A Target-Less Vision-Based Displacement Sensor Based on Image Convex Hull Optimization for Measuring the Dynamic Response of Building Structures.
Existing vision-based displacement sensors (VDSs) extract displacement data through changes in the movement of a target that is identified within the image using natural or artificial structure markers. A target-less vision-based displacement sensor (hereafter called "TVDS") is proposed. It can extract displacement data without targets, which then serve as feature points in the image of the structure. The TVDS can extract and track the feature points without the target in the image through image convex hull optimization, which is done to adjust the threshold values and to optimize them so that they can have the same convex hull in every image frame and so that the center of the convex hull is the feature point. In addition, the pixel coordinates of the feature point can be converted to physical coordinates through a scaling factor map calculated based on the distance, angle, and focal length between the camera and target. The accuracy of the proposed scaling factor map was verified through an experiment in which the diameter of a circular marker was estimated. A white-noise excitation test was conducted, and the reliability of the displacement data obtained from the TVDS was analyzed by comparing the displacement data of the structure measured with a laser displacement sensor (LDS). The dynamic characteristics of the structure, such as the mode shape and natural frequency, were extracted using the obtained displacement data, and were compared with the numerical analysis results. TVDS yielded highly reliable displacement data and highly accurate dynamic characteristics, such as the natural frequency and mode shape of the structure. As the proposed TVDS can easily extract the displacement data even without artificial or natural markers, it has the advantage of extracting displacement data from any portion of the structure in the image.


Criterion validity of the Ekblom-Bak and the Åstrand submaximal test in an elderly population.
The aim of this study was to validate the submaximal Ekblom-Bak test (EB-test) and the Åstrand test (Å-test) for an elderly population. Participants (n = 104), aged 65-75 years, completed a submaximal aerobic test on a cycle ergometer followed by an individually adjusted indirect calorimetry VO2max test on a treadmill. The HR from the submaximal test was used to estimate VO2max using both the EB-test and Å-test equations. The correlation between measured and estimated VO2max using the EB method and Å method in women was r = 0.64 and r = 0.58, respectively and in men r = 0.44 and r = 0.44, respectively. In women, the mean difference between estimated and measured VO2max was - 0.02 L min-1 (95% CI - 0.08 to 0.04) for the EB method and - 0.12 L min-1 (95% CI - 0.22 to - 0.02) for the Å method. Corresponding values for men were 0.05 L min-1 (95% CI - 0.04 to 0.14) and - 0.28 L min-1 (95% CI - 0.42 to - 0.14), respectively. However, the EB method was found to overestimate VO2max in men with low fitness and the Å method was found to underestimate VO2max in both women and men. For women, the coefficient of variance was 11.1%, when using the EB method and 19.8% when using the Å method. Corresponding values for men were 11.6% and 18.9%, respectively. The submaximal EB-test is valid for estimating VO2max in elderly women, but not in all elderly men. The Å-test is not valid for estimating VO2max in the elderly.


Transcytosis in the continuous endothelium of the myocardial microvasculature is inhibited by N-ethylmaleimide.
In a murine heart perfusion system, we were able to "turn off" the transport of derivatized albumin [dinitrophenylated albumin (DNP-albumin)] from the perfusate to the tissue, by preperfusing the system with 1 mM N-ethylmaleimide (NEM) for 5 min at 37 degrees C, followed by a 5-min perfusion of DNP-albumin in the presence of NEM. Using a postembedding immunocytochemical procedure, we showed that (i) a 30-sec to 1-min treatment of heart vasculature with 1 mM NEM reduces the transendothelial transport of DNP-albumin and nearly stops it after 5 min, and (ii) DNP-albumin is detected exclusively in plasmalemmal vesicles (PVs) while in transit across endothelial cells. Perfusion with 10 mM dithiothreitol for 1 min before NEM prevents the inhibition of vesicular transport. To quantitate the NEM effect on vesicular transport inhibition, we developed an ELISA and a dot-blot assay for measuring DNP-albumin in supernatants of perfused whole-heart homogenates. The results obtained indicate that the treatment of the heart vasculature with 1 mM NEM decreases the vesicular transport of DNP-albumin by 78-80%. Since NEM is known to inhibit the fusion of different types of vesicular carriers with their target membranes in other cell types and in in vitro reconstituted cellular systems, by alkylating a NEM-sensitive factor, we assume that the same mechanism applies in our in situ system. The decrease of vesicular transport can be explained by NEM preventing the fusion of recycling vesicles with their targets--i.e., the abluminal and luminal domains of the plasmalemma. The results open to question previous interpretations from other laboratories according to which plasmalemmal vesicles are sessile, immobile structures.


The effect of "multiphase sedation" in the course of computed tomography and magnetic resonance imaging on children, parents and anesthesiologists.
We aimed to investigate the effect on children undergoing Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), their parents and attending anesthesiologist of "multiphase sedation" which we define as "the intended sedation level achieved with one or more agents through the same or different routes with more than one administration". One hundred children and their parents were randomly allocated to one of two study groups. In phase 1; in Group I the patients were given midazolam (0.5mg.kg(-1)) in 5 mL fruit juice, and the ones in control group (Group II) were given only fruit juice. After intravenous (iv) cannulation; in phase II, boluses of propofol were given to achieve the adequate sedation for imaging. Anxiety scores of children and their parents were recorded using Oucher scale and STAI, respectively, and parental satisfaction was evaluated by visual analogue scale (VAS). The number of attempts for iv cannulation, length of time for preparation, and amount of hypnotics were recorded. Anxiety state of children was similar between groups before premedication, but later it was lower in Group I. Before procedure, STAI score of parents was similar and later it was lower in Group I. Parental satisfaction in Group I was higher. The number of attempts for iv cannulation and required propofol dose was less in Group I. "Multiphase sedation" procedure provides children to feel less pain and anxiety, and decreases parental anxiety while increasing their satisfaction. It supplies a comfortable and safe sedation, as it provides a short and problem-free preparation process for the attending anesthetist as well.


Incidence of obesity among young U.S. children living in low-income families, 2008-2011.
To examine the incidence and reverse of obesity among young low-income children and variations across population subgroups. We included 1.2 million participants in federally funded child health and nutrition programs who were 0 to 23 months old in 2008 and were followed up 24 to 35 months later in 2010-2011. Weight and height were measured. Obesity at baseline was defined as gender-specific weight-for-length ≥95th percentile on the 2000 Centers for Disease Control and Prevention growth charts. Obesity at follow-up was defined as gender-specific BMI-for-age ≥95th percentile. We used a multivariable log-binomial model to estimate relative risk of obesity adjusting for gender, baseline age, race/ethnicity, duration of follow-up, and baseline weight-for-length percentile. The incidence of obesity was 11.0% after the follow-up period. The incidence was significantly higher among boys versus girls and higher among children aged 0 to 11 months at baseline versus those older. Compared with non-Hispanic whites, the risk of obesity was 35% higher among Hispanics and 49% higher among American Indians (AIs)/Alaska Natives (ANs), but 8% lower among non-Hispanic African Americans. Among children who were obese at baseline, 36.5% remained obese and 63.5% were nonobese at follow-up. The proportion of reversing of obesity was significantly lower among Hispanics and AIs/ANs than that among other racial/ethnic groups. The high incidence underscores the importance of early-life obesity prevention in multiple settings for low-income children and their families. The variations within population subgroups suggest that culturally appropriate intervention efforts should be focused on Hispanics and AIs/ANs.


Integration of ceramic membrane and compressed air-assisted solvent extraction (CASX) for metal recovery.
In our previous publications, compressed air-assisted solvent extraction process (CASX) was developed and proved to be kinetically efficient process for metal removal. In the current study, CASX with a ceramic MF membrane integrated for separation of spent solvent was employed to remove and recover metal from wastewater. MF was operated either in crossflow mode or dead-end with intermittent flushing mode. Under crossflow mode, three distinct stages of flux vs. TMP (trans-membrane pressure) relationship were observed. In the first stage, flux increases with increasing TMP which is followed by the stage of stable flux with increasing TMP. After reaching a threshold TMP which is dependent of crossflow velocity, flux increases again with increasing TMP. At the last stage, solvent was pushed through membrane pores as indicated by increasing permeate COD. In dead-end with intermittent flushing mode, an intermittent flushing flow (2 min after a 10-min or a 30-min dead-end filtration) was incorporated to reduce membrane fouling by flush out MSAB accumulated on membrane surface. Effects of solvent concentration and composition were also investigated. Solvent concentrations ranging from 0.1 to 1% (w/w) have no adverse effect in terms of membrane fouling. However, solvent composition, i.e. D(2)EHPA/kerosene ratio, shows impact on membrane fouling. The type of metal extractants employed in CASX has significant impact on both membrane fouling and the quality of filtrate due to the differences in their viscosity and water solubility. Separation of MSAB was the limiting process controlling metal removal efficiency, and the removal efficiency of Cd(II) and Cr(VI) followed the same trend as that for COD.


Epidemiology of Drowning in Bangladesh: An Update.
Over one-quarter of deaths among 1-4 year-olds in Bangladesh were due to drowning in 2003, and the proportion increased to 42% in 2011. This study describes the current burden and risk factors for drowning across all demographics in rural Bangladesh. A household survey was carried out in 51 union parishads of rural Bangladesh between June and November 2013, covering 1.17 million individuals. Information on fatal and nonfatal drowning events was collected by face-to-face interviews using a structured questionnaire. Fatal and non-fatal drowning rates were 15.8/100,000/year and 318.4/100,000/6 months, respectively, for all age groups. The highest rates of fatal (121.5/100,000/year) and non-fatal (3057.7/100,000/6 months) drowning were observed among children 1 to 4 years of age. These children had higher rates of fatal (13 times) and non-fatal drowning (16 times) compared with infants. Males had slightly higher rates of both fatal and non-fatal drowning. Individuals with no education had 3 times higher rates of non-fatal drowning compared with those with high school or higher education. Non-fatal drowning rates increased significantly with decrease in socio-economic status (SES) quintiles, from the highest to the lowest. Drowning is a major public health issue in Bangladesh, and is now a major threat to child survival.


Utilizing Neurons for Digital Logic Circuits: A Molecular Communications Analysis.
With the advancement of synthetic biology, several new tools have been conceptualized over the years as alternative treatments for current medical procedures. As part of this work, we investigate how synthetically engineered neurons can operate as digital logic gates that can be used towards bio-computing inside the brain and its impact on epileptic seizure-like behaviour. We quantify the accuracy of logic gates under high firing rates amid a network of neurons and by how much it can smooth out uncontrolled neuronal firings. To test the efficacy of our method, simulations composed of computational models of neurons connected in a structure that represents a logic gate are performed. Our simulations demonstrate the accuracy of performing the correct logic operation, and how specific properties such as the firing rate can play an important role in the accuracy. As part of the analysis, the mean squared error is used to quantify the quality of our proposed model and predict the accurate operation of a gate based on different sampling frequencies. As an application, the logic gates were used to smooth out epileptic seizure-like activity in a biological neuronal network, where the results demonstrated the effectiveness of reducing its mean firing rate. Our proposed system has the potential to be used in future approaches to treating neurological conditions in the brain.


Leukotriene constriction of mouse pial arterioles in vivo is endothelium-dependent and receptor-mediated.
The diameters of pial arterioles of mice were monitored in vivo with an image-splitting technique and television microscopy. Concentrations of leukotriene C4 as low as 10(-7) M constricted the arterioles. The leukotriene C4-D4 receptor blocker ICI 198615 (10(-8) M) inhibited the response. Endothelial injury by helium-neon laser/Evans blue technique eliminated the constriction and unmasked a slight but consistent relaxation that was not inhibited by 10(-8) M ICI 198615. Since leukotrienes are produced by the brain and enter the cerebrospinal fluid in ischemia, head trauma, and subarachnoid hemorrhage, the possibility that leukotrienes C4 and D4 contribute to decreases in cerebral blood flow during these conditions should be considered. However, the present data makes such a possibility far less likely because the endothelium is frequently injured in these conditions, and therefore the ability of leukotrienes to constrict vessels would be severely curtailed.


Establishment of normal reference ranges for glycemic variability in Chinese subjects using continuous glucose monitoring.
Glycemic variability is increasingly recognized as an important issue in diabetes management. However, the lack of normative values may limit its applicability in the clinical setting. The objective of this study was to establish preliminary normal reference ranges for glycemic variability by analyzing continuous glucose monitoring (CGM) data obtained from healthy Chinese adults. Three-day CGM data were obtained from 434 healthy adults at 10 academic hospitals throughout China. Glycemic variability was calculated as the 24-hour mean amplitude of glycemic excursions (MAGE) and standard deviations (SD) of blood glucose readings. 434 healthy subjects (male 213, female 221; age 43 ± 14, 20-69 years old; BMI 21.8 ± 1.7 kg/m2, 18.5-24.9 kg/m2) completed the study. MAGE and SD values for the 434 healthy subjects were 1.73 (1.08) mmol/L and 0.75 (0.42) mmol/L [median (interquartile range)], respectively. In both men and women, MAGE and SD tended to increase with age. Neither MAGE nor SD showed a significant difference between men and women. Values for both parameters were non-normally distributed within the population. The 95th percentiles of MAGE and SD were 3.86 and 1.40 mmol/L, respectively. These values were adopted as the upper limits of normal.< MAGE <3.9 mmol/L and SD <1.4 mmol/L are recommended as the normal reference ranges for glycemic variability in Chinese adults. The values established in this study may facilitate the adoption of glycemic variability as a metric of overall glycemic control in diabetes.


Mitogenomic phylogenetic analyses of the Delphinidae with an emphasis on the Globicephalinae.
Previous DNA-based phylogenetic studies of the Delphinidae family suggest it has undergone rapid diversification, as characterised by unresolved and poorly supported taxonomic relationships (polytomies) for some of the species within this group. Using an increased amount of sequence data we test between alternative hypotheses of soft polytomies caused by rapid speciation, slow evolutionary rate and/or insufficient sequence data, and hard polytomies caused by simultaneous speciation within this family. Combining the mitogenome sequences of five new and 12 previously published species within the Delphinidae, we used Bayesian and maximum-likelihood methods to estimate the phylogeny from partitioned and unpartitioned mitogenome sequences. Further ad hoc tests were then conducted to estimate the support for alternative topologies. We found high support for all the relationships within our reconstructed phylogenies, and topologies were consistent between the Bayesian and maximum-likelihood trees inferred from partitioned and unpartitioned data. Resolved relationships included the placement of the killer whale (Orcinus orca) as sister taxon to the rest of the Globicephalinae subfamily, placement of the Risso's dolphin (Grampus griseus) within the Globicephalinae subfamily, removal of the white-beaked dolphin (Lagenorhynchus albirostris) from the Delphininae subfamily and the placement of the rough-toothed dolphin (Steno bredanensis) as sister taxon to the rest of the Delphininae subfamily rather than within the Globicephalinae subfamily. The additional testing of alternative topologies allowed us to reject all other putative relationships, with the exception that we were unable to reject the hypothesis that the relationship between L. albirostris and the Globicephalinae and Delphininae subfamilies was polytomic. Despite their rapid diversification, the increased sequence data yielded by mitogenomes enables the resolution of a strongly supported, bifurcating phylogeny, and a chronology of the divergences within the Delphinidae family. This highlights the benefits and potential application of large mitogenome datasets to resolve long-standing phylogenetic uncertainties.


Homologous Recombination between Genetically Divergent Campylobacter fetus Lineages Supports Host-Associated Speciation.
Homologous recombination is a major driver of bacterial speciation. Genetic divergence and host association are important factors influencing homologous recombination. Here, we study these factors for Campylobacter fetus, which shows a distinct intraspecific host dichotomy. Campylobacter fetus subspecies fetus (Cff) and venerealis are associated with mammals, whereas C. fetus subsp. testudinum (Cft) is associated with reptiles. Recombination between these genetically divergent C. fetus lineages is extremely rare. Previously it was impossible to show whether this barrier to recombination was determined by the differential host preferences, by the genetic divergence between both lineages or by other factors influencing recombination, such as restriction-modification, CRISPR/Cas, and transformation systems. Fortuitously, a distinct C. fetus lineage (ST69) was found, which was highly related to mammal-associated C. fetus, yet isolated from a chelonian. The whole genome sequences of two C. fetus ST69 isolates were compared with those of mammal- and reptile-associated C. fetus strains for phylogenetic and recombination analysis. In total, 5.1-5.5% of the core genome of both ST69 isolates showed signs of recombination. Of the predicted recombination regions, 80.4% were most closely related to Cft, 14.3% to Cff, and 5.6% to C. iguaniorum. Recombination from C. fetus ST69 to Cft was also detected, but to a lesser extent and only in chelonian-associated Cft strains. This study shows that despite substantial genetic divergence no absolute barrier to homologous recombination exists between two distinct C. fetus lineages when occurring in the same host type, which provides valuable insights in bacterial speciation and evolution.


First Report of Ascochyta Leaf Spot of Quinoa Caused by Ascochyta sp. in the United States.
The Andean crop quinoa (Chenopodium quinoa Willd.), an amaranthaceous pseudograin, is an important food and export crop for this region. Quinoa is susceptible to Ascochyta leaf spot reportedly caused by Ascochyta hyalospora and/or A. caulina (1,2), and quinoa seeds can be infested by A. hyalospora (3). Quinoa fields were established in Pennsylvania during summer 2011. Widespread leafspot symptoms were observed on quinoa in mid-August 2011 in Centre County, PA. Tan to reddish-brown, irregularly shaped lesions were observed with numerous black pycnidia randomly distributed within each lesion. Crushed pycnidia revealed sub-hyaline to light brown, 1 to 2, or less often 3 septate, cylindrical to ovoid spores, 13 to 25 μm long by 5 to 10 μm wide. Pure cultures of Ascochyta were obtained by plating pycnidia from surface disinfested leaves onto half strength acidified potato dextrose agar (APDA). To obtain conidia for pathogenicity trials, cultures were transferred to oatmeal agar and placed in a 20°C incubator with a 12-h photoperiod. Conidia were harvested by scraping 2-week-old cultures. The conidial suspension was filtered through cheesecloth and adjusted to 1.8 × 105 conidia/mL. Tween 20 (0.1%) was added to the final inoculum and sprayed (with a Crown Spra-tool) onto ten 1-month old quinoa plants. Six plants sprayed with sterile water with 0.1% Tween 20 served as controls. Plants were placed in a growth chamber and bagged for 48 h to maintain >95% humidity. After 48 h, tan, irregularly shaped lesions were observed on inoculated plants, but no symptoms were observed on control plants. Plants were grown for 2 more weeks to observe symptom development, and then leaves with characteristic lesions were collected for isolation. Symptomatic leaves were surface disinfested in 10% bleach for 1 min and tissue from the lesion periphery was plated onto APDA. Obtained cultures were morphologically and molecularly identical to those obtained from quinoa fields. For molecular identification of the pathogen, DNA was extracted from cultures of Ascochyta and amplified using ITS4 (TCCTCCGCTTATTGATATGC) and ITS5 (GGAAGTAAAAGTCGTAACAAGG) primers. Sequences obtained shared 99% maximum identity with a GenBank accession of A. obiones (GU230752.1), a species closely related to A. hyalospora and A. caulina (4). However, the obtained pathogen is morphologically more similar to A. hyalospora and A. chenopodii, but not to A. caulina or A. obiones. At this time, final species identification is impossible because no GenBank sequence data is available for A. hyalospora or A. chenopodii. To our knowledge, this is the first report of Ascochyta leaf spot of quinoa in the United States. The impact of Ascochyta leaf spot on domestic and global quinoa production is unknown, but management of foliar diseases of quinoa, including Ascochyta leaf spot, is a critical component of any disease management program for quinoa. References: (1) S. Danielsen. Food Rev. Int. 19:43, 2003. (2) M. Drimalkova. Plant Protect. Sci. 39:146, 2003. (3) G. Boerema. Neth. J. Plant. Pathol. 83:153, 1977. (4) J. de Gruyter. Stud. Mycol. 75:1, 2012.


Is the spiritual life of cancer patients a resource to be taken into account by professional caregivers from the time of diagnosis?
Spiritual life can be defined as the search for personal contact with the transcendent. Careful assessment of spiritual life can help to value its importance to cancer patients from the moment of their diagnosis. This is a cross-sectional study. Two hundred fifty-seven patients undergoing cancer treatment filled in the validated Italian version of the Systems of Belief Inventory (SBI-15R). Patients were also asked to attribute themselves to one of the following, mutually exclusive categories: believer and churchgoer, believer but no churchgoer, and non-believer. Five patients did not report their religious stance and were therefore excluded from the analysis. Of the remaining 252 patients, 49% declared to be believers and churchgoers, 43% believers but not churchgoers, and 8% non-believers. Of the 20 cancer patients who declared not to have a religious faith, 7 patients agreed with the statement that they felt certain that God exists in some form, and 4 had experienced peace of mind through prayer and meditation. Almost all of the patients who declared to have a religious faith and to be churchgoers explicitly affirmed to have been helped by prayer and meditation in coping with their illness. Among believer churchgoers, only 30% declared to seek out the religious or spiritual community when they needed help. A large proportion of cancer patients find themselves involved with the search for a personal contact with the transcendent, also beyond any specific religious affiliation. These spiritual issues may be important even when they are not expressed as participation in religious rituals or adherence to specific religious beliefs. On the other hand, participation in religious rituals often implies the need for a personal spiritual life, both through those rituals and beyond them, as through personal prayer and meditation. These results ask for more attention on the part of professionals towards spiritual resources among cancer patients. It might be appropriate to look systematically for these resources from the moment of the diagnosis, through the sensitive administration of an easy and valid assessment tool like the SBI-15R.


Aggression: the testosterone-serotonin link.
The relevance of central neurotransmission to aggressive and impulsive behavior has become more evident due to extensive research in humans and animals. Among other findings, there are abundant data relating low serotonergic activity--as measured by low cerebrospinal fluid 5-hydroxyindolacetic acid, and a blunted response of prolactin to fenfluramine--to impulsive behavior. Many studies on testosterone activity show a relation between high plasma levels and a tendency towards aggression. It is hypothesized that the interaction between low serotonin and high testosterone levels in the central nervous system has a significant effect on the neural mechanisms involved in the expression of aggressive behavior. It seems that testosterone modulates serotonergic receptor activity in a way that directly affects aggression, fear and anxiety. Our survey reviews the main findings on serotonin, testosterone and the possible interaction between them with regard to these behavioral phenomena.


Evading Pgp activity in drug-resistant cancer cells: a structural and functional study of antitubulin furan metotica compounds.
Tumor resistance to antitubulin drugs resulting from P-glycoprotein (Pgp) drug-efflux activity, increased expression of the βIII tubulin isotype, and alterations in the drug-binding sites are major obstacles in cancer therapy. Consequently, novel antitubulin drugs that overcome these challenges are of substantial interest. Here, we study a novel chemotype named furan metotica that localizes to the colchicine-binding site in β-tubulin, inhibits tubulin polymerization, and is not antagonized by Pgp. To elucidate the structure-activity properties of this chiral chemotype, the enantiomers of its most potent member were separated and their absolute configurations determined by X-ray crystallography. Both isomers were active and inhibited all 60 primary cancer cell lines tested at the U.S. National Cancer Institute. They also efficiently killed drug-resistant cancer cells that overexpressed the Pgp drug-efflux pump 10(6)-fold. In vitro, the R-isomer inhibited tubulin polymerization at least 4-fold more potently than the S-isomer, whereas in human cells the difference was 30-fold. Molecular modeling showed that the two isomers bind to β-tubulin in distinct manners: the R-isomer binds in a colchicine-like mode and the S-isomer in a podophyllotoxin-like fashion. In addition, the dynamic binding trajectory and occupancy state of the R-isomer were energetically more favorable then those of the S-isomer, explaining the observed differences in biologic activities. The ability of a racemic drug to assume the binding modes of two prototypical colchicine-site binders represents a novel mechanistic basis for antitubulin activity and paves the way toward a comprehensive design of novel anticancer agents.


An IoT Reader for Wireless Passive Electromagnetic Sensors.
In the last years, many passive electromagnetic sensors have been reported. Some of these sensors are used for measuring harmful substances. Moreover, the response of these sensors is usually obtained with laboratory equipment. This approach highly increases the total cost and complexity of the sensing system. In this work, a novel low-cost and portable Internet-of-Things (IoT) reader for passive wireless electromagnetic sensors is proposed. The reader is used to interrogate the sensors within a short-range wireless link avoiding the direct contact with the substances under test. The IoT functionalities of the reader allows remote sensing from computers and handheld devices. For that purpose, the proposed design is based on four functional layers: the radiating layer, the RF interface, the IoT mini-computer and the power unit. In this paper a demonstrator of the proposed reader is designed and manufactured. The demonstrator shows, through the remote measurement of different substances, that the proposed system can estimate the dielectric permittivity. It has been demonstrated that a linear approximation with a small error can be extracted from the reader measurements. It is remarkable that the proposed reader can be used with other type of electromagnetic sensors, which transduce the magnitude variations in the frequency domain.


The Impact of Nurse-Led Clinics on the Mortality and Morbidity of Patients with Cardiovascular Diseases: A Systematic Review and Meta-analysis.
Nurse-led clinics (NLCs) have been developed in several health specialties in recent years. The aim of this analysis is to summarize and appraise the available evidence about the effectiveness of NLCs on the morbidity and mortality outcomes in patients with cardiovascular diseases (CVDs). We searched Cochrane databases, MEDLINE, Web of Science, PubMed, EMBASE, Google Scholar, BIOSIS, and bibliography of secondary sources from inception through February 20, 2013. Studies were selected and data were extracted independently by 2 investigators. Eligible studies were randomized trials of NLCs of patients with CVD. Of 56 potentially relevant articles screened initially, 12 trials met the inclusion criteria. The outcomes of interest were all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, major adverse cardiac events, revascularization, lipids control, and adherence to antiplatelet medications. We performed random-effects meta-analysis to estimate summary risk ratios and quantified between-studies heterogeneity with the I2 statistic. The 12 trials allocated 4886 patients to NLCs and 4954 patients to usual care. The NLC patients had decreased all-cause mortality (odds ratio, 0.78; 95% confidence interval [CI], 0.65-0.95; P < .01) and myocardial infarction (odds ratio, 0.63; 95% CI, 0.39-1.00; P = .05) and had higher adherence to lipid-lowering medication (odds ratio, 1.57; 95% CI, 1.14-2.17; P = .006) compared with controls. They also had increased adherence to antiplatelet therapy compared with controls (odds ratio, 1.42; 95% CI, 1.01-1.98; P = .04). There was no statistically significant difference in the risk of cardiovascular death (odds ratio, 0.68; 95% CI, 0.40-1.15; P = .68), major adverse cardiac events (odds ratio, 0.79; 95% CI, 0.55-1.14; P = .21),or revascularization (odds ratio, 0.87; 95% CI, 0.66-1.16; P = .36) between NLC patients and controls. The available evidence suggests a favorable effect of NLCs on all-cause mortality, rate of major adverse cardiac events, and adherence to medications in patients with CVD.


Impact of hyperbaric oxygen on diabetic ulcers is unaffected by glycemic control.
Hyperbaric oxygen (HBO2) therapy is an established intervention for treating chronic diabetic lower extremity ulcers, but the impact of glycemic control on its efficacy has not been determined. The purpose of this study was to evaluate the impact of blood glucose control at initiation of HBO2 treatment on wound healing. Hemoglobin A1c (HbA1c) was measured at start of HBO2 therapy for 22 patients undergoing treatment of chronic lower extremity ulcers at two regional wound care centers. Patients with HbA1c < 7.5% were stratified into a "good glycemic control" group (n = 12, mean HbA1c 6.5 ± 0.8%), and patients with HbA1c ≥ 7.5% were stratified into a "poor glycemic control" group (n = 10, mean HbA1c 8.8 ± 1.4%, p = 0.004 compared to "good glycemic control group"). After 20 HBO2 sessions over 30 days in addition to standard wound care interventions, there was no difference in wound healing between the two glycemic control groups as indicated by. reduction from baseline in ulcer surface area, depth, or volume. The diabetic lower extremity wound response to HBO2 therapy is unaffected by glycemic control prior to treatment, and HBO2 treatment should not be delayed for suboptimal blood glucose control.


A Monte Carlo study of tests on data originating from quadrat sampling. I: Data from a Poisson distribution.
Computer simulations are used to examine the significance levels and powers of several tests which have been employed to compare the means of Poisson distributions. In particular, attention is focused on the behaviour of the tests when the means are small, as is often the case in ecological studies when populations of organisms are sampled using quadrats. Two approaches to testing are considered. The first assumes a log linear model for the Poisson data and leads to tests based on the deviance. The second employs standard analysis of variance tests following data transformations, including the often used logarithmic and square root transformations. For very small means it is found that a deviance-based test has the most favourable characteristics, generally outperforming analysis of variance tests on transformed data; none of the latter appears consistently better than any other. For larger means the standard analysis of variance on untransformed data performs well.


Sap fluxes from different parts of the rootzone modulate xylem ABA concentration during partial rootzone drying and re-wetting.
Previous studies with partial rootzone drying (PRD) irrigation demonstrated that alternating the wet and dry parts of the rootzone (PRD-Alternated) increased leaf xylem ABA concentration ([X-ABA]leaf) compared with maintaining the same wet and dry parts of the rootzone (PRD-Fixed). To determine the relative contributions of different parts of the rootzone to this ABA signal, [X-ABA]leaf of potted, split-root tomato (Solanum lycopersicum) plants was modelled by quantifying the proportional water uptake from different soil compartments, and [X-ABA]leaf responses to the entire pot soil-water content (θpot). Continuously measuring soil-moisture depletion by, or sap fluxes from, different parts of the root system revealed that water uptake rapidly declined (within hours) after withholding water from part of the rootzone, but was rapidly restored (within minutes) upon re-watering. Two hours after re-watering part of the rootzone, [X-ABA]leaf was equally well predicted according to θpot alone and by accounting for the proportional water uptake from different parts of the rootzone. Six hours after re-watering part of the rootzone, water uptake by roots in drying soil was minimal and, instead, occurred mainly from the newly irrigated part of the rootzone, thus [X-ABA]leaf was best predicted by accounting for the proportional water uptake from different parts of the rootzone. Contrary to previous results, alternating the wet and dry parts of the rootzone did not enhance [X-ABA]leaf compared with PRD-Fixed irrigation. Further work is required to establish whether altered root-to-shoot ABA signalling contributes to the improved yields of crops grown with alternate, rather than fixed, PRD.


A Spatiotemporal DNA Endoploidy Map of the Arabidopsis Root Reveals Roles for the Endocycle in Root Development and Stress Adaptation.
Somatic polyploidy caused by endoreplication is observed in arthropods, molluscs, and vertebrates but is especially prominent in higher plants, where it has been postulated to be essential for cell growth and fate maintenance. However, a comprehensive understanding of the physiological significance of plant endopolyploidy has remained elusive. Here, we modeled and experimentally verified a high-resolution DNA endoploidy map of the developing Arabidopsis thaliana root, revealing a remarkable spatiotemporal control of DNA endoploidy levels across tissues. Fitting of a simplified model to publicly available data sets profiling root gene expression under various environmental stress conditions suggested that this root endoploidy patterning may be stress-responsive. Furthermore, cellular and transcriptomic analyses revealed that inhibition of endoreplication onset alters the nuclear-to-cellular volume ratio and the expression of cell wall-modifying genes, in correlation with the appearance of cell structural changes. Our data indicate that endopolyploidy might serve to coordinate cell expansion with structural stability and that spatiotemporal endoreplication pattern changes may buffer for stress conditions, which may explain the widespread occurrence of the endocycle in plant species growing in extreme or variable environments.


Feasibility and Acceptability of a Type 2 Diabetes Prevention Intervention for Mothers and Children at a Federally Qualified Healthcare Center.
Maternal obesity and gestational diabetes mellitus (GDM) contribute to increased risk for type 2 diabetes mellitus (T2DM) among both mothers and their offspring. Randomized trials demonstrated T2DM risk reduction in adults following lifestyle behavior change and modest weight loss; the evidence base for at-risk children remains limited. Evaluate the feasibility, acceptability, and preliminary efficacy of a T2DM prevention intervention for mother-child dyads delivered by Federally Qualified Health Center staff. A group randomized design tested the effects of a behavioral lifestyle intervention on T2DM risk factors in women with a history of GDM and their 8- to 12-year-old children. Mother-child dyads were recruited and randomized to intervention or wait-listed control conditions. Intervention participants completed the 13-week intervention; control participants received standard of care. Baseline and 13-week measures assessed program acceptability and feasibility, and explored effects on body weight, waist circumference, hemoglobin A1c, and lifestyle behaviors. Forty-two dyads were randomized and 35 (83%) completed pre-/post-measurements. Participants and program leaders positively rated content and engagement. Nearly all strongly agreed that activities were enjoyable (97%), applicable (96%), useful (97%), and motivational (96%). Attendance averaged 65% across 2 cohorts; delivery costs were approximately $225/dyad. There were no significant differences in body weight, BMI (or BMI z-score), waist circumference, hemoglobin A1c, diet quality, physical activity, sleep, or home environment changes between intervention and control groups. A family T2DM prevention program was feasibly delivered by FQHC staff, and acceptable to mothers and children. Program efficacy will be evaluated in an adequately powered clinical trial.


Disease Monitoring Related Adherence and Its Association with Mortality in Lower Austrian Diabetes Patients.
Patient adherence is an important component of an efficient therapy. For diabetes patients it may contribute to controlled glucose values and reduction of adverse outcomes. We aim to examine a potential association of Lower Austrian diabetes patients' adherence concerning their disease monitoring and mortality. Using a retrospective cohort study design, claims data of 55,873 diabetes patients were examined for regular HbA1c lab tests that served as a proxy for monitoring related adherence. The cumulative incidence of mortality was estimated in the total study population and separately for different levels of adherence using the product-limit method. Mortality was compared between the different levels of adherence by the log-rank test. The cumulative incidence of mortality after one and two years was 4.2% and 8.7%. Patients with low adherence had a significantly higher risk of mortality than patients with high adherence (p < 0.001). Further results of a multivariable analysis will be presented at the conference. According to our preliminary univariate analysis, monitoring related adherence seems to be substantially beneficial for diabetes patients in Lower Austria.


Tetralogy of Fallot With Pulmonary Atresia: Anatomy, Physiology, Imaging, and Perioperative Management.
Tetralogy of Fallot (ToF) with pulmonary atresia (ToF-PA) is a complex congenital heart defect at the extreme end of the spectrum of ToF, with no antegrade flow into the pulmonary arteries. Patients differ with regard to the sources of pulmonary blood flow. In the milder spectrum of disease, there are confluent branch pulmonary arteries fed by ductus arteriosus. In more severe cases, however, the ductus arteriosus is absent, and the sole source of pulmonary blood flow is via major aortopulmonary collateral arteries (MAPCAs). The variability in the origin, size, number, and clinical course of these MAPCAs adds to the complexity of these patients. Currently, the goal of management is to establish pulmonary blood flow from the right ventricle (RV) with RV pressures that are ideally less than half of the systemic pressure to allow for closure of the ventricular septal defect. In the long term, patients with ToF-PA are at higher risk for reinterventions to address pulmonary arterial or RV-pulmonary artery conduit stenosis, progressive aortic root dilation and aortic insufficiency, and late mortality than those with less severe forms of ToF.


Design rules for optimizing unipolar coded Brillouin optical time-domain analyzers.
The performance of unipolar unicolor coded Brillouin optical time-domain analysis (BOTDA) is evaluated based on both Simplex and Golay codes. Four major detrimental factors that limit the system performance, including decoded-gain trace distortion, coding pulse power non-uniformity, polarization pulling and higher-order non-local effects, are thoroughly investigated. Through theoretical analysis and an experimental validations, solutions and optimal design conditions for unipolar unicolor coded BOTDA are clearly established. First, a logarithmic normalization approach is proposed to resolve the linear accumulated Brillouin amplification without distortion. Then it is found out that Simplex codes are more robust to pulse power non-uniformity compared to Golay codes; whilst the use of a polarization scrambler must be preferred in comparison to a polarization switch to mitigate uncompensated fading induced by polarization pulling in the decoded traces. These optimal conditions enables the sensing performance only limited by higher-order non-local effects. To secure systematic errors below 1.3 MHz on the Brillouin frequency estimation, while simultaneously reaching the maximum signal-to-noise ratio (SNR), a mathematical model is established to trade-off the key parameters in the design, i.e., the single-pulse Brillouin amplification, code length and probe power. It turns out that the optimal SNR performance depends in inverse proportion on the value of maximum single-pulse Brillouin amplification, which is ultimately determined by the spatial resolution. The analysis here presented is expected to serve as a quantitative guideline to design a distortion-free coded BOTDA system operating at maximum SNR.


Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities.
Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.


Globalization and pollution: tele-connecting local primary PM2.5 emissions to global consumption.
Globalization pushes production and consumption to geographically diverse locations and generates a variety of sizeable opportunities and challenges. The distribution and associated effects of short-lived primary fine particulate matter (PM2.5), a representative of local pollution, are significantly affected by the consumption through global supply chain. Tele-connection is used here to represent the link between production and consumption activity at large distances. In this study, we develop a global consumption-based primary PM2.5 emission inventory to track primary PM2.5 emissions embodied in the supply chain and evaluate the extent to which local PM2.5 emissions are triggered by international trade. We further adopt consumption-based accounting and identify the global original source that produced the emissions. We find that anthropogenic PM2.5 emissions from industrial sectors accounted for 24 Tg globally in 2007; approximately 30% (7.2 Tg) of these emissions were embodied in export of products principally from Brazil, South Africa, India and China (3.8 Tg) to developed countries. Large differences (up to 10 times) in the embodied emissions intensity between net importers and exporters greatly increased total global PM2.5 emissions. Tele-connecting production and consumption activity provides valuable insights with respect to mitigating long-range transboundary air pollution and prompts concerted efforts aiming at more environmentally conscious globalization.


Interventions for chronic non-hypovolaemic hypotonic hyponatraemia.
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain. This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia. We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies. We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors. Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI). We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent. In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.


Protein interaction mapping: a Drosophila case study.
The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional motifs allow the elaboration of known complexes and the identification of new ones. The full data set can be visualized using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps.


Calcium phosphate barrier for augmentation of bone in noncontained periodontal osseous defects: a novel approach.
The aim of this technique is to augment bone in non-contained osseous deformities using a unique self-sustaining calcium phosphate barrier. Bone has the inherent ability to regenerate completely if it is provided with a fracture space or an undisturbed enclosed scaffold. A secluded environment is essential as it provides a secured, sterile and stable wound system that regenerates lost bone by a process of osteopromotion. Reconstructive techniques using bone grafts and barrier membranes utilize this principle for augmentation of deficient bony sites by providing a closed environment that promotes clot stability, graft retention, and facilitates correct cell repopulation. However, in noncontained bone defects like one walled infrabony periodontal defect or sites with horizontal bone loss, regeneration of bone still remains an unrealistic situation since osseous topography at such sites does not favor membrane stability or bone grafts retention. This case report presents a promising technique to augment bone in areas with horizontal loss. Augmentation of bone in the interdental area with horizontal bone loss was accomplished by building a contained defect using a unique self sustaining calcium phosphate cement formulation. The calcium phosphate barrier stimulates the lost cortical plates and promotes graft retention and clot stability. At 6 months, there was a significant bone fill and trabecular formation in the interdental area and reduction in tooth mobility. This promising technique could prove to be a good alternative to the conventional approaches for treating osseous deformities. Calcium phosphate is a promising barrier graft for repair of noncontained periodontal osseous defect. This technique cues both the clinicians and manufacturers to develop moldable tissue engineered constructs for osseous repair.


Vitamin B12 and folate deficiency in chronic heart failure.
To determine the prevalence, clinical correlates and the effects on outcome of vitamin B12 and folic acid levels in patients with chronic heart failure (HF). We studied an international pooled cohort comprising 610 patients with chronic HF. The main outcome measure was all-cause mortality. Mean age of the patients was 68±12 years and median serum N-terminal prohormone brain natriuretic peptide level was 1801 pg/mL (IQR 705-4335). Thirteen per cent of the patients had an LVEF >45%. Vitamin B12 deficiency (serum level <200 pg/mL), folate deficiency (serum level <4.0 ng/mL) and iron deficiency (serum ferritin level <100 µg/L, or 100-299 µg/L with a transferrin saturation <20%) were present in 5%, 4% and 58% of the patients, respectively. No significant correlation between mean corpuscular volume and vitamin B12, folic acid or ferritin levels was observed. Lower folate levels were associated with an impaired health-related quality of life (p=0.029). During a median follow-up of 2.10 years (1.31-3.60 years), 254 subjects died. In multivariable proportional hazard models, vitamin B12 and folic acid levels were not associated with prognosis. Vitamin B12 and folate deficiency are relatively rare in patients with chronic HF. Since no significant association was observed between mean corpuscular volume and neither vitamin B12 nor folic acid levels, this cellular index should be used with caution in the differential diagnosis of anaemia in patients with chronic HF. In contrast to iron deficiency, vitamin B12 and folic acid levels were not related to prognosis.


The transition into veterinary practice: opinions of recent graduates and final year students.
The transition from veterinary student to member of the veterinary profession is known to be challenging. This study aimed to determine and compare the opinions of final year veterinary students and recent graduates on graduate attributes that ease this transition. The study was carried out across 3 veterinary schools in the United Kingdom. Paper based or electronic surveys were used. Final year students in the 3 schools were surveyed either electronically (school A) or on paper (schools B and C). Student cohort sizes were 112, 227 and 102 respectively. Recent graduates were contacted either at a reunion event (school A) or electronically from database records (school B and school C). Cohort sizes of contacted graduates were 80, 175 and 91 respectively. Respondents were asked to rate 42 individual attributes on a 5 point Likert scale. Focus groups with final year students and recent graduates and telephone interviews with recent graduates were carried out. Data were analysed by two researchers through a combination of manual coding and thematic analysis. Data were grouped into broad themes then sorted into narrower themes. Data were then searched for counter examples. Response rates for final year students were 34% (school A), 36% (school B) and 40% (school C). Response rates for recent graduates were 56% (school A), 20% (school B) and 11% (school C). There was a high level of agreement between the cohorts with respect to communication skills, problem solving and decision making skills, recognition of own limitations and the ability to cope with pressure all rated unanimously important or very important. Business acumen, knowledge of veterinary practice management and research skills were the 3 attributes ranked at the bottom of the list. Nine attributes were identified with a significantly different (p < 0.05) ranking between the cohorts. Final year students ranked veterinary clinical knowledge, knowledge of veterinary public health and zoonotic issues, veterinary legislation and veterinary practice management, commitment to continuing professional development and ability to evaluate information higher than recent graduates. Recent graduates ranked the attributes of integrity, friendliness and compassion higher than final year students. Recent graduates and final year students rate highly the attributes which help foster the client/veterinarian relationship. Recent graduates reflect that a focus on knowledge based attributes is less important once in practice when compared to final year. The study confirms the importance to recent graduates and final year students of attributes considered as non-technical in the transition to working in the veterinary profession.


Maternal hyperglycemia during pregnancy predicts adiposity of the offspring.
To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity. We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls' adiposity, measured annually: (1) ≥85th age-specific percentile for BMI; (2) percent body fat (%BF); and (3) waist-to-height ratio (WHR). Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl's age, and girl's age at onset of puberty, having a mother with GDM increased a girl's risk of having a BMI ≥85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28-9.92]; OR 3.13 [95% CI 1.08-9.09]; and OR 2.80 [95% CI 1.00-7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ≥85th percentile (OR 5.56 [95%CI 1.70-18.2]; Q4 %BF, OR 6.04 [95% CI 1.76-20.7]; and Q4 WHR, OR 3.60 [95% CI 1.35-9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity. Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.


Tryptophan metabolism in the central nervous system: medical implications.
The metabolism of the amino acid L-tryptophan is a highly regulated physiological process leading to the generation of several neuroactive compounds within the central nervous system. These include the aminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), products of the kynurenine pathway of tryptophan metabolism (including 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and kynurenic acid), the neurohormone melatonin, several neuroactive kynuramine metabolites of melatonin, and the trace amine tryptamine. The integral role of central serotonergic systems in the modulation of physiology and behaviour has been well documented since the first description of serotonergic neurons in the brain some 40 years ago. However, while the significance of the peripheral kynurenine pathway of tryptophan metabolism has also been recognised for several decades, it has only recently been appreciated that the synthesis of kynurenines within the central nervous system has important consequences for physiology and behaviour. Altered kynurenine metabolism has been implicated in the pathophysiology of conditions such as acquired immunodeficiency syndrome (AIDS)-related dementia, Huntington's disease and Alzheimer's disease. In this review we discuss the molecular mechanisms involved in regulating the metabolism of tryptophan and consider the medical implications associated with dysregulation of both serotonergic and kynurenine pathways of tryptophan metabolism.


Cerebral distribution of 133-Xe and blood flow measured with high purity germanium.
Distribution of cerebral blood flow was measured with an array of 200 ultra-pure germanium radiation detectors and 133-Xe by inhalation. The array "sees" the head as a composite of different subvolumes and enables measurement of the concentration history of tracer every 1-10 sec in each subvolume simultaneously. Subvolume mean flows, (fm), and partition coefficients, lambda m, are derived by compartmental analysis of tissue concentration washout curves. Errors from "cross talk," scalp radiation, "look through," and assumed partition coefficients are eliminated. Average fm adjusted for 40 mm Hg PACO2 in 14 cortical subvolumes (7 right, 7 left) of four normal 21-24 year old controls ranged from 50 to 60 ml/100 cc tissue/min, and lambda m ranged from 0.97 to 1.14. Average fm and lambda m in white matter was 24 ml/100 cc/min and 1.42 - 1.14 respectively. During CO2 inhalation, right and left hemispheric fm increased 6.4% and 5.7%/mm Hg respectively, whereas white matter fm increased 2.2% and 3.4% mm Hg respectively. There was no systematic difference between front and back or dominant vs non-dominant sides. Three 73-84 year old controls had reduced fm and CO2 reactivity in all subvolumes, lambda m was in the same range as in younger controls. Two patients with intracranial cerebrovascular disease showed excellent localization of ischemic subvolumes. One patient with asymptomatic unilateral 98% stenosis of the internal carotid artery had a similar distribution of blood flow in both hemispheres.


A micropatterned hepatocyte coculture model for assessment of liver toxicity using high-content imaging analysis.
The current landscape of in vitro models used to identify drug- or chemical-induced hepatotoxicity relies heavily on cell culture models consisting of HepG2, induced pluripotent stem cell-derived, or primary hepatocytes. While these in vitro models offer powerful approaches for predicting toxicity, each system has challenges, including variable metabolic capacity, brief ex vivo life span in culture, and adoption with standard automated microscopy high-content screening (HCS) systems to measure reproducibility data at the single-cell level. In this report we introduce a novel primary hepatocyte coculture model, HepatoPac™, as an alternative to current model systems for evaluation of in vitro hepatotoxicity in 96-well microtiter plate format examined by HCS. The coculture model consists of primary hepatocytes that are micropatterned to form a discrete microarchitecture or "hepatocyte islands" that are surrounded by supporting fibroblasts resulting in long-term viability and metabolic function of primary hepatocytes. Using multiple HCS image capture and image analysis strategies, we established methods to interrogate various morphometric parameters, such as size, shape, and intensity, at the island or single-cell level. We applied these approaches to identify subpopulations of both fibroblasts and hepatocytes that exhibited alterations in nuclear parameters, cell permeability, mitochondria function, and apoptosis using known reference control compounds and an eight-point dose curve. Subpopulation analysis with additional bioprobe sets can provide a powerful means of addressing differential cell and tissue susceptibilities during compound profiling. Our data show that the HepatoPac is amendable for HCS imaging applications and provides a unique approach for studying hepatotoxicity over prolonged periods of time.


Beyond intercalation-based Li-ion batteries: the state of the art and challenges of electrode materials reacting through conversion reactions.
Despite the imminent commercial introduction of Li-ion batteries in electric drive vehicles and their proposed use as enablers of smart grids based on renewable energy technologies, an intensive quest for new electrode materials that bring about improvements in energy density, cycle life, cost, and safety is still underway. This Progress Report highlights the recent developments and the future prospects of the use of phases that react through conversion reactions as both positive and negative electrode materials in Li-ion batteries. By moving beyond classical intercalation reactions, a variety of low cost compounds with gravimetric specific capacities that are two-to-five times larger than those attained with currently used materials, such as graphite and LiCoO(2), can be achieved. Nonetheless, several factors currently handicap the applicability of electrode materials entailing conversion reactions. These factors, together with the scientific breakthroughs that are necessary to fully assess the practicality of this concept, are reviewed in this report.


Prioritization of Chicken Meat Processing Interventions on the Basis of Reducing the Salmonella Residual Relative Risk.
Protecting public health by controlling Salmonella in chicken meat products continues to be a challenge to both industry and policymakers. Studies evaluating the combined use of commercially available antimicrobial interventions are scarce. The aim of this work was to develop a risk-based prioritization framework to rank chicken meat processing interventions that achieve the greatest Salmonella relative risk reduction. A baseline model characterizing the current U.S. broiler industry food safety intervention practices was created from direct observation of processes and expert elicitation. Results showed the combination of chlorine at the bird wash station and peroxyacetic acid at the on-line reprocessing and chill stages as the most common U.S. processing scenario. Irradiation at packaging and acidified sodium chlorite at evisceration were the most effective single processing interventions (98.8 and 91.6% risk reduction, respectively); however, no single intervention was able to comply with the current Food Safety and Inspection Service Salmonella postchill performance standards. The combination of peroxyacetic acid in at least one of the chicken processing stages with the current set of U.S. baseline interventions achieved >99% Salmonella relative risk reduction and ensured Food Safety and Inspection Service compliance. Adding more than one intervention to the U.S. current practice did not enhance (<2%) the overall Salmonella risk reduction. This study can help poultry processors to prioritize food safety interventions to maximize Salmonella reduction and public health protection.


A habenula-insular circuit encodes the willingness to act.
The decision that it is worth doing something rather than nothing is a core yet understudied feature of voluntary behaviour. Here we study "willingness to act", the probability of making a response given the context. Human volunteers encountered opportunities to make effortful actions in order to receive rewards, while watching a movie inside a 7 T MRI scanner. Reward and other context features determined willingness-to-act. Activity in the habenula tracked trial-by-trial variation in participants' willingness-to-act. The anterior insula encoded individual environment features that determined this willingness. We identify a multi-layered network in which contextual information is encoded in the anterior insula, converges on the habenula, and is then transmitted to the supplementary motor area, where the decision is made to either act or refrain from acting via the nigrostriatal pathway.


Roof-harvested rainwater for potable purposes: application of solar collector disinfection (SOCO-DIS).
The efficiency of solar disinfection (SODIS), recommended by the World Health Organization, has been determined for rainwater disinfection, and potential benefits and limitations discussed. The limitations of SODIS have now been overcome by the use of solar collector disinfection (SOCO-DIS), for potential use of rainwater as a small-scale potable water supply, especially in developing countries. Rainwater samples collected from the underground storage tanks of a rooftop rainwater harvesting (RWH) system were exposed to different conditions of sunlight radiation in 2-L polyethylene terephthalate bottles in a solar collector with rectangular base and reflective open wings. Total and fecal coliforms were used, together with Escherichia coli and heterotrophic plate counts, as basic microbial and indicator organisms of water quality for disinfection efficiency evaluation. In the SOCO-DIS system, disinfection improved by 20-30% compared with the SODIS system, and rainwater was fully disinfected even under moderate weather conditions, due to the effects of concentrated sunlight radiation and the synergistic effects of thermal and optical inactivation. The SOCO-DIS system was optimized based on the collector configuration and the reflective base: an inclined position led to an increased disinfection efficiency of 10-15%. Microbial inactivation increased by 10-20% simply by reducing the initial pH value of the rainwater to 5. High turbidities also affected the SOCO-DIS system; the disinfection efficiency decreased by 10-15%, which indicated that rainwater needed to be filtered before treatment. The problem of microbial regrowth was significantly reduced in the SOCO-DIS system compared with the SODIS system because of residual sunlight effects. Only total coliform regrowth was detected at higher turbidities. The SOCO-DIS system was ineffective only under poor weather conditions, when longer exposure times or other practical means of reducing the pH were required for the treatment of stored rainwater for potable purposes.


HIV prevention for people who use substances: evidence-based strategies.
Evidence-based strategies to guide HIV prevention for people who use substances can be grouped into approaches that lower infectiousness among substance users living with HIV and those that prevent HIV acquisition among those who are uninfected. Dramatic successes in HIV prevention involving access to antiretroviral therapy (ART), opioid substitution therapies, and needle and syringe exchange programs have reduced both prevalence and incidence in the United States for people who use injection drugs, and modeling studies suggest that scale-up of these approaches will have a parallel impact worldwide. Medical HIV-prevention strategies that reduce infectiousness ("treatment as prevention" or early ART initiation) and that block HIV acquisition (pre-exposure prophylaxis, post-exposure prophylaxis) can constitute key elements of novel combination HIV-prevention approaches to the goals of reducing infectiousness and reducing acquisition of HIV among people who use substances. For individuals who use substances but do not inject, drug dependence treatments as HIV prevention have a meager evidence-base, with most consistent findings being reduction of sexual transmission behaviors that correspond with reductions in substance use, though not with prevention of HIV transmission. This approach may have value, however, when working with groups of substance users who face high rates of HIV prevalence and incidence. Some evidence exists to support HIV prevention interventions that target reduction of sexual risk behaviors in the setting of active stimulant use.


Investigations of the Copper Peptide Hepcidin-25 by LC-MS/MS and NMR.
Hepcidin-25 was identified as the main iron regulator in the human body, and it by binds to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as the ATCUN (amino-terminal Cu(II)- and Ni(II)-binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the complex formed between hepcidin-25 and copper could reveal insight into its biological role. The present work focuses on metal-bound hepcidin-25 that can be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25 achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry (MS/MS), high-resolution mass spectrometry (HRMS)) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a three-dimensional (3D) model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.


A rare case of Diffuse Alveolar Hemorrhage (DAH) due to warfarin toxicity.
Warfarin is one of the most frequently used anticoagulant agents in the clinic. The most important adverse effect of warfarin is hemorrhage of vital organs, such as lung and brain. Diffuse Alveolar Hemorrhage (DAH) is a rare clinical condition which occurs due to variety of medical disorders. Although it's rarely reported, DAH can be a result of coagulopathy prompted by warfarin therapy. In this study we present a case of DAH, caused by warfarin toxicity which referred to the hospital with non-specific respiratory symptoms. A 41-year-old female patient referred to the hospital complaining of shortness of breath, cough and dizziness. She had been taking warfarin due to mitral valve replacement for the past 10 years. Her recent symptoms began shortly after taking amoxicillin, a few days before admission. Early clinical examination and paraclinical studies reveal DAH as the cause of respiratory symptoms. The patient was then intubated and received fresh frozen plasma, packed cells and oral vitamin K. Laboratory findings apart from increased INR, PT, ESR and CRP were all within normal range. After the initiation of treatment patient's INR decreased and her clinical condition improved. Follow-up CT-Scan and bronchoscopy also confirmed resolving DAH. The usage of warfarin in anticoagulation should be closely monitored due to its narrow therapeutic window and other factors, including its interaction with other medications such as antibiotics. Warfarin toxicity can lead to DAH, a life-threatening condition which can be presented with non-specific symptoms and deteriorate patient's clinical condition in a short time. Therefore, it is of utmost importance to watch closely for primary symptoms of such rare incident in patients under warfarin therapy and initiate treatment as soon as possible, to prevent mortality.


Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages.
Components of Trypanosoma cruzi able to induce the production of IL-12 and other proinflammatory cytokines by macrophages were identified. Murine inflammatory macrophages were cultured with live parasites or with cellular components from different developmental forms of T. cruzi (i.e., trypomastigotes, amastigotes, metacyclic trypomastigotes, and epimastigotes), and the cytokine levels were measured after 24 and 48 h. Our results indicate that live trypomastigotes or live amastigotes (but not live epimastigotes or live metacyclic trypomastigotes) as well as trypomastigote extracts (but not extracts derived from epimastigotes) induce IL-12 and TNF-alpha synthesis by macrophages. Such biological activity is enhanced in membrane preparations from trypomastigotes. Further enrichment of the trypomastigote-derived monokine-inducing factor was obtained by solvent extraction and hydrophobic-interaction chromatography. The resultant purified molecules are a family of closely related glycoconjugates with predominant species at 70 to 80 and 120 to 200 kDa. These molecules are composed of carbohydrate chains O-linked to a polypeptide backbone that is anchored to the trypomastigote membrane via a glycosylphosphatidylinositol structure. The trypomastigote-derived glycoconjugates are active in inducing cytokine synthesis by macrophages at concentrations of 100 ng/ml. These effects are highly potentiated by IFN-gamma. Mapping of the glycoconjugate molecules to characterize the structural requirements for macrophage activation suggested that nonsaturated acyl fatty acid chains and periodate-sensitive units from the glycosylphosphatidylinositol anchor are important elements for the infective trypomastigote form to initiate cytokine synthesis by macrophages.


Adapting the Finetech-Brindley Sacral Anterior Root Stimulator for Bioelectronic Medicine.
The Finetech-Brindley Sacral Anterior Root Stimulator (SARS) is a low cost and reliable system. The architecture has been used for various bioelectric treatments, including several thousand implanted systems for restoring bladder function following spinal cord injury (SCI). Extending the operational frequency range would expand the capability of the system; enabling, for example, the exploration of eliminating the rhizotomy through an electrical nerve block. The distributed architecture of the SARS system enables stimulation parameters to be adjusted without modifying the implant design or manufacturing. To explore the design degrees-of-freedom, a circuit simulation was created and validated using a modified SARS system that supported stimulation frequencies up to 600 Hz. The simulation was also used to explore high frequency (up to 30kHz) behaviour, and to determine the constraints on charge delivered at the higher rates. A key constraint found was the DC blocking capacitors, designed originally for low frequency operation, not fully discharging within a shortened stimulation period. Within these current implant constraints, we demonstrate the potential capability for higher frequency operation that is consistent with presynaptic stimulation block, and also define targeted circuit improvements for future extension of stimulation capability.


Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor.
Jak3 is a protein tyrosine kinase that is associated with the shared gamma chain of receptors for cytokines IL2, IL4, IL7, IL9, and IL13. We have discovered that a pyridone-containing tetracycle (6) may be prepared from trisubstituted imidazole (5) in high yield by irradiation with >350 nm light. Compound 6 inhibits Jak3 with K(I)=5 nM; it also inhibits Jak family members Tyk2 and Jak2 with IC(50)=1 nM and murine Jak1with IC(50)=15 nM. Compound 6 was tested as an inhibitor of 21 other protein kinases; it inhibited these kinases with IC(50)s ranging from 130 nM to >10 microM. Compound 6 also blocks IL2 and IL4 dependent proliferation of CTLL cells and inhibits the phosphorylation of STAT5 (an in vivo substrate of the Jak family) as measured by Western blotting.


Deep vision: an in-trawl stereo camera makes a step forward in monitoring the pelagic community.
Ecosystem surveys are carried out annually in the Barents Sea by Russia and Norway to monitor the spatial distribution of ecosystem components and to study population dynamics. One component of the survey is mapping the upper pelagic zone using a trawl towed at several depths. However, the current technique with a single codend does not provide fine-scale spatial data needed to directly study species overlaps. An in-trawl camera system, Deep Vision, was mounted in front of the codend in order to acquire continuous images of all organisms passing. It was possible to identify and quantify of most young-of-the-year fish (e.g. Gadus morhua, Boreogadus saida and Reinhardtius hippoglossoides) and zooplankton, including Ctenophora, which are usually damaged in the codend. The system showed potential for measuring the length of small organisms and also recorded the vertical and horizontal positions where individuals were imaged. Young-of-the-year fish were difficult to identify when passing the camera at maximum range and to quantify during high densities. In addition, a large number of fish with damaged opercula were observed passing the Deep Vision camera during heaving; suggesting individuals had become entangled in meshes farther forward in the trawl. This indicates that unknown numbers of fish are probably lost in forward sections of the trawl and that the heaving procedure may influence the number of fish entering the codend, with implications for abundance indices and understanding population dynamics. This study suggests modifications to the Deep Vision and the trawl to increase our understanding of the population dynamics.


Elevated pCO2 affects tissue biomass composition, but not calcification, in a reef coral under two light regimes.
Ocean acidification (OA) is predicted to reduce reef coral calcification rates and threaten the long-term growth of coral reefs under climate change. Reduced coral growth at elevated pCO2 may be buffered by sufficiently high irradiances; however, the interactive effects of OA and irradiance on other fundamental aspects of coral physiology, such as the composition and energetics of coral biomass, remain largely unexplored. This study tested the effects of two light treatments (7.5 versus 15.7 mol photons m-2 d-1) at ambient or elevated pCO2 (435 versus 957 µatm) on calcification, photopigment and symbiont densities, biomass reserves (lipids, carbohydrates, proteins), and biomass energy content (kJ) of the reef coral Pocillopora acuta from Kāne'ohe Bay, Hawai'i. While pCO2 and light had no effect on either area- or biomass-normalized calcification, tissue lipids gdw-1 and kJ gdw-1 were reduced 15% and 14% at high pCO2, and carbohydrate content increased 15% under high light. The combination of high light and high pCO2 reduced protein biomass (per unit area) by approximately 20%. Thus, under ecologically relevant irradiances, P. acuta in Kāne'ohe Bay does not exhibit OA-driven reductions in calcification reported for other corals; however, reductions in tissue lipids, energy content and protein biomass suggest OA induced an energetic deficit and compensatory catabolism of tissue biomass. The null effects of OA on calcification at two irradiances support a growing body of work concluding some reef corals may be able to employ compensatory physiological mechanisms that maintain present-day levels of calcification under OA. However, negative effects of OA on P. acuta biomass composition and energy content may impact the long-term performance and scope for growth of this species in a high pCO2 world.


Distribution of low-density lipoprotein-bound low-molecular-weight thiols: a new analytical approach.
We have recently demonstrated that low-density lipoprotein (LDL) apoprotein is able to bind the most concentrated plasma thiols such as cysteine, cysteinylglycine, and homocysteine by disulfide linkage. However, the LIF CE assay employed to measure linked thiols was not sensitive enough to verify whether low concentrated plasma thiols as glutathione and glutamylcysteine are also linked to apoprotein. By modifying sample treatment and electrophoretic parameters we set up a new method with an LOQ of about 1.5 nmol/L, by which we demonstrate that LDL apoprotein binds all physiological plasma thiols. The increased sensitivity was obtained by drying released apoB thiols after reduction treatment, dissolving them directly in a low volume of derivatization buffer and decreasing the dilution factor of derivatized sample before CE injection. Moreover, by increasing the concentration of the electrolyte buffer, we improved the selectivity of peaks, in particular between glutathione (GSH) and the impurity peak derived from unreacted 5-iodoacetamidofluorescein, which in the previous electrophoretic conditions were overlapped. The method optimization, reached by searching the best combination between sample matrix and CE run buffer, is fully described. Given the potential pathologic significance of protein thiolation, the proposed method may be useful to understand the mechanisms and the balances that regulate the interaction between thiols and -SH free groups of proteins.


A new crystal structure of deoxyhypusine synthase reveals the configuration of the active enzyme and of an enzyme.NAD.inhibitor ternary complex.
Deoxyhypusine synthase catalyzes the first step in the two-step post-translational synthesis of hypusine, which is uniquely present in eukaryotic initiation factor 5A (eIF5A). Deoxyhypusine synthase and eIF5A are conserved throughout the eukaryotic kingdom, and both are essential for cell proliferation and survival. A previous study (Liao, D. I., Wolff, E. C., Park, M. H., and Davies, D. R. (1998) Structure 6, 23-32) of human deoxyhypusine synthase revealed four active sites of the homotetrameric enzyme located within deep tunnels. These Form I crystals were obtained under conditions of acidic pH and high ionic strength and likely contain an inactive enzyme. Each active-site entrance is blocked by a ball-and-chain motif composed of a region of extended structure capped by a two-turn alpha-helix. We report here at 2.2 A a new Form II crystal of the deoxyhypusine synthase:NAD holoenzyme grown at low ionic strength and pH 8.0, near the optimal pH for enzymatic activity. The ball-and-chain motif could not be detected in the electron density, suggesting that it swings freely and thus it no longer obstructs the active-site entrance. The deoxyhypusine synthase competitive inhibitor N(1)-guanyl-1,7-diaminoheptane (GC(7))is observed bound within the putative active site of the enzyme in the new crystal form (Form II) after exposure to the inhibitor. This first structure of a deoxyhypusine synthase.NAD.inhibitor ternary complex under physiological conditions now provides a structural context to discuss the results of previous biochemical investigations of the deoxyhypusine synthase reaction mechanism. This structure also provides a basis for the development of improved inhibitors and antiproliferative agents.


Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats.
Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction. We examined myocardia in Wistar rats after 10 weeks of HFD (45 kcal% fat, n=6) or standard diet (SD, n=6). Echocardiography, histomorphologic analysis, and electron microscopy were performed. The expression levels of mitochondrial oxidative phosphorylation (OXPHOS) subunit genes, peroxisome-proliferator-activated receptor γ co-activator-1α (PGC1α) and anti-oxidant enzymes were assessed. Markers of oxidative stress damage, mitochondrial DNA copy number and myocardial ATP level were also examined. After 10 weeks, the body weight of the HFD group (349.6±22.7 g) was significantly higher than that of the SD group (286.8±14.9 g), and the perigonadal and epicardial fat weights of the HFD group were significantly higher than that of the SD group. Histomorphologic and electron microscopic images were similar between the two groups. However, in the myocardium of the HFD group, the expression levels of OXPHOS subunit NDUFB5 in complex I and PGC1α, and the mitochondrial DNA copy number were decreased and the oxidative stress damage marker 8-hydroxydeoxyguanosine was increased, accompanied by reduced ATP levels. Diastolic dysfunction was accompanied by the mitochondrial abnormality and reduced ATP levels in the myocardium of 10 weeks-HFD-induced rats.


Health Gain, Cost Impacts, and Cost-Effectiveness of a Mass Media Campaign to Promote Smartphone Apps for Physical Activity: Modeling Study.
Physical activity smartphone apps are a promising strategy to increase population physical activity, but it is unclear whether government mass media campaigns to promote these apps would be a cost-effective use of public funds. We aimed to estimate the health impacts, costs, and cost-effectiveness of a one-off national mass media campaign to promote the use of physical activity apps. We used an established multistate life table model to estimate the lifetime health gains (in quality-adjusted life years [QALYs]) that would accrue if New Zealand adults were exposed to a one-off national mass media campaign to promote physical activity app use, with a 1-year impact on physical activity, compared to business-as-usual. A health-system perspective was used to assess cost-effectiveness. and a 3% discount rate was applied to future health gains and health system costs. The modeled intervention resulted in 28 QALYs (95% uncertainty interval [UI] 8-72) gained at a cost of NZ $81,000/QALY (2018 US $59,500; 95% UI 17,000-345,000), over the remaining life course of the 2011 New Zealand population. The intervention had a low probability (20%) of being cost-effective at a cost-effectiveness threshold of NZ $45,000 (US $32,900) per QALY. The health impact and cost-effectiveness of the intervention were highly sensitive to assumptions around the maintenance of physical activity behaviors beyond the duration of the intervention. A mass media campaign to promote smartphone apps for physical activity is unlikely to generate much health gain or be cost-effective at the population level. Other investments to promote physical activity, particularly those that result in sustained behavior change, are likely to have greater health impacts.


Evidence for a curvilinear relationship between posttraumatic growth and posttrauma depression and PTSD in assault survivors.
Two studies of assault survivors (Ns = 180, 70) examined associations between posttraumatic growth (PTG) and posttrauma psychopathology. Both studies found significant curvilinear associations between PTG and posttraumatic stress disorder, whereas only Study 1 found a curvilinear association between PTG and depression symptom severity. Survivors with no or high growth levels reported fewer symptoms than those who reported moderate growth. Study 1 also investigated potential PTG predictors. Non-Caucasian ethnicity, religiousness, peritraumatic fear, shame, and ruminative thinking style, assessed at 2 weeks, predicted growth at 6 months. Posttraumatic growth may thus be most relevant in trauma survivors who attach enduring significance to the trauma for their lives and show initial distress. Moderate levels of PTG do not seem to ameliorate posttrauma psychopathology.


Gene selection for multiclass prediction by weighted Fisher criterion.
Gene expression profiling has been widely used to study molecular signatures of many diseases and to develop molecular diagnostics for disease prediction. Gene selection, as an important step for improved diagnostics, screens tens of thousands of genes and identifies a small subset that discriminates between disease types. A two-step gene selection method is proposed to identify informative gene subsets for accurate classification of multiclass phenotypes. In the first step, individually discriminatory genes (IDGs) are identified by using one-dimensional weighted Fisher criterion (wFC). In the second step, jointly discriminatory genes (JDGs) are selected by sequential search methods, based on their joint class separability measured by multidimensional weighted Fisher criterion (wFC). The performance of the selected gene subsets for multiclass prediction is evaluated by artificial neural networks (ANNs) and/or support vector machines (SVMs). By applying the proposed IDG/JDG approach to two microarray studies, that is, small round blue cell tumors (SRBCTs) and muscular dystrophies (MDs), we successfully identified a much smaller yet efficient set of JDGs for diagnosing SRBCTs and MDs with high prediction accuracies (96.9% for SRBCTs and 92.3% for MDs, resp.). These experimental results demonstrated that the two-step gene selection method is able to identify a subset of highly discriminative genes for improved multiclass prediction.