Identification of sources of Salmonella organisms in a veterinary teaching hospital and evaluation of the effects of disinfectants on detection of Salmonella organisms on surface materials.
To determine sources of Salmonella organisms in a veterinary teaching hospital, compare bacterial culture with polymerase chain reaction (PCR) testing for detection of Salmonella organisms in environmental samples, and evaluate the effects of various disinfectants on detection of Salmonella organisms on surface materials. Prospective study. Fecal samples from 638 hospitalized horses and 783 environmental samples. Standard bacterial culture techniques were used; the PCR test amplified a segment of the Salmonella DNA. Five disinfectants were mixed with Salmonella suspensions, and bacterial culture was performed. Swab samples were collected from 7 surface materials after inoculation of the surfaces with Salmonella Typhimurium, with or without addition of a disinfectant, and submitted for bacterial culture and PCR testing. Salmonella organisms were detected in fecal samples from 35 (5.5%) horses. For environmental samples, the proportion of positive bacterial culture results (1/783) was significantly less than the proportion of positive PCR test results (110/783), probably because of detection of nonviable DNA by the PCR test. Detection of Salmonella organisms varied with the surface material tested, the method of detection (bacterial culture vs PCR testing), and the presence and type of disinfectant. Results of the present study suggested that Salmonella organisms can be isolated from feces of hospitalized horses and a variety of environmental surfaces in a large animal hospital. Although recovery of Salmonella organisms was affected by surface material and disinfectant, bleach was the most effective disinfectant on the largest number of surfaces tested.


Physical interpretation of Mueller matrix spectra: a versatile method applied to gold gratings.
The interaction of nanostructures, periodic or random, with polarized light creates very rich physics where scattering, diffraction and absorbance are linked to a variety of dispersive modes and coupling effects. Each of these excitations depends strongly on polarization, angle of incidence, azimuthal orientation of the sample and wavelength. The entire optical response can be obtained, independently from any model, by measuring the Mueller matrices at various k-vectors over a broad frequency range. This results in complex data hiding the underlying physics. Here we present a simple but versatile method to identify the physical properties present in the Mueller matrices. This method is applicable to a wide variety of photonic and plasmonic samples. Based on the simple example of a one-dimensional gold grating where the optical response is characterized not only by diffraction but also by a complex mixing of polarization, we present a very general procedure to analyze the Mueller matrix data using simple analytical tools. The calculated Mueller matrix contour plots obtained from an effective anisotropic layer model are completed by the presence of plasmonic modes, Rayleigh-Woods anomalies and the interband transition absorbance. A comparison of the so-constructed contour plots with the measured ones satisfactorily connects the optical properties of the grating to their physical origin. This straightforward procedure is very general and will be powerful for the analysis of complex optical nanostructures.


The effect of age in the cardiac MRI evaluation of the athlete's heart.
Increasing age is accompanied by a higher risk of sports-related death, especially from coronary disease and cardiomyopathies. It is unclear if the mature athlete's heart differs from young athletes. Our aim was to assess the effect of age on ventricular volumes and wall-mass. We also established maximum cardiac MRI (CMR) reference values in mature athletes to facilitate differentiation from cardiomyopathy. 143 healthy persons aged 40-60 years (mean age 49±6 years [±SD], 39% women) underwent CMR: 78 athletes (exercising 9-18 h/week), and 65 age and gender matched non-athletes (≤3 h/week). From a larger study, cardiac MRI data of 195 healthy persons aged 18-39 years (mean age 28±6, 48% women) were included for statistical analysis: 81 athletes and 114 matched non-athletes. With multivariate analysis, age only has limited effect on ventricular volumes (LV 1%, RV 3%) and wall-mass (0.01%). Only athletes show significant decrease in right and left ventricular volumes and LV-mass with increasing age (p<0.05). RV wall-mass remains unaffected by age. Ventricular diameters, volumes and wall-mass are significantly lower in mature athletes compared to young athletes, and significantly higher compared to mature non-athlete controls (p<0.05). Only athletes show a significant decrease in ventricular volumes and LV wall-mass with increasing age, which probably reflects decreasing training intensity rather than the effect of age. Mature athletes form a distinct group requiring separate reference values as they have significantly lower ventricular volumes and wall-mass as compared to young athletes, however, still significantly higher values than mature non-athletes.


Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer.
Persistent colonization of the human stomach by Helicobacter pylori is associated with asymptomatic gastric inflammation (gastritis) and an increased risk of duodenal ulceration, gastric ulceration, and non-cardia gastric cancer. In previous studies, the genome sequences of H. pylori strains from patients with gastritis or duodenal ulcer disease have been analyzed. In this study, we analyzed the genome sequences of an H. pylori strain (98-10) isolated from a patient with gastric cancer and an H. pylori strain (B128) isolated from a patient with gastric ulcer disease. Based on multilocus sequence typing, strain 98-10 was most closely related to H. pylori strains of East Asian origin and strain B128 was most closely related to strains of European origin. Strain 98-10 contained multiple features characteristic of East Asian strains, including a type s1c vacA allele and a cagA allele encoding an EPIYA-D tyrosine phosphorylation motif. A core genome of 1237 genes was present in all five strains for which genome sequences were available. Among the 1237 core genes, a subset of alleles was highly divergent in the East Asian strain 98-10, encoding proteins that exhibited <90% amino acid sequence identity compared to corresponding proteins in the other four strains. Unique strain-specific genes were identified in each of the newly sequenced strains, and a set of strain-specific genes was shared among H. pylori strains associated with gastric cancer or premalignant gastric lesions. These data provide insight into the diversity that exists among H. pylori strains from diverse clinical and geographic origins. Highly divergent alleles and strain-specific genes identified in this study may represent useful biomarkers for analyzing geographic partitioning of H. pylori and for identifying strains capable of inducing malignant or premalignant gastric lesions.


Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.
Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and post-translationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immuno-blotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.


The involvement of brain-derived neurotrophic factor in 3,4-methylenedioxymethamphetamine-induced place preference and behavioral sensitization.
3,4-Methylenedioxymethamphetamine (MDMA) is known to induce dependence and psychosis in humans. Brain-derived neurotrophic factor (BDNF) is involved in the synaptic plasticity and neurotrophy in midbrain dopaminergic neurons. This study aimed to investigate the role of BDNF in MDMA-induced dependence and psychosis. A single dose of MDMA (10mg/kg) induced BDNF mRNA expression in the prefrontal cortex, nucleus accumbens, and amygdala, but not in the striatum or the hippocampus. However, repeated MDMA administration for 7 days induced BDNF mRNA expression in the striatum and hippocampus. Both precursor and mature BDNF protein expression increased in the nucleus accumbens, mainly in the neurons. Additionally, rapidly increased extracellular serotonin levels and gradually and modestly increased extracellular dopamine levels were noted within the nucleus accumbens of mice after repeated MDMA administration. Dopamine receptor antagonists attenuated the effect of repeated MDMA administration on BDNF mRNA expression in the nucleus accumbens. To examine the role of endogenous BDNF in the behavioral and neurochemical effects of MDMA, we used mice with heterozygous deletions of the BDNF gene. MDMA-induced place preference, behavioral sensitization, and an increase in the levels of extracellular serotonin and dopamine within the nucleus accumbens, were attenuated in BDNF heterozygous knockout mice. These results suggest that BDNF is implicated in MDMA-induced dependence and psychosis by activating the midbrain serotonergic and dopaminergic neurons.


Intraoperative brain cancer detection with Raman spectroscopy in humans.
Cancers are often impossible to visually distinguish from normal tissue. This is critical for brain cancer where residual invasive cancer cells frequently remain after surgery, leading to disease recurrence and a negative impact on overall survival. No preoperative or intraoperative technology exists to identify all cancer cells that have invaded normal brain. To address this problem, we developed a handheld contact Raman spectroscopy probe technique for live, local detection of cancer cells in the human brain. Using this probe intraoperatively, we were able to accurately differentiate normal brain from dense cancer and normal brain invaded by cancer cells, with a sensitivity of 93% and a specificity of 91%. This Raman-based probe enabled detection of the previously undetectable diffusely invasive brain cancer cells at cellular resolution in patients with grade 2 to 4 gliomas. This intraoperative technology may therefore be able to classify cell populations in real time, making it an ideal guide for surgical resection and decision-making.


Anatomic and visual acuity outcomes following thermal laser photocoagulation or photodynamic therapy for symptomatic circumscribed choroidal hemangioma with associated serous retinal detachment.
This study reports and compares the anatomic and visual acuity outcomes of patients treated with either thermal laser photocoagulation or photodynamic therapy for circumscribed choroidal hemangioma with associated serous retinal detachment. Retrospective, consecutive, interventional case series of patients treated for symptomatic circumscribed choroidal hemangioma. Thirteen of 23 patients (57%) treated with thermal laser photocoagulation exhibited complete resolution of subretinal fluid, 6 (26%) had partial resolution of subretinal fluid, and 4 (17%) had persistent subretinal fluid despite therapy. At 3 months posttreatment, visual acuity was improved in 6 (26%), stable in 13 (57%), and worsened in 4 (17%) of 23 patients. All 5 patients who underwent photodynamic therapy had complete resolution of subretinal fluid. At 3 months posttreatment, visual acuity improved in 4 (80%), remained stable in 1 (20%), and worsened in 0 (0%) patients. Photodynamic therapy shows similar if not better anatomic and visual acuity results than thermal laser photocoagulation when treating symptomatic circumscribed choroidal hemangioma.


Protective Properties of a Microstructure Composed of Barrier Nanostructured Organics and SiOx Layers Deposited on a Polymer Matrix.
The SiOx barrier nanocoatings have been prepared on selected polymer matrices to increase their resistance against permeation of toxic substances. The aim has been to find out whether the method of vacuum plasma deposition of SiOx barrier nanocoatings on a polyethylene terephthalate (PET) foil used by Aluminium Company of Canada (ALCAN) company (ALCAN Packaging Kreuzlingen AG (SA/Ltd., Kreuzlingen, Switzerland) within the production of CERAMIS® packaging materials with barrier properties can also be used to increase the resistance of foils from other polymers against the permeation of organic solvents and other toxic liquids. The scanning electron microscopy (SEM) microstructure of SiOx nanocoatings prepared by thermal deposition from SiO in vacuum by the Plasma Assisted Physical Vapour Deposition (PA-PVD) method or vacuum deposition of hexamethyldisiloxane (HMDSO) by the Plasma-enhanced chemical vapour deposition (PECVD) method have been studied. The microstructure and behavior of samples when exposed to a liquid test substance in relation to the barrier properties is described.


Screening for atrial fibrillation in hospitalised geriatric patients.
To assess whether daily short-term rhythm strip recordings on top of routine clinical care could increase the atrial fibrillation (AF) detection rate in the hospitalised elderly. A hand-held device storing a bipolar ECG during 1 min was used for daily rhythm recording in hospitalised elderly patients. During 2 months, all patients admitted to the Department of Geriatric Medicine were screened (n=327). Five patients refused to participate in the study and 70 patients were unable to hold the device due to severe mental (n=46) or motor impairment (n=24). In the remaining 252 patients, 1582 recordings were successfully obtained after 1624 attempts with a median acquisition time of 1 min (min 1, max 9, IQR 1-2 min). The rhythm strips were not reliable interpretable due to artefacts in three patients or an implantable cardiac pulse generator in another 28 patients. Detailed clinical information was available in 214/221 patients. Mean age was 84±6 years. On top of 71 (33%) patients with AF identified by routine clinical care (history, n=64 or de novo detected during current hospitalisation, n=7), review of all rhythm strips identified another 28 patients (13%) with AF. All these patients had a CHA2DS2VASc score ≥2. A contraindication for anticoagulation was present in only 8/28 (25%) of identified patients. On top of routine clinical care, daily short-term rhythm strip recordings identified another 13% of elderly hospitalised patients with AF, leading to an overall prevalence of 46% in hospitalised patients. This can have significant therapeutic implications with respect to initiation of anticoagulation.


Calliope: Automatic Visual Data Story Generation from a Spreadsheet.
Visual data stories shown in the form of narrative visualizations such as a poster or a data video, are frequently used in data-oriented storytelling to facilitate the understanding and memorization of the story content. Although useful, technique barriers, such as data analysis, visualization, and scripting, make the generation of a visual data story difficult. Existing authoring tools rely on users' skills and experiences, which are usually inefficient and still difficult. In this paper, we introduce a novel visual data story generating system, Calliope, which creates visual data stories from an input spreadsheet through an automatic process and facilities the easy revision of the generated story based on an online story editor. Particularly, Calliope incorporates a new logic-oriented Monte Carlo tree search algorithm that explores the data space given by the input spreadsheet to progressively generate story pieces (i.e., data facts) and organize them in a logical order. The importance of data facts is measured based on information theory, and each data fact is visualized in a chart and captioned by an automatically generated description. We evaluate the proposed technique through three example stories, two controlled experiments, and a series of interviews with 10 domain experts. Our evaluation shows that Calliope is beneficial to efficient visual data story generation.


The effects of training volume and repetition distance on session rating of perceived exertion and internal load in swimmers.
To assess swimmers' session rating of perceived exertion (sRPE) after standardized sets of interval swimming training performed at the same relative intensity but with different total volume and repetition distance. Thirteen moderately trained swimmers (21.1 ± 1.1 y, 178 ± 6 cm, 74.1 ± 8.3 kg, 100-m freestyle 60.2 ± 2.9 s) performed 4 standardized sets (10 × 100-m, 20 × 100-m, 10 × 200-m, and 5 × 400-m) at the same relative intensity (ie, critical speed), and 1 coach (age 31 y, 7 y coaching experience) rated their efforts. Swimmers' sRPE was assessed 30 min after the training session. Coach sRPE was collected before each training session. Internal load was calculated by multiplying sRPE by session duration. When bouts with the same repetition distance and different volumes (10 × 100-m vs 20 × 100-m) are compared, sRPE and internal load are higher in 20 × 100-m bouts. When maintaining constant volume, sRPE and internal load (20 × 100-m, 10 × 200-m, and 5 × 400-m) are higher only in 5 × 400-m bouts. The coach's and swimmers' sRPE differed in 10 × 200-m and 5 × 400-m. These results indicate that sRPE in swimming is affected not only by intensity but also by volume and repetition distance. In addition, swimmers' and the coach's sRPE were different when longer repetition distances were used during training sessions. Therefore, care should be taken when prescribing swimming sessions with longer volume and/or longer repetition distances.


A high-energy-density sugar biobattery based on a synthetic enzymatic pathway.
High-energy-density, green, safe batteries are highly desirable for meeting the rapidly growing needs of portable electronics. The incomplete oxidation of sugars mediated by one or a few enzymes in enzymatic fuel cells suffers from low energy densities and slow reaction rates. Here we show that nearly 24 electrons per glucose unit of maltodextrin can be produced through a synthetic catabolic pathway that comprises 13 enzymes in an air-breathing enzymatic fuel cell. This enzymatic fuel cell is based on non-immobilized enzymes that exhibit a maximum power output of 0.8 mW cm(-2) and a maximum current density of 6 mA cm(-2), which are far higher than the values for systems based on immobilized enzymes. Enzymatic fuel cells containing a 15% (wt/v) maltodextrin solution have an energy-storage density of 596 Ah kg(-1), which is one order of magnitude higher than that of lithium-ion batteries. Sugar-powered biobatteries could serve as next-generation green power sources, particularly for portable electronics.


Current views on HIV-1 latency, persistence, and cure.
HIV-1 infection cannot be cured as it persists in latently infected cells that are targeted neither by the immune system nor by available therapeutic approaches. Consequently, a lifelong therapy suppressing only the actively replicating virus is necessary. The latent reservoir has been defined and characterized in various experimental models and in human patients, allowing research and development of approaches targeting individual steps critical for HIV-1 latency establishment, maintenance, and reactivation. However, additional mechanisms and processes driving the remaining low-level HIV-1 replication in the presence of the suppressive therapy still remain to be identified and targeted. Current approaches toward HIV-1 cure involve namely attempts to reactivate and purge HIV latently infected cells (so-called "shock and kill" strategy), as well as approaches involving gene therapy and/or gene editing and stem cell transplantation aiming at generation of cells resistant to HIV-1. This review summarizes current views and concepts underlying different approaches aiming at functional or sterilizing cure of HIV-1 infection.


Rule-based deduplication of article records from bibliographic databases.
We recently designed and deployed a metasearch engine, Metta, that sends queries and retrieves search results from five leading biomedical databases: PubMed, EMBASE, CINAHL, PsycINFO and the Cochrane Central Register of Controlled Trials. Because many articles are indexed in more than one of these databases, it is desirable to deduplicate the retrieved article records. This is not a trivial problem because data fields contain a lot of missing and erroneous entries, and because certain types of information are recorded differently (and inconsistently) in the different databases. The present report describes our rule-based method for deduplicating article records across databases and includes an open-source script module that can be deployed freely. Metta was designed to satisfy the particular needs of people who are writing systematic reviews in evidence-based medicine. These users want the highest possible recall in retrieval, so it is important to err on the side of not deduplicating any records that refer to distinct articles, and it is important to perform deduplication online in real time. Our deduplication module is designed with these constraints in mind. Articles that share the same publication year are compared sequentially on parameters including PubMed ID number, digital object identifier, journal name, article title and author list, using text approximation techniques. In a review of Metta searches carried out by public users, we found that the deduplication module was more effective at identifying duplicates than EndNote without making any erroneous assignments.


Molecular and fossil evidence place the origin of cichlid fishes long after Gondwanan rifting.
Cichlid fishes are a key model system in the study of adaptive radiation, speciation and evolutionary developmental biology. More than 1600 cichlid species inhabit freshwater and marginal marine environments across several southern landmasses. This distributional pattern, combined with parallels between cichlid phylogeny and sequences of Mesozoic continental rifting, has led to the widely accepted hypothesis that cichlids are an ancient group whose major biogeographic patterns arose from Gondwanan vicariance. Although the Early Cretaceous (ca 135 Ma) divergence of living cichlids demanded by the vicariance model now represents a key calibration for teleost molecular clocks, this putative split pre-dates the oldest cichlid fossils by nearly 90 Myr. Here, we provide independent palaeontological and relaxed-molecular-clock estimates for the time of cichlid origin that collectively reject the antiquity of the group required by the Gondwanan vicariance scenario. The distribution of cichlid fossil horizons, the age of stratigraphically consistent outgroup lineages to cichlids and relaxed-clock analysis of a DNA sequence dataset consisting of 10 nuclear genes all deliver overlapping estimates for crown cichlid origin centred on the Palaeocene (ca 65-57 Ma), substantially post-dating the tectonic fragmentation of Gondwana. Our results provide a revised macroevolutionary time scale for cichlids, imply a role for dispersal in generating the observed geographical distribution of this important model clade and add to a growing debate that questions the dominance of the vicariance paradigm of historical biogeography.


Multiscale modeling of the neuromuscular system: Coupling neurophysiology and skeletal muscle mechanics.
Mathematical models and computer simulations have the great potential to substantially increase our understanding of the biophysical behavior of the neuromuscular system. This, however, requires detailed multiscale, and multiphysics models. Once validated, such models allow systematic in silico investigations that are not necessarily feasible within experiments and, therefore, have the ability to provide valuable insights into the complex interrelations within the healthy system and for pathological conditions. Most of the existing models focus on individual parts of the neuromuscular system and do not consider the neuromuscular system as an integrated physiological system. Hence, the aim of this advanced review is to facilitate the prospective development of detailed biophysical models of the entire neuromuscular system. For this purpose, this review is subdivided into three parts. The first part introduces the key anatomical and physiological aspects of the healthy neuromuscular system necessary for modeling the neuromuscular system. The second part provides an overview on state-of-the-art modeling approaches representing all major components of the neuromuscular system on different time and length scales. Within the last part, a specific multiscale neuromuscular system model is introduced. The integrated system model combines existing models of the motor neuron pool, of the sensory system and of a multiscale model describing the mechanical behavior of skeletal muscles. Since many sub-models are based on strictly biophysical modeling approaches, it closely represents the underlying physiological system and thus could be employed as starting point for further improvements and future developments. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Analytical and Computational Methods > Computational Methods Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models.


Naprapathic manual therapy or conventional orthopedic care for outpatients on orthopedic waiting lists?: A pragmatic randomized controlled trial.
Traditionally, orthopedic outpatient waiting lists are long, and many referrals are for conditions that do not respond to interventions available at an orthopedic outpatient department. The overall objective of this trial was to investigate whether it is possible to reduce orthopedic waiting lists through integrative medicine. Specific aims were to compare the effects of naprapathic manual therapy to conventional orthopedic care for outpatients with nonurgent musculoskeletal disorders unlikely to benefit from surgery regarding pain, physical function, and perceived recovery. Seventy-eight patients referred to an orthopedic outpatient department in Sweden were included in this pragmatic randomized controlled trial. The 2 interventions compared were naprapathic manual therapy (index group) and conventional orthopedic care (control group). Pain, physical function, and perceived recovery were measured by questionnaires at baseline and after 12, 24, and 52 weeks. The number of patients being discharged from the waiting lists and the level of agreement concerning management decisions between the naprapath and the orthopedists were also estimated. After 52 weeks, statistically significant differences between the groups were found regarding impairment in pain, increased physical function, and regarding perceived recovery, favoring the index group. Sixty-two percent of the patients in the index group agreed to be discharged from the waiting list. The level of agreement concerning the management decisions was 80%. The trial suggests that naprapathic manual therapy may be an alternative to consider for orthopedic outpatients with disorders unlikely to benefit from surgery.


Matching trajectories between video sequences by exploiting a sparse projective invariant representation.
Identifying correspondences between trajectory segments observed from nonsynchronized cameras is important for reconstruction of the complete trajectory of moving targets in a large scene. Such a reconstruction can be obtained from motion data by comparing the trajectory segments and estimating both the spatial and temporal alignments. Exhaustive testing of all possible correspondences of trajectories over a temporal window is only viable in the cases with a limited number of moving targets and large view overlaps. Therefore, alternative solutions are required for situations with several trajectories that are only partially visible in each view. In this paper, we propose a new method that is based on view-invariant representation of trajectories, which is used to produce a sparse set of salient points for trajectory segments observed in each view. Only the neighborhoods at these salient points in the view--invariant representation are then used to estimate the spatial and temporal alignment of trajectory pairs in different views. It is demonstrated that, for planar scenes, the method is able to recover with good precision and efficiency both spatial and temporal alignments, even given relatively small overlap between views and arbitrary (unknown) temporal shifts of the cameras. The method also provides the same capabilities in the case of trajectories that are only locally planar, but exhibit some nonplanarity at a global level.


Poetic rhyme reflects cross-linguistic differences in information structure.
Identical rhymes (right/write, attire/retire) are considered satisfactory and even artistic in French poetry but are considered unsatisfactory in English. This has been a consistent generalization over the course of centuries, a surprising fact given that other aspects of poetic form in French were happily applied in English. This paper puts forward the hypothesis that this difference is not merely one of poetic tradition, but is grounded in the distinct ways in which information-structure affects prosody in the two languages. A study of rhyme usage in poetry and a perception experiment confirm that native speakers' intuitions about rhyming in the two languages indeed differ, and a further perception experiment supports the hypothesis that this fact is due to a constraint on prosody that is active in English but not in French. The findings suggest that certain forms of artistic expression in poetry are influenced, and even constrained, by more general properties of a language.


Adolescent girls' preferences for HPV vaccines: a discrete choice experiment.
To measure adolescent girls' preferences over features of human papillomavirus (HPV) vaccines in order to provide quantitative estimates of the perceived benefits of vaccination and potential vaccine uptake. A discrete choice experiment (DCE) survey was developed to measure adolescent girls' preferences over features of HPV vaccines. The survey was fielded to a U.S. sample of 307 girls aged 13-17 years who had not yet received an HPV vaccine in June 2008. In a latent class logit model, two distinct groups were identified--one with strong preferences against vaccination which largely did not differentiate between vaccine features, and another that was receptive to vaccination and had well-defined preferences over vaccine features. Based on the mean estimates over the entire sample, we estimate that girls' valuation of bivalent and quadrivalent HPV vaccines ranged between $400 and $460 in 2008, measured as willingness-to-pay (WTP). The additional value of genital warts protection was $145, although cervical cancer efficacy was the most preferred feature. We estimate maximum uptake of 54-65%, close to the 53% reported for one dose in 2011 surveillance data, but higher than the 35% for three doses in surveillance data. We conclude that adolescent girls do form clear opinions and some place significant value on HPV vaccination, making research on their preferences vital to understanding the determinants of HPV vaccine demand. DCE studies may be used to design more effective vaccine-promotion programs and for reassessing public health recommendations and guidelines as new vaccines are made available.


Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease.
Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects. Higher dietary intakes of folate, vitamin B12, and vitamin B6 (cofactors in homocysteine metabolism) might decrease the risk of PD through decreasing plasma homocysteine. Moreover, vitamin B6 might influence the risk of PD through antioxidant effects unrelated to homocysteine metabolism and through its role in dopamine synthesis. In the Rotterdam Study, a prospective, population-based cohort study of people aged 55 years and older, the authors evaluated the association between dietary intake of folate, vitamin B12, and vitamin B6 and the risk of incident PD among 5,289 participants who were free of dementia and parkinsonism and underwent complete dietary assessment at baseline. PD was assessed through repeated in-person examination and continuous monitoring by computer linkage to medical records. Data were analyzed using Cox proportional hazards regression analysis. After a mean follow-up of 9.7 years, the authors identified 72 participants with incident PD. Higher dietary intake of vitamin B6 was associated with a significantly decreased risk of PD (hazard ratio per SD, 0.69 [95% CI 0.50 to 0.96]; for highest vs lowest tertile, 0.46 [0.22 to 0.96]). Stratified analyses showed that this association was restricted to smokers. No association was observed for dietary folate and vitamin B(12). Dietary vitamin B6 may decrease the risk of Parkinson disease, probably through mechanisms unrelated to homocysteine metabolism.


First Report of Laetisaria fuciformis Causing Red Thread on Seashore Paspalum (Paspalum vaginatum) in South China.
Seashore paspalum (Paspalum vaginatum Swartz.) is a prostrate-growing, perennial, warm-season turfgrass native to tropical and coastal areas (2). Because of its good texture and natural tolerance to various environmental stresses, seashore paspalum has been introduced to golf courses in coastal regions of southern China. In April 2010, circular or irregular pink patches ranging from 5 to 50 cm in diameter were observed in the golf course fairway and rough established with cv. Salam on two golf courses in Haikou, Hainan Province, China. When morning dew was present or rainfall occurred, a pink layer of gelatinous fungal growth could be observed on leaves and sheaths. The green leaves of infected plants initially became water soaked, then tan to bleached, shriveled, and infested with pink or reddish, gelatinous, stranded hyphae. The hyphae matted together, then formed threadlike or antlerlike stromata from the tips of blighted leaves. Two isolates from each golf course were collected by plating diseased leaf blades, stromata, or hyphal aggregates from the blighted leaves directly onto antibiotic (0.01% gentamicin sulfate) amended potato dextrose agar. To confirm pathogenicity, isolates were inoculated on 6-week-old P. vaginatum (cv. Seaspray) planted (0.5 mg seed/cm-2) in 10-cm pots. Inoculum was prepared by culturing isolates separately on an autoclaved mixture of 100 g of rye grain and 20 ml of water for 3 weeks at 25°C. Pots were inoculated by placing 2 g of infected grain within the center of the turf canopy or 2 g of sterilized, uninfested grains to serve as controls, with four replications of each treatment. After inoculation, each pot was placed in a translucent plastic bag and placed into a greenhouse at 24 ± 2°C with a 12-h photoperiod (1). Two days after inoculation, the fungus was observed on the leaves. Approximately 40% of leaves in inoculated pots were necrotic after 7 days, and this increased to 80% after 21 days. Diseased plants in inoculated pots displayed symptoms similar to those observed in the field and no symptoms were detected on the control plants. The two isolates were successfully reisolated from all symptomatic tissues, completing Koch's postulates. Sequences of mitochondrial small subunit ribosomal RNA (mt-SSU) were amplified from the two isolates by primers MS1 and MS2, and the sequences showed 99% similarity with Laetisaria fuciformis from the NCBI database (Accession No. AY293232). Red thread on turfgrass has been commonly observed in temperate climates during periods of cool and humid weather (3). To our knowledge, this is the first report of L. fuciformis causing red thread on P. vaginatum or from any host plant in China. References: (1) L. L. Burpee and L. G. Goulty. Phytopathology. 74:692, 1984. (2) R. R. Duncan and R. N. Carrow. Seashore Paspalum: The Environmental Turfgrass. John Wiley and Sons, Toronto, ON, Canada, 2000. (3) R. W. Smiley et al. Page 38 in: Compendium of Turfgrass Diseases. 3rd ed. The American Phytopathological Society, St. Paul, MN, 2005.


The role of macrophage cell death in tuberculosis.
Studies of host responses to infection have traditionally focused on the direct antimicrobial activity of effector molecules (antibodies, complement, defensins, reactive oxygen and nitrogen intermediates) and immunocytes (macrophages, lymphocytes, and neutrophils among others). The discovery of the systems for programmed cell death of eukaryotic cells has revealed a unique role for this process in the complex interplay between microorganisms and their cellular targets or responding immunocytes. In particular, cells of the monocyte/macrophage lineage have been demonstrated to undergo apoptosis following intracellular infection with certain pathogens that are otherwise capable of surviving within the hostile environment of the phagosome or which can escape the phagosome. Mycobacterium tuberculosis is a prototypical 'intracellular parasite' of macrophages, and the direct induction of macrophage apoptosis by this organism has recently been reported from several laboratories. This paper reviews the current understanding of the mechanism and regulation of macrophage apoptosis in response to M. tuberculosis and examines the role this process plays in protective immunity and microbial virulence.


ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2.
Both sporadic and autosomal dominant forms of Parkinson's disease (PD) have been causally linked to mutations in leucine-rich repeat kinase 2 (LRRK2), a large protein with multiple domains. The kinase domain plays an important role in LRRK2-mediated toxicity. Although a number of investigations have focused on LRRK2 kinase activity, less is known about the GTPase function of LRRK2. The activity of GTPases is regulated by GTPase activating proteins (GAPs) and GTP exchange factors. Here, we identify ArfGAP1 as the first GAP for LRRK2. ArfGAP1 binds LRRK2 predominantly via the WD40 and kinase domain of LRRK2, and it increases LRRK2 GTPase activity and regulates LRRK2 toxicity both in vitro and in vivo in Drosophila melanogaster. Unexpectedly, ArfGAP1 is an LRRK2 kinase substrate whose GAP activity is inhibited by LRRK2, whereas wild-type and G2019S LRRK2 autophosphorylation and kinase activity are significantly reduced in the presence of ArfGAP1. Overexpressed ArfGAP1 exhibits toxicity that is reduced by LRRK2 both in vitro and in vivo. Δ64-ArfGAP1, a dominant-negative ArfGAP1, and shRNA knockdown of ArfGAP1 reduce LRRK2 toxicity. Thus, LRRK2 and ArfGAP1 reciprocally regulate the activity of each other. Our results provide insight into the basic pathobiology of LRRK2 and indicate an important role for the GTPase domain and ArfGAP1 in LRRK2-mediated toxicity. These data suggest that agents targeted toward regulation of LRRK2 GTP hydrolysis might be therapeutic agents for the treatment of PD.


Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care.
Osteoarthritis is the single most common cause of disability in older adults, and most patients with the condition will be managed in the community and primary care. To discuss case definition of knee osteoarthritis for primary care and to summarise the burden of the condition in the community and related use of primary health care in the United Kingdom. Narrative review. A literature search identified studies of incidence and prevalence of knee pain, disability, and radiographic osteoarthritis in the general population, and data related to primary care consultations. Findings from UK studies were summarised with reference to European and international studies. During a one year period 25% of people over 55 years have a persistent episode of knee pain, of whom about one in six in the UK and the Netherlands consult their general practitioner about it in the same time period. The prevalence of painful disabling knee osteoarthritis in people over 55 years is 10%, of whom one quarter are severely disabled. Knee osteoarthritis sufficiently severe to consider joint replacement represents a minority of all knee pain and disability suffered by older people. Healthcare provision in primary care needs to focus on this broader group to impact on community levels of pain and disability.


The predictive value of OCT characteristics for the visual outcome in neovascular AMD.
The intravitreal injection of an anti-VEGF compound is the current standard of care in neovascular AMD. The response to this therapy varies greatly. To date it was not possible to determine clear predictive factors in regard to therapy response, thus making it difficult when counselling patients regarding the probability for visual improvement. The aim of this study was to evaluate baseline OCT characteristics in regard to their predictive value on the outcome of visual acuity (VA) after 12 months. A retrospective analysis of 75 eyes with neovascular AMD treated with intravitreal anti-VEGF injections at the University Hospital of Zurich with a documented follow-up of at least 12 months. Measurement and comparison of the following OCT structures were undertaken: central retinal thickness (CRT), integrity of the IS/OS junction, and presence of intra- or subretinal fluid. VA at baseline and after 12 months was evaluated. OCT findings were compared between eyes that gained ≥ 5 letters ETDRS (group 1) and eyes that did not (group 2). 75 eyes with a mean baseline VA of 57.2 ± 15 letters and a mean baseline CRT of 430 ± 226 μm were analyzed. Although baseline VA did not differ statistically significantly, eyes in group 2 had a higher VA than eyes in group 1 (60.2 ± 16.2 vs. 54.9 ± 13.6, p = 0.123). In group 1 the change of VA after 12 months was 12.6 ± 8.0 letters while it was -5.0 ± 7.8 letters in group 2. No statistically significant differences between the two groups with respect to the analyzed OCT parameters were found. None of the analyzed OCT factors had a predictive value regarding the VA outcome at month 12. Our study was not able to find baseline OCT parameters that could predict the course of VA after 12 months. However, eyes with a thicker central retinal thickness at presentation showed a greater reduction in CRT during the analyzed period. This was associated with a more favourable course in VA. Perhaps this might be due to a less pronounced initial morphological retinal damage.


Purification, cloning and characterization of a GPI inositol deacylase from Trypanosoma brucei.
Inositol acylation is an obligatory step in glycosylphosphatidylinositol (GPI) biosynthesis whereas mature GPI anchors often lack this modification. The GPI anchors of Trypanosoma brucei variant surface glycoproteins (VSGs) undergo rounds of inositol acylation and deacylation during GPI biosynthesis and the deacylation reactions are inhibited by diisopropylfluorophosphate (DFP). Inositol deacylase was affinity labelled with [3H]DFP and purified. Peptide sequencing was used to clone GPIdeAc, which encodes a protein with significant sequence and hydropathy similarity to mammalian acyloxyacyl hydrolase, an enzyme that removes fatty acids from bacterial lipopolysaccharide. Both contain a signal sequence followed by a saposin domain and a GDSL-lipase domain. GPIdeAc(-/-) trypanosomes were viable in vitro and in animals. Affinity-purified HA-tagged GPIdeAc was shown to have inositol deacylase activity. However, total inositol deacylase activity was only reduced in GPIdeAc(-/-) trypanosomes and the VSG GPI anchor was indistinguishable from wild type. These results suggest that there is redundancy in T.brucei inositol deacylase activity and that there is another enzyme whose sequence is not recognizably related to GPIdeAc.


Separate neural representations of prediction error valence and surprise: Evidence from an fMRI meta-analysis.
Learning occurs when an outcome differs from expectations, generating a reward prediction error signal (RPE). The RPE signal has been hypothesized to simultaneously embody the valence of an outcome (better or worse than expected) and its surprise (how far from expectations). Nonetheless, growing evidence suggests that separate representations of the two RPE components exist in the human brain. Meta-analyses provide an opportunity to test this hypothesis and directly probe the extent to which the valence and surprise of the error signal are encoded in separate or overlapping networks. We carried out several meta-analyses on a large set of fMRI studies investigating the neural basis of RPE, locked at decision outcome. We identified two valence learning systems by pooling studies searching for differential neural activity in response to categorical positive-versus-negative outcomes. The first valence network (negative > positive) involved areas regulating alertness and switching behaviours such as the midcingulate cortex, the thalamus and the dorsolateral prefrontal cortex whereas the second valence network (positive > negative) encompassed regions of the human reward circuitry such as the ventral striatum and the ventromedial prefrontal cortex. We also found evidence of a largely distinct surprise-encoding network including the anterior cingulate cortex, anterior insula and dorsal striatum. Together with recent animal and electrophysiological evidence this meta-analysis points to a sequential and distributed encoding of different components of the RPE signal, with potentially distinct functional roles.


Dynamic multicompartment-core micelles in aqueous media.
We investigate micellar aggregates of amphiphilic block terpolymers, polybutadiene-block-poly(2-vinyl pyridine)-block-poly(methacrylic acid) (PB800P2VP190PMAA550) and their quaternized analogues polybutadiene-block-poly(N-methyl-2-vinylpyridinium)-block-poly(methacrylic acid) (PB800P2VPq190PMAA550) in aqueous solution using light scattering (DLS, SLS) and cryogenic transmission electron microscopy (cryo-TEM). At high pH, PB800P2VP190PMAA550 forms core--shell--corona micelles with a hydrodynamic radius Rh approximately 100 nm and a continuous shell of P2VP. However, at pH 4 partial intramicellar interpolyelectrolyte complex (im-IPEC) formation between P2VP and PMAA results in a patchy, collapsed shell. This is far more pronounced for the quaternized analogue, PB800P2VPq190PMAA550, which forms aggregates of similar size, also exhibiting a noncontinuous, patchy shell. Here, these im-IPECs of the positively charged P2VPq and the partially negatively charged PMAA are present over the whole investigated pH range (4-10). We further demonstrate that size and charge of the corona can be tuned through the block terpolymer composition, in particular, the ratio between P2VPq and PMAA. These micelles are dynamic and able to react to changes in pH or salinity in terms of corona diameter and aggregation number.


Growth of the chorioallantoic membrane into a rapid-prototyped model pore system: experiments and mathematical model.
This paper presents a mathematical model to describe the growth of tissue into a rapid-prototyped porous scaffold when it is implanted onto the chorioallantoic membrane (CAM). The scaffold was designed to study the effects of the size and shape of pores on tissue growth into conventional tissue engineering scaffolds, and consists of an array of pores each having a pre-specified shape. The experimental observations revealed that the CAM grows through each pore as an intact layer of tissue, provided the width of the pore exceeds a threshold value. Based on these results a mathematical model is described to simulate the growth of the membrane, assuming that the growth is a function of the local isotropic membrane tension. The model predictions are compared against measurements of the extent of membrane growth through the pores as a function of time for pores with different dimensions.


Cerebrocortical activity during self-paced exercise in temperate, hot and hypoxic conditions.
Heat stress and hypoxia independently influence cerebrocortical activity and impair prolonged exercise performance. This study examined the relationship between electroencephalography (EEG) activity and self-paced exercise performance in control (CON, 18 °C, 40% RH), hot (HOT, 35 °C, 60% RH) and hypoxic (HYP, 18 °C, 40% RH FiO2 : 0.145) conditions. Eleven well-trained cyclists completed a 750 kJ cycling time trial in each condition on separate days in a counterbalanced order. EEG activity was recorded with α- and β-activity evaluated in the frontal (F3 and F4) and central (C3 and C4) areas. Standardized low-resolution brain electromagnetic tomography (sLORETA) was also utilized to localize changes in cerebrocortical activity. Both α- and β-activity decreased in the frontal and central areas during exercise in HOT relative to CON (P < 0.05). α-activity was also lower in HYP compared with CON (P < 0.05), whereas β-activity remained similar. β-activity was higher in HYP than in HOT (P < 0.05). sLORETA revealed that α- and β-activity increased at the onset of exercise in the primary somatosensory and motor cortices in CON and HYP, while only β-activity increased in HOT. A decrease in α- and β-activity occurred thereafter in all conditions, with α-activity being lower in the somatosensory and somatosensory association cortices in HOT relative to CON. High-intensity prolonged self-paced exercise induces cerebrocortical activity alterations in areas of the brain associated with the ability to inhibit conflicting attentional processing under hot and hypoxic conditions, along with the capacity to sustain mental readiness and arousal under heat stress.


Contractures in partially depolarized muscle treated with caffeine or nitrate.
Frog toe muscles partially depolarized with a subcontracture concentration (15 or 20mM) of K+ rapidly developed tension when exposed to 1 mM caffeine, which alone did not cause contracture. This action resulted from a lowering of the mechanical threshold by the caffeine and thus was similar to that caused by replacement of Cl- with NO3-. Maximal tension was the same in the caffeine and NO3- media but took much longer to develop in the former. Equilibrating the muscles with caffeine for 60 s (the time calculated for complete diffusion) did not reduce contraction time significantly. However, prolonging the exposure of muscles to caffeine beyond this time enhanced the drug's capacity to potentiate both the twitch and 30 mM K+ contractures and shortened the contraction time of the contractures. Toe muscles that had undergone a contracture in 100 mM K+ and were recovering in 15 mM K+-Ringer generated tension in the presence of 1 mM caffeine or NO3- but only after enough repolarization had been achieved so that a response to a second challenge with 100 mM K+ could be demonstrated. Although prolonged immersion in the K+-enriched recovery solution caused a disappearance of sensitivity to a test depolarization, addition of 1 mM caffeine or replacement of Cl- with NO3- promptly evoked a contracture. These results imply a reversible step in the recovery process that is both potential and time dependent. Since application of 5 mM caffeine to either normally polarized or depolarized muscles always immediately causes contracture, more than one site of action for caffeine is indicated. After disruption of the transverse tubules, partially depolarized muscles showed no response to NO3- or 1 mM caffeine but contracted vigorously when exposed to 5 mM caffeine.


Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS.
Common variants of the gene encoding transcription factor 7-like 2 (TCF7L2) have a powerful effect on individual risk of type 2 diabetes (per allele odds ratio approximately 1.35). Polycystic ovary syndrome (PCOS) and type 2 diabetes are familial conditions sharing common features. Based on this, the aim of the present study was to establish whether variation in TCF7L2 also influences the development of PCOS. We conducted a genetic association study of variants of TCF7L2 (rs7903146 and rs12255372) using both case-control and quantitative trait approaches. Case-control analyses were conducted in (1) 369 PCOS cases and 2574 controls of UK British/Irish origin, and (2) 540 women with PCOS symptoms and 1083 controls from the Northern Finland Birth Cohort of 1966. Quantitative trait analyses (androgen levels) were also performed (1249 individuals). There was no association between rs7903146 and PCOS in the UK case-control study (Cochran-Armitage test, p = 0.51); nor with symptomatic status in the Finnish cohort (p = 0.36). In addition, there were no relationships between the TCF7L2 single nucleotide polymorphism rs7903146 and androgen levels (UK cases, p = 0.99; Finnish controls, p = 0.57; Finnish symptomatic cases, p = 0.80). Results at rs12255372 were similar, reflecting strong linkage disequilibrium with rs7903146. Our study was powered to detect an effect on PCOS susceptibility similar to that previously reported for these variants on type 2 diabetes. Failure to detect any evident association with PCOS provides the strongest evidence yet that the genetic architecture of these related conditions is qualitatively distinct.


SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma.
Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy that can recur locally or disseminate even after multidisciplinary care. Genetically amplified and expressed MDM2, often referred to as a "hallmark" of DDLPS, mostly sustains a wild-type p53 genotype, substantiating the MDM2:p53 axis as a potential therapeutic target for DDLPS. Here, we report on the preclinical effects of SAR405838, a novel and highly selective MDM2 small-molecule inhibitor, in both in vitro and in vivo DDLPS models. The therapeutic effectiveness of SAR405838 was compared with the known MDM2 antagonists Nutlin-3a and MI-219. The effects of MDM2 inhibition were assessed in both in vitro and in vivo. In vitro and in vivo microarray analyses were performed to assess differentially expressed genes induced by SAR405838, as well as the pathways that these modulated genes enriched. SAR405838 effectively stabilized p53 and activated the p53 pathway, resulting in abrogated cellular proliferation, cell-cycle arrest, and apoptosis. Similar results were observed with Nutlin-3a and MI-219; however, significantly higher concentrations were required. In vitro effectiveness of SAR405838 activity was recapitulated in DDLPS xenograft models where significant decreases in tumorigenicity were observed. Microarray analyses revealed genes enriching the p53 signaling pathway as well as genomic stability and DNA damage following SAR405838 treatment. SAR405838 is currently in early-phase clinical trials for a number of malignancies, including sarcoma, and our in vitro and in vivo results support its use as a potential therapeutic strategy for the treatment of DDLPS.


Genetic architecture of sex determination in fish: applications to sex ratio control in aquaculture.
Controlling the sex ratio is essential in finfish farming. A balanced sex ratio is usually good for broodstock management, since it enables to develop appropriate breeding schemes. However, in some species the production of monosex populations is desirable because the existence of sexual dimorphism, primarily in growth or first time of sexual maturation, but also in color or shape, can render one sex more valuable. The knowledge of the genetic architecture of sex determination (SD) is convenient for controlling sex ratio and for the implementation of breeding programs. Unlike mammals and birds, which show highly conserved master genes that control a conserved genetic network responsible for gonad differentiation (GD), a huge diversity of SD mechanisms has been reported in fish. Despite theory predictions, more than one gene is in many cases involved in fish SD and genetic differences have been observed in the GD network. Environmental factors also play a relevant role and epigenetic mechanisms are becoming increasingly recognized for the establishment and maintenance of the GD pathways. Although major genetic factors are frequently involved in fish SD, these observations strongly suggest that SD in this group resembles a complex trait. Accordingly, the application of quantitative genetics combined with genomic tools is desirable to address its study and in fact, when applied, it has frequently demonstrated a multigene trait interacting with environmental factors in model and cultured fish species. This scenario has notable implications for aquaculture and, depending upon the species, from chromosome manipulation or environmental control techniques up to classical selection or marker assisted selection programs, are being applied. In this review, we selected four relevant species or fish groups to illustrate this diversity and hence the technologies that can be used by the industry for the control of sex ratio: turbot and European sea bass, two reference species of the European aquaculture, and salmonids and tilapia, representing the fish for which there are well established breeding programs.


Anthelmintic resistance in gastrointestinal nematodes in sheep raised under mountain farming conditions in Northern Italy.
Anthelmintic resistance (AR) in sheep raised under mountain farming conditions in South Tyrol (Northern Italy) was assessed on eight farms (n=99 animals). A faecal egg count reduction (FECR) test was done after routine anthelmintic treatments. Furthermore, on 27 farms (n=306 animals), a FECR test was conducted after oral formulations of a macrocyclic lactone (ML), benzimidazole (BZ) (partly in combination with salicylanilide (SA)) or a combination of imidazothiazole and SA were applied under controlled conditions on the same farm. Following routine treatments, three of five ML-treated flocks showed an adequate efficacy, while the other two reached a FECR of only around 75 per cent. A wide range of gastrointestinal nematode genera were identified in one flock following the treatment. From the three BZ-treated flocks, only one showed an adequate FECR, both other farms reached 68 per cent and 84 per cent, respectively. Under controlled conditions, FECR ranged between 77 per cent and 81 per cent indicating AR for all the applied anthelmintics. Trichostrongylus species, Teladorsagia species and Haemonchus species were identified after ML treatment, Teladorsagia species after BZ treatment and Trichostrongylus species and Haemonchus species after combined BZ and SA application. Taking into consideration that underdosing might have affected results of the routine treatments, a high prevalence of AR was found in sheep under mountain farming conditions.


Survival of patients ventilated in an intensive therapy unit.
The survival of patients who were artificially ventilated in an intensive therapy unit (ITU) of a district general hospital was studied. The first 100 such patients admitted were followed up for at least four years. Of these, 67 survived treatment in the ITU, 47 were discharged from hospital, and 30 survived four years. (Survival in the ITU of patients who did not require ventilation was 89%.) The effects of age, duration of ventilation, and disease were studied, and a higher survival was found in children, in patients ventilated for under 24 hours, and in patients admitted with drug overdosage. Survival was poor in patients aged over 75 and in those who required ventilation after cardiac arrest or myocardial infarction or for chronic obstructive lung disease. The cost of a bed in an ITUs to be used to the greatest effect it is important to define those patients who are most likely to benefit from the facilities they offer.


SU-E-I-39: Intensive Monitoring of System Performance and Protocols on CT Systems.
The regulatory response to the recent CT overdoses is still in the process of being implemented. The more action taken before the regulations take effect reduces the exposure of the institution to medical and legal problems. Therefore, eighteen months ago we implemented an intensive QC program to ensure CT safety. The first component was to monitor the dose and SNR produced by a single CT examination weekly to identify changes. The second was to monitor changes in the protocols. We measured the CTDI and SNR for the routine head examination. We developed a script to identify and log changes in any of the 234 protocols. Surprisingly, there were many changes to the protocols: on one unit 388 protocols were changed on 26 dates over the 18 month period. The reasons included: protocol optimization, scanner service, software reloads, mistakes, mistakenly loading the protocols from another section's scanner. The standard deviation of the CTDI was 2% to 3%. The dominant source of variation was probably positioning. The standard deviation of the SNR was 4% to 9%. The entire procedure requires 30min to 50min to test five CT scanners each week. The standard deviations of the CTDI values and of the SNR values are sufficiently small to allow anomalies to be identified using these relatively simple methods. Frequent protocol checking is an important component to any QC program.


What triggers an episode of acute low back pain? A case-crossover study.
To investigate a range of transient risk factors for an episode of sudden-onset, acute low back pain (LBP). This case-crossover study recruited 999 subjects with a new episode of acute LBP between October 2011 and November 2012 from 300 primary care clinics in Sydney, Australia. Each participant was asked to report exposure to 12 putative triggers over the 96 hours preceding the onset of back pain. Conditional logistic regression was used to estimate odds ratios (ORs) expressing the magnitude of increased risk with exposure to each trigger. Exposure to a range of physical and psychosocial triggers significantly increased the risk of a new onset of LBP; ORs ranged from 2.7 (moderate or vigorous physical activity) to 25.0 (distracted during an activity or task). Age moderated the effect of exposure to heavy loads and sexual activity. The ORs for heavy loads for people ages 20, 40, or 60 years were 13.6, 6.0, and 2.7, respectively. The risk of developing back pain was greatest between 7:00 AM and noon. Transient exposure to a number of modifiable physical and psychosocial triggers substantially increases risk for a new episode of LBP. Triggers previously evaluated in occupational injury studies, but never in LBP, have been shown to significantly increase risk. These results aid our understanding of the causes of LBP and can inform the development of new prevention approaches.


Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the Literature.
Detection of clinically significant prostate cancer (PCa) is a major challenge. It has been shown that multiparametric magnetic resonance imaging (mpMRI) facilitates localisation of PCa and can help in targeting prostate biopsy. To systematically review the literature to determine the diagnostic accuracy of mpMRI in the detection of clinically significant PCa. The Pubmed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from January 1, 2000 to September 30, 2014, using the search criteria "prostate OR Pca OR PSA OR prostatic OR prostate cancer" AND "MR OR NMR OR NMRI OR MRI OR magnetic resonance OR ADC OR DWI OR DCE OR diffusion weighted OR dynamic contrast OR multiparametric OR MRSI OR MR spectroscopy". Two reviewers independently assessed 1729 records. Two independent reviewers assessed the methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) 2 tool. Twelve articles were eventually selected. Patients had a median age of 62-65 yr (range 39-83 yr), a median prostate-specific antigen (PSA) level of 5.1-13.4 ng/ml (range 1.2-228 ng/ml), and Gleason score of 6-10. Various definitions of clinical significance were used, mainly based on maximum cancer core length and grade at biopsy, number of positive cores, and PSA. Detection of clinically significant PCa using mpMRI ranged from 44% to 87% in biopsy-naïve males and men with prior negative biopsies using prostate biopsy or definitive pathology of a radical prostatectomy specimen as the reference standard. The negative predictive value for exclusion of significant disease ranged from 63% to 98%. mpMRI is able to detect significant PCa in biopsy-naïve males and men with prior negative biopsies. The negative predictive value of mpMRI is important to the clinician because mpMRI could be used to rule out significant disease. This may result in fewer or no systematic or targeted biopsies in patients with PSA suspicious for prostate cancer. We reviewed the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for the detection of clinically significant prostate cancer (PCa). We conclude that mpMRI is able to detect significant PCa and may used to target prostate biopsies.


Impact of obesity on quality of life, psychological status, and disease activity in psoriatic arthritis: a multi‑center study.
This article aims to evaluate the possible effect of obesity on quality of life, psychological status, and other clinical variables in Psoriatic arthritis (PsA). PsA patients have been recruited by the Turkish League Against Rheumatism-Network from various centers in Turkey in this cross-sectional study. Patients with a body mass index (BMI) ≥ of 30 kg/m2 were considered obese. Differences among patients with regard to obesity status were assessed with health-related quality of life measures (PsA Quality of Life Questionnaire [PsAQoL]), psychological status (Hospital Anxiety and Depression Scale [HADS]), and disease activity parameters (the Disease Activity index for PSoriatic Arthritis [DAPSA], Disease Activity Score 28-C-reactive protein [DAS28-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Psoriasis Area and Severity Index [PASI]), physical functions (Ankylosing Spondylitis Functional Index [BASFI], Health Assessment Questionnaire [HAQ], and Health Assessment Questionnaire for the spondyloarthropathies [HAQ-S]). Pain was assessed using visual analog scale of pain (VAS-P), and fatigue was evaluated using visual analog scale of fatigue (VAS-F) and Functional Assessment of Chronic Illness Therapy (FACIT). A total of 1033 patients with PsA, 650 (62.9%) non-obese and 383 (37.1%) obese were included in the study. The PsAQoL, HADS-Anxiety, HADS-Depression, DAPSA, DAS28-CRP, BASDAI, BASFI, HAQ and HAQ-S scores of the obese group were higher than the non-obese group (p < 0.05). VAS-P and PASI scores were similar between group of patients with and without obesity. Obese patients had higher median scores of VAS-F and FACIT than non-obese patients (p < 0.05). Linear regression analysis showed that BMI affects the quality of life, depression, and disease activity. Consequently, obesity has significant associations with higher disease activity, lower QoL, risk of anxiety, depression, and fatigue. Therefore, obesity should also be taken into account in the management of PsA patients.


Evolution of anti-CD20 monoclonal antibody therapeutics in oncology.
Approval of an anti-CD20 chimeric monoclonal antibody, rituximab, has revolutionized cancer treatment and also validated CD20 targeting for providing benefit and improvement of overall response rate in B cell malignancies. Although many patients have benefited from the treatment of rituximab, there are still significant numbers of patients who are refractory or develop resistance to the treatment. Here we discuss pre-clinically well-defined potential mechanisms of action for rituximab and review the ways next generation anti-CD20 monoclonal antibodies can potentially exploit them to further enhance the treatment of B cell malignancies. Although the relative importance of each of these mechanism remains to be established in the clinic, well-designed clinical trials will help to define the efficacy and understanding of which effector activity of modified next generation anti-CD20 mAb will be important in the treatment of B-cell malignancies.


Prevalence and influences of preschoolers' sedentary behaviors in early learning centers: a cross-sectional study.
Recent research has highlighted the need for increased evidence regarding the sedentary activity levels of preschoolers. Given the large proportion of time this population spends in various early learning facilities, the exploration of sedentary behaviors within this particular environment should be a priority. The purpose of the study was two-fold: (1) to compare sedentary time of preschoolers in three different early learning environments (i.e., full-day kindergarten [FDK], center-, and home-based childcare); and (2) to assess which characteristics (i.e., staff behaviors, sedentary environment, fixed play environment, portable play environment, sedentary opportunities) of these early learning environments influence preschoolers' sedentary time. Data collection occurred between September 2011 and June 2012. Preschoolers' sedentary time was measured using Actical(™) accelerometers at a 15 s epoch. The Environment and Policy Assessment and Observation (EPAO) tool was used to assess the sedentary environment of participating early learning classrooms, and those subscales (n = 5) that were evidence-informed as potentially influencing sedentary time in early learning centers were explored in the current study. A linear mixed model ANCOVA was carried out to determine the differences in sedentary time based on type of early learning environment while direct entry regression analyses were performed to describe the relationships between sedentary time and the five sedentary-specific EPAO subscale. Preschoolers (n = 218) from 28 early learning programs (i.e., 8 FDK, 9 centre-, and 8 home-based childcare facilities) participated. Accelerometry data revealed that preschoolers attending centre-based childcare engaged in the highest rate of sedentary time (41.62 mins/hr, SD = 3.78) compared to preschoolers in home-based childcare (40.72 mins/hr, SD = 6.34) and FDK (39.68 mins/hr, SD = 3.43). The models for FDK, center-based childcare, and home-based childcare, comprised each of the five EPAO subscales accounted for 10.5%, 5.9%, and 40.78% of the variability in sedentary time, respectively. Only the models for FDK and home-based childcare were found to be statistically significant (p < .05). This is the first exploration of differences in sedentary time among preschoolers in different early learning arrangements. Findings highlight the substantial portion of the day preschoolers spend in sedentary pursuits, and subsequently, the ongoing need to reduce preschoolers' sedentary time in early learning programs, particularly among those attending centre-based childcare facilities.


Motivational interviewing to improve adherence behaviours for the prevention of diabetic foot ulceration.
Diabetic foot ulceration is a major complication associated with high morbidity. Little evidence exists on which interventions are effective at preventing ulceration. Participants who are adherent to self-care behaviours have significantly better outcomes. Motivational interviewing is an intervention that has been used successfully for conditions where adherence is important, such as reduction of obesity and HbA1c levels. A systematic review was conducted to determine whether motivational interviewing is effective at improving adherence for the prevention of Diabetic Foot Ulceration. Electronic searches were run without date or language restrictions in MEDLINE (viaEBSCOhost), CINAHL (viaEBSCOhost), ProQuest (Health and Medical Collection, Nursing and Allied Health Database, PsycINFO, Psychology, PsychArticles), AMED, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, and Web of Science Core Collections. Papers were included if participants had or were at risk of diabetic foot ulceration. Studies required motivational interviewing or a motivational approach as the sole intervention or as a component. Randomised controlled trials and quasi-experimental studies were included if ulceration and/or at least one behavioural outcome was measured before and after the intervention. Five studies met the inclusion criteria. Heterogeneity prevented the pooling of data. One study used motivational interviewing as the sole intervention. This study found a short-term positive effect on footwear adherence. The remaining four studies had a motivational component within their interventions. Two of these studies showed the intervention to be effective but both were at a high risk of bias. This review demonstrates an evidence gap. More research is needed.


Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox.
Aberrant activation of tyrosine kinases is linked causally to human cancers. Activated Cdc42-associated kinase (Ack1), an intracellular tyrosine kinase, has primarily been studied for its signaling properties but has not been linked to specific pathologic conditions. Herein, we report that expression of activated Ack1 in LNCaP cells, while minimally increasing growth in culture, enhanced anchorage-independent growth in vitro and dramatically accelerated tumorigenesis in nude mice. Molecular chaperone heat shock protein 90beta (Hsp90beta)-bound Ack1 and treatment of cells with geldanamycin, a Hsp90 inhibitor, inhibited Ack1 kinase activity and suppressed tumorigenesis. Further, we identify the tumor suppressor WW domain containing oxidoreductase (Wwox) as an Ack1-interacting protein. Activated Ack1 tyrosine phosphorylated Wwox, leading to rapid dissociation of the Ack1-Wwox complex and concomitant Wwox polyubiquitination followed by degradation. Tyrosine phosphorylation of Wwox was critical for its degradation, as splice variant WwoxDelta5-8 that was not phosphorylated by Ack1 failed to undergo polyubiquitination and degradation. It has been reported that phosphorylation of Wwox at Tyr33 stimulated its proapoptotic activity. We observed that Y33F Wwox mutant was still tyrosine phosphorylated and polyubiquitinated by Ack1 action. Site-directed mutagenesis revealed that activated Ack1 primarily phosphorylated Wwox at Tyr287, suggesting that phosphorylation of distinct tyrosine residues activate or degrade Wwox. Primary androgen-independent prostate tumors but not benign prostate showed increased tyrosine-phosphorylated Ack1 and decreased Wwox. Taken together, these data indicate that Ack1 stimulated prostate tumorigenesis in part by negatively regulating the proapoptotic tumor suppressor, Wwox. Further, these findings suggest that Ack1 could be a novel therapeutic target for prostate cancer.


Primary vaginal cancer and chemoradiotherapy: a patterns-of-care analysis.
No prospective randomized trials exist to delineate the role of combined chemoradiotherapy (CRT) in the treatment of vaginal cancer (VC). We sought to describe the utilization rate of CRT and evaluate the potential survival benefit of CRT over radiotherapy alone in VC. A retrospective analysis of the SEER-Medicare-linked database was performed analyzing women with VC treated with external beam radiation and/or brachytherapy and diagnosed between 1991 and 2005. Of the 1709 primary VC patients in the SEER-Medicare database, 326 met inclusion criteria. Most were white (80.1%) and in the 70- to 74-year age group (42.1%). Squamous cell carcinoma was the most predominant histologic diagnosis (80.4%). Brachytherapy was used in 34% of patients, whereas cisplatin was the chemotherapy of choice in 59% of CRT patients. Median follow-up was 21.5 months. Kaplan-Meier estimated that 5-year cause-specific survival (CSS) and overall survival (OS) was 67.6% and 27.1%, respectively. Before 1999, CRT was used in 7.5% of patients compared with 36.1% of patients thereafter (P < 0.001). Chemoradiotherapy was less likely to be used in patients older than 80 years (P < 0.001) but was otherwise balanced in race, stage, grade, histologic diagnosis, comorbidities, and brachytherapy use. Chemoradiotherapy did not correlate with CSS (hazard ratio [HR], 0.91; P = 0.84) or OS (HR, 1.34; P = 0.21) by multivariate analysis. Factors associated with worse CSS include stage IVA disease (HR, 4.2; P = 0.003) and 2 or more comorbidities (HR, 2.89; P = 0.03). Factors associated with worse OS include age older than 80 years (HR, 1.78; P = 0.04), stage IVA disease (HR, 3.35; P < 0.0001), and 2 or more comorbidities (HR, 2.58; P = 0.001). Chemoradiotherapy utilization for VC has increased since 1999. We failed to delineate a CSS or OS benefit for CRT in this cohort.


Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study.
Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001). Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.


Effect of antiviral therapy on hepatitis C virus related glomerulopathy.
To determine the efficacy of antiviral therapy in hepatitis C virus associated glomerulopathy, we studied 30 patients with HCV-associated glomerulopathy at Sheikh Zayed Hospital, Lahore, Pakistan from June 2004 to February 2007. Membranoproliferative glomerulonephritis (MPGN) was the commonest kidney lesion, being reported in 25/30 (83%), followed by membranous glomerulonephritis (MGN) in 3/30 (10%) and mesangioproliferative glomerulonephritis (MesGN) in 2/30 (7%). Cryoglobulinaemia was positive in 8/20 (40%) cases. Most common HCV genotype was 3a. All the patients received interferon alpha combined with ribavirin therapy for 6-12 months based on viral genotypes and doses were adjusted according to renal function. Anti-viral response was achieved in the form of aviremia at completion of 6 months treatment in 8/30 (26.6%), decreased transaminases levels from a mean of 96.4 +/- 72.2 to 60.1 +/- 44.3 IU/L, p= 0.005, 24-hour proteinuria decreased significantly from a mean of 4.8 g to 1.20 g, p= 0.001, and complement C3 and C4 concentrations returned to normal in those subjects who responded to treatment. The rate of relapse was 50%. We conclude that though the overall antiviral response of HCV was not high, there was a significant reduction in proteinuria suggesting indirectly an improvement in renal pathology. Further studies with large number of patients with follow-up renal biopsies are warranted.


Activation of microRNA-378a-3p biogenesis promotes hepatic secretion of VLDL and hyperlipidemia by modulating ApoB100-Sortilin1 axis.
Rationale: Hyperlipidemia is a major risk factor of atherosclerosis and cardiovascular diseases (CVD). As a standard-of-care approach for hyperlipidemia, statins only reduce the risk of coronary artery disease by 20-40%, underscoring the importance of identifying molecular pathways for the design of drugs against this disorder. Alterations in microRNA (miRNA) expression have been reported in patients with hyperlipidemia and CVD. This study was designed to determine the mechanism of dysregulated miR-378a-3p under the status of hyperlipidemia and evaluate how miR-378a-3p regulates hepatic secretion of VLDL. Methods: Wild-type mice kept on a high fat diet were injected with miR-378a-3p inhibitor or a mini-circle expression system containing miR-378a precursor to study loss and gain-of functions of miR-378a-3p. Mice were treated with Triton WR1339 and 35S-methionine/cysteine to determine the effect of miR-378a-3p on hepatic secretion of VLDL. Database mining, luciferase assay, and ChIP (chromatin immunoprecipitation) were used to study the mechanism of dysregulated miR-378a-3p biogenesis. Results: miR-378a-3p expression is significantly increased in livers of hyperlipidemic mice. Sort1 (sortilin 1) was identified as a direct target of miR-378a-3p. By inhibiting the function of sortilin 1 as a transmembrane trafficking receptor, miR-378a-3p stabilized ApoB100 and promoted ApoB100 secretion in vitro. Liver-specific expression of miR-378a-3p stabilized ApoB100 and facilitated hepatic secretion of VLDL, which subsequently increased levels of VLDL/LDL cholesterol as well as triglycerides. In contrast, antagonizing miR-378a-3p using its inhibitor increased hepatic expression of Sort1 and reduced hepatic export of VLDL with its consequent effects of serum lipid levels. Additional knockdown of up-regulated Sort1 in livers of mice offset the effects of miR-378a-3p inhibitor, suggesting that Sort1 was indispensable for miR-378a-3p to promote secretion of VLDL and thereby high levels of circulating VLDL/LDL cholesterol and triglycerides. Furthermore, oncogenic E2F1 (E2F transcription factor 1) was identified as a transcriptional activator of miR-378a-3p. E2f1 knockdown, through reducing miR-378a-3p, impaired secretion of VLDL and reduced levels of VLDL/LDL cholesterol and triglycerides. Conclusions: This study defines a novel pathway of E2F1-miR-378a-3p-SORT1-ApoB100 that controls levels of circulating VLDL/LDL cholesterol and triglycerides by modulating degradation and secretion of ApoB100, and suggests the use of miR-378a-3p as a potential therapeutic target for dyslipidemia.


Acute Colitis Drives Tolerance by Persistently Altering the Epithelial Barrier and Innate and Adaptive Immunity.
Inflammatory bowel disease (IBD) has a remitting and relapsing disease course; however, relatively little is understood regarding how inflammatory damage in acute colitis influences the microbiota, epithelial barrier, and immune function in subsequent colitis. Mice were administered trinitrobenzene sulphonic acid (TNBS) via enema, and inflammation was assessed 2 days (d2) or 28 days (d28) later. Colitis was reactivated in some mice by re-treating at 28 days with TNBS and assessing 2 days later (d30). Epithelial responsiveness to secretagogues, microbiota composition, colonic infiltration, and immune activation was compared between all groups. At day 28, the distal colon had healed, mucosa was restored, and innate immune response had subsided, but colonic transepithelial transport (P = 0.048), regulatory T-cell (TREG) infiltration (P = 0.014), adherent microbiota composition (P = 0.0081), and responsiveness of stimulated innate immune bone marrow cells (P < 0.0001 for IL-1β) differed relative to health. Two days after subsequent instillation of TNBS (d30 mice), the effects on inflammatory damage (P < 0.0001), paracellular permeability (P < 0.0001), and innate immune infiltration (P < 0.0001 for Ly6C+ Ly6G- macrophages) were reduced relative to d2 colitis. However, TREG infiltration was increased (P < 0.0001), and the responsiveness of stimulated T cells in the mesenteric lymph nodes shifted from pro-inflammatory at d2 to immune-suppressive at d30 (P < 0.0001 for IL-10). These effects were observed despite similar colonic microbiota composition and degradation of the mucosal layer between d2 and d30. Collectively, these results indicate that acute colitis chronically alters epithelial barrier function and both innate and adaptive immune responses. These effects reduce the consequences of a subsequent colitis event, warranting longitudinal studies in human IBD subjects.


Theory of terahertz generation by optical rectification using tilted-pulse-fronts.
A model for terahertz (THz) generation by optical rectification using tilted-pulse-fronts is developed. It simultaneously accounts for in two spatial dimensions (2-D) (i) the spatio-temporal variations of the optical pump pulse imparted by the tilted-pulse-front setup, (ii) the nonlinear coupled interaction of THz and optical radiation, (iii) self-phase modulation and (iv) stimulated Raman scattering. The model is validated by quantitative agreement with experiments and analytic calculations. We show that the optical pump beam is significantly broadened in the transverse-momentum (kx) domain as a consequence of its spectral broadening due to THz generation. In the presence of this large frequency and transverse-momentum (or angular) spread, group velocity dispersion causes a spatio-temporal break-up of the optical pump pulse which inhibits further THz generation. The implications of these effects on energy scaling and optimization of optical-to-THz conversion efficiency are discussed. This suggests the use of optical pump pulses with elliptical beam profiles for large optical pump energies. Furthermore, it is seen that optimization of the setup is highly dependent on optical pump conditions. Trade-offs in optimizing the optical-to-THz conversion efficiency on the spatial and spectral properties of THz radiation are discussed to guide the development of such sources.


Analysis of the hydrogen and oxygen stable isotope ratios of beverage waters without prior water extraction using isotope ratio infrared spectroscopy.
Hydrogen (δ(2)H) and oxygen (δ(18)O) stable isotope analysis is useful when tracing the origin of water in beverages, but traditional analytical techniques are limited to pure or extracted waters. We measured the isotopic composition of extracted beverage water using both isotope ratio infrared spectroscopy (IRIS; specifically, wavelength-scanned cavity ring-down spectroscopy) and isotope ratio mass spectrometry (IRMS). We also analyzed beer, sodas, juices, and milk 'as is' using IRIS. For IRIS analysis, four sequential injections of each sample were measured and data were corrected for sample-to-sample memory using injections (a) 1-4, (b) 2-4, and (c) 3-4. The variation between δ(2)H and δ(18)O values calculated using the three correction methods was larger for unextracted (i.e., complex) beverages than for waters. The memory correction was smallest when using injections 3-4. Beverage water δ(2)H and δ(18)O values generally fit the Global Meteoric Water Line, with the exception of water from fruit juices. The beverage water stable isotope ratios measured using IRIS agreed well with the IRMS data and fit 1:1 lines, with the exception of sodas and juices (δ(2)H values) and beers (δ(18)O values). The δ(2)H and δ(18)O values of waters extracted from beer, soda, juice, and milk were correlated with complex beverage δ(2)H and δ(18)O values (r = 0.998 and 0.997, respectively) and generally fit 1:1 lines. We conclude that it is possible to analyze complex beverages, without water extraction, using IRIS although caution is needed when analyzing beverages containing sugars, which can clog the syringe and increase memory, or alcohol, a known spectral interference.


Management issues for trauma patients with alcohol.
An estimated 20-25% of patients treated in emergency departments or as inpatients for trauma have been drinking and most of them have BACs of 0.10 gm/dL (22 mmol/L) or higher. Many are problem drinkers or alcoholics, smokers, and also abuse other drugs. Both acute ingestion and chronic abuse of alcohol increase the frequency and severity of injury, and may complicate patient management by mimicking head trauma, masking intra-abdominal injury, causing circulatory collapse, reducing immune response, altering hepatic metabolism, or causing delirium tremens. Proper management of a trauma patient with alcohol includes BAC determination, careful history taking for alcoholism with referral for further evaluation or treatment when indicated, and determination whether other drugs are also being misused. Failure to do these may put a physician at legal risk both for improper care of the patient and for exposing others to injury if the patient crashes after being discharged from the emergency department while still impaired by alcohol.


Diet of eared doves (Zenaida auriculata, Aves, Columbidae) in a sugar-cane colony in South-eastern Brazil.
Farmers in the Paranapanema Valley (São Paulo, Brazil) have reported problems with flocks of Eared Doves (Zenaida auriculata) eating sprouting soybeans. In this region these birds breed colonially in sugar-cane, and eat four crop seeds, using 70% of the dry weight, in the following order of importance: maize, wheat, rice, and soybeans. Three weeds (Euphorbia heterophylla, Brachiaria plantaginea, and Commelina benghalensis) were important. This information suggests that the doves adapted particularly well to the landscape created by the agricultural practices in the region, exploiting many available foods.


Steroid hormones and persistent organic pollutants in plasma from North-eastern Atlantic pilot whales.
Persistent organic pollutants (POPs) are known to have endocrine disruptive effects, interfering with endogenous steroid hormones. The present study examined nine steroid hormones and their relationships with the concentrations of selected POPs in pilot whales (Globicephala melas) from the Faroe Islands, NE Atlantic. The different steroids were detected in 15 to all of the 26 individuals. High concentrations of progesterone (83.3-211.7pmol/g) and pregnenolone (PRE; 4.68-5.69pmol/g) were found in three adult females indicating that they were pregnant or ovulating. High androgen concentrations in two of the males reflected that one was adult and that one (possibly) had reached puberty. In males a significant positive and strong correlation between body length and testosterone (TS) levels was identified. Furthermore, positive and significant correlations were found between 4-OH-CB107/4'-OH-CB108 and 17β-estradiol in males. In adult females significant positive correlations were identified between PRE and CB149 and t-nonachlor, between estrone and CB138, -149, -187 and p,p'-DDE, between androstenedione and CB187, and between TS and CB-99 and -153. Although relationships between the POPs and the steroid hormones reported herein are not evidence of cause-effect relationships, the positive correlations between steroids and POPs, particularly in females, suggest that POPs may have some endocrine disrupting effects on the steroid homeostasis in this species.


Silicon: Potential to Promote Direct and Indirect Effects on Plant Defense Against Arthropod Pests in Agriculture.
Silicon has generally not been considered essential for plant growth, although it is well recognized that many plants, particularly Poaceae, have substantial plant tissue concentrations of this element. Recently, however, the International Plant Nutrition Institute [IPNI] (2015), Georgia, USA has listed it as a "beneficial substance". This reflects that numerous studies have now established that silicon may alleviate both biotic and abiotic stress. This paper explores the existing knowledge and recent advances in elucidating the role of silicon in plant defense against biotic stress, particularly against arthropod pests in agriculture and attraction of beneficial insects. Silicon confers resistance to herbivores via two described mechanisms: physical and biochemical/molecular. Until recently, studies have mainly centered on two trophic levels; the herbivore and plant. However, several studies now describe tri-trophic effects involving silicon that operate by attracting predators or parasitoids to plants under herbivore attack. Indeed, it has been demonstrated that silicon-treated, arthropod-attacked plants display increased attractiveness to natural enemies, an effect that was reflected in elevated biological control in the field. The reported relationships between soluble silicon and the jasmonic acid (JA) defense pathway, and JA and herbivore-induced plant volatiles (HIPVs) suggest that soluble silicon may enhance the production of HIPVs. Further, it is feasible that silicon uptake may affect protein expression (or modify proteins structurally) so that they can produce additional, or modify, the HIPV profile of plants. Ultimately, understanding silicon under plant ecological, physiological, biochemical, and molecular contexts will assist in fully elucidating the mechanisms behind silicon and plant response to biotic stress at both the bi- and tri-trophic levels.


Current treatment of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in Western World and frequently associated with insulin resistance and overweight and occurs often with type 2 diabetes. Interestingly, NAFLD is not only regarded as a hepatic component of the metabolic syndrome but also as an independent risk factor and a marker for increase in cardiovascular disease (CVD). Significantly, NAFLD is associated with an increased risk of all-cause mortality and predicts future CVD events independent of age, sex, LDL-cholesterol and features of metabolic syndrome. Although there was initial concern about drug toxicity with NAFLD, increasing evidence suggests that commonly used drugs such as metformin and statins do not cause harm and the thiazolidinediones (TZDs) may even confer a therapeutic benefit in NAFLD. Interestingly, medical and surgical treatments of obesity show potential benefit in treating NAFLD. In this review, we have focused on the safety and therapeutic impact of TZDs, statins, metformins and obesity medications in NAFLD. The potential benefit of bariatric surgery and the role of weight loss per se in treating NAFLD are also discussed.


Anything but engaged: user involvement in the context of a national electronic health record implementation.
The absence of meaningful end user engagement has repeatedly been highlighted as a key factor contributing to 'failed' implementations of electronic health records (EHRs), but achieving this is particularly challenging in the context of national scale initiatives. In 2002, the National Health Service (NHS) embarked on a so-called 'top-down' national implementation strategy aimed at introducing commercial, centrally procured, EHRs into hospitals throughout England. We aimed to examine approaches to, and experiences of, user engagement in the context of a large-scale EHR implementation across purposefully selected hospital care providers implementing early versions of nationally procured software. We conducted a qualitative, case-study based, socio-technically informed, longitudinal investigation, purposefully sampling and collecting data from four hospitals. Our data comprised a total of 123 semi-structured interviews with users and managers, 15 interviews with additional stakeholders, 43 hours of non-participant observations of meetings and system use, and relevant organisation-specific documents from each case study site. Analysis was thematic, building on an existing model of user engagement that was originally developed in the context of studying the implementation of relatively simple technologies in commercial settings. NVivo8 software was used to facilitate coding. Despite an enduring commitment to the vision of shared EHRs and an appreciation of their potential benefits, meaningful end user engagement was never achieved. Hospital staff were not consulted in systems choice, leading to frustration; they were then further alienated by the implementation of systems that they perceived as inadequately customised. Various efforts to achieve local engagement were attempted, but these were in effect risk mitigation strategies. We found the role of clinical champions to be important in these engagement efforts, but progress was hampered by the hierarchical structures within healthcare teams. As a result, engagement efforts focused mainly on clinical staff with inadequate consideration of management and administrative staff. This work has allowed us to further develop an existing model of user engagement from the commercial sector and adapt it to inform user engagement in the context of large-scale eHealth implementations. By identifying key points of possible engagement, disengagement and re-engagement, this model will we hope both help those planning similar large-scale EHR implementation efforts and act as a much needed catalyst to further research in this neglected field of enquiry.