Pharmacological differentiation between intracellular calcium pump isoforms.
We studied the Ca(2+)-ATPase isoforms of sarco/endoplasmic reticulum (SERCA) derived from cerebellum, cardiac muscle, and skeletal muscle. The Mg2+ dependence varied among the three enzyme preparations. The Ca2+ transport in skeletal muscle vesicles, but not in cerebellar or cardiac vesicles, was activated by free Mg2+ concentrations varying from 0.1 to 0.3 mM. Concentrations of Mg2+ of > 1 mM inhibited Ca2+ transport in all three vesicle preparations but with more pronounced effect in cerebellar and cardiac vesicles. At 10-80 microM, trifluoperazine activated Ca2+ uptake in cerebellar and cardiac vesicles but not in skeletal muscle vesicles. The activation was due to an increase in the coupling ratio between Ca2+ transport and ATP hydrolysis and was observed only in the presence of ATP concentrations of > 100 microM. The Ca2+ transport in all three vesicle preparations was inhibited by trifluoperazine concentrations of > 100 microM. The inhibition promoted by trifluoperazine was prevented by the addition of dimethylsulfoxide (10% v/v) to the medium. The Ca2+ efflux from loaded vesicles was increased by arsenate and even more by trifluoperazine. In skeletal muscle vesicles, the efflux promoted by arsenate was several-fold faster than that promoted in vesicles derived from cerebellum or cardiac muscle. In skeletal muscle, the enhancement of Ca2+ efflux promoted by both arsenate and trifluoperazine was antagonized by thapsigargin, Ca2+, Mg2+, and K+. These agents partly antagonized the enhancement of Ca2+ efflux promoted by trifluoperazine in cardiac vesicles but had little or no effect in the cerebellar vesicles. Finally, Mg.Pi and Mg.ATP, the two substrates that phosphorylate the Ca(2+)-ATPase, antagonized the effect of trifluoperazine in all of the preparations tested. The concentration of ATP needed was in the same range as that of the second K(m) value for ATP (50-300 microM) of the SERCA isoforms. The results indicate that the effect of the drugs on the cytosolic Ca2+ homeostasis may vary depending on the target tissue.


Online access to MEDLINE in clinical settings. A study of use and usefulness.
We introduced self-service access to the medical literature database, MEDLINE, into clinical settings to assess the frequency, patterns, purposes, and success of use. Longitudinal descriptive study. Inpatient and outpatient services of a university medical center. All trainees and attending staff working at the service sites were invited to participate; 158 (84%) did so. Free online access was provided to MEDLINE through GRATEFUL MED software. Participants were offered a 2-hour introduction to online searching and 2 hours of free search time. For each search, a computer program requested identification of the user and the question to be addressed. Search transactions were recorded automatically. Interviews were conducted after a random sample of searches, and search questions were given to more expert searchers to run for comparison with the original. Eighty-one percent of participants did searches on study computers, at a mean rate of 2.7 searches per month. On comparison searches, participants retrieved 55% of the number of relevant articles retrieved by reference librarians (P = 0.024) and 50% more irrelevant articles (P less than 0.001). Forty-seven percent of searches on patient problems affected clinical decisions, but often on scanty information. MEDLINE searching from clinical settings is feasible with brief training and affects clinical decisions. However, inexperienced searchers miss many relevant citations and search inefficiently. Further studies are needed to assess the impact of searching on physician performance and patient care.


Acute kidney injury in Hemiscorpius lepturus scorpion stung children: Risk factors and clinical features.
Acute kidney injury (AKI) is frequently seen in Hemiscorpius lepturus scorpion stung children. We have previously reported several victims with hemolytic uremic syndrome (HUS) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency. Hence, we conducted this study to identify predictive factors and clinical features of AKI in H. lepturus scorpion stung patients. We included all 215 H. lepturus scorpion stung children with no previous renal diseases in two groups (with and without AKI) and compared them based on their clinical and laboratory findings. AKI was found in 27.4% of patients, they were significantly younger and with lower body weight (P = 0.006, P = 0.011, respectively). There was a significant difference between groups with and without AKI in findings such as fever (P = 0.003), hypertension (P <0.001), hemolytic anemia (P <0.001), thrombocytopenia (P <0.001), massive proteinuria (P <0.001), hemoglobinuria (P <0.001), pyuria (P <0.001), and hematuria (P = 0.004). HUS was in 5.5% and disseminated intravascular coagulation in 14.6% which had a significant association with AKI (P <0.001).There were several independent predictors for AKI in a multivariate regression model including thrombocytopenia (P = 0.002), pyuria (P = 0.01), proteinuria (P =0.01), and fever (P = 0.02). Hemodialysis was performed in four patients but kidney function improved in all patients and there was no findings of renal impairment after three months follow-up. We found several predictors for AKI in children following H. lepturus scorpion sting including younger age, delay in receiving medical care, pigmenturia, microangiopathic hemolytic anemia, proteinuria, and pyuria.


Preventive care guidelines: 1991. American College of Physicians. Canadian Task Force on the Periodic Health Examination. United States Preventive Services Task Force.
Clinicians increasingly are urged to integrate preventive services into their clinical practices. To facilitate this process, several groups have developed practice guidelines for preventing disease in asymptomatic patients. In this paper, we compare and contrast preventive guidelines from the American College of Physicians (ACP), the Canadian Task Force on the Periodic Health Examination (CTF), the United States Preventive Services Task Force (USPSTF), and other well-known authorities. We chose these groups because they based their recommendations on explicit methods that include critical appraisal of the pertinent literature. Recommendations from these authorities usually are consistent with each other. Moreover, the ACP, CTF, and USPSTF all favor a shift away from the relatively simple classification of patients by age and sex for general preventive interventions to the more complex stratification of patients by additional risk factors and the formulation of a selective prevention strategy that is specific to each risk profile. Some guidelines, particularly the criteria used to define patients who are at increased risk for preventable disease and who should have more intensive surveillance, are difficult to interpret. Further research is needed to address some areas of disagreement and ambiguity. In addition, new tools must be developed to help physicians apply preventive guidelines, particularly those that require noting many patient-specific characteristics.


MicroRNA-mRNA interactions underlying colorectal cancer molecular subtypes.
Colorectal cancer (CRC) transcriptional subtypes have been recently identified by gene expression profiling. Here we describe an analytical pipeline, microRNA master regulator analysis (MMRA), developed to search for microRNAs potentially driving CRC subtypes. Starting from a microRNA-mRNA tumour expression data set, MMRA identifies candidate regulator microRNAs by assessing their subtype-specific expression, target enrichment in subtype mRNA signatures and network analysis-based contribution to subtype gene expression. When applied to a CRC data set of 450 samples, assigned to subtypes by 3 different transcriptional classifiers, MMRA identifies 24 candidate microRNAs, in most cases downregulated in the stem/serrated/mesenchymal (SSM) poor prognosis subtype. Functional validation in CRC cell lines confirms downregulation of the SSM subtype by miR-194, miR-200b, miR-203 and miR-429, which share target genes and pathways mediating this effect. These results show that, by combining statistical tests, target prediction and network analysis, MMRA effectively identifies microRNAs functionally associated to cancer subtypes.


Diquafosol sodium ophthalmic solution for the treatment of dry eye: clinical evaluation and biochemical analysis of tear composition.
To evaluate the clinical efficacy of 3% diquafosol sodium ophthalmic solution for dry eye, and to analyze the concentration of tear proteins and mucin-like substances after the treatment. Fifty eyes of 25 patients with dry eye syndrome were prospectively enrolled. The patients were treated with diquafosol solution at a dose of 1 drop in each eye 6 times daily for 4 weeks. The parameters of clinical efficacy were tear osmolarity, tear breakup time (BUT), fluorescein staining scores for the cornea and conjunctiva, Schirmer test values, and subjective symptoms evaluated using the ocular surface disease index (OSDI). Tears collected with Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of the total protein and the 4 major tear proteins, namely, secretory IgA, lactoferrin, lipocalin-1, lysozyme, and N-acetyl-neuraminic acid (Neu5Ac), were measured. Neu5Ac is a major sialic acid, a marker of secretory mucins. The BUT, keratoconjunctival staining scores, and Schirmer test values were improved with statistical significance after the treatment with diquafosol solution, while changes in the other parameters, including tear osmolarity, corneal staining scores, and OSDI scores were not significant. The Neu5Ac concentration was significantly increased, which was not accompanied by changes in tear proteins. Topical application of diquafosol significantly improved the clinical parameters of the BUT, keratoconjunctival staining scores, and Schirmer test values and was accompanied by increased sialic acid content in the tears of patients with dry eye.


High levels of Y-chromosome differentiation among native Siberian populations and the genetic signature of a boreal hunter-gatherer way of life.
We examined genetic variation on the nonrecombining portion of the Y chromosome (NRY) to investigate the paternal population structure of indigenous Siberian groups and to reconstruct the historical events leading to the peopling of Siberia. A set of 62 biallelic markers on the NRY were genotyped in 1432 males representing 18 Siberian populations, as well as nine populations from Central and East Asia and one from European Russia. A subset of these markers defines the 18 major NRY haplogroups (A-R) recently described by the Y Chromosome Consortium (YCC 2002). While only four of these 18 major NRY haplogroups accounted for -95% of Siberian Y-chromosome variation, native Siberian populations differed greatly in their haplogroup composition and exhibited the highest phiST value for any region of the world. When we divided our Siberian sample into four geographic regions versus five major linguistic groupings, analyses of molecular variance (AMOVA) indicated higher phiST and phiCT values for linguistic groups than for geographic groups. Mantel tests also supported the existence of NRY genetic patterns that were correlated with language, indicating that language affiliation might be a better predictor of the genetic affinity among Siberians than their present geographic position. The combined results, including those from a nested cladistic analysis, underscored the important role of directed dispersals, range expansions, and long-distance colonizations bound by common ethnic and linguistic affiliation in shaping the genetic landscape of Siberia. The Siberian pattern of reduced haplogroup diversity within populations combined with high levels of differentiation among populations may be a general feature characteristic of indigenous groups that have small effective population sizes and that have been isolated for long periods of time.


Diagnosis and management of renal dysfunction in patients with cirrhosis.
Introduction: Renal dysfunction commonly occurs in patients with cirrhosis and is typically associated with poor prognosis. Several pathophysiologic mechanisms are responsible for renal disease in these patients, prompt identification permits individualized management.Areas covered: Pathophysiology, evaluation and differential diagnosis, management and prognosis of renal disease in patients with cirrhosis. Special focus on management of hepatorenal syndrome and indications for simultaneous liver-kidney transplantation.Literature search methodology: a detailed literature search was performed using PubMed without date restrictions. Published guidelines and position papers were also used and cross-referenced to identify additional studies.Expert opinion: The prognostic significance of renal dysfunction in patients with cirrhosis is highlighted by the inclusion of serum creatinine in the model for end-stage liver disease (MELD). Both acute and chronic renal dysfunction result in increased mortality in patients with cirrhosis, although there are marked differences related to the etiology of renal disease. Early recognition and prompt intervention determined by the most likely etiology are key in the management of these patients. Simultaneous liver-kidney transplantation improves patient survival compared to isolated liver transplantation in patients with cirrhosis and persistent renal impairment; however, selection of candidates must be judicious and individualized due to the ongoing shortage of donor kidneys.


Mesenchymal stem cells for sensorineural hearing loss: a systematic review of preclinical studies.
Sensorineural hearing loss (SNHL) is the most common form of hearing loss that is routinely treated with hearing aids or cochlear implants. Advances in regenerative medicine have now led to animal studies examining the possibility of restoring injured hair cells with mesenchymal stem/stromal cell (MSC) administration. We conducted a systematic review and meta-analysis to collate the existing preclinical literature evaluating MSCs as a treatment for SNHL and quantify the effect of MSCs on functional hearing. Our protocol was published online on CAMARADES. Searches were conducted in four medical databases by two independent investigators. Twelve studies met inclusion and were evaluated for risk of bias using SYRCLE. Rodent models were commonly used (n = 8, 66%), while auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were the most frequent measures assessing hearing loss. MSCs were derived from multiple tissue sources, including bone marrow, adipose tissue, and umbilical cord blood and the dose ranged from 4 × 103 to 1 × 107 cells. Treatment with MSCs resulted in an improvement in ABR and DPOAE (mean difference-15.22, + 9.10, respectively). Despite high heterogeneity and multiple "unclear" domains in the risk of bias, this review provides evidence that MSCs may have a beneficial effect in hearing function.


A synthesis of plant invasion effects on biodiversity across spatial scales.
Invasive plant species are typically thought to pose a large threat to native biodiversity, and local-scale studies typically confirm this view. However, plant invaders rarely cause regional extirpations or global extinctions, causing some to suggest that invasive species' influence on native biodiversity may not be so dire. We aim to synthesize the seemingly conflicting literature in plant invasion biology by evaluating the effects of invasive plant species across spatial scales. We first conducted a meta-analysis on the effects of invasive plants on the species richness of invaded communities across a range of spatial extents. We then discuss studies that consider the role of invasive plants on regional spatial scales for which such meta-analyses are not possible. Finally, we develop a conceptual framework to synthesize the influence of invasive species across spatial scales by explicitly recognizing how invasive species alter species-occupancy distributions. We found a negative relationship between the spatial extent of the study and the effect size of invasive plants on species richness. Our simulation models suggest that this result can occur if invaders, either proportionately or disproportionately, reduce the occupancy of common species to a greater degree than rare species. Future studies should consider the influence of invaders on the abundance and occupancy-level changes in native species to inform how invasive plants will influence native species richness relationships across spatial scales. This approach will allow greater predictive ability for forecasting changes in biodiversity in the face of anthropogenic biological invasions and will inform invasive species management and restoration.


Selective Synergism Created by Interactive Nacre Framework-Associated Proteins Possessing EGF and vWA Motifs: Implications for Mollusk Shell Formation.
In the nacre layer of the Pinctada fucata oyster shell there exists a multimember proteome, known as the framework family, which regulates the formation of the aragonite mesoscale tablets and participates in the creation of an organic coating around each tablet. Several approaches have been developed to understand protein-associated mechanisms of nacre formation, yet we still lack insight into how protein ensembles or proteomes manage nucleation and crystal growth. To provide additional insights we have created a proportionally defined combinatorial model consisting of two recombinant framework proteins, r-Pif97 (containing a von Willebrand Factor Type A domain (vWA)) and r-n16.3 (containing an EGF-like domain), whose individual in vitro mineralization functionalities are distinct from one another. We find that at 1:1 molar ratios r-Pif97 and r-n16.3 exhibit little or no synergistic activity regarding modifying existing calcite crystals. However, during the early stages of nucleation in solution, we note synergistic effects on nucleation kinetics and ACC formation/stability (via dehydration) that are not observed for the individual proteins. This selective synergism is generated by Ca2+-mediated protein-protein interactions (∼4 molecules of r-n16.3 per 1 molecule of r-Pif97) which lead to the formation of nucleation-responsive hybrid hydrogel particles in solution. Interestingly, in the absence of Ca2+ there are no significant interactions occurring between the two proteins. This unique behavior of the framework-associated n16.3 and Pif97 proteins suggests that the Asp/Glu-containing regions of the vWA and EGF-like domains may play a role in both nacre matrix formation and mineralization.


Targeted Removal of Bioavailable Metal as a Detoxification Strategy for Carbon Nanotubes.
There is substantial evidence for toxicity and/or carcinogenicity upon inhalation of pure transition metals in fine particulate form. Carbon nanotube catalyst residues may trigger similar metal-mediated toxicity, but only if the metal is bioavailable and not fully encapsulated within fluid-protective carbon shells. Recent studies have documented the presence of bioavailable iron and nickel in a variety of commercial as-produced and vendor "purified" nanotubes, and the present article examines techniques to avoid or remove this bioavailable metal. First, data are presented on the mechanisms potentially responsible for free metal in "purified" samples, including kinetic limitations during metal dissolution, the re-deposition or adsorption of metal on nanotube outer surfaces, and carbon shell damage during last-step oxidation or one-pot purification. Optimized acid treatment protocols are presented for targeting the free metal, considering the effects of acid strength, composition, time, and conditions for post-treatment water washing. Finally, after optimized acid treatment, it is shown that the remaining, non-bioavailable (encapsulated) metal persists in a stable and biologically unavailable form up to two months in an in vitro biopersistence assay, suggesting that simple removal of bioavailable (free) metal is a promising strategy for reducing nanotube health risks.


Traumatic Brain Injury in Mice Induces Acute Bacterial Dysbiosis Within the Fecal Microbiome.
The secondary injury cascade that is activated following traumatic brain injury (TBI) induces responses from multiple physiological systems, including the immune system. These responses are not limited to the area of brain injury; they can also alter peripheral organs such as the intestinal tract. Gut microbiota play a role in the regulation of immune cell populations and microglia activation, and microbiome dysbiosis is implicated in immune dysregulation and behavioral abnormalities. However, changes to the gut microbiome induced after acute TBI remains largely unexplored. In this study, we have investigated the impact of TBI on bacterial dysbiosis. To test the hypothesis that TBI results in changes in microbiome composition, we performed controlled cortical impact (CCI) or sham injury in male 9-weeks old C57BL/6J mice. Fresh stool pellets were collected at baseline and at 24 h post-CCI. 16S rRNA based microbiome analysis was performed to identify differential abundance in bacteria at the genus and species level. In all baseline vs. 24 h post-CCI samples, we evaluated species-level differential abundances via clustered and annotated operational taxonomic units (OTU). At a high-level view, we observed significant changes in two genera after TBI, Marvinbryantia, and Clostridiales. At the species-level, we found significant decreases in three species (Lactobacillus gasseri, Ruminococcus flavefaciens, and Eubacterium ventriosum), and significant increases in two additional species (Eubacterium sulci, and Marvinbryantia formatexigens). These results pinpoint critical changes in the genus-level and species-level microbiome composition in injured mice compared to baseline; highlighting a previously unreported acute dysbiosis in the microbiome after TBI.


Locality and universality in gyrokinetic turbulence.
The nature of nonlinear interactions in gyrokinetic turbulence, driven by the ion-temperature gradient instability, is investigated using direct numerical simulations in toroidal flux tube geometry. To account for the level of separation existing between scales involved in an energetic interaction, the degree of locality of the free energy scale flux is analyzed employing Kraichnan's infrared (IR) and ultraviolet locality functions. Because of the nontrivial dissipative nature of gyrokinetic turbulence, an asymptotic level for the locality exponents, indicative of a universal dynamical regime for gyrokinetics, is not recovered and an accentuated nonlocal behavior of the IR interactions is found instead, in spite of the local energy cascade observed.


Molecular dynamics simulation study of the influence of chirality on the stability of the smectic Q liquid crystal phase.
The structure of smectic Q (SmQ) liquid crystal phase consisting of a dichiral molecule, called M7BBM7, was studied by submicrosecond molecular dynamics (MD) simulation. A detailed atomic model was used to study the stability of a model SmQ structure proposed by Levelut et al. (Levelut, A.-M.; Hallouin, E.; Bennemenn, D.; Heppke, G.; Lotzsch, D. J. Phys. II 1997, 7, 981) and its difference between (S,S)-, (S,R)-M7BBM7 and racemic mixture systems. Negative values of the fourth-rank orientational order parameter (<P4>), which characterize the model SmQ structure, were stably kept up to a 100 ns MD run only in the (S,S)-M7BBM7 system and lost in the other systems. The results correspond well to the marked chiral sensitivity in real systems where only the (S,S)-M7BBM7 system (among the three above-mentioned systems) shows the SmQ phase. Our simulation results imply that the asymmetric intramolecular potentials and resultant chirality-dependent molecular conformations are primarily responsible for keeping the negative values of <P4> and the model SmQ structure.


Advanced oxidation treatment of physico-chemically pre-treated olive mill industry effluent.
In this study, the applicability of physico-chemical methods was investigated for the pre-treatment of the olive mill effluents prior to the discharge into the common sewerage ending with a municipal wastewater treatment plant. The samples were taken from an olive oil industry operated as three-phase process located in Turkey. Various pre-treatment methods including acid craking, polyelectrolyte and lime additions were applied. Advanced oxidation study using Fenton's process was also investigated following pre-treatment by acid cracking and cationic polyelectrolyte. Acid cracking alone gave satisfactory treatment efficiencies and polyelectrolite additions to the acid-cracked samples enhanced treatment efficiency. Since a complete treatment plant is available at the end of the sewer system, results indicated that the effluents of the investigated industry could be discharged into the municipal sewerage in the case of total chemical oxygen demand (COD(tot)), suspended solid (SS) and volatile suspended solid (VSS) concentrations according to the Turkish Water Pollution Control Regulation after pre-treatment with 5 ppm anionic polyelectrolyte following acid cracking. The minimum COD(tot), SS and VSS removals were observed when raw wastewater was pre-treated with lime and the discharge standards to the municipal sewer system could not be met. Advanced oxidation with Fenton's process was applied after acid cracking and cationic polyelectrolyte treatment in order to investigate further reduction in chemical oxygen demand (COD) concentration for minimizing the influence of this industrial discharge on the existing municipal wastewater treatment plant. Results indicated that COD(tot) removal increased up to 89% from 74% after Fenton's oxidation for the acid cracked samples in which cationic polyelectrolite (10 ppm) was added.


Assessing calcium intake in postmenopausal women.
Because foods fortified with calcium are increasingly available, the calcium content of calcium-fortified foods may not be adequately captured in traditional assessments of dietary intake, such as dietary records analyzed with commercially available software. The primary objective of our study was to design and test a calcium-focused food frequency questionnaire (CFFFQ) including foods naturally rich in calcium and calcium-fortified foods. Secondary objectives were to review calcium sources and adequacy of intake in black and in white postmenopausal women. We studied a convenience sample of 46 black and 139 white postmenopausal women (mean [SD] age 69.4 [5.8] years). Participants completed a multiple-pass interview for 24-hour recall of foods eaten and the 46-item CFFFQ. The correlation between measures for total daily calcium intake was moderately strong (r = 0.53, P < .001). The CFFFQ estimated greater total daily calcium intake than did the 24-hour recall (mean [SD], 1,021 [624] mg/d vs 800 [433] mg/d, P < .001). As daily calcium intake increased, the 24-hour recall increasingly underreported calcium (r = 0.41, P < .001) compared with the CFFFQ. Cross-tabulation and Chi2 analyses found that the CFFFQ had greater specificity for lower calcium intakes. For calcium classified by food groups, there was moderate correlation for dairy (r = 0.56, P < .001) and fruits (r = 0.43, P < .001). The CFFFQ overestimated mean total calcium compared with the 24-hour recall by 221 mg/d (P < .001), including within racial groups (195 mg/d for black women, P = .04, and 229 mg/d for white women, P < .001). Dairy was the primary calcium source for both groups (55% of intake for black women and 57% of intake for white women). The CFFFQ can be used to identify postmenopausal women with inadequate calcium intakes (<800 mg/d) and to identify key sources of dietary calcium. Older black women consume less daily calcium than do older white women.


Robust links between religious/spiritual struggles, psychological distress, and well-being in a national sample of American adults.
This study is one of the first attempts to examine the relationships between religious and spiritual struggles (r/s struggles) measured comprehensively and indicators of psychological distress (i.e., depressive symptoms, generalized anxiety) and well-being (i.e., satisfaction with life, happiness) using a nationally representative sample of American adults (N = 2,208) dealing with a wide range of major life stressors. In addition, it examines the key question of whether these relationships persist after controlling for potentially confounding psychosocial/religious influences. Correlational analyses revealed that all 5 types of the r/s struggles assessed (i.e., divine, demonic, interpersonal, moral, ultimate-meaning) correlated significantly positively with both depressive symptoms and generalized anxiety, and significantly negatively with both satisfaction with life and happiness. Hierarchical regression analyses indicated that even after controlling for the effects of demographics and other potentially confounding variables (i.e., neuroticism, social isolation, religious commitment) the r/s struggle subscales added unique variance to the prediction of all 4 criterion measures. Theoretical and practical implications of the findings are offered, and the limitations of the study are discussed. (PsycINFO Database Record


Multivariate estimation of the limit of detection by orthogonal partial least squares in temperature-modulated MOX sensors.
Metal oxide semiconductor (MOX) sensors are usually temperature-modulated and calibrated with multivariate models such as partial least squares (PLS) to increase the inherent low selectivity of this technology. The multivariate sensor response patterns exhibit heteroscedastic and correlated noise, which suggests that maximum likelihood methods should outperform PLS. One contribution of this paper is the comparison between PLS and maximum likelihood principal components regression (MLPCR) in MOX sensors. PLS is often criticized by the lack of interpretability when the model complexity increases beyond the chemical rank of the problem. This happens in MOX sensors due to cross-sensitivities to interferences, such as temperature or humidity and non-linearity. Additionally, the estimation of fundamental figures of merit, such as the limit of detection (LOD), is still not standardized in multivariate models. Orthogonalization methods, such as orthogonal projection to latent structures (O-PLS), have been successfully applied in other fields to reduce the complexity of PLS models. In this work, we propose a LOD estimation method based on applying the well-accepted univariate LOD formulas to the scores of the first component of an orthogonal PLS model. The resulting LOD is compared to the multivariate LOD range derived from error-propagation. The methodology is applied to data extracted from temperature-modulated MOX sensors (FIS SB-500-12 and Figaro TGS 3870-A04), aiming at the detection of low concentrations of carbon monoxide in the presence of uncontrolled humidity (chemical noise). We found that PLS models were simpler and more accurate than MLPCR models. Average LOD values of 0.79 ppm (FIS) and 1.06 ppm (Figaro) were found using the approach described in this paper. These values were contained within the LOD ranges obtained with the error-propagation approach. The mean LOD increased to 1.13 ppm (FIS) and 1.59 ppm (Figaro) when considering validation samples collected two weeks after calibration, which represents a 43% and 46% degradation, respectively. The orthogonal score-plot was a very convenient tool to visualize MOX sensor data and to validate the LOD estimates.


ADAM23 is downregulated in side population and suppresses lung metastasis of lung carcinoma cells.
Cancer cells contain a small population of cancer stem cells or cancer initiating cells, which can be enriched in the side population (SP) after fluorescence activated cell sorting. To examine the members of the ADAM, ADAMTS and MMP gene families related to phenotypes of the SP and the main population (MP), we screened the expression of all the members in the propagated SP and MP of A549 lung adenocarcinoma cells, and found that the relative expression ratio of ADAM23 in the MP to the SP is most highly increased, but none of them are increased in the SP. A similar result on the ADAM23 expression was obtained with another cell line, Calu-3 cells. Overexpression of ADAM23 inhibited colony formation, cell adhesion and migration, and knockdown of ADAM23 by shRNA showed the reverse effects. ADAM23-mediated suppression of colony formation, cell adhesion and migration was greatly reduced by treatment with neutralizing anti-ADAM23 antibody, anti-αvβ3 integrin antibody and/or ADAM23 disintegrin peptide. Expression of cancer stem cell-related genes, including AKRC1/2, TM4SF1 and NR0B1, was increased by knockdown of ADAM23. In addition, lung metastasis of A549 transfectants with different levels of ADAM23 expression was negatively regulated by the ADAM23 expression levels. Our data provide evidence that ADAM23 plays a role in suppression of cancer cell progression through interaction with αvβ3 integrin, and suggest that downregulation of ADAM23 in SP cells may contribute toward providing a cancer stem cell phenotype by facilitating the activity of integrin αvβ3.


Index profile of multilayer fibers of an elliptical cross-section.
A mathematical formula is derived from the multiple-beam Fizeau fringers crossing an elliptical multilayer fiber. A formula for the two-beam interference fringes crossing this fiber is also given. A model that divides the elliptical fiber cross-section into elliptical zones of constant refractive index is assumed. The index profile of the poly(aryl-ether-ether-ketone) fiber is calculated by using the mathematical formulas. Microinterferograms of both the multiple-beam Fizeau fringes and the totally duplicated image of the fiber from a two-beam intereference microscope are used for the determination of the refractiveindex profile of the fiber. The cross-sectional shape is determined from the diffraction pattern of a He-Ne laser beam. Microinterferograms are given for illustration.


Comparative Trap Catches of Male Bactrocera, Dacus, and Zeugodacus Fruit Flies (Diptera: Tephritidae) With Four Floral Phenylbutanoid Lures (Anisyl Acetone, Cue-Lure, Raspberry Ketone, and Zingerone) in Queensland, Australia.
The male fruit fly attractants, cue-lure (CL) and raspberry ketone (RK), are important in pest management. These volatile phenylbutanoids occur in daciniphilous Bulbophyllum Thouar (Orchidaceae: Asparagales) orchids, along with zingerone (ZN) and anisyl acetone (AA). While these four compounds attract a similar range of species, their relative attractiveness to multiple species is unknown. We field tested these compounds in two fruit fly speciose locations in north Queensland, Australia (Lockhart and Cairns) for 8 wk. Of 16 species trapped in significant numbers, 14 were trapped with CL and RK, all in significantly greater numbers with CL traps than RK traps (at least in higher population locations). This included the pest species Bactrocera tryoni (Froggatt) (Diptera: Tephritidae) (CL catches ca. 5× > RK), Bactrocera neohumeralis (Hardy) (Diptera: Tephritidae) and Bactrocera bryoniae (Tryon) (Diptera: Tephritidae) (CL catches ca. 3× > RK), and Bactrocera frauenfeldi (Schiner) (Diptera: Tephritidae) (in Cairns-CL catches ca. 1.6× > RK). Seven species were trapped with AA, and all were also caught in CL and RK traps in significantly greater numbers, with the exception of B. frauenfeldi. For this species, catches were not statistically different with CL, RK, and AA in Lockhart, and RK and AA in Cairns. Seven species were trapped with ZN, two at this lure only, and the remainder also with CL or RK but in significantly greater numbers. This is the first quantitative comparison of the relative attractiveness of CL, RK, AA, and ZN against multiple species, and supports the long-held but untested assumption that CL is broadly more attractive lure than RK.


Quantum information. Unconditional quantum teleportation between distant solid-state quantum bits.
Realizing robust quantum information transfer between long-lived qubit registers is a key challenge for quantum information science and technology. Here we demonstrate unconditional teleportation of arbitrary quantum states between diamond spin qubits separated by 3 meters. We prepare the teleporter through photon-mediated heralded entanglement between two distant electron spins and subsequently encode the source qubit in a single nuclear spin. By realizing a fully deterministic Bell-state measurement combined with real-time feed-forward, quantum teleportation is achieved upon each attempt with an average state fidelity exceeding the classical limit. These results establish diamond spin qubits as a prime candidate for the realization of quantum networks for quantum communication and network-based quantum computing.


The Importance of Physician Climate Advocacy in the Face of Political Denial.
Most physicians accept the general scientific discoveries about anthropogenic global warming and its dangers. Occasional denial by individual physicians of climate change can be readily answered by reference to the scientific consensus. But widespread, organized, political denial of climate change is hazardous to physicians' advocacy for an effective public health and health care response to climate change. This article assumes that physician climate advocacy is ethical and celebrates the many forms of health climate advocacy already under way. It concludes by drawing attention to measures that can scale up and strengthen the health care system's organized response to growing climate health hazards.


[Non-fatal occupational injuries: gender and job contract differences].
In Brazil, workers without a formal job contract comprise more than half of the labor force, a contingent formed mainly by women. This study presents estimates of the annual incidence of non-fatal work-related injuries and their distribution by gender and type of job contract in an urban area of Brazil. This was a community-based study with a random cluster area sample of the inhabitants from the city of Salvador, capital of the State of Bahia. The study population included all individuals from 18 to 65 years of age who reported having a paid job (n = 2,947). Data were obtained through individual household interviews. The overall estimated annual incidence rate was 5.80%, with a non-statistically significant difference between men (6.05%) and women (5.53%) or workers with (5.67%) and without (5.92%) a formal job contract. These similarities between work-related accidents across gender and type of job contract highlighted the need for greater attention to this problem among women and informal workers, who are largely ignored in official statistics.


Contraceptive use and reproductive intentions among women requesting contraceptive counseling.
Limited attention has been paid to the use of contraception in relation to women's family planning intentions. The aim of this study was to investigate the use of contraception during the most recent intercourse as well as the reproductive intentions of Swedish-speaking women requesting contraceptive counseling. A cross-sectional baseline survey in a randomized controlled trial regarding reproductive life planning (before randomization). Women requesting contraceptive counseling answered questions about contraception and whether they wanted to have children/more children in the future. In total, 1946 women participated: 33.7% (n = 656) parous and 65.7% (n = 1279) nulliparous. The majority, 87.1% (n = 1682), had used contraception during their latest intercourse; 64.6% (n = 1239) used short-acting reversible contraception, 22.8% (n = 443) used long-acting reversible contraception (LARC), and 12.9% (n = 251) had not used any contraception. A combined oral contraceptive was more common among nulliparous and LARC among parous. Among all women, 64.8% (n = 1253) intended to have children/more children in the future, among parous women 35.7% (n = 220) and among nulliparous 80.0% (n = 1033). Among women who did not intend to have children/more children, 22.6% (n = 60) of parous and 10% (n = 8) of nulliparous had not used contraceptives during their most recent intercourse. Women did not always use contraceptives that were suitable for their reproductive intentions. Questioning women who request contraceptive counseling about their pregnancy intention can give healthcare providers better opportunities for individualized counseling.


Relations among sodium pump inhibition, Na-Ca and Na-H exchange activities, and Ca-H interaction in cultured chick heart cells.
Sodium pump inhibition in cardiac muscle cells is associated with changes in intracellular sodium, calcium, and hydrogen concentrations as well as in membrane ion transport activity. We examined further the functional relations among these entities using cultured chick ventricular cells. [Ca]i and pHi were determined from fluorescence signals obtained from cells loaded with fura-2 or BCECF, respectively. Ouabain (100 microM) elevated [Ca]i eightfold and decreased pHi by 0.11 unit (a 30% increase in [H+]). In the presence of 10 microM ethylisopropylamiloride, a potent inhibitor of Na-H exchange, ouabain elevated [Ca]i 3.5-fold and reduced pHi by 0.16 unit (a 48% increase in [H+]). Exposure to sodium-free (sodium replaced with potassium) medium produced a twelvefold increase in [Ca]i and a 0.12 pH unit decrease in pHi. In cells treated with 100 microM ouabain, exposure to sodium-free (lithium) medium resulted in a 22-fold sustained increase in [Ca]i and a rapid intracellular acidification (pH 7.15 to 6.60). The effect of ouabain or sodium-free medium on pHi was abolished in calcium-free medium; addition of 1 mM Ca rapidly increased [Ca]i and decreased pHi. In cells treated with subtoxic (3 microM) or toxic (100 microM) concentrations of ouabain, initial 24Na uptake rates were significantly greater than in control cells and were significantly reduced in the presence of 10 microM ethylisopropylamiloride. We conclude that ouabain (100 microM) produces intracellular acidification as a result of sodium pump inhibition; calcium accumulation via Na-Ca exchange, and subsequent Ca-H interaction within the cell.(ABSTRACT TRUNCATED AT 250 WORDS)


An electrophysiological dissociation between orbitofrontal reality filtering and context source monitoring.
Memory influences behavior in multiple ways. One important aspect is to remember in what precise context in the past a piece of information was acquired (context source monitoring). Another important aspect is to sense whether an upcoming thought, composed of fragments of memories, refers to present reality and can be acted upon (orbitofrontal reality filtering). Whether these memory control processes share common underlying mechanisms is unknown. Failures of both have been held accountable for false memories, including confabulation. Electrophysiological and imaging studies suggest a dissociation but used very different paradigms. In this study, we juxtaposed the requirements of context source monitoring and reality filtering within a unique continuous recognition task, which healthy participants performed while high-resolution evoked potentials were recorded. The mechanisms dissociated both behaviorally and electrophysiologically: Reality filtering induced a frontal positivity, absence of a specific electrocortical configuration, and posterior medial orbitofrontal activity at 200-300 msec. Context source monitoring had no electrophysiological expression in this early period. It was slower and less accurate than reality filtering and induced a prolonged positive potential over frontal leads starting at 400 msec. The study demonstrates a hitherto unrecognized separation between orbitofrontal reality filtering and source monitoring. Whereas deficient orbitofrontal reality filtering is associated with reality confusion in thinking, the behavioral correlates of deficient source monitoring should be verified with controlled experimental exploration.


Stimulation of human whole-body energy expenditure by salsalate is fueled by higher lipid oxidation under fasting conditions and by higher oxidative glucose disposal under insulin-stimulated conditions.
Nonsteroidal antiinflammatory drugs appear to improve insulin sensitivity and are currently tested in clinical trials. Salsalate, however, may blunt mitochondrial function, an unwarranted side effect for type 2 diabetics. We examined the effect of salsalate on ex vivo mitochondrial function and lipid-induced insulin resistance. In a crossover design, nine volunteers underwent a hyperinsulinemic-euglycemic clamp with simultaneous infusion of glycerol (control), Intralipid, or Intralipid preceded by 4 d of salsalate (4000 mg Disalsid). Oxidative glucose disposal and nonoxidative glucose disposal (NOGD), metabolic flexibility, energy expenditure (EE), and ex vivo muscle mitochondrial function were measured. Lipid infusion reduced insulin-stimulated glucose disposal by approximately 40%, glucose oxidation (CHOox) by approximately 50%, and NOGD by approximately 35%. Lipid-induced whole-body insulin resistance and decreased NOGD were not ameliorated by salsalate. However, salsalate repressed lipid-induced reduction in CHOox and reduced insulin clearance, resulting in higher insulin levels under basal as well as under clamp conditions (∼25 and ∼39%, respectively). Intriguingly, EE was higher after administration of salsalate (∼18 and ∼16% under basal and clamp conditions, respectively) and was fueled by increased fat oxidation in the basal state and increased CHOox upon insulin stimulation. Salsalate did not affect mitochondrial function and coupling. We conclude that salsalate failed to improve whole-body insulin sensitivity but increased basal fat oxidation and insulin-stimulated CHOox, indicating improved metabolic flexibility. The beneficial effects of salsalate on CHOox can be attributed to elevated insulin levels. Mitochondrial respirometry revealed no indications that the changes in substrate selection and EE could be attributed to changes in skeletal muscle mitochondrial capacity or mitochondrial coupling.


The effects of metal nanoparticles incorporation on the mechanical properties of denture base acrylic resin.
The aim of this study was to examine the flexural strength of acrylic resin base material incorporated with iron, copper, and titanium nanoparticles. Seventy bars of samples (65x10x2.5 mm3) were divided into seven groups. Acrylic samples were prepared according to the manufacturer's instructions. Fe2O3, CuO and TiO2 nanoparticles were manually added in a proportion of 1wt% and 3wt% to the heat-polymerized acrylic resin. The Universal Testing Machine was used for 3-point flexural test of 5 mm/min force. ANOVA and Weibull analyses were used for the statistical analyses. A statistical difference was found between the nanoparticle-added group and the control group. The highest mean value was observed for the 1wt% TiO2 added group, (84.99 MPa) and the lowest value was for the 3wt% CuO added group (71.32 MPa) (p<0,001). The 3wt% Fe2O3 and CuO added groups showed lower values than the control group. The incorporation of TiO2 nanoparticles into acrylic resin in a proportion of 1wt% increased the flexural strength values of the resins. Within the limitations, the nanoparticle addition to acrylic resins could improve the mechanical properties; however, when the percentage of nanoparticle addition increases, the flexural strength values of the acrylic resins decrease.


Nicotiana megalosiphon, a Highly Susceptible, New, and Useful Host for Potato Virus A.
Potato virus A (PVA; genus Potyvirus, family Potyviridae) occurs wherever potatoes are grown and may reduce tuber yields as much as 40%. Its host range consists of six experimental hosts (Lycopersicon pimpinellifolium (Jusl.) P. Mill., Nicandra physalodes (L.) Gaertn., Nicotiana tabacum L., Solanum demissum Lindl., S. demissum × S. tuberosum [2], and Nicotiana debneyi Domin.) and two natural hosts (S. tuberosum L. and S. betaceae (Cav.) Sendt.) (2). Aphids transmit PVA in a stylet-born manner. Its difficult mechanical transmission, caused by a low virus concentration in potato and other hosts (1), has constrained pathological research on the virus. In routine studies to identify virus isolates from the field, we discovered that N. megalosiphon Van Heurck & Mull. Agr. is a superior host of PVA that markedly facilitated diagnosis, selection for resistance to PVA, and other research applications. The efficiency of mechanical transmission of PVA to potato (5 duplicated assays and 10 plants per assay) ranged from 0 to 10% with PVA-infected potato as the virus source, 0 to 30% with Nicandra physalodes, 10 to 30% with N. tabacum cv. Samsun, and 20 to 80% with N. megalosiphon as the source of virus. The efficiency of mechanical transmission to four systemic hosts of PVA with potato (cv. Russet Burbank) as the source of virus (5 duplicated assays and 10 plants per assay) ranged from 0 to 20% to potato, 0 to 30% to Nicandra physalodes, 10 to 40% to N. tabacum cv. Samsun, and 80 to 100% to N. megalosiphon. The superiority of N. megalosiphon as a host and source of PVA was associated with a high virus concentration in tissues. Infected potato leaves yielded 0.32 to 0.54 mg of virus per kg of infected leaves, Nicandra physalodes yielded 0.37 to 0.66 mg per kg, N. tabacum cv. Samsun yielded 0.78 to 1.22 mg per kg, and N. megalosiphon yielded 5.16 to 9.39 mg per kg of infected leaves in five different purification experiments. These yields are based on the amount of virus isolated in sucrose gradients subjected to rate-zonal centrifugation as the last step in purification (3). The virus antigen concentrations of the original PVA-infected tissues measured using quantitative enzyme-linked immunosorbent assay ranked virus concentrations in the same relative order as purification but were nearly 2 times higher than were the purification yields. Similarly, local lesion assays on S. demissum A leaves (4) ranked infectious virus concentrations in the same order as did purification. Efficiency of aphid transmission from the four hosts was not assayed. Infected N. megalosiphon plants survived and served as sources of PVA for at least 1 year in a greenhouse. N. megalosiphon is an important new host of PVA because it facilitates the routine transmission of the virus and other manipulations essential for efficient research on control of the virus disease. References: (1) R. Bartels. No. 54 in: Descriptions of Plant Viruses. CMI, Kew, Surrey, UK, 1971. (2) A. Brunt. Page 77 in: Virus and Virus-Like Diseases of Potatoes and Production of Seed Potatoes. G Loebenstein et al., eds. Kluwer Academic Publishers, Dordrecht, the Netherlands, 2001. (3) P. E. Thomas and W. K. Kaniewski. Page 285 in: Virus and Virus-Like Diseases of Potatoes and Production of Seed Potatoes, G. Loebenstein et al., eds. Kluwer Academic Publishers, Dordrecht, the Netherlands, 2001. (4) R. E. Webb and R. W. Buck. Am Potato J. 32:248, 1955.


Resting-State Functional Connectivity of the Habenula in Mood Disorder Patients With and Without Suicide-Related Behaviors.
The habenula is a small midbrain structure that is important for brain signaling and learning from negative events. Thus, the habenula is strongly connected to both the reward system and motor regions. Increasing evidence suggests a role for the habenula in the etiology of psychiatric disorders, including mood and substance use disorders. However, no studies to date have investigated habenular resting-state functional connectivity (rsFC) in suicide-related behaviors (SB). The authors enrolled 123 individuals with major depressive disorder (MDD) or bipolar disorder and a history of suicide-related behaviors (SB+), 74 individuals with MDD or bipolar disorder and a history of suicidal ideation but no history of SB (SB-), and 75 healthy control subjects (HC). A seed-based approach was used to identify regions showing different rsFC with the habenula followed by region of interest to region of interest post hoc comparisons. Compared with both the SB- and HC groups, the SB+ group showed higher connectivity between the left habenula and the left parahippocampal gyrus, the right amygdala, and the right precentral and postcentral gyri. Patients with mood disorders displayed higher rsFC between the left habenula and left middle temporal gyrus, the left angular gyrus, and the left posterior cingulate cortex, as well as lower rsFC between the right habenula and the left thalamus, when compared with HCs. These findings suggest that the habenula is involved in the neural circuitry of suicide. The higher habenular rsFC found in the SB+ group may mediate a dysfunction in the mechanism that links the habenula with motor activity and contextual associative processing.


Minutes, MET minutes, and METs: unpacking socio-economic gradients in physical activity in adolescents.
There is conflicting evidence regarding the relationship between socio-economic position (SEP) and physical activity in adolescents. The aim of this study was to investigate associations between SEP and characteristics of physical activity in Australian adolescents using a high-resolution use-of-time tool. Use-of-time and pedometer data were collected on a random sample of 2071 9-16-year-old Australian children. Use-of-time was recorded using a computerised 24-h use-of-time recall, the Multimedia Activity Recall for Children and Adults. Reported household income was used as a marker of SEP. There were no differences in self-reported minutes of moderate to vigorous physical activity (MVPA) across the income bands and only very small differences in the number of daily steps. However, the mix of MVPA components varied across income bands, with adolescents from low-SEP families experiencing less sport but more active transport. Because the mean rate of energy expenditure was greater in sport than in other forms of MVPA (play, active transport or chores), there were significant differences in MVPA-related and total daily energy expenditure across income bands, with the lower bands having significantly lower values. Differences in total daily energy expenditure were almost entirely explained by differences in energy expenditure associated with sport. Physical activity patterns vary across SEP bands in Australian adolescents, with sport being the major locus of differences. Instruments which do not account for the energy costs of various activities may fail to detect important relationships.


Polyphyly of true branching cyanobacteria (Stigonematales).
Cyanobacteria with true branching are classified in Subsection V (formerly order Stigonematales) in the phylum CYANOBACTERIA: They exhibit a high degree of morphological complexity and are known from particular biotopes. Only a few stigonematalean morphotypes have been cultured, and therefore the high variability of morphotypes found in nature is under-represented in culture. Axenic cultures of Chlorogloeopsis and Fischerella sensu Rippka et al. were, to date, the only representatives of this Subsection in phylogenetic studies. The 16S rDNA sequence analysis data in this report confirm that heterocyst-forming cyanobacteria are a monophyletic group. However, unlike previous studies have suggested, these 16S rDNA data on new Stigonematales strains show that the true branching cyanobacteria are polyphyletic and can be separated into at least two major groups defined by their branching type, the first group being characterized by T-branching and the second group by Y-branching. Cyanobacteria with intercalary heterocysts and either no branching or false-branching also formed separate clusters. In consequence, our phylogenetic data do not correlate with the bacteriological and traditional classifications, which distinguish filamentous heterocystous cyanobacteria with or without true branching (Nostocales/Stigonematales).


Anaemia and iron deficiency in cardiac patients: what do nurses and allied professionals know?
Cardiac nurses and allied professionals often take care of patients who also have anaemia or iron deficiency. To deliver optimal care, professionals should be knowledgeable about the prevalence, diagnosis, pathophysiology, and therapeutic management of these conditions. We therefore set out a survey to get a first impression on the current knowledge of nurses and allied professionals on anaemia and iron deficiency. A questionnaire was designed for this study by the Undertaking Nursing Interventions Throughout Europe (UNITE) Study Group. Data were collected from 125 cardiovascular nurses and allied professionals visiting the 11th Annual Spring Meeting of the Council on Cardiovascular Nursing and Allied Professionals of the European Society of Cardiology. Most respondents had general knowledge on the definition of anaemia and iron deficiency and 54% of the respondents rated anaemia and iron deficiency as important when evaluating a cardiac patient. Specific knowledge regarding anaemia and more prominently of iron deficiency was not optimal. Although cardiac nurses and allied professionals have basic knowledge of anaemia and iron deficiency, they would benefit from additional knowledge and skills to optimally deliver patient care.


Dynamic range improvement of a microwave photonic link based on bi-directional use of a polarization modulator in a Sagnac loop.
A novel microwave photonic link (MPL) with an improved spurious-free dynamic range (SFDR) based on a bidirectional use of a polarization modulator (PolM) in a Sagnac loop is proposed and demonstrated. The PolM in the loop functions, in conjunction with a polarization controller and a polarization beam combiner, as a Mach Zehnder modulator (MZM), which only modulates the incident light wave along the clockwise direction, leaving the counter-clockwise light wave unmodulated due to the velocity mismatch. Two clockwise intensity-modulated signals along two paths (Path 1 and Path 2) are generated, with one (Path 2) combined with the non-modulated light wave from the counter-clockwise direction to suppress part of the optical carrier. By controlling the power relationship between the two paths, the third-order intermodulation distortion (IMD3) can be fully suppressed, and thus an MPL with improved dynamic range is achieved. A theoretical analysis is presented, which is validated by an experiment. The IMD3 can be suppressed by 50 dB, giving an improvement in SFDR of 16 dB.


Comparison of piperacillin/tazobactam and imipenem/cilastatin, both in combination with tobramycin, administered every 6 h for treatment of nosocomial pneumonia.
This randomized, double-blind, multicenter study compared the efficacy and safety of piperacillin/tazobactam (P/T) and imipenem/cilastatin (IMP), both in combination with an aminoglycoside, in hospitalized patients with acute nosocomial pneumonia (NP). Patients with acute NP, defined as pneumonia with symptoms > or = 48 h after admission or < or =7 days after hospital discharge, received infusions of 4 g/500 mg P/T or 500 mg/500 mg IMP every 6 h. Endpoints were clinical cure and microbiological response rates; pathogen eradication rates; length of hospital stay; hospital readmissions; and adverse events (AEs). Of 437 patients in the intent-to-treat population, 197 were efficacy evaluable. At test-of-cure, response rates were similar between groups. Within the efficacy evaluable population, 68% of P/T patients and 61% of IMP patients were clinically cured (P = 0.256). Microbiological responses for P/T and IMP patients were: eradication, 64% versus 59%; persistence, 29% versus 21%; relapse, 0% versus 5%; and superinfection, 7% versus 15%, respectively. Gram-positive isolates were eradicated in 83% of P/T patients and 75% of IMP patients; Gram-negative pathogens were eradicated in 72% of P/T patients and 77% of IMP patients. Treatment groups had similar number of mean hospital days, readmission rates, and frequency of AEs. This study showed that P/T administered four times per day was as safe and efficacious as IMP in treating hospitalized patients with NP.


Mitotic spindle asymmetry: a Wnt/PCP-regulated mechanism generating asymmetrical division in cortical precursors.
The regulation of asymmetric cell division (ACD) during corticogenesis is incompletely understood. We document that spindle-size asymmetry (SSA) between the two poles occurs during corticogenesis and parallels ACD. SSA appears at metaphase and is maintained throughout division, and we show it is necessary for proper neurogenesis. Imaging of spindle behavior and division outcome reveals that neurons preferentially arise from the larger-spindle pole. Mechanistically, SSA magnitude is controlled by Wnt7a and Vangl2, both members of the Wnt/planar cell polarity (PCP)-signaling pathway, and relayed to the cell cortex by P-ERM proteins. In vivo, Vangl2 and P-ERM downregulation promotes early cell-cycle exit and prevents the proper generation of late-born neurons. Thus, SSA is a core component of ACD that is conserved in invertebrates and vertebrates and plays a key role in the tight spatiotemporal control of self-renewal and differentiation during mammalian corticogenesis.


Functional and histological differences in autogenous and allogenic vein grafts: two different vasculopathies?
The long-term biological characteristics and the functional and morphological changes that occur in fresh allografts are poorly understood. This study tests the hypothesis that the development of intimal hyperplasia and its associated functional changes are accelerated in an allograft compared to an autograft due to the additional immunological stimuli. Common carotid vein bypass grafts were performed in 40 New Zealand White rabbits: 20 received their ipsilateral jugular veins (autologous) and 20 received the fresh contralateral jugular veins from the control rabbit (allogenic). Electron microscopy was performed and intimal and medial dimensions were determined by videoplanimetry at 7, 14, and 28 days. Contraction and relaxation studies to a panel of agonists were also performed. The EC50's (agonist concentration which produces 50% of the maximal response) were calculated. All grafts remained patent. Allografts showed a 51% decrease in overall mean intimal thickness (41 +/- 3 microns vs. 83 +/- 12 microns; P < 0.01) and a 97% increase in overall mean medial thickness (140 +/- 15 microns vs. 71 +/- 3 microns; P < 0.01) compared to the autografts. The lumen of the allogenic vein grafts was equivalent to the autologous vein grafts. Overall mean total wall thickness only increased by 17%, 181 microns vs. 154 microns for allo- and autografts, respectively. The EC50 for norepinephrine, histamine, and bradykinin were similar in the auto- and allografts, while the EC50 to serotonin was significantly less in the allografts than in the autografts. Neither the precontracted auto- or allografts relaxed to acetylcholine or serotonin (receptor mediated, endothelium dependent). The EC50 for calcium ionophore (nonreceptor mediated, endothelium dependent) was equivalent in the auto- and allografts. The EC50 for the sodium nitroprusside-induced relaxation (endothelium independent) was significantly higher in the allograft than in the autograft. This study demonstrates that there are two different vasculopathies occurring in autografts and allografts: intimal hyperplasia is predominant in the autograft while an exaggerated medial response is predominant in the allograft. Serotonin contractility and endothelial-independent relaxation are enhanced in the allograft compared to the autograft.


A randomized clinical trial to compare diagnostic casts made using plastic and metal trays.
Virtually every prosthodontic rehabilitation involves making diagnostic casts for analysis and prosthesis fabrication. Frequently, these casts are produced using irreversible hydrocolloid (IH) impression materials in stock metal or plastic trays. However, it is unclear whether one technique produces a more accurate cast. The purpose of this randomized clinical trial was to compare the linear accuracy of diagnostic casts produced using IH with 1 of 3 different tray types: (1) perforated metal trays, (2) stock plastic trays, and (3) directed-flow stock plastic trays. All groups were compared to casts produced with custom trays and vinyl polysiloxane (VPS) impression materials, which were considered the control. Seven subjects participated in this trial. IH impressions were made in a random order using 1 of 3 tray types: stock plastic, perforated metal, or plastic directed flow. These were compared to VPS impressions using custom trays (control group). Each impression technique was repeated 3 times per subject, for a total of 84 observations. Impressions were disinfected and poured in a type IV stone. Linear accuracy of casts was measured using computer software analysis of scanned images of the casts at x30 magnification. Three linear measurements were made on each cast: second molar to second molar, right second molar to left first premolar, and left second molar to right first premolar. Measurements were compared among techniques using mixed-model analysis of variance to account for correlation among the multiple measurements made on each subject. Dunnett's adjustment for multiple comparisons with control was used (α=.05). For molar-to-molar and right second molar to the left first premolar measurements, there were no significant differences in linear dimensions between casts made from different trays. However, linear measurements from the left second molar to the right first premolar demonstrated significant differences for casts made with stock metal, directed-flow, and stock plastic trays compared to custom trays. In this group, casts produced by stock metal, directed-flow, and stock plastic trays differed from controls by 102, 68, and 71 um, respectively. Generally, casts made with plastic trays (stock plastic and directed flow) had values closer to those of custom trays than did casts made with metal trays. Impressions made with irreversible hydrocolloid produced casts that were significantly different in linear dimension than casts produced by custom trays and VPS impressions. These differences were not uniform, but varied by location on the cast.


Exploiting the chemical differences between Ag and Au colloids allows dramatically improved SERS detection of "non-adsorbing" molecules.
In colloidal SERS only analytes that can spontaneously adsorb onto nanoparticles are detected. Therefore, considerable effort has been placed on modifying the surface properties of colloidal particles, particularly Ag particles, to promote the absorption of "difficult" analytes which do not spontaneously adsorb to as-prepared nanoparticles. In contrast, much less attention has been paid to the role which the identity of the underlying metal plays in the absorption since it is widely believed that the chemical properties of Ag and Au are very similar. This leads to the assumption that molecules which do not adsorb to Ag, such as hydrocarbons, will also not adsorb to aggregated Au colloids for SERS measurements. Here, we challenge this common perception by showing that SERS detection of "difficult" aromatic targets such as naphthalene, trinitrotoluene and 3,4-methylenedioxymethamphetamine which cannot be achieved even at >10-3 M concentrations with bare aggregated Ag colloids is possible at ≥10-8 M with unmodified aggregated Au colloids. For naphthalene and 3,4-methylenedioxymethamphetamine the detection limit obtained in this work with bare citrate-capped Au particles exceeds the previous best limit of detection obtained with surface-modified nanoparticles by an order of magnitude.


Kir6.2-containing ATP-sensitive K(+) channel is required for cardioprotection of resveratrol in mice.
Resveratrol is a natural compound that affects energy metabolism and is also known to possess an array of cardioprotective effects. However, its overall effects on energy metabolism and the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothesize that ATP-sensitive potassium (K-ATP) channels as molecular sensors of cellular metabolism may mediate the cardioprotective effects of resveratrol. Kir6.2 knockout, Kir6.1 heterozygous and wild-type (WT) mice were subjected to ischemia/reperfusion injury and were injected with resveratrol (10 mg/kg, i.p). Myocardial infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities were determined. Neonatal cardiomyocytes were used in in vitro assays to investigate the underlying mechanism of resveratrol in cardioprotection. Resveratrol treatment significantly reduced myocardial infarct size and serum LDH and CK activity and inhibited oxygen-glucose deprivation/reoxygenation - induced cardiomyocyte apoptosis in WT and Kir6.1 heterozygous mice, but Kir6.2 deficiency can abolish the cardioprotective effects of resveratrol in vivo and in vitro. We further found that resveratrol enhanced 5'-AMP-activated protein kinase (AMPK) phosphorylation and promoted the association of AMPK with Kir6.2. Suppression of AMPK attenuated and activation of AMPK mimicked the cardioprotective effects of resveratrol in cardiomyocytes. Notably, Kir6.2 knockout also reversed the cardioprotection of AMPK activator. Our study demonstrates that resveratrol exerts cardioprotective effects through AMPK -Kir6.2/K-ATP signal pathway and Kir6.2-containing K-ATP channel is required for cardioprotection of resveratrol.


Palliative care needs in Malawi: Care received by people living with HIV.
Infection with human immunodeficiency virus (HIV) has changed from an acute to a chronic illness in the past decade, because of highly active antiretroviral therapy (ART). Malawi's response to the HIV challenge included provision of ART for people living with HIV or AIDS (PLWHA), which significantly reduced HIV- and AIDS-related mortality. In addition, palliative care for PLWHA was introduced as a strategy that improves the success of ART. The purpose of the study was to explore the needs of PLWHA concerning care received from primary caregivers and palliative care nurses in Malawi. A qualitative, explorative design was used and 18 participants were selected purposefully and interviewed individually using a semi-structured interview guide. Data were analysed using NVivo software package version 10. Results revealed that PLWHA needed physical care from the primary caregivers due to severity of illness, integration of healthcare services, and continuity of care and proper care from nurses. They also needed knowledge from nurses in several areas which affected decision-making and needed financial and nutritional support. More could be done in meeting needs of PLWHA to improve their health and survival and assist them to achieve a better quality of life.


HAC stability in murine cells is influenced by nuclear localization and chromatin organization.
Human artificial chromosomes (HAC) are small functional extrachromosomal elements, which segregate correctly during each cell division. In human cells, they are mitotically stable, however when the HAC are transferred to murine cells they show an increased and variable rate of loss. In some cell lines the HAC are lost over a short period of time, while in others the HAC become stable without acquiring murine DNA. In this study, we linked the loss rate to the position of the HAC in the murine cell nucleus with respect to the chromocenters. HAC that associated preferentially with the chromocenter displayed a lower loss rate compared to the HAC that are less frequently associated. The chromocenter acts as a hub for the deposition of heterochromatic markers, controlling centromeric and pericentromeric DNA replication timing and chromosome segregation. The HAC which localized more frequently outside the chromocenters bound variable amounts of histone H3 tri-methylated at lysine 9, and the high level of intraclonal variability was associated with an increase in HAC segregation errors and delayed DNA replication timing. This is a novel result indicating that HAC segregation is closely linked to the position in the murine nucleus and gives important insight for HAC gene expression studies in murine cells and establishing murine models of human genetic disease.


The computation of multiple matching doubly ambiguous stereograms with transparent planes.
Psychophysical experiments have been previously described Weinshall, D. (1989) Nature 341, 737-739; (1991) Vision Research 31, 1731-1748 that involved the perception of many transparent layers, corresponding to multiple matching, in doubly ambiguous random-dot stereograms. Additional experiments are described in the first part of this paper. In one experiment, subjects were required to report the density of dots on each transparent layer. In another experiment, the minimal density of dots on each layer, which is required for the subjects to perceive it as a distinct transparent layer, was measured. The difficulties encountered by stereo matching algorithms, when applied to doubly ambiguous stereograms, are described in the second part of this paper. Algorithms that can be modified to perform consistently with human perception, and the constraints imposed on their parameters by human perception, are discussed.


Ionization-Induced Structural Changes in Uracil Dimers and Their Spectroscopic Signatures.
The electronic structure of the three representative isomers of the ionized uracil dimers is characterized by high-level electronic structure calculations. Noncovalent interactions between the fragments lower the vertical ionization energies by 0.13-0.35 eV, the largest drop being observed for the stacked and the T-shaped isomers. The initial hole is delocalized in the stacked and the H-bonded isomers and is localized in the T-shaped one. The ionization induces significant structural relaxation and increases the binding energies. The stacked dimer cation relaxes to the symmetric structure bound by 22.7 kcal/mol. The T-shaped dimer cation has a binding energy of 25.1 kcal/mol. Thus, the relative order of the stacked and T-shaped isomers is reversed upon ionization. Finally, the H-bonded isomer, which relaxes to the proton-transferred structure, is bound by 37.0 kcal/mol. The electronic spectra of all three isomers characterized at the vertical and the relaxed geometries show different patterns, which may be exploited in spectroscopic probing of ionization-induced dynamics in these species.


History of Spine Deformity in Turkey.
Spine deformities are among the most important spinal disorders, affecting health-related life quality. Although there are some studies in past centuries, most spine deformity-related studies and research has started in the last century. Many surgical techniques, performed between 1960 and 1990, made scoliosis a touchable pathology. These techniques started with Harrington"s system, wiring techniques, pedicle screw techniques, and all other universal techniques. Anterior and 360 degree techniques contributed to this process. The use of spinal osteotomies, and recent technologies such as magnetic rods, intraoperative neuromonitoring added much to the body of knowledge of literature and improved the outcome. Advancement has not been limited to surgery only and diagnostic advancements had also impact to this process. Surgical techniques performed in the west have been performed soon in our countries. Currently almost all surgical techniques for treatment of spine deformities can be performed in our country. This article reviews historical aspects related to the diagnosis and treatment of spine deformities in Turkey.


Nociceptin/orphanin FQ and its receptor--potential targets for pain therapy?
The neuropeptide nociceptin, also called orphanin FQ (N/OFQ), is the endogenous agonist of the N/OFQ peptide receptor (NOP receptor). Both N/OFQ and the NOP receptor share a high degree of homology with classical opioid peptides and opioid receptors, respectively, and use similar signal transduction pathways as classical opioids. The NOP receptor has thus been regarded as the fourth member of the opioid receptor family. Despite this close relationship, 7 years of research have demonstrated that the N/OFQ system has a distinct pharmacological profile and serves different physiological functions. In particular, its role in the control of pain and analgesia at different levels of integration appears quite different from that of classical opioids. The recent development of specific antagonists at the NOP receptor and of NOP receptor or N/OFQ precursor knock-out mice have generated new insights into the role of N/OFQ in pain processing and help to evaluate the N/OFQ-NOP system as a potential target for new analgesic drugs.


Toward deterministic and semiautomated SPADE analysis.
SPADE stands for spanning-tree progression analysis for density-normalized events. It combines downsampling, clustering and a minimum-spanning tree to provide an intuitive visualization of high-dimensional single-cell data, which assists with the interpretation of the cellular heterogeneity underlying the data. SPADE has been widely used for analysis of high-content flow cytometry data and CyTOF data. The downsampling and clustering components of SPADE are both stochastic, which lead to stochasticity in the tree visualization it generates. Running SPADE twice on the same data may generate two different tree structures. Although they typically lead to the same biological interpretation of subpopulations present in the data, robustness of the algorithm can be improved. Another avenue of improvement is the interpretation of the SPADE tree, which involves visual inspection of multiple colored versions of the tree based on expression of measured markers. This is essentially manual gating on the SPADE tree and can benefit from automated algorithms. This article presents improvements of SPADE in both aspects above, leading to a deterministic SPADE algorithm and a software implementation for semiautomated interpretation. © 2017 International Society for Advancement of Cytometry.


Susceptibility of Pseudomonas aeruginosa to tobramycin or gentamicin alone and combined with carbenicillin.
To explore more effective therapy for Pseudomonas aeruginosa, 264 recent clinical isolates were tested by agar dilution using gentamicin and tobramycin alone and combined with carbenicillin to seek synergistic effects. Synergism was defined as a fourfold or greater decrease in the minimal inhibitory concentration of each drug in a pair. At a concentration of 3.12 mug/ml, gentamicin inhibited 73% of the strains and tobramycin inhibited 98%. The gentamicin-carbenicillin combination was synergistically active against 57% of the strains, and tobramycin-carbenicillin was active against 46%. The effect did not correlate with either susceptibility or resistance to gentamicin or tobramycin alone. The data suggest that tobramycin or tobramycin plus carbenicillin may provide alternate therapy where susceptibility to gentamicin or synergism between gentamicin and carbenicillin cannot be demonstrated; however, the degree of susceptibility to either aminoglycoside antibiotic alone cannot be used to predict a synergistic effect.


Low antibody titers 5 years after vaccination with the CYD-TDV dengue vaccine in both pre-immune and naïve vaccinees.
Globally, dengue virus (DENV) is one of the most widespread vector-borne viruses. Dengue disease affects populations in endemic areas and, increasingly, tourists who travel to these countries, but there is currently no approved vaccine for dengue. A phase 3 efficacy trial with Sanofi-Pasteur's recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) conducted in South East Asia showed an overall efficacy of 56% against virologically confirmed dengue infections of any severity and any of the 4 serotypes, but the long-term protection of the vaccine has yet to be demonstrated. To address longevity of antibody titers and B cell memory, we recalled study participants from an earlier CYD immunogenicity study (Phase 2) conducted in Singapore that enrolled healthy volunteers in the year 2009. Depending on the age group, 57-84% of the participants initially generated a neutralizing antibody titer ≥ 10 to all 4 DENV serotypes 28 d after the third and final dose. We observed very low antibody titers in blood samples collected from 23 vaccinees 5 y after the first dose, particularly titers of antibodies binding to virus particles compared with those binding to recombinant E protein. The in vivo efficacy of plasma antibodies against DENV-2 challenge was also tested in a mouse model, which found that only 2 out of 23 samples were able to reduce viremia. Although the sample size is too small for general conclusions, dengue immune memory after vaccination with CYD-TDV appears relatively low.


Copper signaling axis as a target for prostate cancer therapeutics.
Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro. With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a "conditional lethal" screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species-dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer. Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)-positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR. Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose disease is resistant to classical androgen ablation therapies.


Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy.
The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. In 8 HIV-1-positive adults who were receiving ART and had CD4(+) T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. HIV DNA and RNA levels per CD4(+) T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. ClinicalTrials.gov identifier: NCT00884793 (PLUS1).


The Muslim headscarf and face perception: "they all look the same, don't they?".
The headscarf conceals hair and other external features of a head (such as the ears). It therefore may have implications for the way in which such faces are perceived. Images of faces with hair (H) or alternatively, covered by a headscarf (HS) were used in three experiments. In Experiment 1 participants saw both H and HS faces in a yes/no recognition task in which the external features either remained the same between learning and test (Same) or switched (Switch). Performance was similar for H and HS faces in both the Same and Switch condition, but in the Switch condition it dropped substantially compared to the Same condition. This implies that the mere presence of the headscarf does not reduce performance, rather, the change between the type of external feature (hair or headscarf) causes the drop in performance. In Experiment 2, which used eye-tracking methodology, it was found that almost all fixations were to internal regions, and that there was no difference in the proportion of fixations to external features between the Same and Switch conditions, implying that the headscarf influenced processing by virtue of extrafoveal viewing. In Experiment 3, similarity ratings of the internal features of pairs of HS faces were higher than pairs of H faces, confirming that the internal and external features of a face are perceived as a whole rather than as separate components.


[Anesthesia in child with Pallister-Killian syndrome: case report.].
Pallister-Killian Syndrome (PKS) is a rare genetic disease due to a mosaic anomaly of chromosome 12. There is little information about PKS in the anesthetic literature. This report aimed at discussing aspects of this syndrome that may be relevant to anesthesia. A 5-year-old male patient with typical PKS characteristics (facial dimorphism, temporal alopecia, micrognathia, macroglossia, mental retardation, seizures and pigmentary skin lesions) was scheduled to magnetic resonance of the head under general anesthesia. He was induced and maintained with sevoflurane under facial mask and oropharyngeal canulla. Pulmonary ventilation was manually assisted during induction. There has been no complication and the procedure was performed in outpatient regimen. The importance of a thorough preanesthetic evaluation is emphasized due to possible malformations associated to PKS, including cardiopathies. Attention to difficult intubation or maintenance of the airways is recommended.


Rapid rate transcranial magnetic stimulation--a safety study.
We assessed the safety of repeated short trains (4 stimuli) of rapid-rate transcranial magnetic stimulation (rrTMS) over the left motor cortex in 6 healthy normal subjects. rrTMS involved two separate blocks of 50 consecutive trains of 4 stimuli at a frequency of 20 Hz and an intensity of 5-10% above active motor threshold. We monitored EEG, and assessed aspects of neurological (balance, gait, two-point discrimination, blood pressure, pulse rate), cognitive (attention, memory, executive function) and motor function (speed of movement initiation and execution and manual dexterity) before and after the two blocks of rrTMS. EMG was also recorded from a number of hand, forearm and arm muscles contralateral to the site of stimulation. Two blocks of repeated rrTMS at 20 Hz and 5-10% above active motor threshold did not produce any adverse effects. Measures of neurological, cognitive and motor function showed no change following rrTMS. From the EMG recording there was evidence of increase in the amplitude of the motor evoked potentials (MEPs) recorded from the biceps in one subject during the first block of rrTMS, but this did not occur in the second block. A similar magnification of MEPs was also observed in another subject only during the second block of stimulation. When applied using parameters falling within published guidelines (Pascual-Leone et al., 1993; Pascual-Leone et al., 1994), repeated rrTMS is a relatively safe technique in healthy normal subjects. As rrTMS allows disruption of cortical function for a longer period, it has the potential of becoming a particularly useful tool for the study of cognitive function as well as sensory or motor function.


Eye contricks.
Pictorial images are icons as well as eye-cons: they provide distillations of objects or ideas into simpler shapes. They create the impression of representing that which cannot be presented. Even at the level of the photograph, the links between icon and object are tenuous. The dimensions of depth and motion are missing from icons, and these alone introduce all manner of potential ambiguities. The history of art can be considered as exploring the missing link between icon and object. Eye-cons can also be illusions-tricks of vision so that what is seen does not necessarily correspond to what is physically presented. Pictorial images can be spatialised or stylised; spatialised images generally share some of the projective characteristics of the object represented. Written words are also icons, but they do not resemble the objects they represent-they are stylised or conventional. Icons as stylised words and spatialised images were set in delightful opposition by René Magritte in a series of pipe paintings, and this theme is here alluded to. Most of visual science is now concerned with icons-two-dimensional displays on computer monitors. Is vision now the science of eye-cons?


Interaction of androgens and estrogens in the control of sexual behavior in male Japanese quail.
A series of 4 experiments was performed to study the relative contribution of androgens and estrogens in the activation of sexual behavior in castrated male quail. The synthetic androgen methyltrienolone (R 1881) which is not metabolized in androgen target tissues activated sexual behavior in castrated birds and at the dose level of 0.5-1 mg/day/animal had the same potency as testosterone (T). However R 1881 was much more active than T in the induction of cloacal gland growth and activation of crowing, two typically androgen-dependent responses. This suggests that sexual behavior is not controlled by exactly the same mechanism as crowing or cloacal gland growth. In another experiment, estradiol (E2) alone activated sexual behavior but it is only at very high doses which had clear toxic effects that a significant behavioral activation could be observed. This questions the role of E2 as the physiological agent stimulating copulation in intact birds unless it is assumed that centrally administered E2 would be much more active compared to peripheral E2 which is exposed to a very intense peripheral catabolism. In the last two experiments, a clear synergism could be detected between 5 alpha-dihydrotestosterone (5 alpha-DHT) and E2 in the activation of sexual activity and doses of hormones could be defined which had almost no activity by themselves but significantly stimulated sexual behavior when given simultaneously. It was however impossible to define a hormonal treatment with T metabolites which restored behavior to its precastration level, a result very easily achieved with T treatments. Taken together, these data suggest that activation of sexual behavior in quail does not depend only on E2, nor 5 alpha-DHT nor even on their combined action. Considering that specific T receptors which probably do not bind 5 alpha-DHT are present in the brain, it would seem justified to reconsider the possible role played by T itself in the activation of behavior.


The effect of the interaction of propofol and alfentanil on recall, loss of consciousness, and the Bispectral Index.
The Bispectral Index (BIS) correlates well with the level of consciousness with single anesthetic drugs. We studied the effect of the interaction of propofol with alfentanil on propofol concentration and BIS associated with 50% probability of loss of consciousness and lack of recall (Cp50 and BIS50, respectively). We studied 40 consenting volunteers at two institutions who were randomly assigned to receive stepped increases of propofol (10 subjects at each site), propofol plus alfentanil 50 ng/mL (10 subjects at Emory site), or propofol plus alfentanil 100 ng/mL (10 subjects at Duke site) by using a target-controlled infusion device. Measures of sedation, BIS, deltaBIS (absolute change of BIS after a painful stimulus), memory, and drug concentration were obtained at each target drug concentration. The relation among BIS, measured drug concentration, sedation score, and presence or absence of recall was determined by linear and logistic regression for different drug regimens, and the prediction probability (Pk) was calculated. The addition of alfentanil in increasing doses did not significantly affect the BIS50 and propofol Cp50 values for loss of consciousness and lack of recall. DeltaBIS was significantly decreased by both an increase in the concentration of propofol and the presence of alfentanil. The Pk for BIS was >0.93 with all drug regimens, better than those of the target and measured propofol concentrations. We conclude that BIS correlated well with the hypnotic component of anesthesia independent of the presence of an opioid. Moreover, the level of consciousness, and, therefore, the BIS index, is affected by a painful stimulus, and this response is ablated either by opioids or increasing propofol concentration. In volunteers, the sedation and changes in memory function produced by propofol correlated well with changes in the Bispectral Index. This relationship was not altered by the addition of an analgesic (alfentanil). However, in moderately sedated patients who received a painful stimulus, the Bispectral Index increased, but this response was blocked by the analgesic or increasing propofol concentrations.


Therapeutic use of OKT3 monoclonal antibody for acute renal allograft rejection.
OKT3, a murine monoclonal anti-T-cell antibody, was used to treat acute renal allograft rejection crises in 140 patients. When used for primary treatment of initial rejections, it was effective in all 20 recipients of related-donor (RD) grafts and in 70 of 74 recipients of cadaver-donor (CD) grafts. OKT3 was also used for resistant rejection unresponsive to conventional antirejection drugs and was effective in 11 of 13 RD and in 26 of 33 CD recipients. Rerejection occurred in 58% of patients in the OKT3 primary treatment group and in 35% of patients in the OKT3 rescue group. Fifty-nine percent of the patients produced anti-OKT3 antibodies. Nearly all recipients experienced a flu-like syndrome following the first and second daily doses of OKT3. Two-year actuarial patient survivals were 100 and 96% for RD and CD recipients, respectively. In the OKT3 primary treatment group, two-year actuarial RD and CD graft survivals were 91 and 76%, respectively. In the OKT3 rescue group, the two-year actuarial RD and CD graft survivals were 85 and 55%, respectively. A proposed immunosuppressive effect of OKT3 is T-cell inactivation by blocking antigen receptors linked to OKT3-reactive molecules. Reuse of OKT3 for recurrent rejection or subsequent organs may be hampered by anti-OKT3 antibody production. OKT3 is an effective steroid-sparing treatment for renal allograft rejection.


Global and regional dissemination and evolution of Burkholderia pseudomallei.
The environmental bacterium Burkholderia pseudomallei causes an estimated 165,000 cases of human melioidosis per year worldwide and is also classified as a biothreat agent. We used whole genome sequences of 469 B. pseudomallei isolates from 30 countries collected over 79 years to explore its geographic transmission. Our data point to Australia as an early reservoir, with transmission to Southeast Asia followed by onward transmission to South Asia and East Asia. Repeated reintroductions were observed within the Malay Peninsula and between countries bordered by the Mekong River. Our data support an African origin of the Central and South American isolates with introduction of B. pseudomallei into the Americas between 1650 and 1850, providing a temporal link with the slave trade. We also identified geographically distinct genes/variants in Australasian or Southeast Asian isolates alone, with virulence-associated genes being among those over-represented. This provides a potential explanation for clinical manifestations of melioidosis that are geographically restricted.


The use of larval therapy to reduce the bacterial load in chronic wounds.
To ascertain the effect of larval therapy against bacteria associated with infected chronic wounds, and determine if larvae therapy actively reduces the bacterial load in chronic wounds. An extended literature review was undertaken using online databases: Athens, Medline, EMBASE, British Nursing Index and Allied and Complementary Medicine via OV ID and Cumulative Index to Nursing and Allied Health. Key terms were searched worldwide from 1950 to 2011. Four themes emerged: Gram-positive and Gram-negative bacteria, MRSA, quorum sensing: biofilm consideration and bacterial burden. This suggests larvae debridement therapy is differentially effective against both Gram-positive and Gram-negative bacterial strains, namely Staphylococcus aureus, Pseudomonas aeruginosa and meticillin-resistant Staphylococcus aureus. The evidence supports the use of antimicrobial properties of larvae therapy against the bacteria of infected chronic wounds. There were no external sources of funding for this literature review. This paper is based on an independent study submitted as part of the BSc Health Care Studies, (Tissue Viability), University of Nottingham, UK. The authors have no competing or financial interest to declare and ethical approval and funding were not required to undertake the study.