bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed chimerism in haemoglobinopathies: from risk of graft rejection to immune tolerance
Authors: Andreani M. , Testi M. , Lucarelli G.
Published: February 2014

Mixed chimerism (MC), the simultaneous presence of both host‐ and donor‐derived cells in the recipient, is observed in a large proportion of patients after haematopoietic stem cell transplant (HSCT) to treat haemoglobinopathies. Detected early after transplantation, MC often moves towards complete chimerism, although sometimes it may evolve into graft rejection, especially if the proportion of donor cells is very low. However, some patients develop stable MC, defined as persistent when donor‐ and host‐derived cells coexist for periods longer than 2 years after HSCT. Patients with persistent mixed chimerism (PMC) do not require additional red blood cell support and, regardless of the presence in some cases of an extremely low percentage of donor‐derived nucleated cells in the bone marrow, their condition is clinically controlled by an incomplete but functional graft, as they express a two‐ to fivefold enrichment of donor‐derived mature erythrocytes in the peripheral blood. These findings have tremendous implications not only in the context of allogeneic HSCT but also in the design of gene therapy trials based on the autologous transplantation of genetically modified CD34+ cells. Recent studies have shown that durable allograft tolerance has been achieved by induction of haematopoietic chimerism in clinical kidney transplantation, showing the involvement of regulatory T cells. Similarly, it has been shown that the regulatory T cells play a pivotal role in promoting and maintaining immune tolerance in patients that develop a status of PMC after HSCT for Thalassemia.
Study on the coalescence of dislocation-free GaN nanowires on Si and SiOx
Authors: Fan Shizhao , Zhao Songrui , Liu Xuedong , Mi Zetian
Published: February 2014

The authors have studied the epitaxial growth and structural characterization of coalesced GaN nanowire arrays formed directly on Si and SiOx substrates. It was observed that the coalescence can be induced by the tilting or the enhanced lateral growth of the nanowires. Dislocations at the coalescence interface are largely localized, leading to the formation of nearly defect-free GaN microcrystals. In addition, high quality GaN epilayers can be grown directly on SiOx with buffer layer less than 1 μm by optimizing the growth parameters in nanowire nucleation and coalescence stages.
Influence of photon beam energy on the dose enhancement factor caused by gold and silver nanoparticles: An experimental approach
Authors: Guidelli Eder José , Baffa Oswaldo
Published: February 2014

Purpose:

Noble metal nanoparticles have found several medical applications in the areas of radiation detection; x‐ray contrast agents and cancer radiation therapy. Based on computational methods, many papers have reported the nanoparticle effect on the dose deposition in the surrounding medium. Here the authors report experimental results on how silver and gold nanoparticles affect the dose deposition in alanine dosimeters containing several concentrations of silver and gold nanoparticles, for five different beam energies, using electron spin resonance spectroscopy (ESR).

Methods:

The authors produced alanine dosimeters containing several mass percentage of silver and gold nanoparticles. Nanoparticle sizes were measured by dynamic light scattering and by transmission electron microscopy. The authors determined the dose enhancement factor (DEF) theoretically, using a widely accepted method, and experimentally, using ESR spectroscopy.

Results:

The DEF is governed by nanoparticle concentration, size, and position in the alanine matrix. Samples containing gold nanoparticles afford a DEF higher than 1.0, because gold nanoparticle size is homogeneous for all gold concentrations utilized. For samples containing silver particles, the silver mass percentage governs the nanoparticles size, which, in turns, modifies nanoparticle position in the alanine dosimeters. In this sense, DEF decreases for dosimeters containing large and segregated particles. The influence of nanoparticle size‐position is more noticeable for dosimeters irradiated with higher beam energies, and dosimeters containing large and segregated particles become less sensitive than pure alanine (DEF < 1).

Conclusions:

ESR dosimetry gives the DEF in a medium containing metal nanoparticles, although particle concentration, size, and position are closely related in the system. Because this is also the case as in many real systems of materials containing inorganic nanoparticles, ESR is a valuable tool for investigating DEF. Moreover, these results alert to the importance of controlling the size‐position of nanoparticles to enhance DEF.
Musician effect in cochlear implant simulated gender categorization
Authors: Fuller Christina D. , Galvin John J. , Free Rolien H. , Başkent Deniz
Published: February 2014

Musicians have been shown to better perceive pitch and timbre cues in speech and music, compared to non-musicians. It is unclear whether this “musician advantage” persists under conditions of spectro-temporal degradation, as experienced by cochlear-implant (CI) users. In this study, gender categorization was measured in normal-hearing musicians and non-musicians listening to acoustic CI simulations. Recordings of Dutch words were synthesized to systematically vary fundamental frequency, vocal-tract length, or both to create voices from the female source talker to a synthesized male talker. Results showed an overall musician effect, mainly due to musicians weighting fundamental frequency more than non-musicians in CI simulations.
Model adaptation method for recognition of speech with missing frames
Authors: Lee Lee-Min , Jean Fu-Rong
Published: February 2014

In distributed speech recognition (DSR), data packets may be lost over error prone channels. A commonly used approach to rectify this is to reconstruct a full frame rate data sequence for recognition using linear interpolation. In this study, an error-concealment decoding method that dynamically adapts the transition probabilities of hidden Markov models to match the frame loss observation sequence is proposed. Experimental results show that a DSR system using the proposed method can achieve the same level of accuracy as a data reconstruction method, is more robust against heavy frame loss, and significantly reduces the computation time.
A scaled mapping parabolic equation for sloping range-dependent environments
Authors: Metzler Adam M. , Moran Daniel , Collis Jon M. , Martin P. A. , Siegmann William L.
Published: February 2014

Parabolic equation solutions use various techniques for approximating range-dependent interfaces. One is a mapping approach [M. D. Collins et al., J. Acoust. Soc. Am. 107, 1937–1942 (2000)] where at each range the domain is vertically translated so that sloping bathymetry becomes horizontal, and range dependence is transferred to the upper surface. In this paper, a scaled mapping is suggested where the domain is vertically distorted so that both the bathymetry and upper surface are horizontal. Accuracy is demonstrated for problems involving fluid sediments. Generalizations of the approach should be useful for environments with layer thicknesses that vary with range.
Dimethylglycine Provides Salt and Temperature Stress Protection to Bacillus subtilis
Authors: Bashir Abdallah , Hoffmann Tamara , Smits Sander H. J. , Bremer Erhard
Published: February 2014

Glycine betaine is a potent osmotic and thermal stress protectant of many microorganisms. Its synthesis from glycine results in the formation of the intermediates monomethylglycine (sarcosine) and dimethylglycine (DMG), and these compounds are also produced when it is catabolized.
Bacillus subtilis
does not produce sarcosine or DMG, and it cannot metabolize these compounds. Here we have studied the potential of sarcosine and DMG to protect
B. subtilis
against osmotic, heat, and cold stress. Sarcosine, a compatible solute that possesses considerable protein-stabilizing properties, did not serve as a stress protectant of
B. subtilis
. DMG, on the other hand, proved to be only moderately effective as an osmotic stress protectant, but it exhibited good heat stress-relieving and excellent cold stress-relieving properties. DMG is imported into
B. subtilis
cells primarily under osmotic and temperature stress conditions via OpuA, a member of the ABC family of transporters. Ligand-binding studies with the extracellular solute receptor (OpuAC) of the OpuA system showed that OpuAC possesses a moderate affinity for DMG, with a

K
d

value of approximate 172 μM; its

K
d

for glycine betaine is about 26 μM. Docking studies using the crystal structures of the OpuAC protein with the sulfur analog of DMG, dimethylsulfonioacetate, as a template suggest a model of how the DMG molecule can be stably accommodated within the aromatic cage of the OpuAC ligand-binding pocket. Collectively, our data show that the ability to acquire DMG from exogenous sources under stressful environmental conditions helps the
B. subtilis
cell to cope with growth-restricting osmotic and temperature challenges.
Superoxide Production by a Manganese-Oxidizing Bacterium Facilitates Iodide Oxidation
Authors: Li Hsiu-Ping , Daniel Benjamin , Creeley Danielle , Grandbois Russell , Zhang Saijin , Xu Chen , Ho Yi-Fang , Schwehr Kathy A. , Kaplan Daniel I. , Santschi Peter H. , Hansel Colleen M. , Yeager Chris M.
Published: February 2014

The release of radioactive iodine (i.e., iodine-129 and iodine-131) from nuclear reprocessing facilities is a potential threat to human health. The fate and transport of iodine are determined primarily by its redox status, but processes that affect iodine oxidation states in the environment are poorly characterized. Given the difficulty in removing electrons from iodide (I
−
), naturally occurring iodide oxidation processes require strong oxidants, such as Mn oxides or microbial enzymes. In this study, we examine iodide oxidation by a marine bacterium,
Roseobacter
sp. AzwK-3b, which promotes Mn(II) oxidation by catalyzing the production of extracellular superoxide (O
2
−
). In the absence of Mn
2+
,
Roseobacter
sp. AzwK-3b cultures oxidized ∼90% of the provided iodide (10 μM) within 6 days, whereas in the presence of Mn(II), iodide oxidation occurred only after Mn(IV) formation ceased. Iodide oxidation was not observed during incubations in spent medium or with whole cells under anaerobic conditions or following heat treatment (boiling). Furthermore, iodide oxidation was significantly inhibited in the presence of superoxide dismutase and diphenylene iodonium (a general inhibitor of NADH oxidoreductases). In contrast, the addition of exogenous NADH enhanced iodide oxidation. Taken together, the results indicate that iodide oxidation was mediated primarily by extracellular superoxide generated by
Roseobacter
sp. AzwK-3b and not by the Mn oxides formed by this organism. Considering that extracellular superoxide formation is a widespread phenomenon among marine and terrestrial bacteria, this could represent an important pathway for iodide oxidation in some environments.
Bioconversion of Pinoresinol into Matairesinol by Use of Recombinant Escherichia coli
Authors: Kuo Han-Jung , Wei Zhi-Yu , Lu Pei-Chun , Huang Pung-Ling , Lee Kung-Ta
Published: February 2014

Lignans, a class of dimeric phenylpropanoid derivative found in plants, such as whole grains and sesame and flax seeds, have anticancer activity and can act as phytoestrogens. The lignans secoisolariciresinol and matairesinol can be converted in the mammalian proximal colon into enterolactone and enterodiol, respectively, which reduce the risk of breast and colon cancer. To establish an efficient bioconversion system to generate matairesinol from pinoresinol, the genes encoding pinoresinol-lariciresinol reductase (PLR) and secoisolariciresinol dehydrogenase (SDH) were cloned from
Podophyllum pleianthum
Hance, an endangered herb in Taiwan, and the recombinant proteins, rPLR and rSDH, were expressed in
Escherichia coli
and purified. The two genes, termed
plr-PpH
and
sdh-PpH
, were also linked to form two bifunctional fusion genes,
plr-sdh
and
sdh-plr
, which were also expressed in
E. coli
and purified. Bioconversion
in vitro
at 22°C for 60 min showed that the conversion efficiency of fusion protein PLR-SDH was higher than that of the mixture of rPLR and rSDH. The percent conversion of (+)-pinoresinol to matairesinol was 49.8% using PLR-SDH and only 17.7% using a mixture of rPLR and rSDH. However, conversion of (+)-pinoresinol by fusion protein SDH-PLR stopped at the intermediate product, secoisolariciresinol.
In vivo
, (+)-pinoresinol was completely converted to matairesinol by living recombinant
E. coli
expressing PLR-SDH without addition of cofactors.
Predicting the Concentration of Verotoxin-Producing Escherichia coli Bacteria during Processing and Storage of Fermented Raw-Meat Sausages
Authors: Quinto E. J. , Arinder P. , Axelsson L. , Heir E. , Holck A. , Lindqvist R. , Lindblad M. , Andreou P. , Lauzon H. L. , Marteinsson V. Þ. , Pin C.
Published: February 2014

A model to predict the population density of verotoxigenic
Escherichia coli
(VTEC) throughout the elaboration and storage of fermented raw-meat sausages (FRMS) was developed. Probabilistic and kinetic measurement data sets collected from publicly available resources were completed with new measurements when required and used to quantify the dependence of VTEC growth and inactivation on the temperature, pH, water activity (a
w
), and concentration of lactic acid. Predictions were compared with observations in VTEC-contaminated FRMS manufactured in a pilot plant. Slight differences in the reduction of VTEC were predicted according to the fermentation temperature, 24 or 34°C, with greater inactivation at the highest temperature. The greatest reduction was observed during storage at high temperatures. A population decrease greater than 6 decimal logarithmic units was observed after 66 days of storage at 25°C, while a reduction of only ca. 1 logarithmic unit was detected at 12°C. The performance of our model and other modeling approaches was evaluated throughout the processing of dry and semidry FRMS. The greatest inactivation of VTEC was predicted in dry FRMS with long drying periods, while the smallest reduction was predicted in semidry FMRS with short drying periods. The model is implemented in a computing tool,
E. coli
SafeFerment (EcSF), freely available from
http://www.ifr.ac.uk/safety/EcoliSafeFerment
. EcSF integrates growth, probability of growth, and thermal and nonthermal inactivation models to predict the VTEC concentration throughout FRMS manufacturing and storage under constant or fluctuating environmental conditions.
Gene and Protein Sequence Optimization for High-Level Production of Fully Active and Aglycosylated Lysostaphin in Pichia pastoris
Authors: Zhao Hongliang , Blazanovic Kristina , Choi Yoonjoo , Bailey-Kellogg Chris , Griswold Karl E.
Published: February 2014

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant
Staphylococcus aureus
(MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While
Pichia pastoris
is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can be overcome with a synthetic gene incorporating improved codon usage and balanced A+T/G+C content, and the second barrier can be overcome by disrupting an N-linked glycosylation sequon using a broadened choice of mutations that yield aglyscosylated and fully active lysostaphin. The optimized lysostaphin variants could be produced at approximately 500 mg/liter in a small-scale bioreactor, and 50% of that material could be recovered at high purity with a simple 2-step purification. It is anticipated that this novel high-level expression system will bring down one of the major barriers to future development of biomedical, veterinary, and research applications of lysostaphin and its engineered variants.
Performance and Specificity of the Covalently Linked Immunomagnetic Separation-ATP Method for Rapid Detection and Enumeration of Enterococci in Coastal Environments
Authors: Zimmer-Faust Amity G. , Thulsiraj Vanessa , Ferguson Donna , Jay Jennifer A.
Published: February 2014

The performance and specificity of the covalently linked immunomagnetic separation-ATP (Cov-IMS/ATP) method for the detection and enumeration of enterococci was evaluated in recreational waters. Cov-IMS/ATP performance was compared with standard methods: defined substrate technology (Enterolert; IDEXX Laboratories), membrane filtration (EPA Method 1600), and an
Enterococcus
-specific quantitative PCR (qPCR) assay (EPA Method A). We extend previous studies by (i) analyzing the stability of the relationship between the Cov-IMS/ATP method and culture-based methods at different field sites, (ii) evaluating specificity of the assay for seven ATCC
Enterococcus
species, (iii) identifying cross-reacting organisms binding the antibody-bead complexes with 16S rRNA gene sequencing and evaluating specificity of the assay to five nonenterococcus species, and (iv) conducting preliminary tests of preabsorption as a means of improving the assay. Cov-IMS/ATP was found to perform consistently and with strong agreement rates (based on exceedance/compliance with regulatory limits) of between 83% and 100% compared to the culture-based Enterolert method at a variety of sites with complex inputs. The Cov-IMS/ATP method is specific to five of seven different
Enterococcus
spp. tested. However, there is potential for nontarget bacteria to bind the antibody, which may be reduced by purification of the IgG serum with preabsorption at problematic sites. The findings of this study help to validate the Cov-IMS/ATP method, suggesting a predictable relationship between the Cov-IMS/ATP method and traditional culture-based methods, which will allow for more widespread application of this rapid and field-portable method for coastal water quality assessment.
Multilocus Sequence Typing Identifies Epidemic Clones of Flavobacterium psychrophilum in Nordic Countries
Authors: Nilsen Hanne , Sundell Krister , Duchaud Eric , Nicolas Pierre , Dalsgaard Inger , Madsen Lone , Aspán Anna , Jansson Eva , Colquhoun Duncan J. , Wiklund Tom
Published: February 2014

Flavobacterium psychrophilum
is the causative agent of bacterial cold water disease (BCWD), which affects a variety of freshwater-reared salmonid species. A large-scale study was performed to investigate the genetic diversity of
F. psychrophilum
in the four Nordic countries: Denmark, Finland, Norway, and Sweden. Multilocus sequence typing of 560 geographically and temporally disparate
F. psychrophilum
isolates collected from various sources between 1983 and 2012 revealed 81 different sequence types (STs) belonging to 12 clonal complexes (CCs) and 30 singleton STs. The largest CC, CC-ST10, which represented almost exclusively isolates from rainbow trout and included the most predominant genotype, ST2, comprised 65% of all isolates examined. In Norway, with a shorter history (<10 years) of BCWD in rainbow trout, ST2 was the only isolated CC-ST10 genotype, suggesting a recent introduction of an epidemic clone. The study identified five additional CCs shared between countries and five country-specific CCs, some with apparent host specificity. Almost 80% of the singleton STs were isolated from non-rainbow trout species or the environment. The present study reveals a simultaneous presence of genetically distinct CCs in the Nordic countries and points out specific
F. psychrophilum
STs posing a threat to the salmonid production. The study provides a significant contribution toward mapping the genetic diversity of
F. psychrophilum
globally and support for the existence of an epidemic population structure where recombination is a significant driver in
F. psychrophilum
evolution. Evidence indicating dissemination of a putatively virulent clonal complex (CC-ST10) with commercial movement of fish or fish products is strengthened.
Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA
Authors: Hunter Cameron C. , Siebert Kendra S. , Downes Damien J. , Wong Koon Ho , Kreutzberger Sara D. , Fraser James A. , Clarke David F. , Hynes Michael J. , Davis Meryl A. , Todd Richard B.
Published: February 2014

The
Aspergillus nidulans
GATA transcription factor AreA activates transcription of nitrogen metabolic genes in response to nitrogen limitation and is known to accumulate in the nucleus during nitrogen starvation. Sequence analysis of AreA revealed multiple nuclear localization signals (NLSs), five putative classical NLSs conserved in fungal AreA orthologs but not in the
Saccharomyces cerevisiae
functional orthologs Gln3p and Gat1p, and one putative noncanonical RRX
33
RXR bipartite NLS within the DNA-binding domain. In order to identify the functional NLSs in AreA, we constructed
areA
mutants with mutations in individual putative NLSs or combinations of putative NLSs and strains expressing green fluorescent protein (GFP)-AreA NLS fusion genes. Deletion of all five classical NLSs individually or collectively did not affect utilization of nitrogen sources or AreA-dependent gene expression and did not prevent AreA nuclear localization. Mutation of the bipartite NLS conferred the inability to utilize alternative nitrogen sources and abolished AreA-dependent gene expression likely due to effects on DNA binding but did not prevent AreA nuclear localization. Mutation of all six NLSs simultaneously prevented AreA nuclear accumulation. The bipartite NLS alone strongly directed GFP to the nucleus, whereas the classical NLSs collaborated to direct GFP to the nucleus. Therefore, AreA contains multiple conserved NLSs, which show redundancy and together function to mediate nuclear import. The noncanonical bipartite NLS is conserved in GATA factors from
Aspergillus
, yeast, and mammals, indicating an ancient origin.
The C-Terminal Part of Microcin B Is Crucial for DNA Gyrase Inhibition and Antibiotic Uptake by Sensitive Cells
Authors: Shkundina Irina , Serebryakova Marina , Severinov Konstantin
Published: February 2014

Microcin B (McB) is a ribosomally synthesized antibacterial peptide. It contains up to nine oxazole and thiazole heterocycles that are introduced posttranslationally and are required for activity. McB inhibits the DNA gyrase, a validated drug target. Previous structure-activity analyses indicated that two fused heterocycles located in the central part of McB are important for antibacterial action and gyrase inhibition. Here, we used site-specific mutagenesis of the McB precursor gene to assess the functional significance of the C-terminal part of McB that is located past the second fused heterocycle and contains two single heterocycles as well as an unmodified four-amino-acid C-terminal tail. We found that removal of unmodified C-terminal amino acids of McB, while having no effect on fused heterocycles, has a very strong negative effect on activity
in vivo
and
in vitro
. In fact, even nonconservative point substitutions in the last McB amino acid have a very strong effect by simultaneously decreasing uptake and ability to inhibit the gyrase. The results highlight the importance of unmodified McB amino acids for function and open the way for creation of recombinant McB derivatives with an altered or expanded spectrum of antibacterial action.
The PhoU Protein from Escherichia coli Interacts with PhoR, PstB, and Metals To Form a Phosphate-Signaling Complex at the Membrane
Authors: Gardner Stewart G. , Johns Kristine D. , Tanner Rebecca , McCleary William R.
Published: February 2014

Robust growth in many bacteria is dependent upon proper regulation of the adaptive response to phosphate (P
i
) limitation. This response enables cells to acquire P
i
with high affinity and utilize alternate phosphorous sources. The molecular mechanisms of P
i
signal transduction are not completely understood. PhoU, along with the high-affinity, P
i
-specific ATP-binding cassette transporter PstSCAB and the two-component proteins PhoR and PhoB, is absolutely required for P
i
signaling in
Escherichia coli
. Little is known about the role of PhoU and its function in regulation. We have demonstrated using bacterial two-hybrid analysis and confirmatory coelution experiments that PhoU interacts with PhoR through its PAS (
P
er-
A
RNT-
S
im) domain and that it also interacts with PstB, the cytoplasmic component of the transporter. We have also shown that the soluble form of PhoU is a dimer that binds manganese and magnesium. Alteration of highly conserved residues in PhoU by site-directed mutagenesis shows that these sites play a role in binding metals. Analysis of these
phoU
mutants suggests that metal binding may be important for PhoU membrane interactions. Taken together, these results support the hypothesis that PhoU is involved in the formation of a signaling complex at the cytoplasmic membrane that responds to environmental P
i
levels.
Escherichia coli Isolate for Studying Colonization of the Mouse Intestine and Its Application to Two-Component Signaling Knockouts
Authors: Lasaro Melissa , Liu Zhi , Bishar Rima , Kelly Kathryn , Chattopadhyay Sujay , Paul Sandip , Sokurenko Evgeni , Zhu Jun , Goulian Mark
Published: February 2014

The biology of
Escherichia coli
in its primary niche, the animal intestinal tract, is remarkably unexplored. Studies with the streptomycin-treated mouse model have produced important insights into the metabolic requirements for
Escherichia coli
to colonize mice. However, we still know relatively little about the physiology of this bacterium growing in the complex environment of an intestine that is permissive for the growth of competing flora. We have developed a system for studying colonization using an
E. coli
strain, MP1, isolated from a mouse. MP1 is genetically tractable and does not require continuous antibiotic treatment for stable colonization. As an application of this system, we separately knocked out each two-component system response regulator in MP1 and performed competitions against the wild-type strain. We found that only three response regulators, ArcA, CpxR, and RcsB, produce strong colonization defects, suggesting that in addition to anaerobiosis, adaptation to cell envelope stress is a critical requirement for
E. coli
colonization of the mouse intestine. We also show that the response regulator OmpR, which had previously been hypothesized to be important for adaptation between
in vivo
and
ex vivo
environments, is not required for MP1 colonization due to the presence of a third major porin.
Anterior cruciate ligament injury alters preinjury lower extremity biomechanics in the injured and uninjured leg: the JUMP-ACL study
Authors: Goerger Benjamin M , Marshall Stephen W , Beutler Anthony I , Blackburn J Troy , Wilckens John H , Padua Darin A
Published: February 2014

Background

Information as to how anterior cruciate ligament (ACL) injury and reconstructive surgery (ACLR) alter lower extremity biomechanics may improve rehabilitation and return to play guidelines, reducing the risk for repeat ACL injury.

Aim

To compare lower extremity biomechanics before ACL injury and after subsequent ACLR for the injured and uninjured leg.

Methods

Baseline unilateral lower extremity biomechanics were collected on the dominant leg of participants without ACL injury when they entered the Joint Undertaking to Monitor and Prevent ACL (JUMP-ACL) study. Thirty-one participants with subsequent ACL injury, reconstructive surgery and full return to physical activity completed repeat, follow-up biomechanical testing, as did 39 uninjured, matched controls. Not all injured participants suffered injury to the dominant leg, requiring separation of those with ACL injury into two groups: ACLR-injured leg group (n=12) and ACLR-uninjured leg group (n=19). We compared the landing biomechanics of these three groups (ACLR-injured leg, ACLR-uninjured leg, control) before ACL injury (baseline) with biomechanics after ACL injury, surgery and return to physical activity (follow-up).

Results

ACL injury and ACLR altered lower extremity biomechanics, as both ACLR groups demonstrated increases in frontal plane movement (increased hip adduction and knee valgus). The ACLR-injured leg group also exhibited decreased sagittal plane loading (decreased anterior tibial shear force, knee extension moment and hip flexion moment). No high-risk biomechanical changes were observed in control group participants.

Conclusions

ACL injury and ACLR caused movement pattern alterations of the injured and uninjured leg that have previously shown to increase the risk for future non-contact ACL injury.
Strong evidence against platelet-rich plasma injections for chronic lateral epicondylar tendinopathy: a systematic review
Authors: de Vos Robert-Jan , Windt Johann , Weir Adam
Published: February 2014

Background

Chronic lateral epicondylar tendinopathy is frequent in athletes, and platelet-rich plasma (PRP) is being used increasingly in its treatment.

Objective

To systematically review the literature on the efficacy of PRP injections for chronic lateral epicondylar tendinopathy.

Methods

The databases of PubMed, EMBASE, CINAHL, Medline OvidSP, Scopus, Google Scholar, Web of Science and Cochrane Library were searched in October 2013. Inclusion criteria were a clinical diagnosis of chronic lateral epicondylar tendinopathy, a randomised controlled trial, an intervention with a PRP injection and the outcome measures described in terms of pain and/or function. One author screened the search results and two authors independently assessed the study quality using the Physiotherapy Evidence Database (PEDro) score. A study was considered to be of high quality if its PEDro score was ≥6. A best evidence synthesis was used to identify the level of evidence.

Results

6 studies were included, of which four were considered to be of high quality. Three high-quality studies (75%) and two low-quality studies showed no significant benefit at the final follow-up measurement or predefined primary outcome score when compared with a control group. One high-quality study (25%) showed a beneficial effect of a PRP injection when compared with a corticosteroid injection (corticosteroid injections are harmful in tendinopathy). Based on the best evidence synthesis, there is strong evidence that PRP injections are not efficacious in chronic lateral epicondylar tendinopathy.

Conclusions

There is strong evidence that PRP injections are not efficacious in the management of chronic lateral elbow tendinopathy.
Visual or computer-based measurements: important for interpretation of athletes’ ECG
Authors: Berge H M , Steine K , Andersen T E , Solberg E E , Gjesdal K
Published: February 2014

Background

ECG is recommended for preparticipation health examination in athletes. Owing to a lack of consensus on how to read and interpret athletes’ ECGs, different criteria for abnormality are used.

Aims

To compare the prevalence of abnormal ECGs and test the correlation between visual and computer-based measurements.

Methods

In a preparticipation cardiac screening examination of 595 male professional soccer players aged 18–38 years, ECGs were categorised according to the European Society of Cardiology's (ESC) recommendations and the Seattle criteria, respectively. Visual measurements were conducted with callipers on-screen on the averaged PQRST complex in each lead, calculated by the trimmed mean. Computer-based measurements were derived from the medium beat. Heart rhythm and conduction were scored visually by a cardiologist. Categorical variables were compared by κ statistics (K) and continuous variables by intraclass correlation.

Results

ECGs of good quality were available from 579 players. According to the ESC's recommendations and Seattle criteria, respectively, ECGs were categorised as abnormal in 171 (29.5%) vs 64 (11.1%) players after visual assessment, and in 293 (50.6%; K=0.395) vs 127 (21.9%; K=0.564) after computer-based measurements. Intraclass correlation was very good for measurements of R and S wave amplitudes and moderate to very good for intervals. K was very good for pathological Q wave amplitudes and moderate for T wave inversions.

Conclusions

Abnormal ECGs were more than twice as common after computer-based than after visual measurements. Such a difference will markedly influence the number of athletes who need further examinations. Reference values may need adjustments dependent on measurement methods.
Which lipid measurement should we monitor? An analysis of the LIPID study
Authors: Glasziou Paul P , Irwig Les , Kirby Adrienne C , Tonkin Andrew M , Simes R John
Published: February 2014

Objectives

To evaluate the optimal lipid to measure in monitoring patients, we assessed three factors that influence the choice of monitoring tests: (1) clinical validity; (2) responsiveness to therapy changes and (3) the size of the long-term ‘signal-to-noise’ ratio.

Design

Longitudinal analyses of repeated lipid measurement over 5 years.

Setting

Subsidiary analysis of a Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study—a clinical trial in Australia, New Zealand and Finland.

Participants

9014 patients aged 31–75 years with previous acute coronary syndromes.

Interventions

Patients were randomly assigned to 40 mg daily pravastatin or placebo.

Primary and secondary outcome measures

We used data on serial lipid measurements—at randomisation, 6 months and 12 months, and then annually to 5 years—of total cholesterol; low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and their ratios; triglycerides; and apolipoproteins A and B and their ratio and their ability to predict coronary events.

Results

All the lipid measures were statistically significantly associated with future coronary events, but the associations between each of the three ratio measures (total or LDL cholesterol to HDL cholesterol, and apolipoprotein B to apolipoprotein A1) and the time to a coronary event were better than those for any of the single lipid measures. The two cholesterol ratios also ranked highly for the long-term signal-to-noise ratios. However, LDL cholesterol and non-HDL cholesterol showed the most responsiveness to treatment change.

Conclusions

Lipid monitoring is increasingly common, but current guidelines vary. No single measure was best on all three criteria. Total cholesterol did not rank highly on any single criterion. However, measurements based on cholesterol subfractions—non-HDL cholesterol (total cholesterol minus HDL cholesterol) and the two ratios—appeared superior to total cholesterol or any of the apolipoprotein options. Guidelines should consider using non-HDL cholesterol or a ratio measure for initial treatment decisions and subsequent monitoring.
The routine collection of patient-reported outcome measures (PROMs) for long-term conditions in primary care: a cohort survey
Authors: Peters Michele , Crocker Helen , Jenkinson Crispin , Doll Helen , Fitzpatrick Ray
Published: February 2014

Objectives

To evaluate the feasibility of using patient-reported outcome measures (PROMs) for long-term conditions (LTCs) in primary care.

Design

A cohort postal survey conducted from September 2010 to April 2012.

Setting

Primary care practices (n=33) in London and the North-West of England.

Participants

4484 patients with a diagnosis of asthma, chronic obstructive pulmonary disease, diabetes, epilepsy, heart failure or stroke were sent a survey at baseline.

Main outcome

The main outcome was to evaluate the feasibility of and the recruitment strategies for collecting PROMs data in LTCs by assessing the response rates for the baseline and follow-up surveys. Secondary outcomes were the evaluation of change scores of the EQ-5D index and visual analogue scale (VAS) between baseline and follow-up surveys.

Results

The baseline survey achieved a response rate of 38.4% (n=1721/4485) and at follow-up 71.5% (n=1136/1589). Response rates varied by LTC. Little change was found in health-related quality of life for the total sample (−0.001 for the EQ-5D index score and 0.12 for the EQ-5D VAS) between patients responding to both the baseline and follow-up surveys.

Conclusions

The response rate to the baseline survey was similar to that of other general practice surveys. Current UK policy aims to assess health service performance in LTCs by means of using PROMs. It thus would be desirable to improve response rates by making the invitation to self-reports of health-related quality of life more engaging for patients. Results on the EQ-5D score raise questions about optimal indicators for LTCs and appropriate timelines for assessment.
Non-aristolochic acid prescribed Chinese herbal medicines and the risk of mortality in patients with chronic kidney disease: results from a population-based follow-up study
Authors: Hsieh Chuan Fa , Huang Song Lih , Chen Chien Lung , Chen Wei Ta , Chang Huan Cheng , Yang Chen Chang
Published: February 2014

Objectives

To evaluate the relationship between the use of non-aristolochic acid (AA) prescribed Chinese herbal medicines (CHMs) and the risk of mortality in patients with chronic kidney disease (CKD).

Design

Nationwide population-based follow-up study.

Setting

Longitudinal health insurance database sampled from the Taiwan National Health Insurance Research Database.

Participants

A total of 47 876 patients with CKD were identified. Participants who had ever used AA-containing CHMs, had cancer or HIV prior to the diagnosis of CKD, died within the first month of CKD diagnosis and who were not Taiwanese citizens were excluded. A total of 13 864 participants were eligible for final analysis.

Primary and secondary outcome measures

All-cause mortality among patients with CKD between 2000 and 2008.

Results

After controlling for potential confounders, we found that participants who started to receive non-AA prescribed CHMs after the diagnosis of CKD had a lower risk of mortality as compared with non-users of non-AA prescribed CHMs (adjusted HR (aHR) 0.6; 95% CI 0.4 to 0.7, p<0.001). Moreover, participants who had used non-AA prescribed CHMs prior to and after the diagnosis of CKD also had a lower risk of mortality than non-users (aHR 0.6; 95% CI 0.5 to 0.8, p<0.001). In subgroup analyses, we found that such an inverse association was present only among patients who were not eligible to receive erythropoietin therapy (ie, serum creatinine ≦6 mg/dL and/or haematocrit value ≧28%).

Conclusions

Patients who received non-AA prescribed CHMs after the diagnosis of CKD, yet before the start of erythropoietin therapy had a lower risk of mortality than those who did not.
Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score
Authors: Fox Keith A A , FitzGerald Gordon , Puymirat Etienne , Huang Wei , Carruthers Kathryn , Simon Tabassome , Coste Pierre , Monsegu Jacques , Gabriel Steg Philippe , Danchin Nicolas , Anderson Fred
Published: February 2014

Objectives

Risk scores are recommended in guidelines to facilitate the management of patients who present with acute coronary syndromes (ACS). Internationally, such scores are not systematically used because they are not easy to apply and some risk indicators are not available at first presentation. We aimed to derive and externally validate a more accurate version of the Global Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of death or death/myocardial infarction (MI) both acutely and over the longer term. The risk score was designed to be suitable for acute and emergency clinical settings and usable in electronic devices.

Design and setting

The GRACE risk score (2.0) was derived in 32 037 patients from the GRACE registry (14 countries, 94 hospitals) and validated externally in the French registry of Acute ST-elevation and non-ST-elevation MI (FAST-MI) 2005.

Participants

Patients presenting with ST-elevation and non-ST elevation ACS and with long-term outcomes.

Outcome measures

The GRACE Score (2.0) predicts the risk of short-term and long-term mortality, and death/MI, overall and in hospital survivors.

Results

For key independent risk predictors of death (1 year), non-linear associations (vs linear) were found for age (p<0.0005), systolic blood pressure (p<0.0001), pulse (p<0.0001) and creatinine (p<0.0001). By employing non-linear algorithms, there was improved model discrimination, validated externally. Using the FAST-MI 2005 cohort, the c indices for death exceeded 0.82 for the overall population at 1 year and also at 3 years. Discrimination for death or MI was slightly lower than for death alone (c=0.78). Similar results were obtained for hospital survivors, and with substitutions for creatinine and Killip class, the model performed nearly as well.

Conclusions

The updated GRACE risk score has better discrimination and is easier to use than the previous score based on linear associations. GRACE Risk (2.0) performed equally well acutely and over the longer term and can be used in a variety of clinical settings to aid management decisions.
How complete are our clerkings? A project aimed at improving the quality of medical records by using a standardised proforma.
Authors: Chow Jij , Yvon Camille , Stanger Tim
Published: February 2014

Clerking a patient is the first and most important contact that any medical team has with the patient. It provides information that may not be available later in the admission if recorded improperly, such as referral letters, collateral history, dosette boxes or prescription sheets. The quality of data recorded from this encounter was examined at a busy district general hospital surgical department. Initial measurement demonstrated that less than half of certain key parameters like dosages of medication were being recorded by clerking doctors. A clerking proforma was therefore designed to combat this problem. Over three audit cycles (n = 170, 150, 174) the proforma showed statistically significant improvements in the proportion of data that was captured at initial contact with the patient. We conclude that the introduction of proformas for clerking significantly improves the collection of data that impacts patient care during their hospital stay.
BOTH SIDES OF THE FENCE: METHODOLOGICAL CHALLENGES IN UNDERTAKING RESEARCH INTO END OF LIFE CARE FOR PRISONERS
Authors: Turner M , Peacock M , Froggatt K , Payne S , Fletcher A , Gibson R , Scott G
Published: February 2014

Introduction

The number of older prisoners in the UK has more than doubled in the last decade, with the greatest increases amongst those over 70. Around 40% of older prisoners are sex offenders, many of whom are in prison for the first time due to historic abuse. Longer sentences and more stringent release criteria mean that increasing numbers of anticipated deaths in prison are predicted. Prison staff experience tensions between care and custody and demands for considerable emotional labour in delivering palliative care to such prisoners.

Aim(s) and method(s)

This paper presents some of the methodological challenges encountered during the early stages of the ‘Both sides of the fence’ study, which uses action research to develop a transferable model of integrated palliative care for prisoners. The first phase comprises a detailed situational analysis to explore current palliative care provision in one prison; then healthcare and custodial staff participate in action cycles to implement and evaluate changes to practice.

Results

A prison with a large population of older and disabled prisoners was identified as the research site, and access was granted following ethical and governance approvals. Engagement of diverse groups of staff in the research required multiple meetings, extensive networking and the visible on-site presence of the researcher; this engagement led to an important protocol amendment to include focus groups with prisoners who provide informal care to fellow prisoners.

Conclusion(s)

Establishing effective connections with a wide range of prison staff has been key to overcoming the methodological challenges and progressing the research.
SUPPORTING PATIENTS AND THEIR FAMILIES WHO WISH TO DIE AT HOME - BEREAVED RELATIVES' VIEWS ABOUT THE CARE AND SUPPORT RECEIVED
Authors: Mayland CR , Lees C , West A , Cox T , Mason SR , Ellershaw JE
Published: February 2014

Introduction

Although focus is placed on achieving patient preference to die at home, ensuring the provision of good quality care and family support is equally important.

Aim(s) and method(s)

To assess quality of care and family support, as perceived by bereaved relatives, using ‘Care Of the Dying Evaluation’ (CODE), a 40-item validated post-bereavement questionnaire based on key components of best practice for care of the dying. 291 next-of-kin (NOK) to adult patients, who died an ‘expected’ death at home in Northwest England from advanced incurable illness between July 2011 and December 2012, were identified using the Preferred Place of Care database. All NOK were invited to complete CODE at least two months following the bereavement, with a reminder sent 4 weeks later.

Results

72 NOK (24.7%) returned the completed CODE questionnaire. Participants were mainly female (n=47, 65.3%), a spouse or partner (n=40, 55.6%) and aged 50 years or above (n=57, 79.1%). Most deceased patients had advanced cancer (n=57, 79.2%). Overall, patient care was perceived as good, with 65 NOK (90.3%) reporting the patient was treated with dignity and respect ‘always’ or ‘most of the time’. Only 55 (76.4%) NOK, however, reported they were adequately supported. Unmet emotional support (n=20, 27.7% reporting this was ‘fair’ or ‘poor’) and information needs (n=24, 33.3% reporting discussions about fluids would have been helpful) were identified.

Conclusion(s)

Despite limitations in sample size and participant representativeness, more proactive means to support families and meet communication needs are required to improve the experience for patients and families who wish to die at home.
CANCER CARERS MEDICINES MANAGEMENT: A FEASIBILITY TRIAL OF AN EDUCATIONAL INTERVENTION FOR MANAGING END OF LIFE PAIN MEDICATION
Authors: Latter S , Lowson E , Hopkinson J , Hughes J , Richardson A , Duke S , Anstey S , Bennett M , May C , Smith P
Published: February 2014

Introduction

A majority of people with advanced cancer will experience pain and family carers play an important role in managing pain medication at home. There is evidence carers need support with this, yet no research in the UK has developed and tested theory-driven interventions to help them manage pain medicines. We are conducting a Phase I-II feasibility study (MRC 2008) to develop a new intervention: Cancer Carer Medicines Management (CCMM).

Aim(s) and method(s)

To summarise Phase I, outlining the process of CCMM development. A staged multi-method approach was used to obtain current evidence to inform CCMM's development: a systematic literature review of interventions for carer end of life medicines management; a scoping of practice and theoretical contexts; interviews and user involvement group consultations with patients, carers, and health professionals with palliative care experience. This informed two participatory action research workshops to design and develop an intervention. The resulting prototype intervention was then further refined through a consultative review process.

Results

This staged, collaborative approach is appropriate and successful in enabling an evidence-based, clinically applicable intervention to be developed.

Conclusion(s)

The intervention development process has ensured that CCMM reaches the feasibility trial stage with a robust grounding in carer experience, clinical practice and research evidence. In turn, the intervention has the potential to enhance the nurses' practice in the community to meet carers' needs in pain medication management.