bluuebunny/crossref_metadata_2025 huggingface dataset:
Redox Properties of Iron Complexes with Pentadentate Bispidine Ligands
Authors: Comba Peter , Wadepohl Hubert , Waleska Arkadius
Published: November 2013

The solution coordination chemistry of iron complexes with the pentadentate bispidine ligands L1, L2, and L3 (dimethyl 9-oxo-2,4-di(pyridin-2-yl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate derivatives) was examined. While in acetonitrile, (L1,2)FeII/III species have a preference for Cl– as co-ligand. The corresponding aqua and hydroxido complexes also prevail in the presence of Cl– in aqueous solution. The observed FeII/III potentials in water (cyclic voltammetry) and potentials of (L1–3)FeIV=O (buffered and unbuffered aqueous solutions) are strikingly similar, i.e. the latter are assigned to (L1–3)FeII/III potentials, and published potentials of FeIV=O complexes with other ligands with uncharged amine-pyridine donors, obtained by cyclic voltammetry, have to be considered with caution.
Temporal Changes and Sexual Differences in Spatial Distribution of Burbot in Lake Erie
Authors: Stapanian Martin A. , Witzel Larry D. , Cook Andy
Published: November 2013

We used GIS mapping techniques to examine capture data for Burbot Lota lota from annual gill‐net surveys in Canadian waters of Lake Erie during late August and September 1994–2011. Adult males were captured over a larger area (3–17% for ≥20% maximum yearly catch [MYC]) than adult females. More males than females were caught in the gill nets in 14 of the 15 study years. Collectively, these results support a hypothesis of greater activity by adult males during summer, when Burbot are actively feeding. The area of capture contracted by more than 60% (for ≥20% MYC) for both sexes during the time period, which is consistent with the documented decrease of the Burbot population in the lake. The sex ratio (females: males) varied over the time series but declined steadily from 0.97 in 2001 to 0.59 in 2011. The overlap in the capture areas of adult males and females was scale dependent. The depth distribution at which adult Burbot were caught did not change over the time series, and there was no difference in the median depths (about 30 m) at which adult male and female Burbot were caught. The last results are consistent with the Burbot's reliance on coldwater habitats. Additional research is recommended, including telemetry to describe daily and seasonal movements and assessment of gender bias in active and passive capture gear.
Bioenergetics and Trophic Impacts of the Invasive Indo‐Pacific Lionfish
Authors: Cerino David , Overton Anthony S. , Rice James A. , Morris James A.
Published: November 2013

Indo‐Pacific lionfish, the Red Lionfish Pterois volitans and the Devil Firefish P. miles, are nonnative marine fish that have invaded the western North Atlantic Ocean, Caribbean Sea, and Gulf of Mexico. Rapid population growth of this invasive predator threatens native fish communities. A bioenergetics model was developed for lionfish (i.e., both species) and then applied to estimate the potential impact of these predators on a reef fish community. We conducted a series of laboratory trials to evaluate consumption and respiration rates between 14°C and 32°C for lionfish weighing from 20 to 400 g. Water temperature greatly influenced consumption; mean daily consumption rates increased from 14°C to 29.7°C and declined at 32.5°C. Energy density of the prey was the most sensitive parameter in the model and estimates of food consumption corresponded with empirical and laboratory estimates. To realize population‐level impacts, we applied the bioenergetics model to a size‐structured virtual population of 393 lionfish/ha on a reef in the Bahamas. Model simulations estimated that this population would annually consume 929 kg of prey/ha when feeding at 60% of maximum consumption. This model provides the first comprehensive assessment of lionfish bioenergetics accounting for the effects of size and temperature on prey consumption and improves the capacity to evaluate the trophic impacts of lionfish in the Atlantic Ocean.
Assessing Effects of Stocked Trout on Nongame Fish Assemblages in Southern Appalachian Mountain Streams
Authors: Weaver Daniel M. , Kwak Thomas J.
Published: November 2013

Fisheries managers are faced with the challenge of balancing the management of recreational fisheries with that of conserving native species and preserving ecological integrity. The negative effects that nonnative trout species exert on native trout are well documented and include alteration of competitive interactions, habitat use, and production. However, the effects that nonnative trout may exert on nongame fish assemblages are poorly understood. Our objectives were to quantify the effects of trout stocking on native nongame fish assemblages intensively on one newly stocked river, the North Toe River, North Carolina, and extensively on other southern Appalachian Mountain streams that are annually stocked with trout. In the intensive study, we adopted a before–after, control–impact (BACI) experimental design to detect short‐term effects on the nongame fish assemblage and found no significant differences in fish density, species richness, species diversity, or fish microhabitat use associated with trout stocking. We observed differences in fish microhabitat use between years, however, which suggests there is a response to environmental changes, such as the flow regime, which influence available habitat. In the extensive study, we sampled paired stocked and unstocked stream reaches to detect long‐term effects from trout stocking; however, we detected no differences in nongame fish density, species richness, species diversity, or population size structure between paired sites. Our results revealed high inherent system variation caused by natural and anthropogenic factors that appear to overwhelm any acute or chronic effect of stocked trout. Furthermore, hatchery‐reared trout may be poor competitors in a natural setting and exert a minimal or undetectable impact on native fish assemblages in these streams. These findings provide quantitative results necessary to assist agencies in strategic planning and decision making associated with trout fisheries, stream management, and conservation of native fishes.
Depths and Thermal Habitat Used by Large versus Small Northern Pike in Three Minnesota Lakes
Authors: Pierce Rodney B. , Carlson Andrew J. , Carlson Bruce M. , Hudson Dallas , Staples David F.
Published: November 2013

We monitored depths and temperatures used by large (>71‐cm) versus small Northern Pike Esox lucius in three north‐central Minnesota lakes with either acoustic telemetry or archival tags. Individual Northern Pike demonstrated flexibility in depths used within a season and between years. The fish had some tolerance for low levels of dissolved oxygen (<3 mg/L), but depth selection was generally constrained by low dissolved oxygen in summer and winter. The fish more fully exploited all available depths during winter and thermal turnover periods. During July and August, large Northern Pike tended to follow the thermocline into cooler water as upper water layers warmed. Selection ratios indicated that large Northern Pike preferred water temperatures of 16–21°C during August when temperatures up to 28°C were available. In two lakes providing dense overhead cover from water lilies in shallow water, small Northern Pike used warmer, shallower water compared with large fish during summer. In a third lake providing no such cover, small fish were more often in deeper, cooler water. For small Northern Pike, temperature seemed to be a secondary habitat consideration behind the presence of shallow vegetated cover. This study provided detailed temperature selection information that will be useful when considering temperature as an ecological resource for different sizes of Northern Pike.
Combining optimization and machine learning techniques for genome-wide prediction of human cell cycle-regulated genes
Authors: De Santis Marianna , Rinaldi Francesco , Falcone Emmanuela , Lucidi Stefano , Piaggio Giulia , Gurtner Aymone , Farina Lorenzo
Published: November 2013

Motivation: The identification of cell cycle-regulated genes through the cyclicity of messenger RNAs in genome-wide studies is a difficult task due to the presence of internal and external noise in microarray data. Moreover, the analysis is also complicated by the loss of synchrony occurring in cell cycle experiments, which often results in additional background noise.

Results: To overcome these problems, here we propose the LEON (LEarning and OptimizatioN) algorithm, able to characterize the ‘cyclicity degree’ of a gene expression time profile using a two-step cascade procedure. The first step identifies a potentially cyclic behavior by means of a Support Vector Machine trained with a reliable set of positive and negative examples. The second step selects those genes having peak timing consistency along two cell cycles by means of a non-linear optimization technique using radial basis functions. To prove the effectiveness of our combined approach, we use recently published human fibroblasts cell cycle data and, performing in vivo experiments, we demonstrate that our computational strategy is able not only to confirm well-known cell cycle-regulated genes, but also to predict not yet identified ones.

Availability and implementation: All scripts for implementation can be obtained on request.

Contact:  lorenzo.farina@uniroma1.it or gurtner@ifo.it

Supplementary information:  Supplementary data are available at Bioinformatics online.
A lithium depletion boundary age of 21 Myr for the Beta Pictoris moving group
Authors: Binks A. S. , Jeffries R. D.
Published: November 2013

Optical spectroscopy is used to confirm membership for eight low-mass candidates in the young Beta Pic moving group (BPMG) via their radial velocities, chromospheric activity and kinematic parallaxes. We searched for the presence of the Li i 6708 Å resonance feature and combined the results with literature measurements of other BPMG members to find the age-dependent lithium depletion boundary (LDB) – the luminosity at which Li remains unburned in a coeval group. The LDB age of the BPMG is 21 ± 4 Myr and insensitive to the choice of low-mass evolutionary models. This age is more precise, likely to be more accurate, and much older than that commonly assumed for the BPMG. As a result, substellar and planetary companions of BPMG members will be more massive than previously thought.
DNA secondary structures are associated with recombination in majorPlasmodium falciparumvariable surface antigen gene families
Authors: Sander Adam F. , Lavstsen Thomas , Rask Thomas S. , Lisby Michael , Salanti Ali , Fordyce Sarah L. , Jespersen Jakob S. , Carter Richard , Deitsch Kirk W. , Theander Thor G. , Pedersen Anders Gorm , Arnot David E.
Published: November 2013

Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens.
Effect of Catechol-o-methyltransferase-gene (COMT) Variants on Experimental and Acute Postoperative Pain in 1,000 Women undergoing Surgery for Breast Cancer
Authors: Kambur Oleg , Kaunisto Mari A. , Tikkanen Emmi , Leal Suzanne M. , Ripatti Samuli , Kalso Eija A.
Published: November 2013

Background:

Catechol-O-methyltransferase (COMT) metabolizes catecholamines in different tissues. Polymorphisms in COMT gene can attenuate COMT activity and increase sensitivity to pain. Human studies exploring the effect of COMT polymorphisms on pain sensitivity have mostly included small, heterogeneous samples and have ignored several important single nucleotide polymorphisms (SNPs). This study examines the effect of COMT polymorphisms on experimental and postoperative pain phenotypes in a large ethnically homogeneous female patient cohort.

Methods:

Intensity of cold (+2-4°C) and heat (+48°C) pain and tolerance to cold pain were assessed in 1,000 patients scheduled for breast cancer surgery. Acute postoperative pain and oxycodone requirements were recorded. Twenty-two COMT SNPs were genotyped and their association with six pain phenotypes analyzed with linear regression.

Results:

There was no association between any of the tested pain phenotypes and SNP rs4680. The strongest association signals were seen between rs165774 and heat pain intensity as well as rs887200 and cold pain intensity. In both cases, minor allele carriers reported less pain. Neither of these results remained significant after strict multiple testing corrections. When analyzed further, the effect of rs887200 was, however, shown to be significant and consistent throughout the cold pressure test. No evidence of association between the SNPs and postoperative oxycodone consumption was found.

Conclusions:

SNPs rs887200 and rs165774 located in the untranslated regions of the gene had the strongest effects on pain sensitivity. Their effect on pain is described here for the first time. These results should be confirmed in further studies and the potential functional mechanisms of the variants studied.
Mechanosensitive channels and bacterial cell wall integrity: does life end with a bang or a whimper?
Authors: Reuter Marcel , Hayward Nicholas J. , Black Susan S. , Miller Samantha , Dryden David T. F. , Booth Ian R.
Published: November 2013

Mechanogated channels are fundamental components of bacterial cells that enable retention of physical integrity during extreme increases in cell turgor. Optical tweezers combined with microfluidics have been used to study the fate of individual
Escherichia coli
cells lacking such channels when subjected to a bursting stress caused by increased turgor. Fluorescence-activated cell sorting and electron microscopy complement these studies. These analyses show that lysis occurs with a high probability, but the precise path differs between individual cells. By monitoring the loss of cytoplasmic green fluorescent protein, we have determined that some cells release this protein but remain phase dark (granular) consistent with the retention of the majority of large proteins. By contrast, most cells suffer cataclysmic wall failure leading to loss of granularity but with the retention of DNA and overall cell shape (protein-depleted ghosts). The time span of these events induced by hypo-osmotic shock varies but is of the order of milliseconds. The data are interpreted in terms of the timing of mechanosensitive channel gating relative to osmotically induced water influx.
Ultraviolet vision in birds: the importance of transparent eye media
Authors: Lind Olle , Mitkus Mindaugas , Olsson Peter , Kelber Almut
Published: November 2013

Ultraviolet (UV)-sensitive visual pigments are widespread in the animal kingdom but many animals, for example primates, block UV light from reaching their retina by pigmented lenses. Birds have UV-sensitive (UVS) visual pigments with sensitivity maxima around 360–373 nm (UVS) or 402–426 nm (violet-sensitive, VS). We describe how these pigments are matched by the ocular media transmittance in 38 bird species. Birds with UVS pigments have ocular media that transmit more UV light (wavelength of 50% transmittance,λT0.5, 323 nm) than birds with VS pigments (λT0.5, 358 nm). Yet, visual models predict that colour discrimination in bright light is mostly dependent on the visual pigment (UVS or VS) and little on the ocular media. We hypothesize that the precise spectral tuning of the ocular media is mostly relevant for detecting weak UV signals, e.g. in dim hollow-nests of passerines and parrots. The correlation between eye size and UV transparency of the ocular media suggests little or no lens pigmentation. Therefore, only small birds gain the full advantage from shifting pigment sensitivity from VS to UVS. On the other hand, some birds with VS pigments have unexpectedly low UV transmission of the ocular media, probably because of UV blocking lens pigmentation.
Arroyo del Vizcaíno, Uruguay: a fossil-rich 30-ka-old megafaunal locality with cut-marked bones
Authors: Fariña Richard A. , Tambusso P. Sebastián , Varela Luciano , Czerwonogora Ada , Di Giacomo Mariana , Musso Marcos , Bracco Roberto , Gascue Andrés
Published: November 2013

Human–megafauna interaction in the Americas has great scientific and ethical interest because of its implications on Pleistocene extinction. The Arroyo del Vizcaíno site near Sauce, Uruguay has already yielded over 1000 bones belonging to at least 27 individuals, mostly of the giant slothLestodon. The assemblage shows some taphonomic features suggestive of human presence, such as a mortality profile dominated by prime adults and little evidence of major fluvial transport. In addition, several bones present deep, asymmetrical, microstriated, sharp and shouldered marks similar to those produced by human stone tools. A few possible lithic elements have also been collected, one of which has the shape of a scraper and micropolish consistent with usage on dry hide. However, the radiocarbon age of the site is unexpectedly old (between 27 and 30 thousand years ago), and thus may be important for understanding the timing of the peopling of America.
The selectivity of aversive memory reconsolidation and extinction processes depends on the initial encoding of the Pavlovian association
Authors: Debiec Jacek , Diaz-Mataix Lorenzo , Bush David E.A. , Doyère Valérie , LeDoux Joseph E.
Published: November 2013

In reconsolidation studies, memories are typically retrieved by an exposure to a single conditioned stimulus (CS). We have previously demonstrated that reconsolidation processes are CS-selective, suggesting that memories retrieved by the CS exposure are discrete and reconsolidate separately. Here, using a compound stimulus in which two distinct CSs are concomitantly paired with the same aversive unconditioned stimulus (US), we show in rats that reexposure to one of the components of the compound CS triggers extinction or reconsolidation of the other component. This suggests that the original training conditions play a critical role in memory retrieval and reconsolidation.
Determination of Residues Responsible for Substrate and Product Specificity of Solanum habrochaites Short-Chain cis-Prenyltransferases
Authors: Kang Jin-Ho , Gonzales-Vigil Eliana , Matsuba Yuki , Pichersky Eran , Barry Cornelius S.
Published: November 2013

Isoprenoids are diverse compounds that have their biosynthetic origin in the initial condensation of isopentenyl diphosphate and dimethylallyl diphosphate to form C10 prenyl diphosphates that can be elongated by the addition of subsequent isopentenyl diphosphate units. These reactions are catalyzed by either cis-prenyltransferases (CPTs) or trans-prenyltransferases. The synthesis of volatile terpenes in plants typically proceeds through either geranyl diphosphate (C10) or trans-farnesyl diphosphate (C15), to yield monoterpenes and sesquiterpenes, respectively. However, terpene biosynthesis in glandular trichomes of tomato (Solanum lycopersicum) and related wild relatives also occurs via the cis-substrates neryl diphosphate (NPP) and 2  Z,6  Z-farnesyl diphosphate (Z,Z-FPP). NPP and Z,Z-FPP are synthesized by neryl diphosphate synthase1 (NDPS1) and Z,Z-farnesyl diphosphate synthase (zFPS), which are encoded by the orthologous CPT1 locus in tomato and Solanum habrochaites, respectively. In this study, comparative sequence analysis of NDPS1 and zFPS enzymes from S. habrochaites accessions that synthesize either monoterpenes or sesquiterpenes was performed to identify amino acid residues that correlate with the ability to synthesize NPP or Z,Z-FPP. Subsequent structural modeling, coupled with site-directed mutagenesis, highlighted the importance of four amino acids located within conserved domain II of CPT enzymes that form part of the second α-helix, for determining substrate and product specificity of these enzymes. In particular, the relative positioning of aromatic amino acid residues at positions 100 and 107 determines the ability of these enzymes to synthesize NPP or Z,Z-FPP. This study provides insight into the biochemical evolution of terpene biosynthesis in the glandular trichomes of Solanum species.
Impact on alcohol purchasing of a ban on multi‐buy promotions: a quasi‐experimental evaluation comparing Scotland with England and Wales
Authors: Nakamura Ryota , Suhrcke Marc , Pechey Rachel , Morciano Marcello , Roland Martin , Marteau Theresa M.
Published: November 2013

Aims

To evaluate the impact of the 2011 Scottish ban on multi‐buy promotions of alcohol in retail stores.

Design and setting

Difference‐in‐differences analysis was used to estimate the impact of the ban on the volume of alcohol purchased by Scottish households, compared with those in England and Wales, between January 2010 and June 2012.

Participants

A total of 22 356 households in Scotland, England and Wales.

Measurements

Records of alcohol purchasing from each of four categories (beer and cider, wine, spirits and flavoured alcoholic beverages), as well as total volume of pure alcohol purchased.

Findings

Controlling for general time trends and household heterogeneity, there was no significant effect of the multi‐buy ban in Scotland on volume of alcohol purchased either for the whole population or for individual socio‐economic groups. There was also no significant effect on those who were large pre‐ban purchasers of alcohol. Most multi‐buys were for beer and cider or for wine. The frequency of shopping trips involving beer and cider purchases increased by 9.2% following the ban (P < 0.01), while the number of products purchased on each trip decreased by 8.1% (P < 0.01). For wine, however, these effects were not significant.

Conclusions

Banning multi‐buy promotions for alcohol in Scotland did not reduce alcohol purchasing in the short term. Wider regulation of price promotion and price may be needed to achieve this.
Closed‐loop double‐vasopressor automated system vs manual bolus vasopressor to treat hypotension during spinal anaesthesia for caesarean section: a randomised controlled trial
Authors: Sng B. L. , Tan H. S. , Sia A. T. H.
Published: November 2013

Hypotension necessitating vasopressor administration occurs commonly during caesarean section under spinal anaesthesia. We developed a novel vasopressor delivery system that automatically administers phenylephrine or ephedrine based on continuous non‐invasive arterial pressure monitoring. A phenylephrine bolus of 50 μg was given at 30‐s intervals when systolic blood pressure fell < 90% of baseline; an ephedrine bolus of 4 mg was given instead if systolic pressure fell < 90% of baseline together with a heart rate < 60 beats.min−1. The control group used manual boluses of either phenylephrine 100 μg or ephedrine 8 mg, administered at 1‐min intervals based on the same thresholds for systolic pressure and heart rate. This randomised, controlled, double‐blinded trial involved 213 healthy women who underwent elective caesarean delivery under spinal anaesthesia using 11 mg hyperbaric bupivacaine with 15 μg fentanyl and 100 μg morphine. The automated vasopressor group had better systolic pressure control, with 37/106 (34.9%) having any beat‐to‐beat systolic pressure reading < 80% of baseline compared with 63/107 (58.9%) in the control group (p < 0.001). There was no difference in the incidence of reactive hypertension, defined as systolic pressure > 120% of baseline, with 8/106 (7.5%) in the automated vasopressor group vs 14/107 (13.1%) in the control group, or total dose of vasopressors. The automated vasopressor group had lower median absolute performance error of 8.5% vs control of 9.8% (p = 0.013), and reduced incidence of nausea (1/106 (0.9%) vs 11/107 (10.3%), p = 0.005). Neonatal umbilical cord pH, umbilical lactate and Apgar scores were similar. Hence, our system afforded better control of maternal blood pressure and reduced nausea with no increase in reactive hypertension when compared with manual boluses.
Review article: the epidemiology and therapy of chronic hepatitis C genotypes 4, 5 and 6
Authors: Wantuck J. M. , Ahmed A. , Nguyen M. H.
Published: November 2013

Background

The global burden of hepatitis C (HCV) infection is mostly found in Africa, the Middle East and Asia, where HCV genotypes 4, 5 and 6 are common. The literature on these genotypes is sparse and this synopsis will review characteristics of patients infected with these genotypes.

Aim

To review characteristics of patients infected with HCV genotypes 4, 5 and 6.

Methods

PubMed search for ‘hepatitis C’ AND ‘genotype 4’, ‘hepatitis C’ AND ‘genotype 5’, and ‘hepatitis C’ AND ‘genotype 6’ was conducted and relevant articles were reviewed.

Results

Intravenous drug use is generally responsible for HCV genotype 4 infection in developed countries, but unsafe medical practices cause most cases of HCV genotypes 4, 5 and 6 in endemic countries. The sustained virological response (SVR) rate for patients with HCV genotype 4 who receive pegylated interferon and ribavirin for 48 weeks ranges from 40% to 70% in various small studies. The SVR rate is in the 60–70% range for HCV genotype 5 and 70–80% range for HCV genotype 6 following 48 weeks with pegylated interferon and ribavirin. Preliminary data suggest that a shorter course of 24 weeks of pegylated interferon and ribavirin may be acceptable for HCV genotype 6, with an SVR rate of approximately 70%.

Conclusions

The current standard‐of‐care therapy for HCV genotypes 4, 5 and 6 is pegylated interferon and ribavirin for 48 weeks. A shorter course with 24 weeks of therapy may be considered for patients with genotype 6. Newer and much more effective therapies may be forthcoming in the next few years.
Randomised clinical trial: oral vs. intravenous iron after upper gastrointestinal haemorrhage – a placebo‐controlled study
Authors: Bager P. , Dahlerup J. F.
Published: November 2013

Background

Nonvariceal acute upper gastrointestinal bleeding (AUGIB) is often accompanied by post‐discharge anaemia.

Aim

To investigate whether iron treatment can effectively treat anaemia and to compare a 3‐month regimen of oral iron treatment with a single administration of intravenous iron prior to discharge.

Methods

Ninety‐seven patients with nonvariceal AUGIB and anaemia were enrolled in a double‐blind, placebo‐controlled, randomised study. The patients were allocated to one of three groups, receiving a single intravenous administration of 1000 mg of iron; oral iron treatment, 200 mg daily for 3 months; or placebo, respectively. The patients were followed up for 3 months.

Results

From week 4 onwards, patients receiving treatment had significantly higher haemoglobin levels compared with patients who received placebo only. At the end of treatment, the proportion of patients with anaemia was significantly higher in the placebo group (P < 0.01) than in the treatment groups. Intravenous iron appeared to be more effective than oral iron in ensuring sufficient iron stores.

Conclusions

Iron treatment is effective and essential for treating anaemia after nonvariceal acute upper gastrointestinal bleeding. The route of iron supplementation is less important in terms of the increase in haemoglobin levels. Iron stores are filled most effectively if intravenous iron supplementation is administered (ClinicalTrials.gov identifier: NCT00978575).
LDL‐c‐linked SNPs are associated with LDL‐c and myocardial infarction despite lipid‐lowering therapy in patients with established vascular disease
Authors: van de Woestijne Anton P. , van der Graaf Yolanda , de Bakker Paul I. W. , Asselbergs Folkert W. , de Borst Gert Jan , Algra Ale , Spiering Wilko , Visseren Frank L. J. ,   the SMART Study Group
Published: November 2013

Background

Several single‐nucleotide polymorphisms (SNPs) are associated with both plasma low‐density lipoprotein cholesterol (LDL‐c) level and coronary artery disease in the general population. It is unclear whether these associations also apply to patients with vascular disease and whether the associations are independent of lipid‐lowering therapy.

Design

Single‐nucleotide polymorphisms associated with plasma LDL‐c and vascular risk in the general population (rs11206510 (PCSK9), rs1122608 (LDLR), rs579459 (ABO) and rs599839 (SORT1)) were genotyped in a prospective cohort study of 5482 patients with vascular disease. We determined the association between LDL‐c‐associated alleles and plasma LDL‐c levels and the risk of new vascular events.

Results

All tested SNPs were associated with LDL‐c plasma levels with a magnitude between +0·06 (95% CI 0·02–0·10) mM and +0·14 (95% CI 0·09–0·18) mM per LDL‐c‐increasing allele. The associations were independent of the use of lipid‐lowering medication, except for rs579459, for which the association was not present in patients using lipid‐lowering medication. In patients with 7–8 risk alleles for these SNPs, 59% of the patients treated with lipid‐lowering medication did not reach the LDL‐c target of <2·5 mM compared with 45% in patients with 3 or fewer risk alleles. LDL‐c‐increasing alleles were not associated with increased risk of vascular events in patients not using lipid‐lowering medication (HRs: 1·01; 95% CI: 0·93–1·09). In patients using lipid‐lowering medication, the risk of myocardial infarction increased with 14% (HRs: 1·14; 95% CI: 1·01–1·28) per allele.

Conclusions

In patients with established vascular disease, the studied SNPs increase LDL‐c plasma levels. LDL‐c‐increasing alleles may be associated with increased risk of myocardial infarction in patients treated with lipid‐lowering medication, but not in patients not treated with lipid‐lowering medication.
Improvement in health‐related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study
Authors: Windyga J. , Lin V. W. , Epstein J. D. , Ito D. , Xiong Y. , Abbuehl B. E. , Ramirez J. H.
Published: November 2013

Little is known about the health‐related quality of life (HRQoL) burden of haemophilia B. The aim of this study was to assess HRQoL burden of haemophilia B, the benefit of recombinant factor IX (rFIX) prophylaxis and the HRQoL benefit of achieving a zero annual bleed rate. Subjects receiving rFIX (BAX326) prophylaxis or on‐demand completed the SF‐36 survey. Baseline SF‐36 scores were compared to the general US population scores to understand the HRQoL burden. Changes in SF‐36 scores between baseline and follow‐up were tested using t‐tests. Subgroup analysis was conducted to examine SF‐36 change among subjects who switched to BAX326 prophylaxis. SF‐36 scores were also compared between those with zero bleeds and those who bled during the study. Compared to the US norms, subjects reported lower average scores in all physical and several mental HRQoL domains. At follow‐up, prophylaxis subjects reported statistically significant and clinically meaningful improvements in overall physical HRQoL, as measured by the Physical Component Score (PCS) (mean change 2.60, P = 0.019), Bodily Pain (BP) (3.45, P = 0.015) and Role Physical (RP) domains (3.47, P = 0.016). Subjects who switched to prophylaxis from intermittent prophylaxis or on‐demand experienced more pronounced improvements not only in the PCS (3.21, P = 0.014), BP (3.71, P = 0.026), RP (4.43, P = 0.008) but also in Vitality (3.71, P = 0.04), Social Functioning (5.06, P = 0.002) and General Health domains (3.40, P = 0.009). Subjects achieving zero bleeds reported lower BP (P = 0.038). Prophylaxis with BAX326 significantly improved HRQoL in patients with moderately severe or severe haemophilia B by reducing bleeds.
Tranexamic acid as adjunct therapy to bypassing agents in haemophiliaApatients with inhibitors
Authors: Tran H. T. T. , Sørensen B. , Rea C. J. , Bjørnsen S. , Ueland T. , Pripp A. H. , Tjønnfjord G. E. , Holme P. A.
Published: November 2013

Haemophilia patients with inhibitors require bypassing agents (BPA) like activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rFVIIa) to control bleeds. Adjunct tranexamic acid (TXA) may improve haemostasis. The objective of this study was to investigate safety and haemostatic effect ofTXAgiven in combination withBPA. Healthy volunteers (N = 5) and haemophilia inhibitor patients (N = 6) were enrolled in a prospective case crossover design. Controls were treated withTXA20 mg kg−1orally (O.R.) Patients were treated with aPCC 75 IU kg−1intravenous (I.V.) on day 1 followed byTXA20 mg kg−1O.R. combined with aPCC 75 IU kg−1I.V. on day 2. A 14‐day washout occurred before crossover to rFVIIa 90 μg kg−1I.V. ±TXA. Safety evaluation and blood sampling processes were performed at baseline, 15, 30, 60, 120, 180 and 240 min post treatment. Primary outcome was maximum clot firmness (MCF) evaluated by whole blood thromboelastometry using aTF + tissue plasminogen activator‐based assay. Healthy controls showed a 20‐fold increase inMCFfollowingTXA. AdjunctTXAto aPCC or rFVIIa induced a significant increase inMCF(P < 0.0001) reaching levels indistinguishable from healthy controls treated withTXA(P > 0.05). Infusion of aPCC or rFVIIa alone induced only 3–10 fold increase inMCFfrom baseline, with a decline inMCFstarting after 60–120 min.TXAdid not increase the endogenous thrombin potential. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed. Combination of aPCC or rFVIIa withTXAnormalizes clot stability in haemophilia patients with inhibitor as compared to healthy controls. No clinical or laboratory adverse events were observed.
Stigma towards nurses with mental illnesses: A study of nurses and nurse managers in hospitals in Japan
Authors: Tei‐Tominaga Maki , Asakura Takashi , Asakura Kyoko
Published: November 2013

In the present study, we examined the current situation of nurses with mental illnesses, the stigma associated with these illnesses, and nurses' and nurse managers' perceptions of workplace mental health issues. We conducted a questionnaire survey of 880 nurses and nurse managers in Japan. After we carried out a descriptive analysis to examine the characteristics of stigma, the data of 585 participants were used for comprehensive analyses. In all, 71% of participants reported having worked with nurses with mental illnesses, and 40% reported having supported them. Of the participants, 90% believed a growing number of nurses would have mental illnesses in the near future. Stigma scores were significantly higher for items related to nurses with mental illnesses than for those with physical health problems. There was no significant difference in stigma scores according to sociodemographic and organizational characteristics. Scores for stigma items related to nurses with mental illnesses were significantly higher for participants who had worked with or supported nurses with such illnesses than for those who had not. Our findings suggest that effective approaches are needed to decrease stigma, ensure support in the workplace, and address mental illnesses to counter nurse absenteeism.
Risk factors associated with fatal influenza, Romania, October 2009 – May 2011
Authors: Zolotusca Laurentiu , Jorgensen Pernille , Popovici Odette , Pistol Adriana , Popovici Florin , Widdowson Marc‐Alain , Alexandrescu Viorel , Ivanciuc Alina , Cheng Po‐Yung , Gross Diane , Brown Caroline S. , Mott Joshua A.
Published: November 2013

Background

Limited data are available from Central and Eastern Europe on risk factors for severe complications of influenza. Such data are essential to prioritize prevention and treatment resources and to adapt influenza vaccination recommendations.

Objectives

To use sentinel surveillance data to identify risk factors for fatal outcomes among hospitalized patients with severe acute respiratory infections (SARI) and among hospitalized patients with laboratory‐confirmed influenza.

Methods

Retrospective analysis of case‐based surveillance data collected from sentinel hospitals in Romania during the 2009/2010 and 2010/2011 winter influenza seasons was performed to evaluate risk factors for fatal outcomes using multivariate logistic regression.

Results

During 2009/2010 and 2010/2011, sentinel hospitals reported 661 SARI patients of which 230 (35%) tested positive for influenza. In the multivariate analyses, infection with influenza A(H1N1)pdm09 was the strongest risk factor for death among hospitalized SARI patients (OR: 6·6; 95% CI: 3·3–13·1). Among patients positive for influenza A(H1N1)pdm09 virus infection (n = 148), being pregnant (OR: 7·1; 95% CI: 1·6–31·2), clinically obese (OR: 2·9;95% CI: 1·6–31·2), and having an immunocompromising condition (OR: 3·7;95% CI: 1·1–13·4) were significantly associated with fatal outcomes.

Conclusion

These findings are consistent with several other investigations of risk factors associated with influenza A(H1N1)pdm09 virus infections. They also support the more recent 2012 recommendations by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) that pregnant women are an important risk group for influenza vaccination. Ongoing sentinel surveillance can be useful tool to monitor risk factors for complications of influenza virus infections during each influenza season, and pandemics as well.
IL-7 enhancement of antigen-driven activation/expansion of HIV-1-specific cytotoxic T lymphocyte precursors (CTLp)
Authors: FERRARI G , KING K , RATHBUN K , PLACE C A , PACKARD M V , BARTLETT J A , BOLOGNESI D P , WEINHOLD K J
Published: November 2013

CD8+ cytotoxic T lymphocytes are an important component in the immunologic control of human viral diseases. IL-7, a stromal cell-derived cytokine, has been demonstrated to enhance both anti-tumour and anti-viral CTL as well as lymphokine-activated killer (LAK) activity. We studied the ability of IL-7 to support the activation and the growth of in vitro antigen-specific CTL precursors (CTLp) present in peripheral blood mononuclear cells (PBMC) from HIV-infected patients. Results from these studies demonstrate that inclusion of IL-7 in a vaccinia/HIV-1 vector-based stimulation strategy greatly augmented overall CTL reactivities, whereas addition of IL-7 to unstimulated cultures failed to induce any significant anti-viral cytolytic activity. In four of six patients, HIV-specific lytic activities were significantly higher in cultures stimulated with antigen plus IL-7 compared with in vitro stimulation (IVS) with antigen alone. Cytotoxic activity was principally mediated by CD8+ effector cells, and CD3+/CD8+ cell expansion was increased by 2–7-fold in the presence of IL-7. In PBMC from seronegative donors, IL-7 enhanced anti-vaccinia CTL activities with less effect on cell proliferation. Furthermore, anti-gag CTL frequencies determined by limiting dilution analysis were increased by 2- and 10-fold in two asymptomatic patients following IVS plus IL-7 compared with antigen stimulation alone. Cytofluorimetric analysis revealed that IL-7 preferentially expanded CD8 memory cells (CD45RO+) and CD8+ lymphocytes expressing activation molecules. IL-7 was also able to support the growth of CD4+ lymphocytes, while having no effect on natural killer (NK)/K lymphocytes. Taken together, these data suggest that IL-7 acts cooperatively with the antigen supporting in vitro maturation of CTLp into functional cytotoxic effectors. Thus IL-7 may be an important biologic entity to consider as part of future immune-based therapies in which ex vivo expansion of antigen-driven CTL is an important determinant.
Heterochrony and post‐natal growth in mammals – an examination of growth plates in limbs
Authors: Geiger M. , Forasiepi A. M. , Koyabu D. , Sánchez‐Villagra M. R.
Published: November 2013

Mammals display a broad spectrum of limb specializations coupled with different locomotor strategies and habitat occupation. This anatomical diversity reflects different patterns of development and growth, including the timing of epiphyseal growth plate closure in the long bones of the skeleton. We investigated the sequence of union in 15 growth plates in the limbs of about 400 specimens, representing 58 mammalian species: 34 placentals, 23 marsupials and one monotreme. We found a common general pattern of growth plate closure sequence, but one that is universal neither between species nor in higher‐order taxa. Locomotor habitat has no detectable correlation with the growth plate closure sequence, but observed patterns indicate that growth plate closure sequence is determined more strongly through phylogenetic factors. For example, the girdle elements (acetabulum and coracoid process) always ossify first in marsupials, whereas the distal humerus is fused before the girdle elements in some placentals. We also found that heterochronic shifts (changes in timing) in the growth plate closure sequence of marsupials occur with a higher rate than in placentals. This presents a contrast with the more limited variation in timing and morphospace occupation typical for marsupial development. Moreover, unlike placentals, marsupials maintain many epiphyses separated throughout life. However, as complete union of all epiphyseal growth plates is recorded in monotremes, the marsupial condition might represent the derived state.
The place of standardisation in home care practice: an ethnographic study
Authors: Björnsdóttir Kristín
Published: November 2013

Aims and objectives

To explore the benefits and shortcomings of using standardised work methods in home care nursing.

Background

Health care is increasingly shaped by the use of standardised work methods. This trend is reflected in the use of management tools aimed at monitoring service quality and efficiency, as well as in the evidence‐based movement that has led to a shift in focus from the practitioner to the knowledge found in guidelines and clinical protocols. This study addressed the impact of this development on home care services.

Design

This is an ethnographic study involving fieldwork in home care nursing in Iceland.

Methods

The study took place in one neighbourhood in an urban area in Iceland in 2010. Members of five of six home care nursing teams agreed to participate. Team leaders were observed during visits to older person's homes and at team and interdisciplinary meetings. Semi‐structured interviews were conducted with the team leaders and 15 older persons.

Results

The results were presented as three themes: For it all to hang together, which referred to attempts on behalf of the team leaders to coordinate complex services and assistance for the benefit of each patient; Working with more advanced cases, which reflected the uptake of standardised methods to address health matters locally; and Being heard, which reflects the politics of using standardised methods.

Conclusions

Standardised work methods can be helpful and are welcomed by home care nurses as long as they can also use their own discretion and draw on other forms of knowledge when needed.

Relevance to clinical practice

This study brought out the importance of flexibility in home care practice. Standardised work methods are welcomed and seen as helpful as long as they can be used based on the discretion of the practitioner.
Obesity and physical activity patterns in children and adolescents
Authors: Laguna María , Ruiz Jonatan R , Gallardo Cristian , García‐Pastor Teresa , Lara María‐Teresa , Aznar Susana
Published: November 2013

Aim

The aim of this study is to measure objectively and accurately the physical activity (PA) patterns in Spanish children and adolescents according to their obesity status, gender and age groups.

Methods

A sample of 487 children and 274 adolescents from the European Youth Heart Study participated in the study. The variables measured were anthropometric characteristics (height, weight and body mass index), and PA was measured during 6 consecutive days using the GT1M accelerometer.

Results

Three‐way analysis of variance (age × gender × obesity status) showed significant differences in the interaction effect in age, gender and obesity status (normal‐weight and overweight/obesity) for mean of moderate‐to‐vigorous PA (MVPA) (P = 0.02) and vigorous PA (VPA) (P = 0.014) within the sample. Nine‐year‐old normal‐weight children achieved significantly (P < 0.05) more MVPA on weekdays than 9‐year‐old overweight/obesity children. During weekend days, all sample achieved significant more MVPA (P < 0.01) and significant more VPA (P < 0.05) than during weekdays. Few children (37.5% of 9‐year‐old normal‐weight and 34.0% of 9‐year‐old overweight/obese) and adolescents (16.4% and 27.3% normal‐weight and overweight/obese, respectively) met the current health‐related recommendations of 60 min of MVPA daily.

Conclusions

It is clear that activity levels are insufficient for all children, in particular overweight/obese children and adolescents, although the precise nature of the relationship appears to differ between boys and girls.
Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice
Authors: Rathor Naveen , Arora Tarun , Manocha Sachin , Patil Amol N , Mediratta Pramod K , Sharma Krishna K
Published: November 2013

Objectives

The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy.

Methods

In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals.

Key findings

In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group.

Conclusions

The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity.