bluuebunny/crossref_metadata_2025 huggingface dataset:
Early herniorrhaphy of large traumatic abdominal wounds in horses and mules
Authors: Azizi S. , Hashemi‐Asl S.‐M. , Torabi E.
Published: April 2015

Reasons for performing study

Surgical treatment of traumatic abdominal hernias is usually delayed for 2–3 months following injury. The residual defects are then repaired by herniorrhaphy or mesh herniorrhaphy.

Objective

To describe the outcome following herniorrhaphy (without a mesh) within 21 days of initial injury to repair external traumatic lateral abdominal hernias in horses and mules.

Study design

Descriptive case series.

Methods

Twenty‐two cases were included. Surgical treatment involved exposure of the hernia sac and closing of the abdominal wall defect with interrupted Mayo mattress or cruciate sutures after reduction of the herniated organ into the peritoneal cavity. Data collected included cause and site of the hernia, surgical findings, immediate and long‐term post operative complications, return to use, duration of convalescence and hernia recurrence.

Results

Falling while crossing impassable pathways was the most common initial cause of the hernia (9/11 horses and 10/11 mules). Adhesion formation to underlying viscera was found intraoperatively in 2 cases. Uncomplicated healing occurred in all animals except 3 with suture abscesses and one with a subcutaneous seroma. At the time of follow‐up (6–24 months after surgery), complete recovery without recurrence of herniation was achieved and animals had returned to their previous use.

Conclusion

Herniorrhaphy within 21 days using interrupted Mayo mattress or cruciate pattern sutures can be effective for treating external traumatic abdominal hernias in horses and mules.

The Summary is available in Chinese – see Supporting Information.
Integrity testing and the prediction of counterproductive behaviours in the military
Authors: Fine Saul , Goldenberg Judith , Noam Yair
Published: April 2015

While a great deal of research has been carried out on counterproductive work behaviours and integrity testing in civilian organizations, far less is known about these two areas in military settings. The present study developed a military‐oriented integrity test that successfully predicted future disciplinary infractions among a sample of 467 officer training school candidates (ρ = .26), while also discriminating between that sample and a comparable sample of soldiers serving time in military prisons (d = 2.24). In addition to its unique military setting, this study contributes to the integrity test literature by: (1) adopting both individual‐ and group‐level validity paradigms; (2) using a sample of actual job applicants; (3) measuring a reliable objective criterion in a predictive design; and (4) including comparative measures of cognitive ability, personality, and overall assessment centre ratings.

Practitioner points

Military settings may uniquely facilitate the reliable and objective measurement of counterproductive work behaviours.

Integrity testing may be a valid and incremental predictor of counterproductive behaviours in military settings.
The integration of solid-form informatics into solid-form selection
Authors: Feeder Neil , Pidcock Elna , Reilly Anthony M , Sadiq Ghazala , Doherty Cheryl L , Back Kevin R , Meenan Paul , Docherty Robert
Published: April 2015

Objectives

To demonstrate how the use of structural informatics during drug development assists with the assessment of the risk of polymorphism and the selection of a commercial solid form.

Methods

The application of structural chemistry knowledge derived from the hundreds of thousands of crystal structures contained in the Cambridge Structural Database to drug candidates is described. Examples given show the comparison of intermolecular geometries to database-derived statistics, the use of Full Interaction Maps to assess polymorph stability and the calculation of hydrogen bond propensities to provide assurance of a stable solid form. The software tools used are included in the Cambridge Structural Database System and the Solid Form Module of Mercury.

Key findings

The early identification of an unusual supramolecular motif in the development phase of maraviroc led to further experimental work to find the most stable polymorph. Analyses of two polymorphs of a pain candidate drug demonstrated how consideration of molecular conformation and intermolecular interactions were used for the assessment of relative stability. Informatics analysis confirmed that the solid form of crizotinib, a monomorphic system, had a low risk of polymorphism.

Conclusions

The application of informatics-based assessment of new chemical entities complements experimental studies and provides a deeper understanding of the qualities of the structure. The information provided by structural analyses is incorporated into the assessment of risk. Informatics techniques are quick to apply and are straightforward to use, allowing an assessment of progressing drug candidates.
The impact PICU nursing expertise has on a child's unplanned extubation
Authors: Norridge Matthew , While Alison E
Published: April 2015

Background

Unplanned extubations in PICU are used as a measure of quality in clinical governance strategies. While many factors, such as sedation or unit activity, impact negatively on unplanned extubations, high nurse‐patient ratios reduce adverse patient events and improve patient safety. However, optimal nurse‐patient ratios and the impact of the level of nursing expertise on the quality of care are unknown.

Aim

The study aimed to examine the impact of PICU nursing expertise on the unplanned extubations of children.

Design

Audit and analysis of existing adverse event patient and nurse workforce data.

Method

This single‐centre study examined unplanned extubations at a mixed general and cardiac tertiary PICU in the UK. Routinely collected data from nursing and adverse incident databases were examined. The dataset included over 74,477 nurse allocations between August 2006 and April 2011. Unplanned extubations were the adverse event of interest.

Results

A total of 78 unplanned extubations occurred between April 2006 and April 2011. The majority of unplanned extubations occurred when patients were looked after by junior nurses. The seniority of the nurse in‐charge and the qualifications of the patient's nurse were not related to unplanned extubations. However, more unplanned extubations occurred at times of higher patient occupancy.

Conclusions

Nursing expertise and nurse‐patient ratios were not related to unplanned extubations in this study. Further research is needed to explore the non‐workforce factors such as the securing of endotracheal tubes, sedation levels and unit activity and their relationship with adverse events.

Relevance to Clinical Practice

In paediatric intensive care units where nurse‐patient ratios are high, further investigation is needed to establish what impact non‐workforce factors have on unplanned extubations.
Dothistroma needle blight: an emerging epidemic caused by Dothistroma septosporum in Colombia
Authors: Rodas C. A. , Wingfield M. J. , Granados G. M. , Barnes I.
Published: April 2015

Plantation forestry in Colombia is based mainly on non‐native species of Pinus and Eucalyptus. Since 2008, a disease with symptoms similar to those of dothistroma needle blight (DNB) has been found affecting large areas planted to Pinus spp. The aim of this study was to identify the causal pathogen as well as to document the levels of disease incidence and severity. Isolates from each of three forestry zones, collected from different host species, were compared based on rDNA sequence of the ITS regions. These were conclusively identified as Dothistroma septosporum, one of two Dothistroma spp. known to cause DNB. Susceptibility was greatest on low elevation Pinus tecunumanii followed by Pinus kesiya and Pinus oocarpa. Pinus maximinoi and high elevation P. tecunumanii showed tolerance to D. septosporum. The disease incidence in the different zones varied significantly with the North zone being the most severely affected. This constitutes the first report of disease distribution and susceptibility of hosts, as well as the first consideration of the relative importance of D. septosporum in Colombia.
A Neoproterozoic ice advance sequence, Sperry Wash, California
Authors: Busfield Marie E. , Le Heron Daniel P.
Published: April 2015

The Kingston Peak Formation is an archetypal Cryogenian succession that crops out across the Death Valley region of eastern California. Above pre‐glacial strata (KP1), two distinct glacial phases have been recognized and are interpreted to be allied to the panglacial Sturtian (KP2 and KP3) and Marinoan (KP4) icehouse events. The thickest and most extensive unit, KP3, forms the entire exposed section at Sperry Wash. At this locality, ice‐distal turbidites are succeeded in turn by ice‐medial and ice‐proximal facies, comprising a spectrum of ice‐rafted debris‐bearing turbidites, debrites and shales. These are overlain by ice‐marginal grounding‐line fan deposits interbedded with glacitectonically deformed heterolithics, supporting local advance to an ice‐contact position. The succession records accumulation within a glacier‐fed subaqueous shelf, wherein the clear progradational signature is driven by ice advance towards the south‐east. Evolution of the subaqueous complex is five‐fold, comprising: (i) ice‐distal outwash; (ii) build‐out of ice‐medial depositional lobes; (iii) ice‐proximal deposition and increased calving; (iv) resumed ice‐margin advance; and (v) growth of ice‐contact grounding‐line fan. This sequence is unique in the Death Valley region for recording the first evidence of advance to ice‐marginal and ice‐contact settings, thereby enabling the location of the glacier terminus to be documented for the first time.
Female fertility preservation: a fertile future?
Authors: Radon Christina M , Borkar Amol A , Homburg Roy R
Published: April 2015

Key content

Fertility preservation is a rapidly evolving branch of reproductive medicine.

Ovarian senescence, whether physiological or pathologically accelerated, limits the reproductive capacity of women.

Given the increasing numbers of young women surviving cancer, along with increasing numbers of women deferring childbearing for social reasons, the possibility of fertility preservation is assuming ever increasing importance.

Learning objectives

To be aware of all fertility preservation options available to young women.

To acknowledge the appropriate indications or contraindications of individual fertility preservation techniques.

To gain understanding of the key components central to counselling women requesting advice on fertility preservation.

Ethical issues

Encouraging cancer patients to undergo fertility preservation treatments could have the potential to negatively impact their disease prognosis.

Whether fertility preservation is an appropriate allocation of health resources, given that a proportion of women undergoing preservation procedures may remain fertile, may ultimately choose not to pursue parenthood, or, in the case of malignancy, may not even survive their diagnosis.

The availability of fertility preservation for social reasons could encourage women to delay childbearing, creating a society of ‘older mothers’ reproducing beyond their natural reproductive lifespan, and thereby potentially creating a new medical burden on society.
Bayesian network ensemble as a multivariate strategy to predict radiation pneumonitis risk
Authors: Lee Sangkyu , Ybarra Norma , Jeyaseelan Krishinima , Faria Sergio , Kopek Neil , Brisebois Pascale , Bradley Jeffrey D. , Robinson Clifford , Seuntjens Jan , El Naqa Issam
Published: April 2015

Purpose:

Prediction of radiation pneumonitis (RP) has been shown to be challenging due to the involvement of a variety of factors including dose–volume metrics and radiosensitivity biomarkers. Some of these factors are highly correlated and might affect prediction results when combined. Bayesian network (BN) provides a probabilistic framework to represent variable dependencies in a directed acyclic graph. The aim of this study is to integrate the BN framework and a systems’ biology approach to detect possible interactions among RP risk factors and exploit these relationships to enhance both the understanding and prediction of RP.

Methods:

The authors studied 54 nonsmall‐cell lung cancer patients who received curative 3D‐conformal radiotherapy. Nineteen RP events were observed (common toxicity criteria for adverse events grade 2 or higher). Serum concentration of the following four candidate biomarkers were measured at baseline and midtreatment: alpha‐2‐macroglobulin, angiotensin converting enzyme (ACE), transforming growth factor, interleukin‐6. Dose‐volumetric and clinical parameters were also included as covariates. Feature selection was performed using a Markov blanket approach based on the Koller–Sahami filter. The Markov chain Monte Carlo technique estimated the posterior distribution of BN graphs built from the observed data of the selected variables and causality constraints. RP probability was estimated using a limited number of high posterior graphs (ensemble) and was averaged for the final RP estimate using Bayes’ rule. A resampling method based on bootstrapping was applied to model training and validation in order to control under‐ and overfit pitfalls.

Results:

RP prediction power of the BN ensemble approach reached its optimum at a size of 200. The optimized performance of the BN model recorded an area under the receiver operating characteristic curve (AUC) of 0.83, which was significantly higher than multivariate logistic regression (0.77), mean heart dose (0.69), and a pre‐to‐midtreatment change in ACE (0.66). When RP prediction was made only with pretreatment information, the AUC ranged from 0.76 to 0.81 depending on the ensemble size. Bootstrap validation of graph features in the ensemble quantified confidence of association between variables in the graphs where ten interactions were statistically significant.

Conclusions:

The presented BN methodology provides the flexibility to model hierarchical interactions between RP covariates, which is applied to probabilistic inference on RP. The authors’ preliminary results demonstrate that such framework combined with an ensemble method can possibly improve prediction of RP under real‐life clinical circumstances such as missing data or treatment plan adaptation.
A Monte Carlo simulation framework for electron beam dose calculations using Varian phase space files for TrueBeam Linacs
Authors: Rodrigues Anna , Sawkey Daren , Yin Fang‐Fang , Wu Qiuwen
Published: April 2015

Purpose:

To develop a framework for accurate electron Monte Carlo dose calculation. In this study, comprehensive validations of vendor provided electron beam phase space files for Varian TrueBeam Linacs against measurement data are presented.

Methods:

In this framework, the Monte Carlo generated phase space files were provided by the vendor and used as input to the downstream plan‐specific simulations including jaws, electron applicators, and water phantom computed in the EGSnrc environment. The phase space files were generated based on open field commissioning data. A subset of electron energies of 6, 9, 12, 16, and 20 MeV and open and collimated field sizes 3 × 3, 4 × 4, 5 × 5, 6 × 6, 10 × 10, 15 × 15, 20 × 20, and 25 × 25 cm2 were evaluated. Measurements acquired with a CC13 cylindrical ionization chamber and electron diode detector and simulations from this framework were compared for a water phantom geometry. The evaluation metrics include percent depth dose, orthogonal and diagonal profiles at depths R100, R50, Rp, and Rp+ for standard and extended source‐to‐surface distances (SSD), as well as cone and cut‐out output factors.

Results:

Agreement for the percent depth dose and orthogonal profiles between measurement and Monte Carlo was generally within 2% or 1 mm. The largest discrepancies were observed within depths of 5 mm from phantom surface. Differences in field size, penumbra, and flatness for the orthogonal profiles at depths R100, R50, and Rp were within 1 mm, 1 mm, and 2%, respectively. Orthogonal profiles at SSDs of 100 and 120 cm showed the same level of agreement. Cone and cut‐out output factors agreed well with maximum differences within 2.5% for 6 MeV and 1% for all other energies. Cone output factors at extended SSDs of 105, 110, 115, and 120 cm exhibited similar levels of agreement.

Conclusions:

We have presented a Monte Carlo simulation framework for electron beam dose calculations for Varian TrueBeam Linacs. Electron beam energies of 6 to 20 MeV for open and collimated field sizes from 3 × 3 to 25 × 25 cm2 were studied and results were compared to the measurement data with excellent agreement. Application of this framework can thus be used as the platform for treatment planning of dynamic electron arc radiotherapy and other advanced dynamic techniques with electron beams.
Experimental scattershot boson sampling
Authors: Bentivegna Marco , Spagnolo Nicolò , Vitelli Chiara , Flamini Fulvio , Viggianiello Niko , Latmiral Ludovico , Mataloni Paolo , Brod Daniel J. , Galvão Ernesto F. , Crespi Andrea , Ramponi Roberta , Osellame Roberto , Sciarrino Fabio
Published: April 2015

A novel experiment supports quantum computation using photonic circuits to greatly increase quantum device speed.
Quorum-Sensing Mechanisms Mediated by Farnesol in Ophiostoma piceae: Effect on Secretion of Sterol Esterase
Authors: de Salas Felipe , Martínez María Jesús , Barriuso Jorge
Published: April 2015

Ophiostoma piceaeCECT 20416 is a dimorphic wood-staining fungus able to produce an extracellular sterol-esterase/lipase (OPE) that is of great biotechnological interest. In this work, we have studied the morphological change of this fungus from yeast to hyphae, which is associated with the cell density-related mechanism known as quorum sensing (QS), and how this affects the secretion of OPE. The data presented here confirm that the moleculeE,E-farnesol accumulates as the cell number is growing within the population. The exogenous addition of this molecule or spent medium to the cultures increased the extracellular activity of OPE 2.5 times. This fact was related not to an increase in microbial biomass or in the expression of the gene coding for OPE but to a marked morphological transition in the cultures. Moreover, the morphological transition also occurred when a high cell density was inoculated into the medium. The results suggest thatE,E-farnesol regulates through QS mechanisms the morphological transition in the dimorphic fungusO. piceaeand that it is associated with a higher extracellular esterase activity. Furthermore, identification and transcriptional analysis of genestup1andcyr1, which are involved in the response, was carried out. Here we report enhanced production of a sterol-esterase/lipase of biotechnological interest by means of QS mechanisms. These results may be useful in increasing the production of secreted enzymes of other dimorphic fungi of biotechnological interest.
An Invasive Mammal (the Gray Squirrel, Sciurus carolinensis) Commonly Hosts Diverse and Atypical Genotypes of the Zoonotic Pathogen Borrelia burgdorferiSensu Lato
Authors: Millins Caroline , Magierecka Agnieszka , Gilbert Lucy , Edoff Alissa , Brereton Amelia , Kilbride Elizabeth , Denwood Matt , Birtles Richard , Biek Roman
Published: April 2015

Invasive vertebrate species can act as hosts for endemic pathogens and may alter pathogen community composition and dynamics. For the zoonotic pathogen
Borrelia burgdorferi
sensu lato
, the agent of Lyme borreliosis, recent work shows invasive rodent species can be of high epidemiological importance and may support host-specific strains. This study examined the role of gray squirrels (
Sciurus carolinensis
) (
n
= 679), an invasive species in the United Kingdom, as
B. burgdorferi sensu lato
hosts. We found that gray squirrels were frequently infested with
Ixodes ricinus
, the main vector of
B. burgdorferi sensu lato
in the United Kingdom, and 11.9% were infected with
B. burgdorferi sensu lato
. All four genospecies that occur in the United Kingdom were detected in gray squirrels, and unexpectedly, the bird-associated genospecies
Borrelia garinii
was most common. The second most frequent infection was with
Borrelia afzelii
. Genotyping of
B. garinii
and
B. afzelii
produced no evidence for strains associated with gray squirrels. Generalized linear mixed models (GLMM) identified tick infestation and date of capture as significant factors associated with
B. burgdorferi sensu lato
infection in gray squirrels, with infection elevated in early summer in squirrels infested with ticks. Invasive gray squirrels appear to become infected with locally circulating strains of
B. burgdorferi sensu lato
, and further studies are required to determine their role in community disease dynamics. Our findings highlight the fact that the role of introduced host species in
B. burgdorferi sensu lato
epidemiology can be highly variable and thus difficult to predict.
Biosynthesis of
l
-Sorbose and
l
-Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain
Authors: Yang Jiangang , Li Jitao , Men Yan , Zhu Yueming , Zhang Ying , Sun Yuanxia , Ma Yanhe
Published: April 2015

The property of loose stereochemical control at aldol products from aldolases helped to synthesize multiple polyhydroxylated compounds with nonnatural stereoconfiguration. In this study, we discovered for the first time that some fructose 1,6-diphosphate aldolases (FruA) and tagatose 1,6-diphosphate (TagA) aldolases lost their strict stereoselectivity when using
l
-glyceraldehyde and synthesized not only
l
-sorbose but also a high proportion of
l
-psicose. Among the aldolases tested, TagA from
Bacillus licheniformis
(BGatY) showed the highest enzyme activity with
l
-glyceraldehyde. Subsequently, a “one-pot” reaction based on BGatY and fructose-1-phosphatase (YqaB) generated 378 mg/liter
l
-psicose and 199 mg/liter
l
-sorbose from dihydroxyacetone-phosphate (DHAP) and
l
-glyceraldehyde. Because of the high cost and instability of DHAP, a microbial fermentation strategy was used further to produce
l
-sorbose/
l
-psicose from glucose and
l
-glyceraldehyde, in which DHAP was obtained from glucose through the glycolytic pathway, and some recombination pathways based on FruA or TagA and YqaB were constructed in
Escherichia coli
and
Corynebacterium glutamicum
strains. After evaluation of different host cells and combinations of FruA or TagA with YqaB and optimization of gene expression, recombinant
C. glutamicum
strain WT(pXFTY) was selected and produced 2.53 g/liter total ketoses, with a yield of 0.50 g/g
l
-glyceraldehyde. Moreover, deletion of gene
cgl0331
, encoding the Zn-dependent alcohol dehydrogenase in
C. glutamicum
, was confirmed for the first time to significantly decrease conversion of
l
-glyceraldehyde to glycerol and to increase yield of target products. Finally, fed-batch culture of strain SY14(pXFTY) produced 3.5 g/liter
l
-sorbose and 2.3 g/liter
l
-psicose, with a yield of 0.61 g/g
l
-glyceraldehyde. This microbial fermentation strategy also could be applied to efficiently synthesize other
l
-sugars.
Gene Deletions Resulting in Increased Nitrogen Release by Azotobacter vinelandii: Application of a Novel Nitrogen Biosensor
Authors: Barney Brett M. , Eberhart Lauren J. , Ohlert Janet M. , Knutson Carolann M. , Plunkett Mary H.
Published: April 2015

Azotobacter vinelandii
is a widely studied model diazotrophic (nitrogen-fixing) bacterium and also an obligate aerobe, differentiating it from many other diazotrophs that require environments low in oxygen for the function of the nitrogenase. As a free-living bacterium,
A. vinelandii
has evolved enzymes and transporters to minimize the loss of fixed nitrogen to the surrounding environment. In this study, we pursued efforts to target specific enzymes and further developed screens to identify individual colonies of
A. vinelandii
producing elevated levels of extracellular nitrogen. Targeted deletions were done to convert urea into a terminal product by disrupting the urease genes that influence the ability of
A. vinelandii
to recycle the urea nitrogen within the cell. Construction of a nitrogen biosensor strain was done to rapidly screen several thousand colonies disrupted by transposon insertional mutagenesis to identify strains with increased extracellular nitrogen production. Several disruptions were identified in the ammonium transporter gene
amtB
that resulted in the production of sufficient levels of extracellular nitrogen to support the growth of the biosensor strain. Further studies substituting the biosensor strain with the green alga
Chlorella sorokiniana
confirmed that levels of nitrogen produced were sufficient to support the growth of this organism when the medium was supplemented with sufficient sucrose to support the growth of the
A. vinelandii
in coculture. The nature and quantities of nitrogen released by urease and
amtB
disruptions were further compared to strains reported in previous efforts that altered the
nifLA
regulatory system to produce elevated levels of ammonium. These results reveal alternative approaches that can be used in various combinations to yield new strains that might have further application in biofertilizer schemes.
Expanded Natural Product Diversity Revealed by Analysis of Lanthipeptide-Like Gene Clusters in Actinobacteria
Authors: Zhang Qi , Doroghazi James R. , Zhao Xiling , Walker Mark C. , van der Donk Wilfred A.
Published: April 2015

Lanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and posttranslationally modified peptides (RiPPs). Lanthipeptides are widely distributed in taxonomically distant species, and their currently known biosynthetic systems and biological activities are diverse. Building on the recent natural product gene cluster family (GCF) project, we report here large-scale analysis of lanthipeptide-like biosynthetic gene clusters from
Actinobacteria
. Our analysis suggests that lanthipeptide biosynthetic pathways, and by extrapolation the natural products themselves, are much more diverse than currently appreciated and contain many different posttranslational modifications. Furthermore, lanthionine synthetases are much more diverse in sequence and domain topology than currently characterized systems, and they are used by the biosynthetic machineries for natural products other than lanthipeptides. The gene cluster families described here significantly expand the chemical diversity and biosynthetic repertoire of lanthionine-related natural products. Biosynthesis of these novel natural products likely involves unusual and unprecedented biochemistries, as illustrated by several examples discussed in this study. In addition, class IV lanthipeptide gene clusters are shown not to be silent, setting the stage to investigate their biological activities.
Biotin- and Glycoprotein-Coated Microspheres as Surrogates for Studying Filtration Removal of Cryptosporidium parvum in a Granular Limestone Aquifer Medium
Authors: Stevenson M. E. , Blaschke A. P. , Toze S. , Sidhu J. P. S. , Ahmed W. , van Driezum I. H. , Sommer R. , Kirschner A. K. T. , Cervero-Aragó S. , Farnleitner A. H. , Pang L.
Published: April 2015

Members of the genus
Cryptosporidium
are waterborne protozoa of great health concern. Many studies have attempted to find appropriate surrogates for assessing
Cryptosporidium
filtration removal in porous media. In this study, we evaluated the filtration of
Cryptosporidium parvum
in granular limestone medium by the use of biotin- and glycoprotein-coated carboxylated polystyrene microspheres (CPMs) as surrogates. Column experiments were carried out with core material taken from a managed aquifer recharge site in Adelaide, Australia. For the experiments with injection of a single type of particle, we observed the total removal of the oocysts and glycoprotein-coated CPMs, a 4.6- to 6.3-log
10
reduction of biotin-coated CPMs, and a 2.6-log
10
reduction of unmodified CPMs. When two different types of particles were simultaneously injected, glycoprotein-coated CPMs showed a 5.3-log
10
reduction, while the uncoated CPMs displayed a 3.7-log
10
reduction, probably due to particle-particle interactions. Our results confirm that glycoprotein-coated CPMs are the most accurate surrogates for
C. parvum
; biotin-coated CPMs are slightly more conservative, while unmodified CPMs are markedly overly conservative for predicting
C. parvum
removal in granular limestone medium. The total removal of
C. parvum
observed in our study suggests that granular limestone medium is very effective for the filtration removal of
C. parvum
and could potentially be used for the pretreatment of drinking water and aquifer storage recovery of recycled water.
The AngFus3 Mitogen-Activated Protein Kinase Controls Hyphal Differentiation and Secondary Metabolism in Aspergillus niger
Authors: Priegnitz Bert-Ewald , Brandt Ulrike , Pahirulzaman Khomaizon A. K. , Dickschat Jeroen S. , Fleißner André
Published: April 2015

Adaptation to a changing environment is essential for the survival and propagation of sessile organisms, such as plants or fungi. Filamentous fungi commonly respond to a worsening of their growth conditions by differentiation of asexually or sexually produced spores. The formation of these specialized cell types is, however, also triggered as part of the general life cycle by hyphal age or density. Spores typically serve for dispersal and, therefore, translocation but can also act as resting states to endure times of scarcity. Eukaryotic differentiation in response to environmental and self-derived signals is commonly mediated by three-tiered mitogen-activated protein (MAP) kinase signaling cascades. Here, we report that the MAP kinase Fus3 of the black mold
Aspergillus niger
(AngFus3) and its upstream kinase AngSte7 control vegetative spore formation and secondary metabolism. Mutants lacking these kinases are defective in conidium induction in response to hyphal density but are fully competent in starvation-induced sporulation, indicating that conidiation in
A. niger
is triggered by various independent signals. In addition, the mutants exhibit an altered profile of volatile metabolites and secrete dark pigments into the growth medium, suggesting a dysregulation of the secondary metabolism. By assigning the AngFus3 MAP kinase pathway to the transduction of a potentially self-derived trigger, this work contributes to the unraveling of the intricate signaling networks controlling fungal differentiation. Moreover, our data further support earlier observations that differentiation and secondary metabolism are tightly linked in filamentous fungi.
Trypanosoma brucei Bloodstream Forms Depend upon Uptake of
myo
-Inositol for Golgi Complex Phosphatidylinositol Synthesis and Normal Cell Growth
Authors: González-Salgado Amaia , Steinmann Michael , Major Louise L. , Sigel Erwin , Reymond Jean-Louis , Smith Terry K. , Bütikofer Peter
Published: April 2015

myo
-Inositol is a building block for all inositol-containing phospholipids in eukaryotes. It can be synthesized
de novo
from glucose-6-phosphate in the cytosol and endoplasmic reticulum. Alternatively, it can be taken up from the environment via Na
+
- or H
+
-linked
myo
-inositol transporters. While Na
+
-coupled
myo
-inositol transporters are found exclusively in the plasma membrane, H
+
-linked
myo
-inositol transporters are detected in intracellular organelles. In
Trypanosoma brucei
, the causative agent of human African sleeping sickness,
myo
-inositol metabolism is compartmentalized.
De novo
-synthesized
myo
-inositol is used for glycosylphosphatidylinositol production in the endoplasmic reticulum, whereas the
myo
-inositol taken up from the environment is used for bulk phosphatidylinositol synthesis in the Golgi complex. We now provide evidence that the Golgi complex-localized
T. brucei
H
+
-linked
myo
-inositol transporter (TbHMIT) is essential in bloodstream-form
T. brucei
. Downregulation of TbHMIT expression by RNA interference blocked phosphatidylinositol production and inhibited growth of parasites in culture. Characterization of the transporter in a heterologous expression system demonstrated a remarkable selectivity of TbHMIT for
myo
-inositol. It tolerates only a single modification on the inositol ring, such as the removal of a hydroxyl group or the inversion of stereochemistry at a single hydroxyl group relative to
myo
-inositol.
Using multifaceted education to improve management in acute viral bronchiolitis
Authors: Murch Hannah , Oakley Juliette , Pierrepoint Marcus , Powell Colin
Published: April 2015

Objective

To establish current bronchiolitis management across hospitals in Wales, improve compliance with national guidelines and standardise evidence-based clinical practice.

Design

A complete audit cycle with implementation of a multifaceted education bundle prior to the follow-up audit.

Setting

Twelve acute paediatric departments between 1 November and 31 December in 2012 and 2013.

Patients

All infants under 12 months with a clinical diagnosis of bronchiolitis.

Interventions

The first audit assessed management of bronchiolitis with reference to both the Scottish Intercollegiate Guideline Network (SIGN) guidelines and local hospital guidelines. Following analysis and dissemination of these results, an education bundle was implemented nationwide, with completion of the audit cycle to assess change.

Main Outcome Measures

Compliance with SIGN recommendations for investigation, treatment and discharge. Compliance with the education bundle requirements also assessed in 2013.

Results

Data were collected for 1599 infants. The education bundle was delivered in all hospitals. The level of severity, defined by oxygen saturations in air at presentation, length of stay and paediatric intensive care unit transfers, was equivalent for both years. Mean compliance percentage (95% CI) across Wales significantly improved between 2012 and 2013, with compliance with investigations increasing from 50% (46% to 53%) to 71% (68% to 74%), with management increasing from 65% (61% to 68%) to 74% (71% to 77%), and overall compliance improving from 38% (37% to 39%) to 59% (56% to 62%) in 2013.

Conclusions

This audit demonstrated a significant improvement in compliance following implementation of our educational bundle. This has enabled improvement in standardised and evidence-based patient care across Wales.
Establishing a population-based patient-reported outcomes study (PROMs) using national cancer registries across two jurisdictions: the Prostate Cancer Treatment, your experience (PiCTure) study
Authors: Drummond F J , Kinnear H , Donnelly C , O'Leary E , O'Brien K , Burns R M , Gavin A , Sharp L
Published: April 2015

Objective

To establish an international patient-reported outcomes (PROMs) study among prostate cancer survivors, up to 18 years postdiagnosis, in two countries with different healthcare systems and ethical frameworks.

Design

A cross-sectional, postal survey of prostate cancer survivors sampled and recruited via two population-based cancer registries. Healthcare professionals (HCPs) evaluated patients for eligibility to participate. Questionnaires contained validated instruments to assess health-related quality of life and psychological well-being, including QLQ-C30, QLQ-PR25, EQ-5D-5L, 21-question Depression, Anxiety and Stress Scale (DASS-21) and the Decisional Regret Scale.

Setting

Republic of Ireland (RoI) and Northern Ireland (NI).

Primary outcome measures

Registration completeness, predictors of eligibility and response, data missingness, unweighted and weighted PROMs.

Results

Prostate cancer registration was 80% (95% CI 75% to 84%) and 91% (95% CI 89% to 93%) complete 2 years postdiagnosis in NI and RoI, respectively. Of 12 322 survivors sampled from registries, 53% (n=6559) were classified as eligible following HCP screening. In the multivariate analysis, significant predictors of eligibility were: being ≤59 years of age at diagnosis (p<0.001), short-term survivor (<5 years postdiagnosis; p<0.001) and from RoI (p<0.001). 3348 completed the questionnaire, yielding a 54% adjusted response rate. 13% of men or their families called the study freephone with queries for assistance with questionnaire completion or to talk about their experience. Significant predictors of response in multivariate analysis were: being ≤59 years at diagnosis (p<0.001) and from RoI (p=0.016). Mean number of missing questions in validated instruments ranged from 0.12 (SD 0.71; EQ-5D-5L) to 3.72 (SD 6.30; QLQ-PR25). Weighted and unweighted mean EQ-5D-5L, QLQ-C30 and QLQ-PR25 scores were similar, as were the weighted and unweighted prevalences of depression, anxiety and distress.

Conclusions

It was feasible to perform PROMs studies across jurisdictions, using cancer registries as sampling frames; we amassed one of the largest, international, population-based data set of prostate cancer survivors. We highlight improvements which could inform future PROMs studies, including utilising general practitioners to assess eligibility and providing a freephone service.
Analysis of drug interactions at the end of life
Authors: Morgan N A , Rowett D , Currow D C
Published: April 2015

Background

As death approaches, patients are at their most frail, but an increasing symptom burden often necessitates an increase in medications, putting them at higher risk for drug–drug interactions.

Objectives

To assess the potential for drug–drug interactions in routine prescribing at the end of life.

Methods

An Australian retrospective multicentre case-note review of 266 consecutive adult patients who were referred to specialist palliative care, with data available on 166. Medications used in the last 2 weeks of life were screened for potential interactions using the ‘Stockley's Drug Interactions’ software.

Results

The mean number of medications prescribed was 10.8, median 9 (IQR 6–14); all patients received at least one medication. In this study, 72% of patients were at risk of 1 or more potential drug–drug interaction. The mean number of potential interactions was 4.4, with a median of 2.5 (IQR 0–7) per patient. There were only 4/166 (2.4%) prescribed medications with an associated clinical record of an adverse drug reaction.

Conclusions

Potential drug–drug interactions are common for this group of patients. Some interactions may be recognised as an acceptable risk when the prescription is written. Further research is necessary to determine the best way to improve recognition of potential drug–drug interactions and the rates of morbidity or accelerated mortality associated with this. It is likely that palliative care services will need to implement multiple strategies including greater use of computerised prescribing software, and greater closer liaison with clinical pharmacists.
BET 1: The use of bispectral index monitoring (BIS) in conscious sedation
Authors: Williams Alexia , Ruddock Yvette
Published: April 2015

A shortcut review was carried out to establish whether routine use of bispectral index monitoring in emergency department conscious sedation was effective in improving patient safety. Thirteen unique papers were found using the reported searches, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this paper are tabulated. It is concluded that there is currently insufficient evidence to support the routine use of bispectral index monitoring during conscious sedation and further studies are needed to investigate its exact benefits.
THE RECOGNITION OF STEMI BY PARAMEDICS AND THE EFFECT OF COMPUTER INTERPRETATION (RESPECT): A CLUSTER-RANDOMISED CROSSOVER PILOT STUDY
Authors: Pilbery Richard , Teare Dawn , Goodacre Steve , Morris Francis
Published: April 2015

Background

Timely diagnosis and appropriate management of patients with ST-segment elevation myocardial infarction (STEMI) depends on accurate interpretation of the 12-lead ECG by paramedics. Computer interpretation messages on ECGs are often provided, but the effect they exert on paramedics' decision making is not known. The objective of this pilot study was to assess the feasibility of a trial using an online assessment tool, to determine the effect of computer interpretation messages on paramedics' diagnosis of STEMI.

Methods

The RESPECT pilot study is a cluster-randomised crossover trial using a bespoke, web-based assessment tool. Participants were randomly allocated 12 of 48 ECGs, with an equal mix of correct and incorrect computer interpretation messages, and STEMI and STEMI-mimics. These were viewed in two phases, with message visibility reversed between phases.

Results

254 paramedics consented into the study, 205 completing the first phase and 150 completing phase two. The data were analysed in two subsets: computer message correct and computer message incorrect. In the subset of correct computer interpretations, accuracy was 84% (message hidden) and 87% (message visible). The subset of incorrect computer interpretations resulted in an accuracy of 77% (message hidden) and 71% (message visible). For the subset of correct computer interpretation, the unadjusted OR was 1.31 (95% CI 1.01–1.71), adjusted OR, 1.80 (95% CI 0.84–4.80), the ICC for participants was 0.36 and for ECGs, 0.18 Incorrect computer interpretations had an unadjusted OR of 0.76 (95% CI 0.61–0.93), adjusted OR, 0.58 (95% CI 0.41–0.80), the ICC for participants was 0.06 and for ECGs, 0.01.

Conclusion

A randomised crossover trial to determine the effect of computer interpretation messages is feasible. Pilot data have provided an indication about expected rates of discordance and suggest that incorrect computer messages have a stronger influence across participants and ECGs.
PARAMEDIC SUPPLIED “TAKE HOME” NALOXONE: A RANDOMISED FEASIBILITY STUDY
Authors: Moore Chris , Lloyd Gregory , Oretti Rossana , Russell Ian , Snooks Helen
Published: April 2015

Background

“Take Home” Naloxone (THN) kits for use by peers in the event of an opioid overdose may reduce further overdose and deaths, but distribution through Drugs Services may not reach those at highest risk. Attendance by paramedics at emergency calls for patients who have suffered an overdose presents an opportunity to distribute THN kits. In this feasibility study we will assess the acceptability of this intervention, and gather data to inform definitive trial planning.

Design and methods

Cluster randomised trial with staggered allocation of paramedics (clusters) to groups. We will invite paramedics in an urban area of south Wales, UK to participate. Paramedics will be randomly allocated to training sessions during the first four-months of the trial. Patients attended by paramedics who have been trained and issued THN kits will fall into the intervention group. Patients attended by paramedics following usual practice (until they receive their training and THN kits) will fall into the control group. We will gather data about processes and outcomes of care: numbers of patients eligible for intervention, offered and accepted THN, attended Emergency Department, suffered further overdose, died during study period and about follow up rates: numbers of patients consented, completed (postal or telephone) questionnaire. We will gather qualitative data about acceptability to patients and paramedics through interviews and focus groups.

Discussion

Naloxone is considered a very safe drug with few known side effects. However, drug taking or help seeking behaviours may be altered by the provision of the kits and evidence is required to underpin widespread implementation of this new route for THN. This feasibility study will determine the acceptability of the intervention to patients and practitioners, casemix, volume and demographics; recruitment and follow up rates; and preliminary outcome data to inform definitive trial planning.
IMPLEMENTATION OF A NOVEL INTERVENTION TO CARE FOR ELDERLY PATIENTS WHO FALL: PARAMEDICS' VIEWS
Authors: Chatters Robin , Porter Alison
Published: April 2015

Background

The SAFER 2 study, in three UK ambulance services, evaluated a complex intervention to support paramedics safely to leave older patients at home with referral to a falls service, following a call to 999 for a fall. The intervention comprised a training programme, referral pathway, clinical support, clinical decision flowchart and referral feedback. Normalisation Process Theory (NPT) examines the factors required for successful implementation of an intervention such as SAFER 2 into routine practice, through four components: coherence, cognitive participation, collective action and reflexive monitoring. We used NPT to frame an analysis of paramedics' views of implementation of SAFER 2.

Methods

Focus groups and individual interviews were carried out with paramedics before and after the trial, and were recorded and transcribed in full. Transcripts were analysed using the framework approach, informed by NPT, by a team of four researchers.

Results

Pre-trial, there were was not a clear or consistent understanding across sites of what the intervention was, and how it was distinct from similar interventions (coherence). Paramedics anticipated benefits of the new intervention, including improved patient care and job satisfaction, and thought that the referral pathway would be used widely (cognitive participation). During the trial, paramedics found that implementing the intervention led to increases of time on scene (Collective action). The intervention was perceived as advantageous to the ambulance service and patients in post-trial focus groups; paramedics from all three sites suggested improvements to the process which included simplification of the intervention (reflexive monitoring).

Conclusion

Usage of NPT to support analysis of paramedic views on implementation of the SAFER 2 intervention highlighted issues with coherence and collective action that may have affected the trial. The novel intervention was seen as beneficial by paramedics during both pre- and post-trial interviews, although barriers to utilisation were identified.