95% CI1.170 to 3.431)) in both univariable (p=0.011) and multivariable (p=0.013) analyses. In survival analysis, exposure of the GDD occurred earlier for women than for men (58 vs 61 months; p=0.024).White race (vs black) was also associated with increased risk of GDD exposure (OR 1.693 (95% CI 1.011 to 2.833)) in univariable (p=0.044) and multivariable (p=0.046) analyses.

Conclusions

Women are two times more likely to experience GDD exposure than men, independent of age. White race is also a risk factor for exposure.
Triage tests for identifying atrial fibrillation in primary care: a diagnostic accuracy study comparing single-lead ECG and modified BP monitors
Authors: Kearley Karen , Selwood Mary , Van den Bruel Ann , Thompson Matthew , Mant David , Hobbs FD Richard , Fitzmaurice David , Heneghan Carl
Published: May 2014

Objective

New electronic devices offer an opportunity within routine primary care settings for improving the detection of atrial fibrillation (AF), which is a common cardiac arrhythmia and a modifiable risk factor for stroke. We aimed to assess the performance of a modified blood pressure (BP) monitor and two single-lead ECG devices, as diagnostic triage tests for the detection of AF.

Setting

6 General Practices in the UK.

Participants

1000 ambulatory patients aged 75 years and over.

Primary and secondary outcome measures

Comparative diagnostic accuracy of modified BP monitor and single-lead ECG devices, compared to reference standard of 12-lead ECG, independently interpreted by cardiologists.

Results

A total of 79 participants (7.9%) had AF diagnosed by 12-lead ECG. All three devices had a high sensitivity (93.9–98.7%) and are useful for ruling out AF. WatchBP is a better triage test than Omron autoanalysis because it is more specific—89.7% (95% CI 87.5% to 91.6%) compared to 78.3% (95% CI 73.0% to 82.9%), respectively. This would translate into a lower follow-on ECG rate of 17% to rule in/rule out AF compared to 29.7% with the Omron text message in the study population. The overall specificity of single-lead ECGs analysed by a cardiologist was 94.6% for Omron and 90.1% for Merlin.

Conclusions

WatchBP performs better as a triage test for identifying AF in primary care than the single-lead ECG monitors as it does not require expertise for interpretation and its diagnostic performance is comparable to single-lead ECG analysis by cardiologists. It could be used opportunistically to screen elderly patients for undiagnosed AF at regular intervals and/or during BP measurement.
Sex-specific trends in 4-year survival in 37 276 men and women with acute myocardial infarction before the age of 55 years in Sweden, 1987–2006: a register-based cohort study
Authors: Nielsen S , Björck L , Berg J , Giang K W , Zverkova Sandström T , Falk K , Määttä S , Rosengren A
Published: May 2014

Objective

To examine sex-specific trends in 4-year mortality among young patients with first acute myocardial infarction (AMI), 1987–2006.

Design

Prospective cohort study.

Setting

Sweden.

Participants

We identified 37 276 cases (19.4% women; age, 25–54 years) from the Swedish Inpatient Register, 1987–2006, who had survived 28 days after an AMI.

Outcome measures

4-year mortality from all causes and standard mortality ratio (SMR).

Results

From the first to last 5-year period, the absolute excess risk decreased from 1.38 to 0.50 and 1.53 to 0.59 per 100 person-years among men aged 25–44 and 45–54 years, respectively. Corresponding figures for women were a decrease from 2.26 to 1.17 and from 1.93 to 1.45 per 100 person-years, respectively. Trends for women were non-linear, decreasing to the same extent as those for men until the third period, then increasing. For the last 5-year period, the standardised mortality ratio for young survivors of AMI compared with the general population was 4.34 (95% CI 3.04 to 5.87) and 2.43 (95% CI 2.12 to 2.76) for men aged 25–44 and 45–54 years, respectively, and 13.53 (95% CI 8.36 to 19.93) and 6.42 (95% CI 5.24 to 7.73) for women, respectively. Deaths not associated with cardiovascular causes increased from 21.5% to 44.6% in men and 41.5% to 65.9% in women.

Conclusions

Young male survivors of AMI have low absolute long-term mortality rates, but these rates remain twofold to fourfold that of the general population. After favourable development until 2001, women now have higher absolute mortality than men and a 6-fold to 14-fold risk of death compared with women in the general population.
Text messaging reminders for influenza vaccine in primary care: protocol for a cluster randomised controlled trial (TXT4FLUJAB)
Authors: Herrett Emily , van Staa Tjeerd , Free Caroline , Smeeth Liam
Published: May 2014

Introduction

The UK government recommends that at least 75% of people aged under 64 with certain conditions receive an annual influenza vaccination. Primary care practices often fall short of this target and strategies to increase vaccine uptake are required. Text messaging reminders are already used in 30% of practices to remind patients about vaccination, but there has been no trial addressing their effectiveness in increasing influenza vaccine uptake in the UK.

The aims of the study are (1) to develop the methodology for conducting cluster randomised trials of text messaging interventions utilising routine electronic health records and (2) to assess the effectiveness of using a text messaging influenza vaccine reminder in achieving an increase in influenza vaccine uptake in patients aged 18–64 with chronic conditions, compared with standard care.

Methods and analysis

This cluster randomised trial will recruit general practices across three settings in English primary care (Clinical Practice Research Datalink, ResearchOne and London iPLATO text messaging software users) and randomise them to either standard care or a text messaging campaign to eligible patients. Flu vaccine uptake will be ascertained using routinely collected, anonymised electronic patient records. This protocol outlines the proposed study design and analysis methods.

Ethics and dissemination

This study will determine the effectiveness of text messaging vaccine reminders in primary care in increasing influenza vaccine uptake, and will strengthen the methodology for using electronic health records in cluster randomised trials of text messaging interventions. This trial was approved by the Surrey Borders Ethics Committee (13/LO/0872). The trial results will be disseminated at national conferences and published in a peer-reviewed medical journal. The results will also be distributed to the Primary Care Research Network and to all participating general practices.

Trial registration number

This study is registered at controlled-trials.comISRCTN48840025, July 2013.
Patient-reported outcomes at hospital discharge from Heart Centres, a national cross-sectional survey with a register-based follow-up: the DenHeart study protocol
Authors: Berg Selina Kikkenborg , Svanholm Jette , Lauberg Astrid , Borregaard Britt , Herning Margrethe , Mygind Anna , Christensen Anne Vinggaard , Christensen Anne Illemann , Ekholm Ola , Juel Knud , Thrysøe Lars
Published: May 2014

Introduction

Patient reported health status, which includes symptom burden, functional status and quality of life, is an important measure of health. Differences in health status between diagnostic groups within cardiology have only been sparsely investigated. These outcomes may predict morbidity, mortality, labour market affiliation and healthcare utilisation in various diagnostic groups. A national survey aiming to include all cardiac diagnostic groups from a total Heart Centre population has been designed as the DenHeart survey.

Methods and analysis

DenHeart is designed as a cross-sectional survey with a register-based follow-up. All diagnostic groups at the five national Heart Centres are included during 1 year (15 April 2013 to 15 April 2014) and asked to fill out a questionnaire at hospital discharge. The total eligible population, both responders and non-responders, will be followed in national registers. The following instruments are used: SF-12, Hospital Anxiety and Depression Scale, EQ-5D, Brief Illness Perception Questionnaire (B-IPQ), HeartQoL and Edmonton Symptom Assessment Scale. The following variables are collected from national registers: action diagnosis, procedures, comorbidity, length of hospital stay, type of hospitalisation, visits to general practitioners and other agents in primary healthcare, dispensed prescription medication, vital status and cause of death. Labour market affiliation, sick leave, early retirement pension, educational degree and income will be collected from registers. Frequency distributions and multiple logistic regression analyses will be used to describe and assess differences in patient reported outcomes at hospital discharge between diagnostic groups and in-hospital predicting factors. Cox proportional hazards regression models with age as the time scale will be used to investigate associations between patient reported outcomes at baseline and morbidity/mortality, labour market affiliation and healthcare utilisation after 1 year.

Ethics and dissemination

The study complies with the Declaration of Helsinki. The study has been approved by the Danish Data Protection Agency: 2007-58-0015/30-0937 and registered at ClinicalTrials.gov (NCT01926145). Study findings will be disseminated widely through peer reviewed publications and conference presentations.
Rapid Emergency Medicine Score (REMS) in the trauma population: a retrospective study
Authors: Imhoff Bryan F , Thompson Nia J , Hastings Michael A , Nazir Niaman , Moncure Michael , Cannon Chad M
Published: May 2014

Objective

Rapid Emergency Medicine Score (REMS) is an attenuated version of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and has utility in predicting mortality in non-surgical patients, but has yet to be tested among the trauma population. The objective was to evaluate REMS as a risk stratification tool for predicting in-hospital mortality in traumatically injured patients and to compare REMS accuracy in predicting mortality to existing trauma scores, including the Revised Trauma Score (RTS), Injury Severity Score (ISS) and Shock Index (SI).

Design and setting

Retrospective chart review of the trauma registry from an urban academic American College of Surgeons (ACS) level 1 trauma centre.

Participants

3680 patients with trauma aged 14 years and older admitted to the hospital over a 4-year period. Patients transferred from other hospitals were excluded from the study as were those who suffered from burn or drowning-related injuries. Patients with vital sign documentation insufficient to calculate an REMS score were also excluded.

Primary outcome measures

The predictive ability of REMS was evaluated using ORs for in-hospital mortality. The discriminate power of REMS, RTS, ISS and SI was compared using the area under the receiver operating characteristic curve.

Results

Higher REMS was associated with increased mortality (p<0.0001). An increase of 1 point in the 26-point REMS scale was associated with an OR of 1.51 for in-hospital death (95% CI 1.45 to 1.58). REMS (area under the curve (AUC) 0.91±0.02) was found to be similar to RTS (AUC 0.89±0.04) and superior to ISS (AUC 0.87±0.01) and SI (AUC 0.55±0.31) in predicting in-hospital mortality.

Conclusions

In the trauma population, REMS appears to be a simple, accurate predictor of in-hospital mortality. While REMS performed similarly to RTS in predicting mortality, it did outperform other traditionally used trauma scoring systems, specifically ISS and SI.
Acupuncture, counselling or usual care for depression and comorbid pain: secondary analysis of a randomised controlled trial
Authors: Hopton A , MacPherson H , Keding A , Morley S
Published: May 2014

Background

Depression with comorbid pain is associated with a poor response to various treatments. The objective in this secondary analysis was to determine whether patients reporting pain have different depression and pain outcomes over time in response to acupuncture, counselling or usual care.

Methods

Self-reported ratings of depression and pain from 755 patients in a pragmatic randomised controlled trial of acupuncture (302) or counselling (302) compared to usual care alone (151) are described and analysed using a series of regression models and analysis of covariance. Patient-reported outcomes of Patient Health Questionnaire (PHQ)-9 for depression, SF36 bodily pain and EQ-5D, all at baseline, 3, 6, 9 and 12 months.

Results

At baseline, 755 patients reported EQ-5D pain categories; 384 (50.9%) reported moderate-to-extreme pain. Controlling for baseline depression, a linear regression model showed that the presence of pain at baseline was associated with poorer depression outcomes at 3 months mean difference=−1.16, (95% CI 0.12 to 2.2). Participants with moderate-to-extreme pain at baseline did better at 3 months if they received acupuncture (mean reduction in Patient Health Questionnaire 9 (PHQ-9) from baseline=6.0, 95% CI 5.0 to 7.1 and a mean reduction in SF-36 bodily pain=11.2, (95% CI 7.1 to 15.2) compared to improvements for those who received counselling (4.3, 95% CI 3.3 to 5.4; 7.6, 95% CI 3.6 to 11.6) or usual care (2.7, 95% CI 1.50 to 4.0: 7.2, 95% CI 2.3 to 12.1). In comparison, no notable differences were seen between treatment arms within the no pain comparator group.

Conclusions

Patients with depression and pain at baseline recovered less well from treatment over 3 months than those with depression and no pain. Reductions in both depression and pain were most marked in the acupuncture group, followed by the counselling group and then the usual care group.
Engaging the public in healthcare decision-making: quantifying preferences for healthcare through citizens’ juries
Authors: Scuffham Paul A , Ratcliffe Julie , Kendall Elizabeth , Burton Paul , Wilson Andrew , Chalkidou Kalipso , Littlejohns Peter , Whitty Jennifer A
Published: May 2014

Introduction

The optimal approach to engage the public in healthcare decision-making is unclear. Approaches range from deliberative citizens’ juries to large population surveys using discrete choice experiments. This study promotes public engagement and quantifies preferences in two key areas of relevance to the industry partners to identify which approach is most informative for informing healthcare policy.

Methods and analysis

The key areas identified are optimising appropriate use of emergency care and prioritising patients for bariatric surgery. Three citizens’ juries will be undertaken—two in Queensland to address each key issue and one in Adelaide to repeat the bariatric surgery deliberations with a different sample. Jurors will be given a choice experiment before the jury, immediately following the jury and at approximately 1 month following the jury. Control groups for each jury will be given the choice experiment at the same time points to test for convergence. Samples of healthcare decision-makers will be given the choice experiment as will two large samples of the population. Jury and control group participants will be recruited from the Queensland electoral roll and newspaper advertisements in Adelaide. Population samples will be recruited from a large research panel. Jury processes will be analysed qualitatively and choice experiments will be analysed using multinomial logit models and its more generalised forms. Comparisons between preferences across jurors predeliberation and postdeliberation, control participants, healthcare decision-makers and the general public will be undertaken for each key issue.

Ethics and dissemination

The study is approved by Griffith University Human Research Ethics Committee (MED/10/12/HREC). Findings of the juries and the choice experiments will be reported at a workshop of stakeholders to be held in 2015, in reports and in peer reviewed journals.
Improving the Peri-operative care of Patients by instituting a 'Block Room' for Regional Anaesthesia
Authors: Chazapis Maria , Kaur Navkiran , Kamming Damon
Published: May 2014

Regional anaesthesia has multiple known benefits over general anaesthesia alone, but requires time and expertise for its application. This study aimed to decrease anaesthetic time and increase total surgical operative time by instituting a ‘block room’ where regional anaesthesia nerve blocks could be provided by expert anaesthetists in regular scheduled sessions.

A baseline audit showed that 2 hours per day was spent on performing nerve blocks. Development of the block room allowed nerve blocks to be performed in parallel to surgical operations, reducing the mean anaesthetic control time from 44 mins to 27 mins. This freed time for an extra operative case per day. In addition, pooling of expertise to one site has allowed excellent teaching opportunities for anaesthetic trainees, and a specific training programme for regional anaesthesia is being produced.

In conclusion, instituting a block room has improved the efficiency of our theatre complex, and improved the service deliverable to our patients.
Improving access to competitive employment for service users in forensic psychiatric units
Authors: Beck Charlotte , Wernham Connie
Published: May 2014

Employment has been proven to be an effective recovery tool and therapeutic intervention for those with severe and enduring mental health conditions. Aside from monetary reward, employment is a means of structuring time and provides a sense of worth and achievement, which enhances self-esteem and confidence. A social identity is developed through employment, encouraging social support and increasing social networks. Securing employment can bring about improved quality of life and positive change in one’s social circumstances; therefore it can reduce symptoms associated with mental illness and potentially prevent re-offending, as the individual develops a sense of independence, self-efficacy, and value.

Barriers to employment exist for forensic mental health service users and therefore it is imperative that employment needs are addressed at the earliest possible stage in recovery. An evaluation of employment activities across two forensic mental health units revealed a lack of appropriate employment opportunities for service users, and those roles available were not implemented in line with recommended best practice. In response to this issue several enterprises were established to offer opportunities for service users to engage in meaningful employment and develop skills that a future employer would value. Each enterprise responds to a business need within the units to ensure sustainability of services. The enterprises are essentially micro-businesses with social objectives whose surpluses are reinvested for the purpose of increasing opportunities for service users.

The enterprises are underpinned by the philosophy of the Individual Placement and Support (IPS) model; empirical evidence suggests that the IPS model is the most effective intervention, based on the ‘place then train’ philosophy. The model recommends a focus upon rapid job search to achieve competitive employment for those who want to work; opportunities sourced should be consistent with individual preference and benefits counselling offered. Support should be time unlimited and integrated with mental health treatment. A person-centred and strengths-based approach is also adopted to support people to build on their strengths, establish goals, and encourage motivation.
Efficacy of a non‐updated, Matrix‐C‐based equine influenza subunit‐tetanus vaccine following Florida sublineage clade 2 challenge
Authors: Pouwels H. G. W. , Van de Zande S. M. A. , Horspool L. J. I. , Hoeijmakers M. J. H.
Published: May 2014

Assessing the ability of current equine influenza vaccines to provide cross‐protection against emerging strains is important. Horses not vaccinated previously and seronegative for equine influenza based on haemagglutination inhibition (HI) assay were assigned at random to vaccinated (n=7) or non‐vaccinated (control, n=5) groups. Vaccination was performed twice four weeks apart with a 1 ml influenza subunit (A/eq/Prague/1/56, A/eq/Newmarket/1/93, A/eq/Newmarket/2/93), tetanus toxoid vaccine with Matrix‐C adjuvant (EquilisPrequenza Te). All the horses were challenged individually by aerosol with A/eq/Richmond/1/07 three weeks after the second vaccination. Rectal temperature, clinical signs, serology and virus excretion were monitored for 14 days after challenge. There was no pain at the injection site or increases in rectal temperature following vaccination. Increases in rectal temperature and characteristic clinical signs were recorded in the control horses. Clinical signs were minimal in vaccinated horses. Clinical (P=0.0345) and total clinical scores (P=0.0180) were significantly lower in the vaccinated than in the control horses. Vaccination had a significant effect on indicators of viraemia – the extent (P=0.0006) and duration (P=<0.0001) of virus excretion and the total amount of virus excreted (AUC, P=0.0006). Vaccination also had a significant effect (P=0.0017) on whether a horse was positive or negative for virus excretion during the study. Further research is needed to fully understand the specific properties of this vaccine that may contribute to its cross‐protective capacity.
STATISTICAL RELIABILITY ANALYSIS FOR FUEL CELL VEHICLE BASED ON FIELD TEST DATA
Authors: CHEN TIE , ZHENG SONGLIN , LIU XINTIAN , FENG JINZHI
Published: May 2014

Compared to traditional vehicles, the Fuel Cell Vehicle (FCV) is more energy efficient and emission free. As an ideal solution to global energy crisis, FCV has aroused widespread attention in China and abroad. However, the complex structure of FCV and the weak foundation for manufacturing which hinder the improvement of FCV's reliability. In this paper, a statistical analysis that characterizes the reliability of FCV based on field test data is presented. The failure distribution rules and failure reasons of the entire FCV and its subsystems are discussed. Meanwhile, the least squares estimation — correlation coefficient inspection method is proposed to find out the distribution model of the Mileage to First Failure (MFF) and the Mileage between Failures (MBF) for the entire FCV and its subsystems. It is found that they all follow Weibull distribution. Based on the proposed methods and analysis results, the general direction with respect to technological breakthrough is pointed out to make the entire FCV and its subsystems more reliable and durable.
STRONG EQUILIBRIA IN THE VEHICLE ROUTING GAME
Authors: ZENKEVICH NIKOLAY , ZYATCHIN ANDREY
Published: May 2014

This paper introduces an extension of the vehicle routing problem by including several distributors in competition. Each customer is characterized by demand and a wholesale price. Under this scenario a solution may have unserviced customers and elementary routes with no customer visits. The problem is described as a vehicle routing game (VRG) with coordinated strategies. We provide a computable procedure to calculate a strong equilibrium (SE) in the VRG that is stable against deviations from any coalition. Following this procedure, we solve iteratively optimization subproblems for a single distributor, reducing the set of unserviced customers at each iteration. We prove that strong equilibria of one type exist for a VRG, and we provide conditions for another type to exist. We also introduce a semi-cooperative SE that helps reduce a set of strong equilibria in the VRG. Our methodology is suited for parallel computing, and could be efficiently applied to routing vehicles with a few compartments. It also calculates a numerical example for a three person VRG with six cars and twelve customers.
Inequalities detecting entanglement for arbitrary bipartite systems
Authors: Zhao Hui , Fei Shao-Ming , Fan Jiao , Wang Zhi-Xi
Published: May 2014

Based on the generators of SU(n) we present inequalities for detecting quantum entanglement for 2 ⊗ d and M ⊗ N systems. These inequalities provide a sufficient condition of entanglement for bipartite mixed states and give rise to an experimental way of entanglement detection.