bluuebunny/crossref_metadata_2025 huggingface dataset:
A struggle to survive: The experience of awaiting pediatric heart transplantation
Authors: Anthony Samantha J. , Nicholas David B. , Regehr Cheryl , West Lori J.
Published: October 2014

Despite the establishment of heart transplantation as a life‐saving therapy for children and adolescents, little research has focused on the biopsychosocial impact of the transplant process. Few studies have captured the subjective experiences of young heart transplant recipients. This study examined the experiences and perspectives of children and adolescents during the pretransplant phase of waiting for a donor organ. Grounded theory methods guided data collection and analysis. A total of 27 adolescents participated in semistructured qualitative interviews. Findings illuminate the waiting period for pediatric heart transplantation to be a pervasive experience, with consequent impact on physical, psychological, and social well‐being. Participants described various biopsychosocial processes and experiences that occurred during this time, with data analysis yielding themes reflecting notions of “struggling to survive,” including physical limitations, lethargy, social isolation, discomfort with physical appearance, and academic issues. This research identifies the pretransplant experience as a period framed within a text of debilitation and negative self‐perceptions related to health and well‐being. Supporting children and their families as they navigate this complex and uncertain journey is merited, and results invite further interventional development and research.
Tacrolimus therapeutic drug monitoring and pediatric renal transplant graft outcomes
Authors: Larkins Nicholas , Matsell Douglas G.
Published: October 2014

Predose monitoring of tacrolimus levels is standard practice in the care of pediatric renal transplant patients. This is despite a paucity of data investigating the ideal target range in children, and controversy as to whether tacrolimus levels correlate with renal transplant outcomes. We performed a retrospective cohort analysis of 48 renal transplant patients at a single Canadian pediatric transplant center following the initiation of a tacrolimus–mycophenolate–prednisone‐based IS protocol. We analyzed the relationship of graft function, as defined by GFR up to five yr post‐transplant, to the preceding mean tacrolimus level. There was no significant correlation between absolute GFR and mean tacrolimus levels (r = 0.206, p = 0.38). However, a higher mean tacrolimus level, particularly ≥10 ng/mL in the first three months after transplantation, was associated with a slower rate of decline in GFR with time (r = 0.608, p = 0.004) and with a less likelihood of developing CKD five yr after transplant. We suggest that the optimal target range for tacrolimus levels may be at the upper end of what is currently practiced and that further research to validate these findings would be useful.
Compartmentalized gene expression of toll‐like receptors 2, 4 and 9 in the brain and peripheral lymphoid organs during canine visceral leishmaniasis
Authors: Melo G. D. , Silva J. E. S. , Grano F. G. , Homem C. G. , Machado G. F.
Published: October 2014

Visceral leishmaniasis is an important parasitic disease that affects humans and animals. The response against the protozoan involves the interaction of both innate and adaptive branches of the immune system, and an important immune sensor is represented by the toll‐like receptor (TLR) family. Here, we investigated the pattern of TLR‐2, TLR‐4 and TLR‐9 gene expression in different compartments (brain, choroid plexus, spleen and lymph node) of dogs naturally infected with Leishmania infantum. Gene expression of the TLRs varied according to the compartment evaluated. In the brain, there was only an upregulation of TLR‐2, whereas in the choroid plexus, TLR‐2 and TLR‐9 were both upregulated. Further, the peripheral lymphoid organs (spleen and lymph nodes) showed increased TLR‐2 and TLR‐4 expression. This study provides the first insight about TLR expression in the central nervous system of infected dogs, and gives additional evidence of the compartmentalization of the immune response during visceral leishmaniasis.
Post‐encystment/established immunity in cystic echinococcosis: is it really that simple?
Authors: Rogan M. T. , Bodell A. J. , Craig P. S.
Published: October 2014

In 1982, Rickard & Williams stated that immunity to larval taeniid cestodes could be divided into two different phases: the establishment phase, operating against oncospheres, and the established phase, operating against established metacestodes in the tissues. These concepts were largely based on experimental and veterinary data. As a result of subsequent research combined with clinical data, we can consider that, for metacestodes of Echinococcus spp, a single established phase is probably too simple a concept. These parasites show developmental changes in different hosts over time, the most significant being growth, fertility and degeneration. Recent clinical cyst classifications (WHO/IWGE) have highlighted that all hydatid cysts are morphologically not the same. This is important for treatment but fails to completely address variation in the host/parasite response and the understanding of parasite survival. This review attempts to relate the immunological and developmental data obtained from experimental, veterinary and medical studies to update our understanding of established immunity against E. granulosus. It proposes that a single ‘Established’ phase for E. granulosus could be subdivided into four additional phases: maturing; stable; unstable and degenerative. Combining this type of information with existing cyst classification systems could significantly benefit our understanding of the parasites immunobiology.
Living on the edge: the role of geography and environment in structuring genetic variation in the southernmost populations of a tropical oak
Authors: Ortego J. , Bonal R. , Muñoz A. , Espelta J. M.
Published: October 2014

Understanding the factors determining genetic diversity and structure in peripheral populations is a long‐standing goal of evolutionary biogeography, yet little empirical information is available for tropical species. In this study, we combine information from nuclear microsatellite markers and niche modelling to analyse the factors structuring genetic variation across the southernmost populations of the tropical oak Quercus segoviensis. First, we tested the hypothesis that genetic variability decreases with population isolation and increases with local habitat suitability and stability since the Last Glacial Maximum (LGM). Second, we employed a recently developed multiple matrix regression with randomisation (MMRR) approach to study the factors associated with genetic divergence among the studied populations and test the relative contribution of environmental and geographic isolation to contemporary patterns of genetic differentiation. We found that genetic diversity was negatively correlated with average genetic differentiation with other populations, indicating that isolation and limited gene flow have contributed to erode genetic variability in some populations. Considering the relatively small size of the study area (<120 km), analyses of genetic structure indicate a remarkable inter‐population genetic differentiation. Environmental dissimilarity and differences in current and past climate niche suitability and their additive effects were not associated with genetic differentiation after controlling for geographic distance, indicating that local climate does not contribute to explain spatial patterns of genetic structure. Overall, our data indicate that geographic isolation, but not current or past climate, is the main factor determining contemporary patterns of genetic diversity and structure within the southernmost peripheral populations of this tropical oak.
Frequency‐dependent facilitation of synaptic throughput via postsynaptic NMDA receptors in the nucleus of the solitary tract
Authors: Zhao Huan , Peters James H. , Zhu Mingyan , Page Stephen J. , Ritter Robert C. , Appleyard Suzanne M.
Published: October 2014

Key points

Hindbrain NMDA receptors play important roles in reflexive and behavioural responses to vagal activation.

NMDA receptors have also been shown to contribute to the synaptic responses of neurons in the nucleus of the solitary tract (NTS), but their exact role remains unclear.

In this study we used whole cell patch‐clamping techniques in rat horizontal brain slice to investigate the role of NMDA receptors in the fidelity of transmission across solitary tract afferent–NTS neuron synapses.

Results show that NMDA receptors contribute up to 70% of the charge transferred across the synapse at high (>5 Hz) firing rates, but have little contribution at lower firing frequencies. Results also show that NMDA receptors critically contribute to the fidelity of transmission across these synapses during high frequency (>5 Hz) afferent discharge rates.

This novel role of NMDA receptors may explain in part how primary visceral afferents, including vagal afferents, can maintain fidelity of transmission across a broad range of firing frequencies.

Neurons within the nucleus of the solitary tract (NTS) receive vagal afferent innervations that initiate gastrointestinal and cardiovascular reflexes. Glutamate is the fast excitatory neurotransmitter released in the NTS by vagal afferents, which arrive there via the solitary tract (ST). ST stimulation elicits excitatory postsynaptic currents (EPSCs) in NTS neurons mediated by both AMPA‐ and NMDA‐type glutamate receptors (‐Rs). Vagal afferents exhibit a high probability of vesicle release and exhibit robust frequency‐dependent depression due to presynaptic vesicle depletion. Nonetheless, synaptic throughput is maintained even at high frequencies of afferent activation. Here we test the hypothesis that postsynaptic NMDA‐Rs are essential in maintaining throughput across ST–NTS synapses. Using patch clamp electrophysiology in horizontal brainstem slices, we found that NMDA‐Rs, including NR2B subtypes, carry up to 70% of the charge transferred across the synapse during high frequency stimulations (>5 Hz). In contrast, their relative contribution to the ST‐EPSC is much less during low (<2 Hz) frequency stimulations. Afferent‐driven activation of NMDA‐Rs produces a sustained depolarization during high, but not low, frequencies of stimulation as a result of relatively slow decay kinetics. Hence, NMDA‐Rs are critical for maintaining action potential generation at high firing rates. These results demonstrate a novel role for NMDA‐Rs enabling a high probability of release synapse to maintain the fidelity of synaptic transmission during high frequency firing when glutamate release and AMPA‐R responses are reduced. They also suggest why NMDA‐Rs are critical for responses that may depend on high rates of afferent discharge.
Skeletal muscle ATP turnover by 31P magnetic resonance spectroscopy during moderate and heavy bilateral knee extension
Authors: Cannon Daniel T. , Bimson William E. , Hampson Sophie A. , Bowen T. Scott , Murgatroyd Scott R. , Marwood Simon , Kemp Graham J. , Rossiter Harry B.
Published: October 2014

Key points

Heavy‐intensity exercise causes a progressive increase in energy demand that contributes to exercise limitation.

This inefficiency arises within the locomotor muscles and is thought to be due to an increase in the ATP cost of power production; however, the responsible mechanism is unresolved.

We measured whole‐body O2 uptake and skeletal muscle ATP turnover by combined pulmonary gas exchange and magnetic resonance spectroscopy during moderate and heavy exercise in humans.

Muscle ATP synthesis rate increased throughout constant‐power heavy exercise, but this increase was unrelated to the progression of whole‐body inefficiency.

Our data indicate that the increased ATP requirement is not the sole cause of inefficiency during heavy exercise, and other mechanisms, such as increased O2 cost of ATP resynthesis, may contribute.

During constant‐power high‐intensity exercise, the expected increase in oxygen uptake () is supplemented by a  slow component (), reflecting reduced work efficiency, predominantly within the locomotor muscles. The intracellular source of inefficiency is postulated to be an increase in the ATP cost of power production (an increase in P/W). To test this hypothesis, we measured intramuscular ATP turnover with 31P magnetic resonance spectroscopy (MRS) and whole‐body during moderate (MOD) and heavy (HVY) bilateral knee‐extension exercise in healthy participants (n = 14). Unlocalized 31P spectra were collected from the quadriceps throughout using a dual‐tuned (1H and 31P) surface coil with a simple pulse‐and‐acquire sequence. Total ATP turnover rate (ATPtot) was estimated at exercise cessation from direct measurements of the dynamics of phosphocreatine (PCr) and proton handling. Between 3 and 8 min during MOD, there was no discernable (mean ± SD, 0.06 ± 0.12 l min−1) or change in [PCr] (30 ± 8 vs. 32 ± 7 mm) or ATPtot (24 ± 14 vs. 17 ± 14 mm min−1; each P = n.s.). During HVY, the was 0.37 ± 0.16 l min−1 (22 ± 8%), [PCr] decreased (19 ± 7 vs. 18 ± 7 mm, or 12 ± 15%; P < 0.05) and ATPtot increased (38 ± 16 vs. 44 ± 14 mm min−1, or 26 ± 30%; P < 0.05) between 3 and 8 min. However, the increase in ATPtot (ΔATPtot) was not correlated with the during HVY (r2 = 0.06; P = n.s.). This lack of relationship between ΔATPtot and , together with a steepening of the [PCr]– relationship in HVY, suggests that reduced work efficiency during heavy exercise arises from both contractile (P/W) and mitochondrial sources (the O2 cost of ATP resynthesis; P/O).
Prostaglandin E2 differentially modulates the central control of eupnoea, sighs and gasping in mice
Authors: Koch Henner , Caughie Cali , Elsen Frank P. , Doi Atsushi , Garcia Alfredo J. , Zanella Sebastien , Ramirez Jan‐Marino
Published: October 2014

Key points

Prostaglandin E2 (PGE2) augments distinct inspiratory motor patterns, generated within the preBötzinger complex (preBötC), in a dose‐dependent way. The frequency of sighs and gasping are stimulated at low concentrations, while the frequency of eupnoea increases only at high concentrations.

We used in vivo microinjections into the preBötC and in vitro isolated brainstem slice preparations to investigate the dose‐dependent effects of PGE2 on the preBötC activity.

Synaptic measurements in whole cell voltage clamp recordings of inspiratory neurons revealed no changes in inhibitory or excitatory synaptic transmission in response to PGE2 exposure.

In current clamp recordings obtained from inspiratory neurons of the preBötC, we found an increase in the frequency and amplitude of bursting activity in neurons with intrinsic bursting properties after exposure to PGE2.

Riluzole, a blocker of the persistent sodium current, abolished the effect of PGE2 on sigh activity, while flufenamic acid, a blocker of the calcium‐activated non‐selective cation conductance, abolished the effect on eupnoeic activity caused by PGE2.

Prostaglandins are important regulators of autonomic functions in the mammalian organism. Here we demonstrate in vivo that prostaglandin E2 (PGE2) can differentially increase the frequency of eupnoea (normal breathing) and sighs (augmented breaths) when injected into the preBötzinger complex (preBötC), a medullary area that is critical for breathing. Low concentrations of PGE2 (100–300 nm) increased the sigh frequency, while higher concentrations (1–2 μm) were required to increase the eupnoeic frequency. The concentration‐dependent effects were similarly observed in the isolated preBötC. This in vitro preparation also revealed that riluzole, a blocker of the persistent sodium current (INap), abolished the modulatory effect on sighs, while flufenamic acid, an antagonist for the calcium‐activated non‐selective cation conductance (ICAN) abolished the effect of PGE2 on fictive eupnoea at higher concentrations. At the cellular level PGE2 significantly increased the amplitude and frequency of intrinsic bursting in inspiratory neurons. By contrast PGE2 affected neither excitatory nor inhibitory synaptic transmission. We conclude that PGE2 differentially modulates sigh, gasping and eupnoeic activity by differentially increasing INap and ICAN currents in preBötC neurons.
Rest-time effects in repeated shear-startup runs of branched SBR polymers
Authors: Coppola Salvatore , Bacchelli Fabio , Marrucci Giuseppe , Ianniruberto Giovanni
Published: October 2014

New data of shear startup on branched styrene-butadiene random (SBR) copolymers are reported, where the novelty consists in repeating the startup run after different rest times at zero stress. Here, the aim is one of exploring the “damage” introduced by the first run, as well as the subsequent recovery, if any, upon waiting increasingly long times. Differently from a linear sample, our branched melts show multiple peaks during the first run, as previously reported by Bacchelli [Kautschuk Gummi Kunststoffe 61, 188–191 (2008)] for similar SBR samples, and, more recently, by Snijkers et al. [ACS Macro Lett. 2, 601–604 (2013)] for a well-characterized comblike polystyrene melt. The repeated runs show an intriguing novel feature with respect to the case of linear polymers, namely, the first peak goes up initially, instead of down. The second peak goes down and seemingly recovers only after an extremely long time, longer than the largest relaxation time practically accessible to linear viscoelasticity, the latter not reaching the terminal behavior. All such features of nonlinear viscoelasticity of highly branched polymers are interpreted by using a simple theory inspired by the well-known pompom model.
Metabolic Engineering of a Glycerol-Oxidative Pathway in Lactobacillus panis PM1 for Utilization of Bioethanol Thin Stillage: Potential To Produce Platform Chemicals from Glycerol
Authors: Kang Tae Sun , Korber Darren R. , Tanaka Takuji
Published: October 2014

Lactobacillus panis
PM1 has the ability to produce 1,3-propanediol (1,3-PDO) from thin stillage (TS), which is the major waste material after bioethanol production, and is therefore of significance. However, the fact that
L. panis
PM1 cannot use glycerol as a sole carbon source presents a considerable problem in terms of utilization of this strain in a wide range of industrial applications. Accordingly,
L. panis
PM1 was genetically engineered to directly utilize TS as a fermentable substrate for the production of valuable platform chemicals without the need for exogenous nutrient supplementation (e.g., sugars and nitrogen sources). An artificial glycerol-oxidative pathway, comprised of glycerol facilitator, glycerol kinase, glycerol 3-phosphate dehydrogenase, triosephosphate isomerase, and NADPH-dependent aldehyde reductase genes of
Escherichia coli
, was introduced into
L. panis
PM1 in order to directly utilize glycerol for the production of energy for growth and value-added chemicals. A pH 6.5 culture converted glycerol to mainly lactic acid (85.43 mM), whereas a significant amount of 1,3-propanediol (59.96 mM) was formed at pH 7.5. Regardless of the pH, ethanol (82.16 to 83.22 mM) was produced from TS fermentations, confirming that the artificial pathway metabolized glycerol for energy production and converted it into lactic acid or 1,3-PDO and ethanol in a pH-dependent manner. This study demonstrates the cost-effective conversion of TS to value-added chemicals by the engineered PM1 strain cultured under industrial conditions. Thus, application of this strain or these research findings can contribute to reduced costs of bioethanol production.
Construction of a Quadruple Auxotrophic Mutant of an Industrial Polyploid Saccharomyces cerevisiae Strain by Using RNA-Guided Cas9 Nuclease
Authors: Zhang Guo-Chang , Kong In Iok , Kim Heejin , Liu Jing-Jing , Cate Jamie H. D. , Jin Yong-Su
Published: October 2014

Industrial polyploid yeast strains harbor numerous beneficial traits but suffer from a lack of available auxotrophic markers for genetic manipulation. Here we demonstrated a quick and efficient strategy to generate auxotrophic markers in industrial polyploid yeast strains with the RNA-guided Cas9 nuclease. We successfully constructed a quadruple auxotrophic mutant of a popular industrial polyploid yeast strain,
Saccharomyces cerevisiae
ATCC 4124, with
ura3
,
trp1
,
leu2
, and
his3
auxotrophies through RNA-guided Cas9 nuclease. Even though multiple alleles of auxotrophic marker genes had to be disrupted simultaneously, we observed knockouts in up to 60% of the positive colonies after targeted gene disruption. In addition, growth-based spotting assays and fermentation experiments showed that the auxotrophic mutants inherited the beneficial traits of the parental strain, such as tolerance of major fermentation inhibitors and high temperature. Moreover, the auxotrophic mutants could be transformed with plasmids containing selection marker genes. These results indicate that precise gene disruptions based on the RNA-guided Cas9 nuclease now enable metabolic engineering of polyploid
S. cerevisiae
strains that have been widely used in the wine, beer, and fermentation industries.
Detection and Quantification of Flavobacterium psychrophilum-Specific Bacteriophages
In Vivo
in Rainbow Trout upon Oral Administration: Implications for Disease Control in Aquaculture
Authors: Christiansen Rói Hammershaimb , Dalsgaard Inger , Middelboe Mathias , Lauritsen Anne H. , Madsen Lone
Published: October 2014

The use of bacteriophages in the treatment and prevention of infections by the fish pathogen
Flavobacterium psychrophilum
has attracted increased attention in recent years. It has been shown recently that phage delivery via the parenteral route resulted in immediate distribution of phages to the circulatory system and the different organs. However, little is known about phage dispersal and survival
in vivo
in rainbow trout after delivery via the oral route. Here we examined the dispersal and survival of
F. psychrophilum
phage FpV-9
in vivo
in juvenile rainbow trout after administration by three different methods—bath, oral intubation into the stomach, and phage-coated feed—with special emphasis on the oral route of delivery. Phages could be detected in all the organs investigated (intestine, spleen, brain, and kidney) 0.5 h postadministration, reaching concentrations as high as ∼10
5
PFU mg intestine
−1
and ∼10
3
PFU mg spleen
−1
within the first 24 h following the bath and ∼10
7
PFU mg intestine
−1
and ∼10
4
PFU mg spleen
−1
within the first 24 h following oral intubation. The phages were most persistent in the organs for the first 24 h and then decreased exponentially; no phages were detected after 83 h in the organs investigated. Phage administration via feed resulted in the detection of phages in the intestine, spleen, and kidney 1 h after feeding. Average concentrations of ∼10
4
PFU mg intestine
−1
and ∼10
1
PFU mg spleen
−1
were found throughout the experimental period (200 h) following continuous delivery of phages with feed. These experiments clearly demonstrate the ability of the phages to survive passage through the fish stomach and to penetrate the intestinal barrier and enter the circulatory system after oral delivery, although the quantity of phages found in the spleen was 100- to 1,000-fold lower than that in the intestine. It was also shown that phages could tolerate long periods of desiccation on the feed pellets, with 60% survival after storage at −80°C, and 10% survival after storage at 5°C, for ∼8 months. Continuous delivery of phages via coated feed pellets constitutes a promising method of treatment and especially prevention of rainbow trout fry syndrome.
Aerobic Biodegradation of 2,4-Dinitroanisole by Nocardioides sp. Strain JS1661
Authors: Fida Tekle Tafese , Palamuru Shannu , Pandey Gunjan , Spain Jim C.
Published: October 2014

2,4-Dinitroanisole (DNAN) is an insensitive munition ingredient used in explosive formulations as a replacement for 2,4,6-trinitrotoluene (TNT). Little is known about the environmental behavior of DNAN. There are reports of microbial transformation to dead-end products, but no bacteria with complete biodegradation capability have been reported.
Nocardioides
sp. strain JS1661 was isolated from activated sludge based on its ability to grow on DNAN as the sole source of carbon and energy. Enzyme assays indicated that the first reaction involves hydrolytic release of methanol to form 2,4-dinitrophenol (2,4-DNP). Growth yield and enzyme assays indicated that 2,4-DNP underwent subsequent degradation by a previously established pathway involving formation of a hydride-Meisenheimer complex and release of nitrite. Identification of the genes encoding the key enzymes suggested recent evolution of the pathway by recruitment of a novel hydrolase to extend the well-characterized 2,4-DNP pathway.
Protein Phosphatase 2A (PP2A) Regulatory Subunits ParA and PabA Orchestrate Septation and Conidiation and Are Essential for PP2A Activity in Aspergillus nidulans
Authors: Zhong Guo-wei , Jiang Ping , Qiao Wei-ran , Zhang Yuan-wei , Wei Wen-fan , Lu Ling
Published: October 2014

Protein phosphatase 2A (PP2A) is a major intracellular protein phosphatase that regulates multiple aspects of cell growth and metabolism. Different activities of PP2A and subcellular localization are determined by its regulatory subunits. Here we identified and characterized the functions of two protein phosphatase regulatory subunit homologs, ParA and PabA, in
Aspergillus nidulans
. Our results demonstrate that ParA localizes to the septum site and that deletion of
parA
causes hyperseptation, while overexpression of
parA
abolishes septum formation; this suggests that ParA may function as a negative regulator of septation. In comparison, PabA displays a clear colocalization pattern with 4′,6-diamidino-2-phenylindole (DAPI)-stained nuclei, and deletion of
pabA
induces a remarkable delayed-septation phenotype. Both
parA
and
pabA
are required for hyphal growth, conidiation, and self-fertilization, likely to maintain normal levels of PP2A activity. Most interestingly,
parA
deletion is capable of suppressing septation defects in
pabA
mutants, suggesting that ParA counteracts PabA during the septation process. In contrast, double mutants of
parA
and
pabA
led to synthetic defects in colony growth, indicating that ParA functions synthetically with PabA during hyphal growth. Moreover, unlike the case for PP2A-Par1 and PP2A-Pab1 in yeast (which are negative regulators that inactivate the septation initiation network [SIN]), loss of ParA or PabA fails to suppress defects of temperature-sensitive mutants of the SEPH kinase of the SIN. Thus, our findings support the previously unrealized evidence that the B-family subunits of PP2A have comprehensive functions as partners of heterotrimeric enzyme complexes of PP2A, both spatially and temporally, in
A. nidulans
.
Inter-individual variation in midazolam clearance in children
Authors: Altamimi Mohammed I , Sammons Helen , Choonara Imti
Published: October 2014

Objectives

To determine the extent of inter-individual variation in clearance of midazolam in children and establish which factors are responsible for this variation.

Methods

A systematic literature review was performed to identify papers describing the clearance of midazolam in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL and Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.

Results

25 articles were identified. Only 13 studies gave the full range of clearance values for individual patients. The CV was greater in critically ill patients (18%–170%) than non-critically ill patients (13%–54%). Inter-individual variation was a major problem in all age groups of critically ill patients. The CV was 72%–106% in preterm neonates, 18%–73% in term neonates, 31%–130% in infants, 21%–170% in children and 47%–150% in adolescents. The mean clearance was higher in children (1.1–16.7 mL/min/kg) than in neonates (0.78–2.5 mL/min/kg).

Conclusions

Large inter-individual variation was seen in midazolam clearance values in critically ill neonates, infants, children and adolescents.
Health policy research: successes and challenges
Authors: Lemer Claire , Cheung C Ronny , Viner Russell , Wolfe Ingrid
Published: October 2014

This review seeks to explore and explain what health policy research is and why it matters, through pooling the evidence and providing case examples. Alongside examining the types of research involved, and their rationale the paper identifies the challenges taking part in this sort of research may create. Finally the paper suggests how to make clinical research more accessible to policy makers.
Assessing bias in osteoarthritis trials included in Cochrane reviews: protocol for a meta-epidemiological study
Authors: Hansen Julie B , Juhl Carsten B , Boutron Isabelle , Tugwell Peter , Ghogomu Elizabeth A T , Pardo Pardo Jordi , Rader Tamara , Wells George A , Mayhew Alain , Maxwell Lara , Lund Hans , Christensen Robin ,   The Editorial Board of the Cochrane Musculoskeletal Group
Published: October 2014

Introduction

The validity of systematic reviews and meta-analysis depends on methodological quality and unbiased dissemination of trials. Our objective is to evaluate the association of estimates of treatment effects with different bias-related study characteristics in meta-analyses of interventions used for treating pain in osteoarthritis (OA). From the findings, we hope to consolidate guidance on interpreting OA trials in systematic reviews based on empirical evidence from Cochrane reviews.

Methods and analysis

Only systematic reviews that compare experimental interventions with sham, placebo or no intervention control will be considered eligible. Bias will be assessed with the risk of bias tool, used according to the Cochrane Collaboration’s recommendations. Furthermore, center status, trial size and funding will be assessed. The primary outcome (pain) will be abstracted from the first appearing forest plot for overall pain in the Cochrane review. Treatment effect sizes will be expressed as standardised mean differences (SMDs), where the difference in mean values available from the forest plots is divided by the pooled SD. To empirically assess the risk of bias in treatment benefits, we will perform stratified analyses of the trials from the included meta-analyses and assess the interaction between trial characteristics and treatment effect. A relevant study-level covariate is defined as one that decreases the between-study variance (τ2, estimated as Tau-squared) as a consequence of inclusion in the mixed effects statistical model.

Ethics and dissemination

Meta-analyses and randomised controlled trials provide the most reliable basis for treatment of patients with OA, but the actual impact of bias is unclear. This study will systematically examine the methodological quality in OA Cochrane reviews and explore the effect estimates behind possible bias. Since our study does not collect primary data, no formal ethical assessment and informed consent are required.

Trial registration number

PROSPERO (CRD42013006924).
Early life-course socioeconomic position, adult work-related factors and oral health disparities: cross-sectional analysis of the J-SHINE study
Authors: Tsuboya Toru , Aida Jun , Kawachi Ichiro , Katase Kazuo , Osaka Ken
Published: October 2014

Objectives

We examined the association between socioeconomic position (SEP) and oral health, and the associations of economic difficulties in childhood and workplace-related factors on these parameters.

Design

Cross-sectional study.

Participants

A total of 3201 workers aged 25–50 years, living in and around Tokyo, Japan, from the J-SHINE (Japanese study of Stratification, Health, Income, and Neighborhood) study. The response rate was 31.6%.

Outcome measures

Self-rated oral health (SROH)—A logistic regression model was used to estimate ORs for the association between poor SROH and each indicator of SEP (annual household income, wealth, educational attainment, occupation and economic situation in childhood). Multiple imputation was used to address missing values.

Results

Each indicator of SEP, including childhood SEP, was significantly inversely associated with SROH, and all of the workplace-related factors (social support in the workplace, job stress, working hours and type of employment) were also significantly associated with SROH. Compared with professionals, blue-collar workers had a significantly higher OR of poor SROH and the association was substantially explained by the workplace-related factors; ORs ranged from 1.44 in the age-adjusted and sex-adjusted model to 1.18 in the multivariate model. Poverty during childhood at age 5 and at age 15 was associated with poorer SROH, and these two factors seemed to be independently associated with SROH.

Conclusions

We found oral health disparity across SEP among workers in Japan. Approximately 60% of the association between occupation and SROH was explained by job-related factors. Economic difficulties during childhood appear to affect SROH in adulthood separately from sex, age and the current workplace-related factors.
A comparison of calls subjected to a malpractice claim versus ‘normal calls’ within the Swedish Healthcare Direct: a case–control study
Authors: Ernesäter Annica , Engström Maria , Winblad Ulrika , Holmström Inger K
Published: October 2014

Objectives

The purpose of this study is to compare communication patterns in calls subjected to a malpractice claim with matched controls.

Setting

In many countries, telephone advice nursing is patients’ first contact with healthcare. Telenurses’ assessment of callers’ symptoms and needs are based on verbal communication only, and problems with over-triage and under-triage have been reported.

Participants

A total sample of all reported medical errors (n=33) during the period 2003–2010 within Swedish Healthcare Direct was retrieved. Corresponding calls were thereafter identified and collected as sound files from the manager in charge at the respective call centres. For technical reasons, calls from four of the cases were not possible to retrieve. For the present study, matched control calls (n=26) based on the patient's age, gender and main symptom presented by the caller were collected.

Results

Male patients were in majority (n=16), and the most common reasons for calling were abdominal pain (n=10) and chest pain (n=5). There were statistically significant differences between the communication in the cases and controls: telenurses used fewer open-ended medical questions (p<0.001) in the cases compared to the control calls; callers provided telenurses with more medical information in the control calls compared to the cases (p=0.001); and telenurses used more facilitation and patient activation activities in the control calls (p=0.034), such as back-channel response (p=0.001), compared to the cases.

Conclusions

The present study shows that telenurses in malpractice claimed calls used more closed-ended questioning compared to those in control calls, who used more open-ended questioning and back-channel response, which provided them with richer medical descriptions and more information from the caller. Hence, these communicative techniques are important in addition to solid medical and nursing competence and sound decision aid systems.
Implementing family involvement in the treatment of patients with psychosis: a systematic review of facilitating and hindering factors
Authors: Eassom Erica , Giacco Domenico , Dirik Aysegul , Priebe Stefan
Published: October 2014

Objective

To synthesise the evidence on implementing family involvement in the treatment of patients with psychosis with a focus on barriers, problems and facilitating factors.

Design

Systematic review of studies evaluating the involvement of families in tripartite communication between health professionals, ‘families’ (or other unpaid carers) and adult patients, in a single-family context. A theoretical thematic analysis approach and thematic synthesis were used.

Data sources

A systematic electronic search was carried out in seven databases, using database-specific search strategies and controlled vocabulary. A secondary manual search of grey literature was performed as well as using forwards and backwards snowballing techniques.

Results

A total of 43 studies were included. The majority featured qualitative data (n=42), focused solely on staff perspectives (n=32) and were carried out in the UK (n=23). Facilitating the training and ongoing supervision needs of staff are necessary but not sufficient conditions for a consistent involvement of families. Organisational cultures and paradigms can work to limit family involvement, and effective implementation appears to operate via a whole team coordinated effort at every level of the organisation, supported by strong leadership. Reservations about family involvement regarding power relations, fear of negative outcomes and the need for an exclusive patient–professional relationship may be explored and addressed through mutually trusting relationships.

Conclusions

Implementing family involvement carries additional challenges beyond those generally associated with translating research to practice. Implementation may require a cultural and organisational shift towards working with families. Family work can only be implemented if this is considered a shared goal of all members of a clinical team and/or mental health service, including the leaders of the organisation. This may imply a change in the ethos and practices of clinical teams, as well as the establishment of working routines that facilitate family involvement approaches.
Protocol for economic evaluation alongside a cluster-randomised controlled trial of a psychoeducational intervention for the primary prevention of postnatal mental health problems in first-time mothers
Authors: Ride Jemimah , Rowe Heather , Wynter Karen , Fisher Jane , Lorgelly Paula
Published: October 2014

Introduction

Postnatal mental health problems, which are an international public health priority, are a suitable target for preventive approaches. The financial burden of these disorders is borne across sectors in society, including health, early childhood, education, justice and the workforce. This paper describes the planned economic evaluation ofWhat Were We Thinking, a psychoeducational intervention for the prevention of postnatal mental health problems in first-time mothers.

Methods and analysis

The evaluation will be conducted alongside a cluster-randomised controlled trial of its clinical effectiveness. Cost-effectiveness and costs-utility analyses will be conducted, resulting in estimates of cost per percentage point reduction in combined 30-day prevalence of depression, anxiety and adjustment disorders and cost per quality-adjusted life year gained. Uncertainty surrounding these estimates will be addressed using non-parametric bootstrapping and represented using cost-effectiveness acceptability curves. Additional cost analyses relevant for implementation will also be conducted. Modelling will be employed to estimate longer term cost-effectiveness if the intervention is found to be clinically effective during the period of the trial.

Ethics and dissemination

Approval to conduct the study was granted by the Southern Health (now Monash Health) Human Research Ethics Committee (24 April 2013; 11388B). The study was registered with the Monash University Human Research Ethics Committee (30 April 2013; CF12/1022-2012000474). The Education and Policy Research Committee, Victorian Government Department of Education and Early Childhood Development approved the study (22 March 2012; 2012_001472). Use of the EuroQol was registered with the EuroQol Group; 16 August 2012.

Trial registration number

The trial was registered with the Australian New Zealand Clinical Trials Registry on 7 May 2012 (registration number ACTRN12613000506796).
Glasgow Coma Scale is unreliable for the prediction of severe head injury in elderly trauma patients
Authors: Kehoe A , Rennie S , Smith J E
Published: October 2014

Objectives and background

Elderly patients comprise an ever-increasing proportion of major trauma patients. The presenting GCS in elderly patients with traumatic brain injury (TBI) may not reflect the severity of injury as accurately as it does in the younger patient population. However, GCS is often used as part of the decision tool to define the population transferred directly to a major trauma centre. The aim of this study was to explore the relationship between age and presenting GCS in patients with isolated TBI.

Methods

A retrospective database review was undertaken using the Trauma Audit and Research Network database. All patients presenting to Derriford Hospital, Plymouth, between 1 January 2009 and 31 May 2014 with isolated TBI were included. Demographic, mechanistic, physiological, resource use and outcome data were collected. Abbreviated injury scale (AIS) was recorded for all patients. Patients were categorised into those older and younger than 65 years on presentation. Distribution of GCS, categorised into severe (GCS 3–8), moderate (GCS 9–12) and mild TBI (13–15), was compared between the age groups. Median GCS at each AIS level was also compared.

Results

The distribution of GCS differed between young and old patients with TBI (22.1% vs 9.8% had a GCS 3–8, respectively) despite a higher burden of anatomical injury in the elderly group. Presenting GCS was higher in the elderly at each level of AIS. The difference was more apparent in the presence of more severe injury (AIS 5).

Conclusions

Elderly patients who have sustained isolated severe TBI may present with a higher GCS than younger patients. Triage tools using GCS may need to be modified and validated for use in elderly patients with TBI.
Immunohistochemical expression of inflammatory markers in sudden infant death; ancillary tests for identification of infection
Authors: Pryce J W , Bamber A R , Ashworth M T , Klein N J , Sebire N J
Published: October 2014

Aims

Sudden unexpected death in infancy (SUDI) investigation requires extensive ancillary investigations, the results of which, such as postmortem microbiology, can be difficult to interpret. Markers of an inflammatory response, including interleukin 6 (IL-6), c-reactive protein (CRP) and cellular adhesion molecules are elevated in infections, yet little attention has been paid to their assessment after death. This study investigates the role of inflammatory markers in SUDI autopsies for determining cause of death.

Methods

Cases of SUDI over a 14 year period were identified from an autopsy database and 100 cases were selected for immunohistochemical staining of heart and liver for IL-6, CRP, P-selectin, VCAM-1 and ICAM-1 (CD54), with staining patterns compared between five groups, including infectious and unexplained SUDI.

Results

There were significant differences between groups. Cases of histological infection demonstrated strongly positive hepatocyte CRP and ICAM-1 expression and increased myocardial staining for CRP. Half of trauma-related deaths demonstrated diffuse hepatic CRP expression but without myocardial CRP staining. Staining of unexplained SUDI cases were predominantly negative, apart from a subgroup in whomEscherichia Coliwas identified, who had increased expression of hepatic IL-6.

Conclusions

There were distinct patterns of organ-specific CRP and ICAM-1 expression in SUDI by cause of death. These markers of inflammation were rarely present in unexplained SUDI suggesting either a non-inflammatory cause of death or a failure to mount an effective acute phase response. Immunohistochemical staining offers potential to identify infection-related deaths and provides insight into SUDI mechanisms.
A review of the documentation in the British Armed Forces electronic patient record following discharge from the Role 3 Hospital in Camp Bastion
Authors: Cox Andrew T , Linton T , Lentaigne J , Sharma S , Wilson D
Published: October 2014

Introduction

The British Role 3 Hospital in Camp Bastion, Afghanistan, uses a different electronic patient record (EPR) to Defence Primary Health Care and the two cannot directly communicate. Consequently, hospital discharge information is transferred by printed letter to primary care, introducing a step where information can be lost. This study was designed to test the hypothesis that the primary care EPR contained an accurate summary of the secondary care admission.

Methods

Cross-sectional information on consecutive General Internal Medicine patients at the hospital was collected and compared with the primary care EPR.

Results

From April 2011 the hospital records of 270 patients were reviewed. 239 primary care records were available for comparison. Of 185 patients discharged back to their unit the EPR of 43.8% contained a comprehensive summary, 23.2% contained the scanned discharge letter and 50.8% contained an account of their hospital admission but not necessarily a comprehensive summary. Of the 54 patients evacuated to the UK, the EPRs of 48.1% contained a summary, 68.1% contained the scanned discharge letter and 75.9% contained some account of their hospital admission. More of the evacuated group had their admission documented in the primary care EPR (p=0.001). Only 56.5% of all primary care records contained some account of the hospital admission.

Discussion

The primary care record is not a reliable record of operational hospital admission and presents an unrecognised potential patient safety issue. The systems responsible for the transfer of discharge summary data need to be appraised to prevent it continuing. Retrospective action should be considered to rectify this problem in former hospital patients.
Intra-aneurysmal flow rates are reduced by two flow diverters: an experiment using tomographic particle image velocimetry in an aneurysm model
Authors: Dennis Kendall D , Rossman Timothy L , Kallmes David F , Dragomir-Daescu Dan
Published: October 2014

Background

Limitations on treating large, giant, and wide-necked aneurysms with coiling have made flow diverters a promising alternative to current practice by supporting reconstruction of the parent artery.

Objective

To assess the changes to fluid dynamics within an aneurysm by studying two different endoluminal flow diverters on a simple aneurysm model, using tomographic particle image velocimetry to determine which device would better minimize fluid flow into an aneurysm and observe any significant changes in aneurysm fluid structures.

Methods

Steady velocity fields of the model's aneurysm dome and neck were measured at three inlet velocities (18, 39, and 59 cm/s) for two flow diverter diameters with different porosities and compared against a baseline case with no flow diverter.

Results

In the baseline case a large vortex was present inside the dome for all flow rates. However, both devices eliminated this main vortex at all flow rates and reduced the peak aneurysmal velocities by about 90%. A strong correlation between flow diverter porosity and flow reduction was found. In each case the inflow to the aneurysm shifted from the distal neck to the mid- or proximal neck after flow diverter placement.

Conclusions

Even with this relatively simple experimental setup, we were able to observe the major flow field changes, which occurred immediately after the deployment of each flow diverter. Limitations of the study included a simplified geometry and steady-state flow. Constraints included model making and limited availability of flow diverters.