Geophysical and Geochemical Approach for Seawater Intrusion Assessment in the Godavari Delta Basin, A.P., India.
Coastal lands around Bay of Bengal in Central Godavari Delta are mainly agriculture fields and two times annually paddy crops putting in the study area. Canals of Godavari River are the main source of water for irrigation. Geophysical and geochemical investigations were carried out in the study area to decipher subsurface geologic formation and assessing seawater intrusion. Electrical resistivity tomographic surveys carried out in the watershed-indicated low resistivity formation in the upstream area due to the presence of thick marine clays up to thickness of 20-25 m from the surface. Secondly, the lowering of resistivity may be due to the encroachment of seawater in to freshwater zones and infiltration during tidal fluctuation through mainly the Pikaleru drain, and to some extent rarely through Kannvaram and Vasalatippa drains in the downstream area. Groundwater quality analyses were made for major ions revealed brackish nature of groundwater water at shallow depth. The in situ salinity of groundwater is around 5,000 mg/l and there is no groundwater withdrawal for irrigation or drinking purpose in this area except Cairn energy pumping wells which is using for inject brackish water into the oil wells for easy exploration of oil. Chemical analyses of groundwater samples have indicated the range of salt concentrations and correlation of geophysical and borehole litholog data in the study area predicting seawater-contaminated zones and influence of in situ salinity in the upstream of study area. The article suggested further studies and research work that can lead to sustainable exploitation/use and management of groundwater resources in coastal areas.


Protease activation and cleavage of poly(ADP-ribose) polymerase: an integral part of apoptosis in response to photodynamic treatment.
Apoptosis induced by numerous cancer chemotherapeutic and other toxic agents has been shown to proceed through a cascade of proteases, now termed caspases, culminating in cleavage of a set of proteins. The ability of photodynamic treatment (PDT) with the phthalocyanine Pc 4 to activate cellular caspases has been assessed during the rapid apoptosis in murine lymphoma L5178Y-R cells. Cells were exposed to combinations of Pc 4 and activating red light that result in > or =90% cell death, as judged by a clonogenic assay. The rate of entry of cells into apoptosis was dose dependent. For 0.5 microM Pc 4 and either 2.1 or 3 kJ/m2, which kill 90 or 99.9% of the cells, oligonucleosomal fragmentation was visible on agarose gels as early as 60 or 30 min after PDT, respectively. To assess caspase activation, cells were harvested at various times after PDT, and cell proteins were subjected to electrophoresis and Western blot analysis, using an antibody to poly(ADP-ribose) polymerase (PARP). The cleavage of the normally Mr 116,000 PARP into fragments of Mr approximately 90,000 was observed at approximately the same time as the earliest DNA fragmentation. An antibody to the polymer, poly(ADP-ribose), did not recognize the Mr approximately 90,000 PARP cleavage products, in contrast to the parent enzyme. This analysis also revealed that levels of a poly(ADP-ribosylated) Mr 100,000 protein, tentatively identified as topoisomerase I, were maintained in cells after PARP was fully cleaved. Caspase-3 (and/or caspase-7) activity, as measured in cell lysates with the fluorogenic substrate DEVD-AMC, was elevated almost immediately after PDT. The cell-permeable, irreversible caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp(O-methyl)-fluoro-methylketone, inhibited PDT-induced apoptosis and PARP cleavage, whereas the inactive peptide analogue, benzyloxycarbonyl-Phe-Ala-fluoromethyl ketone, was without effect. The results indicate that PDT-induced apoptosis is mediated by activation of caspase-3 and/or other similar caspases.


First year of Maryland's new CRP statute in one state hospital.
The first year of Maryland's new Clinical Review Panel (CRP) statute in one state psychiatric hospital is reviewed. CRPs provide a nonjudicial means to administer medication to an involuntarily committed psychiatric patient refusing medicines in a nonemergency situation. While the statute adds appropriate formal procedural protections and while the CRP process "works," the statute also adds the possibility of unnecessary legal proceedings. Clinical decisions about medications should be made by psychiatrists and not by lawyers or judges.


"In situ similis" Culturing of Plant Microbiota: A Novel Simulated Environmental Method Based on Plant Leaf Blades as Nutritional Pads.
High-throughput cultivation methods have recently been developed to accelerate the recovery of microorganisms reluctant to cultivation. They simulate in situ environmental conditions for the isolation of environmental microbiota through the exchange of growth substrates during cultivation. Here, we introduce leaf-based culture media adopting the concept of the plant being the master architect of the composition of its microbial community. Pre-physical treatments of sunflower plant leaves, namely punching, freezing, and/or autoclavation, allowed the diffusion of electrolytes and other nutrients to configure the leaf surface as a natural pad, i.e., creating an "in situ similis" environment suitable for the growth of rarely isolated microbiota. We used surface inoculation and membrane-filtration methods to assess the culturability of endophytic bacteria from the sunflower phyllosphere and rhizosphere. Both methods supported excellent colony-forming unit (CFU) development when compared to standard R2A medium, with a special affinity to support better growth of epiphytic and endophytic populations of the phyllosphere compared with the rhizosphere. A 16S rRNA gene analysis of >122 representative isolates indicated the cultivation of a diverse set of microorganisms by application of the new methods. It indicated the predominance of 13 genera of >30 potential species, belonging to Firmicutes, Proteobacteria, and Actinobacteria, and especially genera not commonly reported for sunflower, e.g., Rhizobium, Aureimonas, Sphingomonas, Paracoccus, Stenotrophomonas, Pantoea, Kosakonia, and Erwinia. The strategy successfully extended diversity and richness in the endophyllosphere compared to the endorhizosphere, while CFUs grown on the standard R2A medium mainly pertain to Firmicutes, especially Bacillus spp. MALDI-TOF MS analysis clustered the isolates according to their niche and potential functions, where the majority of isolates of the endorhizosphere were clustered away from those of the endophyllosphere. Isolates identified as Gammaproteobacteria and Alphaproteobacteria were distinguishably sub-clustered, which was in contrast to the heterogeneous isolates of Firmicutes (Bacillus spp.). In conclusion, leaf in situ similis cultivation is an effective strategy to support the future application of culturomics of plant microbiota. This is an effort to access novel isolates that are more adapted and competitive in their natural environments, especially those subjected to abiotic stresses like those prevailing in arid/semi-arid zones, and, consequently, to support the application of agro-biotechnologies, among other technologies, to improving agriculture in such zones.


Evaluation of treatment for congestive heart failure in patients aged 60 years and older using generic measures of health status (SF-36 and COOP charts).
to assess the functioning and well-being of older patients presenting with congestive heart failure (CHF) using established generic health status measures-the short form 36 health survey (SF-36) and Dartmouth COOP charts. patients aged 60 or older with CHF were asked if they would take part. They were requested to complete interviewer-administered questionnaires before angiotensin converting enzyme (ACE) inhibitor treatment and at follow-up 4 weeks later. The interviewer administered the SF-36, COOP charts, the oxygen cost diagram and also asked patients to assess their health state overall and, after treatment, to assess changes, if any, in overall health. multi-dimensional health status measures indicate that patient's functioning and well-being is substantially compromised by CHF, especially in areas relating to physical functioning, and that treatment with ACE inhibitors has only limited effect in improving health-related quality of life. However, on simple single-item global assessments of health, patients report that their overall health-related quality of life is good and many report improvements in overall health status at follow-up. ACE inhibitor treatment, whilst lengthening life, has a relatively limited impact on its quality. While multidimensional health status measures indicate CHF to be associated with poor health as measured by the SF-36 and COOP charts. However, when patients are asked simple single-item questions relating to their overall health state and the extent of change experienced after treatment, they report relatively good health and positive improvements as a consequence of therapy. Since elderly patients' expectations of improvement may be modest and their expectations of physical ability relatively limited, relatively small improvements, which may not appear large when reported in effect size statistics, may be important. Standardized questionnaires, and standardized statistical methods of assessing change, may not be appropriate for this patient group. A fuller understanding of their expectations and assessment of treatment outcomes is necessary.


Enzyme-directed assembly and manipulation of organic nanomaterials.
Enzymes are the prime protagonists in the chemistry of living organisms. As such, chemists and biologists have long been fascinated by the array of highly selective transformations possible under biological conditions that are facilitated by enzyme-catalyzed reactions. Moreover, enzymes are involved in replicating, repairing and transmitting information in a highly selective and organized fashion through detection and signal amplification cascades. Indeed, because of their selectivity and potential for use outside of biological systems, enzymes have found immense utility in various biochemical assays and are increasingly finding applications in the preparation of small molecules. By contrast, the use of enzymatic reactions to prepare and build supramolecular and nanoscale materials is relatively rare. In this article, we seek to highlight efforts over the past 10 years at taking advantage of enzymatic reactions to assemble and manipulate complex soft, organic materials on the nanoscale. It is tantalizing to think of these processes as mimics of natural systems where enzymes are used in the assembly and transformation of the most complex nanomaterials known, for example, virus capsid assemblies and the myriad array of nanoscale biomolecular machinery.


Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice.
Following circulation of avian influenza H5 and H7 viruses in poultry, the hemagglutinin (HA) can acquire additional glycosylation sites, and the neuraminidase (NA) stalk becomes shorter. We investigated whether these features play a role in the pathogenesis of infection in mammalian hosts. From 1996 to 2007, H5N1 viruses with a short NA stalk have become widespread in several avian species. Compared to viruses with a long-stalk NA, viruses with a short-stalk NA showed a decreased capacity to elute from red blood cells and an increased virulence in mice, but not in chickens. The presence of additional HA glycosylation sites had less of an effect on virulence than did NA stalk length. The short-stalk NA of H5N1 viruses circulating in Asia may contribute to virulence in humans.


Signaling receptome: a genomic and evolutionary perspective of plasma membrane receptors involved in signal transduction.
Intercellular communication in multicellular organisms requires the relay of extracellular signals by cell surface proteins to the interiors of cells. The availability of genome sequences from humans and several model organisms has facilitated the identification of several human plasma membrane receptor families and allowed the analysis of their phylogeny. This review provides a global categorization of most known signal transduction-associated receptors as enzymes, recruiters, and latent transcription factors. The evolution of known families of human plasma membrane signaling receptors was traced in current literature and validated by sequence relatedness. This global analysis reveals themes that recur during receptor evolution and allows the formulation of hypotheses for the origins of receptors. The human receptor families involved in signaling (with the exception of channels) are presented in the Human Plasma Membrane Receptome database.


Molecular evolution of regulatory genes in spruces from different species and continents: heterogeneous patterns of linkage disequilibrium and selection but correlated recent demographic changes.
Genes involved in transcription regulation may represent valuable targets in association genetics studies because of their key roles in plant development and potential selection at the molecular level. Selection and demographic signatures at the sequence level were investigated for five regulatory genes belonging to the knox-I family (KN1, KN2, KN3, KN4) and the HD-Zip III family (HB-3) in three Picea species affected by post-glacial recolonization in North America and Europe. To disentangle neutral and selective forces and estimate linkage disequilibrium (LD) on a gene basis, complete or nearly complete gene sequences were analysed. Nucleotide variation within species, haplotype structure, LD, and neutrality tests, in addition to coalescent simulations based on Tajima's D and Fay and Wu's H, were estimated. Nucleotide diversity was generally low in all species (average pi = 0.002-0.003) and much heterogeneity was seen in LD and selection signatures among genes and species. Most of the genes harboured an excess of both rare and frequent alleles in the three species. Simulations showed that this excess was significantly higher than that expected under neutrality and a bottleneck during the Last Glacial Maximum followed by population expansion at the Pleistocene/Holocene boundary or shortly after best explains the correlated sequence patterns. These results indicate that despite recent large demographic changes in the three boreal species from two continents, species-specific selection signatures could still be detected from the analysis of nearly complete regulatory gene sequences. Such different signatures indicate differential subfunctionalization of gene family members in the three congeneric species.


Tel1/ETV6 specifies blood stem cells through the agency of VEGF signaling.
The regulation of stem cell ontogeny is poorly understood. We show that the leukemia-associated Ets transcription factor, Tel1/ETV6, specifies the first hematopoietic stem cells (HSCs) in the dorsal aorta (DA). In contrast, Tel1/ETV6 has little effect on embryonic blood formation, further distinguishing the programming of the long- and short-term blood populations. Consistent with the notion of concordance of arterial and HSC programs, we show that Tel1/ETV6 is also required for the specification of the DA as an artery. We further show that Tel1/ETV6 acts by regulating the transcription of VegfA in both the lateral plate mesoderm and also in the somites. Exogenous VEGFA rescues Tel1/ETV6 morphants, and depletion of VEGFA or its receptor, Flk1, largely phenocopies Tel1/ETV6 depletion. Few such links between intrinsic and extrinsic programming of stem cells have been reported previously. Our data place Tel1/ETV6 at the apex of the genetic regulatory cascade leading to HSC production.


Antibacterial membrane attack by a pore-forming intestinal C-type lectin.
Human body-surface epithelia coexist in close association with complex bacterial communities and are protected by a variety of antibacterial proteins. C-type lectins of the RegIII family are bactericidal proteins that limit direct contact between bacteria and the intestinal epithelium and thus promote tolerance to the intestinal microbiota. RegIII lectins recognize their bacterial targets by binding peptidoglycan carbohydrate, but the mechanism by which they kill bacteria is unknown. Here we elucidate the mechanistic basis for RegIII bactericidal activity. We show that human RegIIIα (also known as HIP/PAP) binds membrane phospholipids and kills bacteria by forming a hexameric membrane-permeabilizing oligomeric pore. We derive a three-dimensional model of the RegIIIα pore by docking the RegIIIα crystal structure into a cryo-electron microscopic map of the pore complex, and show that the model accords with experimentally determined properties of the pore. Lipopolysaccharide inhibits RegIIIα pore-forming activity, explaining why RegIIIα is bactericidal for Gram-positive but not Gram-negative bacteria. Our findings identify C-type lectins as mediators of membrane attack in the mucosal immune system, and provide detailed insight into an antibacterial mechanism that promotes mutualism with the resident microbiota.


Complications associated with prolonged hypertonic saline therapy in children with elevated intracranial pressure.
Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline. Retrospective chart analysis. PICU in university-affiliated children's hospital. All children from 2004 to 2009 requiring intracranial pressure monitoring (external ventricular drain or fiberoptic intraparenchymal monitor) for at least 4 days who were treated with hypertonic saline infusion for elevated intracranial pressure and did not meet exclusion criteria. Continuous hypertonic saline infusion on a sliding scale was used to achieve target sodium levels that would keep intracranial pressure less than 20 mm Hg once the conventional therapies failed. Eighty-eight children met inclusion criteria. Etiologies of elevated intracranial pressure included trauma (n = 48), ischemic or hemorrhagic stroke (n = 20), infection (n = 8), acute disseminated encephalomyelitis (n = 5), neoplasm (n = 2), and others (n = 5). The mean peak serum sodium was 171.3 mEq/L (range, 150-202). The mean Glasgow Outcome Score was 2.8 (± 1.1) at time of discharge from the hospital. Overall mortality was 15.9%. Children with sustained (> 72 hr) serum sodium levels above 170 mEq/L had a significantly higher occurrence of thrombocytopenia (p < 0.001), renal failure (p < 0.001), neutropenia (p = 0.006), and acute respiratory distress syndrome (p = 0.029) after controlling for variables of age, gender, Pediatric Risk of Mortality score, duration of barbiturate-induced coma, duration of intracranial pressure monitoring, vasopressor requirements, and underlying pathology. Children with sustained serum sodium levels greater than 165 mEq/L had a significantly higher prevalence of anemia (p < 0.001). Children treated by continuous hypertonic saline infusion for intracranial hypertension whose serum sodium levels exceeded certain thresholds experienced significantly more events of acute renal failure, thrombocytopenia, neutropenia, anemia, and acute respiratory distress syndrome than those whose sodium level was maintained below these thresholds.


Gene-environment correlation linking aggression and peer victimization: do classroom behavioral norms matter?
Using a genetically informed design based on 197 Monozygotic and Dizygotic twin pairs assessed in grade 4, this study examined 1) whether, in line with a gene-environment correlation (rGE), a genetic disposition for physical aggression or relational aggression puts children at risk of being victimized by their classmates, and 2) whether this rGE is moderated by classroom injunctive norm salience in regard to physical or relational aggression. Physical aggression and relational aggression, as well as injunctive classroom norm salience in regard to these behaviors, were measured via peer nominations. Peer victimization was measured via self-reports. Multi-Level Mixed modeling revealed that children with a genetic disposition for either aggressive behavior are at higher risk of being victimized by their peers only when classroom norms are unfavourable toward such behaviors. However, when classroom injunctive norms favor aggressive behaviors, a genetic disposition for physical or relational aggression may actually protect children against peer victimization. These results lend further support to the notion that bullying interventions must include the larger peer context instead of a sole focus on victims and bullies.


Group A Streptococcus secreted esterase hydrolyzes platelet-activating factor to impede neutrophil recruitment and facilitate innate immune evasion.
The innate immune system is the first line of host defense against invading organisms. Thus, pathogens have developed virulence mechanisms to evade the innate immune system. Here, we report a novel means for inhibition of neutrophil recruitment by Group A Streptococcus (GAS). Deletion of the secreted esterase gene (designated sse) in M1T1 GAS strains with (MGAS5005) and without (MGAS2221) a null covS mutation enhances neutrophil ingress to infection sites in the skin of mice. In trans expression of SsE in MGAS2221 reduces neutrophil recruitment and enhances skin invasion. The sse deletion mutant of MGAS5005 (Δsse(MGAS5005)) is more efficiently cleared from skin than the parent strain. SsE hydrolyzes the sn-2 ester bond of platelet-activating factor (PAF), converting biologically active PAF into inactive lyso-PAF. K(M) and k(cat) of SsE for hydrolysis of 2-thio-PAF were similar to those of the human plasma PAF acetylhydrolase. Treatment of PAF with SsE abolishes the capacity of PAF to induce activation and chemotaxis of human neutrophils. More importantly, PAF receptor-deficient mice significantly reduce neutrophil infiltration to the site of Δsse(MGAS5005) infection. These findings identify the first secreted PAF acetylhydrolase of bacterial pathogens and support a novel GAS evasion mechanism that reduces phagocyte recruitment to sites of infection by inactivating PAF, providing a new paradigm for bacterial evasion of neutrophil responses.


Sticking to (first) principles: quantum molecular dynamics and Bayesian probabilistic methods to simulate aquatic pollutant absorption spectra.
This work explores the relationship between theoretically predicted excitation energies and experimental molar absorption spectra as they pertain to environmental aquatic photochemistry. An overview of pertinent Quantum Chemical descriptions of sunlight-driven electronic transitions in organic pollutants is presented. Second, a combined molecular dynamics (MD), time-dependent density functional theory (TD-DFT) analysis of the ultraviolet to visible (UV-Vis) absorption spectra of six model organic compounds is presented alongside accurate experimental data. The functional relationship between the experimentally observed molar absorption spectrum and the discrete quantum transitions is examined. A rigorous comparison of the accuracy of the theoretical transition energies (ΔES0→Sn) and oscillator strength (fS0→Sn) is afforded by the probabilistic convolution and deconvolution procedure described. This method of deconvolution of experimental spectra using a Gaussian Mixture Model combined with Bayesian Information Criteria (BIC) to determine the mean (μ) and standard deviation (σ) as well as the number of observed singlet to singlet transition energy state distributions. This procedure allows a direct comparison of the one-electron (quantum) transitions that are the result of quantum chemical calculations and the ensemble of non-adiabatic quantum states that produce the macroscopic effect of a molar absorption spectrum. Poor agreement between the vertical excitation energies produced from TD-DFT calculations with five different functionals (CAM-B3LYP, PBE0, M06-2X, BP86, and LC-BLYP) suggest a failure of the theory to capture the low energy, environmentally important, electronic transitions in our model organic pollutants. However, the method of explicit-solvation of the organic solute using the quantum Effective Fragment Potential (EFP) in a density functional molecular dynamics trajectory simulation shows promise as a robust model of the hydrated organic pollutant. Furthermore, the described protocol can be extended using higher-level equilibration and vertical excitation methods to increase the numerical accuracy and describe multi-reference electronic transitions. Finally, a measure of the accuracy of theoretically derived absorption spectra is discussed as a tool to further develop our capacity to produce accurate a priori simulations of sunlight-driven photochemistry in natural waters.


Topography, structure and function of the patella and the patelloid in marsupials.
The patella is a sesamoid bone that is found in most mammals and is regularly located in the insertion tendon of the quadriceps femoris muscle. Up to now, only a little has been known about the topography, structure and function of the patella in marsupials. Therefore the stifles of 61 marsupials of 30 different species were studied by radiography, necropsy and light microscopy. It was found that only the family of bandicoots (Peramelidae) possessed a typical patella. The other species revealed a patelloid consisting of fibrocartilage. The structure of the patelloid revealed common characteristic features in the following families of marsupials: (1) Dasyuridae, Phalangeridae. Pseudocheriidae, and Potoroidae; (2) Burramyidae; (3) Phascolarctidae, Vombatidae, and Dendrolagus; and (4) Superfamily Macropodoidea (except Dendrolagus and Potoroidae). Our results imply that the degree of differentiation in the fibrocartilage of the patelloid was strongly correlated to the mechanical forces acting on the patelloid which are a result of the specific kind of locomotion and the way of life. Generally the bony patella does not belong to the phylogenetic programme of the marsupials--with the exception of the bandicoots which are very closely related to the subclass of placental mammals (Eutheria).


The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma.
Quality of response is associated with prolonged overall survival (OS) in newly diagnosed multiple myeloma patients. This cohort study within the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of bortezomib versus dexamethasone in relapsed myeloma assessed the relationship between quality of response to bortezomib (n = 315) and clinical benefit. Treatment-free interval (TFI), time to alternative therapy (TTAT), time to progression (TTP) and OS were assessed in response-evaluable patients in the bortezomib arm in cohorts defined by achievement of complete response (CR; n = 27), very good partial response (VGPR; n = 31), partial response (PR; n = 77), minimal response (MR; n = 21) or non-response (NR, including stable and progressive disease; n = 159). CR was associated with significantly longer median TFI (24.1 vs. 6.9/6.4 months) and TTAT (27.1 vs. 13.6/14 months) versus VGPR/PR. Median TTP was similar in CR, VGPR and PR cohorts; median OS was not reached. Patients achieving MR appeared to have prolonged median TFI (3.8 vs. 2.3 months), TTAT (8.7 vs. 6.2 months), TTP (4.9 vs. 2.8 months) and OS (24.9 vs. 18.7 months) versus NR. In conclusion, bortezomib had substantial activity in relapsed myeloma patients; CR may be a surrogate marker for significant clinical benefit with bortezomib. MR appeared to be valid as a separate response category in this setting.


Evaluation of a pharmacology-driven dosing algorithm of 3-weekly paclitaxel using therapeutic drug monitoring: a pharmacokinetic-pharmacodynamic simulation study.
Severe neutropenia is the most frequent and important toxicity of 3-weekly paclitaxel and puts patients at substantial risk of infectious complications. It is well known that the time during which paclitaxel plasma concentrations exceed 0.05 μmol/L (T(C>0.05)) correlates with the extent of neutropenia. This study was initiated to develop a dosing algorithm that would be able to reduce severe neutropenia by targeting an individual paclitaxel T(C>0.05) between 26 and 31 hours, and could be validated in a prospective randomized trial by comparing it to conventional dosing of paclitaxel. Paclitaxel plasma concentration-time (n = 273) and absolute neutrophil count (ANC) data (152 of the 273 patients) were pooled from two previous studies and submitted to population pharmacokinetic and pharmacodynamic modelling using nonlinear mixed-effects modelling software NONMEM® version VII. To fit the data, we used a previously described 3-compartment model with saturable elimination and distribution, coupled to a semiphysiological model with a linear function to describe the myelotoxic effect of paclitaxel (E(paclitaxel)) on circulating neutrophils (neutropenia). Patient age, sex, body surface area (BSA), bilirubin and renal function were tested as potential covariates on the maximum elimination capacity of paclitaxel (VM(EL)). Limited sampling strategies were tested on the pharmacokinetic model for their accuracy to predict paclitaxel T(C>0.05). Subsequently, we proposed a first-cycle dosing algorithm that accounted for BSA, patient age and sex, while later cycles accounted for the previous-cycle paclitaxel T(C>0.05) (target: 26 to 31 hours) and ANC nadir to adapt the paclitaxel dose for the next treatment cycle. To test the adequacy of the proposed dosing algorithm, we used extensive data simulations on the final pharmacokinetic/pharmacodynamic model, generating datasets of 1000 patients for six subsequent treatment cycles. Grade 4 neutropenia was tested as a potential endpoint for a prospective clinical trial and simulated for two scenarios, i.e. conventional dosing of paclitaxel 200 mg/m(2) every 3 weeks, and personalized, pharmacology-driven dosing as outlined above. Concentration-time data for paclitaxel were adequately described by the 3-compartment model. Also, individual ANC counts were adequately described by the semiphysiological model using a linear function to describe E(paclitaxel) on neutropenia. Patient age, sex, bilirubin and BSA were significant and independent covariates on the elimination of paclitaxel. Paclitaxel VM(EL) was 16% higher in males than in female patients, and a 10-year increase in age led to a 13% decrease in VM(EL). A single paclitaxel plasma concentration 24 hours after the start of infusion was adequate to predict paclitaxel T(C>0.05) (root squared mean error [RSME] = +0.5%), and the addition of an end-of-infusion sample did not further improve precision (RSME = -0.6%). Data simulations on the final pharmacokinetic/pharmacodynamic model and using the proposed dosing algorithm resulted in a first-cycle paclitaxel dose ranging from 150 to 185 mg/m(2) for women and from 165 to 200 mg/m(2) for men. Dose adaptations for cycles two to six ranged from -40% to +30%, with a final median paclitaxel dose of 167 mg/m(2) (range 76 to 311 mg/m(2)). When compared with conventional dosing (paclitaxel 200 mg/m(2) every 3 weeks), personalized dosing reduced grade 4 neutropenia in cycle one from 15% to 7%, and further to 4% in cycle 2. This study proposes a pharmacology-driven dosing algorithm of 3-weekly paclitaxel to reduce the incidence of grade 4 neutropenia. A randomized clinical trial comparing this dosing algorithm with conventional BSA-based dosing of paclitaxel in patients with advanced non-small cell lung cancer is currently ongoing.


Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease.
Endemic skeletal fluorosis is a chronic metabolic bone and joint disease caused by ingesting large amounts of fluoride either through water or rarely from foods of endemic areas. Fluoride is a cumulative toxin which can alter accretion and resorption of bone tissue. It also affects the homeostasis of bone mineral metabolism. The total quantity of ingested fluoride is the single most important factor which determines the clinical course of the disease which is characterized by immobilization of joints of the axial skeleton and of the major joints of the extremities. A combination of osteosclerosis, osteomalacia and osteoporosis of varying degrees as well as exostosis formation characterizes the bone lesions. In a proportion of cases secondary hyperparathyroidism is observed with associated characteristic bone changes. Contrary to earlier thinking, severe crippling forms of skeletal fluorosis are seen in paediatric age group too. Increased metabolic turnover of the bone, impaired bone collagen synthesis and increased avidity for calcium are features in fluoride toxicity. Osteosclerotic picture is evident when small doses of fluoride are ingested over a long period of time during which calcium intakes are apparently normal while osteoporotic forms are common in paediatric age group and with higher body load of the element. Alterations in hormones concerned with bone mineral metabolism are seen in fluorosis. Kidney is the primary organ of excretion for fluorides. Age, sex, calcium intake in the diet, dose and duration of fluoride intake and renal efficiency in fluoride handling are the factors which influence the outcome. Serum parameters rarely help in the diagnosis. Elevated urinary fluoride and increased bone fluoride content are indicators of fluoride toxicity. Fluorosis is a preventable crippling disease. No effective therapeutic agent is available which can cure fluorosis. Industrial fluorosis is on the increase on a global basis. Bone density measurement is a tool for early diagnosis.


Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance.
We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals.


Perceived differences in social status between speaker and listener affect the speaker's vocal characteristics.
Non-verbal behaviours, including voice characteristics during speech, are an important way to communicate social status. Research suggests that individuals can obtain high social status through dominance (using force and intimidation) or through prestige (by being knowledgeable and skilful). However, little is known regarding differences in the vocal behaviour of men and women in response to dominant and prestigious individuals. Here, we tested within-subject differences in vocal parameters of interviewees during simulated job interviews with dominant, prestigious, and neutral employers (targets), while responding to questions which were classified as introductory, personal, and interpersonal. We found that vocal modulations were apparent between responses to the neutral and high-status targets, with participants, especially those who perceived themselves as low in dominance, increasing fundamental frequency (F0) in response to the dominant and prestigious targets relative to the neutral target. Self-perceived prestige, however, was less related to contextual vocal modulations than self-perceived dominance. Finally, we found that differences in the context of the interview questions participants were asked to respond to (introductory, personal, interpersonal), also affected their vocal parameters, being more prominent in responses to personal and interpersonal questions. Overall, our results suggest that people adjust their vocal parameters according to the perceived social status of the listener as well as their own self-perceived social status.


Thyroid dysfunction following a kelp-containing marketed diet.
Complementary medications and herbal medicine for weight loss have become very popular. We report a case of thyroid dysfunction following the ingestion of a kelp-containing marketed diet in a 45-year-old woman with no previous thyroid disease. Signs of hyperthyroidism occurred shortly after a kelp-containing diet. Hyperthyroidism lasted 2 months and was followed by an overt hypothyroidism. The thyroid scintiscan exhibited an extremely low uptake and colour-Doppler ultrasonography revealed multiple small areas of pulsatile flow. After 3 months of levothyroxine substitutive therapy, normal thyroid function was recovered after levothyroxine discontinuation. This clinical history is compatible with a case of iodine-induced thyrotoxicosis followed by prolonged block of the sodium-iodide symporter activity as a consequence of excessive iodine consumption from kelp. Consumers of marketed diets containing kelp or other iodine-rich ingredients should be advised of the risk to develop a thyroid dysfunction also in the absence of underlying thyroid disease.


Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthma.
In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/β and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coated well-plates and 3-dimensional collagen gels was assessed by measurement of inflammatory mediators and ECM proteins by ELISA and western blot, as well as collagen fiber formation using non-linear optical microscopy after 24-hours. The production of IL-1α is elevated in undifferentiated asthmatic-PAECs compared to controls. IL-1α/β induced fibroblast pro-inflammatory responses (CXCL8/IL-8, IL-6, TSLP, GM-CSF) and suppressed ECM-production (collagen, fibronectin, periostin) and the cell's ability to repair and remodel fibrillar collagen I via LOX, LOXL1 and LOXL2 activity, as confirmed by inhibition with β-aminopropionitrile. These data support a role for epithelial-derived-IL-1 in the dysregulated repair of the asthmatic-EMTU and provides new insights into the contribution of airway fibroblasts in inflammation and airway remodeling in asthma.


Bullying among 18 to 23-year-old women in 2013.
To identify the prevalence of bullying among women aged 18-23 in 2013, and to describe the demographic characteristics, health and risk factors of those who experienced bullying. Cross-sectional analysis using data from the 1989-95 cohort of the Australian Longitudinal Study on Women's Health, a nationally representative cohort (n=16,801). More than one-quarter of women (28.4%) indicated they had never been bullied, 53.4% reported experiencing bullying in the past and 18.2% indicated that they were recently bullied. Women who had experienced bullying were more likely to have lower levels of education, less likely to be studying or employed, and had more difficulty managing on their income. Women who experienced bullying were more likely to use tobacco or illicit drugs, be overweight or obese and to be sedentary. Even after adjusting for these factors, women who had experienced bullying were at risk of poor physical health, psychological distress, suicidal thoughts and self-harm. This is the first nationally representative study to demonstrate the strong association between being a victim of bullying and health outcomes in a post-school-age population. Implications for public health: The findings highlight the need for interventions for women who have already experienced bullying and are past school age.


Gene conversion at the SMN locus in autosomal recessive spinal muscular atrophy does not predict a mild phenotype.
Autosomal recessive proximal spinal muscular atrophy (SMA) is a disease of motor neuron death and a common cause of morbidity in childhood. It has been mapped to 5q13 and shown to be associated with deletions in a gene which has been called the survival motor neuron (SMN) gene. SMN exists in two copies in 5q13 and deletions in exon 7 and 8 of the telomeric copy (SMNtel) occur in over 90% of patients regardless of disease severity. In contrast, deletion of exon 7 and 8 of the centromeric copy of SMN is present in 3-5% of the normal population. In a minority of patients, exon 7 but not exon 8 of SMNtel appears deleted. The purpose of this study was to analyse this latter type of deletion in more detail. In all patients where there was absence of PCR amplification of exon 7 but not exon 8 of SMNtel this was found to be due to replacement with the homologous copy of SMNcen by a possible gene conversion event. This type of mutation occurred in all grades of severity of SMA.


Self-assembly of bis-salphen compounds: from semiflexible chains to webs of nanorings.
The recently-observed self-assembly of certain salphen-based compounds into neuron-like networks of microrings interconnected with nano-thin strings may suggest a new highly-potent tool for nanoscale patterning. However, the mechanism behind such phenomena needs to be clarified before they can be applied in materials design. Here we show that, in contrast with what was initially presumed, the emergence of a "rings-and-rods" pattern is unlikely to be explained by merging, collapse and piercing of vesicles as in previously reported cases of nanorings self-assembly via non-bonding interactions. We propose an alternative explanation: the compounds under study form a 1D coordination polymer, the fibres of which are elastic enough to fold into toroidal globules upon solvent evaporation, while being able to link separate chains into extended networks. This becomes possible because the structure of the compound's scaffold is found to adopt a very different conformation from that inferred in the original work. Based on ab initio and molecular dynamics calculations we propose a step-by-step description of self-assembly process of a supramolecular structure which explains all the observed phenomena in a simple and clear way. The individual roles of the compound' s scaffold structure, coordination centres, functional groups and solvent effects are also explained, opening a route to control the morphology of self-assembled networks and to synthesize new compounds exhibiting similar behaviour.


High [CO2] and Temperature Increase Resistance to Cyhalofop-Butyl in Multiple-Resistant Echinochloa colona.
Changes in the environment, specifically rising temperature and increasing atmospheric carbon dioxide concentration [CO2], can alter the growth and physiology of weedy plants. These changes could alter herbicide efficacy, crop-weed interaction, and weed management. The objectives of this research were to quantify the effects of increased atmospheric [CO2] and temperature on absorption, translocation and efficacy of cyhalofop-butyl on multiple-resistant (MR) and susceptible (S) Echinochloa colona genotypes. E. colona, or junglerice, is a troublesome weed in rice and in agronomic and horticultural crops worldwide. Cyhalofop-butyl is a grass herbicide that selectively controls Echinochloa spp. in rice. Maximum 14C-cyhalofop-butyl absorption occurred at 120 h after herbicide treatment (HAT) with >97% of cyhalofop-butyl retained in the treated leaf regardless of [CO2], temperature, or genotype. Neither temperature nor [CO2] affected herbicide absorption into the leaf. The translocation of herbicide was slightly reduced in the MR plants vs. S plants either under elevated [CO2] or high temperature. Although plants grown under high [CO2] or high temperature were taller than those in ambient conditions, neither high [CO2] nor high temperature reduced the herbicide efficacy on susceptible plants. However, herbicide efficacy was reduced on MR plants grown under high [CO2] or high temperature about 50% compared to MR plants at ambient conditions. High [CO2] and high temperature increased the resistance level of MR E. colona to cyhalofop-butyl. To mitigate rapid resistance evolution under a changing climate, weed management practitioners must implement measures to reduce the herbicide selection pressure. These measures include reduction of weed population size through reduction of the soil seedbank, ensuring complete control of current infestations with multiple herbicide modes of action in mixture and in sequence, augmenting herbicides with mechanical control where possible, rotation with weed-competitive crops, use of weed-competitive cultivars, use of weed-suppressive cover crops, and other practices recommended for integrated weed management.


Working Memory: Maintenance, Updating, and the Realization of Intentions.
"Working memory" refers to a vast set of mnemonic processes and associated brain networks, relates to basic intellectual abilities, and underlies many real-world functions. Working-memory maintenance involves frontoparietal regions and distributed representational areas, and can be based on persistent activity in reentrant loops, synchronous oscillations, or changes in synaptic strength. Manipulation of content of working memory depends on the dorsofrontal cortex, and updating is realized by a frontostriatal '"gating" function. Goals and intentions are represented as cognitive and motivational contexts in the rostrofrontal cortex. Different working-memory networks are linked via associative reinforcement-learning mechanisms into a self-organizing system. Normal capacity variation, as well as working-memory deficits, can largely be accounted for by the effectiveness and integrity of the basal ganglia and dopaminergic neurotransmission.


Sodium transport kinetics in erythrocytes from spontaneously hypertensive rats.
Rat erythrocytes with five different amounts of Na+ content have been prepared by using a new, nondetrimental Na+-loading method (net NaHPO4-influx through the anion carrier). This method allowed the determination of 1) maximal translocation rates and apparent dissociation constants for internal Na+ of the Na+-K+ pump, outward Na+-K+ cotransport, and Na+-Li+ countertransport and 2) rate constants of Na+ leak in erythrocytes from spontaneously hypertensive rats of the Okamoto strain and Wistar-Kyoto normotensive controls aged 2 to 26 weeks. Two major abnormalities were found in erythrocytes from spontaneously hypertensive rats: 1) a decreased cotransport affinity for internal Na+, which was constantly observed from 2 to 26 weeks of age (mean intracellular Na+ content for half-maximal stimulation of outward Na+-K+ cotransport = 33.1 +/- 7.0 [SD] mmol/L cells in spontaneously hypertensive rats vs 16.7 +/- 4.7 mmol/L cells in Wistar-Kyoto rats; p less than 0.001), and 2) a decreased maximal pump rate in adult (15- to 26-week-old) spontaneously hypertensive as compared with that for age-matched Wistar-Kyoto rats (9-37 vs 34-70 mmol/L cells/hr). Therefore, the low cotransport affinity for internal Na+ appears to be a stable, possibly genetic defect of spontaneously hypertensive rats. Conversely, the decreased maximal pump rate may be a secondary event, possibly reflecting the appearance of endogenous pump inhibitors in the plasma of adult spontaneously hypertensive rats.


Evidence for separate modes of action in thermal radiosensitization and direct thermal cell death.
It is not known whether heat potentiation of radiation damage and direct heat death are mediated by the same or by different heat lesions within the cell. In this study, three types of experiments were performed on BP-8 murine sarcoma cells to provide evidence against a common mode of action: (1)Evaluation of the kinetics of cell death from heat, radiation, and combined heat-radiation treatments: direct heat death is rapid and essentially complete within 24-48 hours after heat exposure, whereas radiation death develops only after a delay period of several days. Radiosensitization by heat affects only the delayed component of cell death, that is, the radiation component of death. (2)Thermal radiosensitization and direct heat death as a function of heating time: thermal radiosensitization requires only short exposures to heat; prolonged heating does not further enhance this effect. In contrast, direct heat death increases with increasing duration of heat exposure. (3)Independent modification of radiosensitization and thermal death: addition of 5% glycerol to the incubation medium protects cells against direct heat death, but not against thermal radiosensitization. In combination, these findings suggest that heat potentiation of radiation lethality and direct heat death are two distinct phenomena mediated by different cellular mechanisms.


An outbreak of campylobacteriosis at a hotel in England: the ongoing risk due to consumption of chicken liver dishes.
Despite a sizeable evidence base for the risk of campylobacteriosis associated with eating chicken liver pâté, associated outbreaks continue to occur. In January 2017, six cases of campylobacteriosis reported having eaten a Christmas set-menu meal at the same hotel in North Yorkshire, England on the same day. A retrospective cohort study was undertaken to test the null hypothesis that consumption of individual food items was not associated with an increased risk of illness. There were 19 cases of campylobacteriosis linked to the outbreak; seven confirmed and 12 probable cases. Chicken liver pâté was the food item most strongly associated with illness (P < 0.001) with a corresponding high crude relative risk (12.95). This relationship was supported by multivariable analysis, sensitivity analyses and a clear dose-response relationship. Three cases reported an incubation period of <24 h, consistent with other outbreaks of campylobacteriosis associated with consumption of poultry liver. The findings were suggestive of a single point source exposure with a strong association between the consumption of chicken liver pâté and campylobacteriosis. This outbreak highlights that despite evidence that simple cooking techniques can ensure that all campylobacter are killed during cooking, outbreaks continue to occur. Public and professional awareness needs to be raised through a strategic communication plan to reduce the risk of further outbreaks of campylobacteriosis linked to incorrectly cooked chicken liver dishes.


Corruption of innate immunity by bacterial proteases.
The innate immune system of the human body has developed numerous mechanisms to control endogenous and exogenous bacteria and thus prevent infections by these microorganisms. These mechanisms range from physical barriers such as the skin or mucosal epithelium to a sophisticated array of molecules and cells that function to suppress or prevent bacterial infection. Many bacteria express a variety of proteases, ranging from non-specific and powerful enzymes that degrade many proteins involved in innate immunity to proteases that are extremely precise and specific in their mode of action. Here we have assembled a comprehensive picture of how bacterial proteases affect the host's innate immune system to gain advantage and cause infection. This picture is far from being complete since the numbers of mechanisms utilized are as astonishing as they are diverse, ranging from degradation of molecules vital to innate immune mechanisms to subversion of the mechanisms to allow the bacterium to hide from the system or take advantage of it. It is vital that such mechanisms are elucidated to allow strategies to be developed to aid the innate immune system in controlling bacterial infections.


Selecting controls for schizophrenia research studies: the use of the National Adult Reading Test (NART) is a measure of premorbid ability.
The National Adult Reading Test (NART) has achieved popularity as a measure of pre-morbid intellectual ability, based on the premises that pronunciation of irregular words is unaffected in many clinical disorders and that performance is highly correlated with general intellectual ability. Recently, schizophrenia research studies have begun to appear in the literature, where the NART has been used to estimate pre-morbid ability. However, this use has preceded the basic required demonstration that, in fact, NART performance is unaffected by the schizophrenic process. In the present study, NART performance was compared across three groups; 20 acutely ill unmedicated DSM-IIIR schizophrenics, 10 other unmedicated acute psychotics, and 20 control subjects. When demographic variability between the groups was controlled for, there were no group differences in terms of NART performance. NART performance was not correlated with Brief Psychiatric Rating Scale scores, and in all three groups, no significant differences emerged when demographically predicted intelligence quotients were compared with NART estimated intelligence quotients. NART performance (predicted on the basis of demographic variables) was not significantly different from observed NART performance in any of the three experimental groups. However, within the sample with schizophrenia, NART estimated pre-morbid IQ was significantly higher than currently measured intellectual abilities. These results suggest that the National Adult Reading Test provides a reasonable estimate of pre-morbid ability in acutely ill, unmedicated schizophrenic patients.


Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm.
Yes-associated protein (YAP), the central mediator of Hippo pathway, not only regulates a diversity of cellular processes during development but also plays a pivotal role in tumorigenesis. YAP is overexpressed in many types of human cancers with its expression level being associated with patient outcomes. Thus, inhibiting YAP function could provide a novel therapeutic approach. Verteporfin, a photosensitizer, which has been used in photodynamic therapy (PDT), was recently identified as an inhibitor of the interaction of YAP with TEAD, which, in turn, blocks transcriptional activation of targets downstream of YAP. However, the mechanism by which Verteporfin inhibits YAP activity remains to be elucidated. We demonstrate that overexpression of YAP stimulates cell proliferation whereas knocking down YAP or treating cells with Verteporfin inhibited cell proliferation, even in the presence of growth factors. Protoporphyrin IX, another photosensitizer, did not have similar activity demonstrating specificity to Verteporfin. Verteporfin induced sequestration of YAP in cytoplasm through increasing levels of 14-3-3σ, a YAP chaperon protein that retains YAP in cytoplasm and targets it for degradation in the proteosome. Interestingly, while knockdown of YAP had no effect on the ability of Verteporfin to induce 14-3-3σ, p53 is required for this effect of Verteporfin. This provides potential approaches to select patients likely to benefit from Verteporfin.


Anatomic and functional asymmetries interactively shape human early visual cortex responses.
Early visual processing is surprisingly flexible even in the adult brain. This flexibility involves both long-term structural plasticity and online adaptations conveyed by top-down feedback. Although this view is supported by rich evidence from both human behavioral studies and invasive electrophysiology in nonhuman models, it has proven difficult to close the gap between species. In particular, it remains debated whether noninvasive measures of neural activity can capture top-down modulations of the earliest stages of processing in the human visual cortex. We previously reported modulations of retinotopic C1, the earliest component of the human visual evoked potential. However, these effects were selectively observed in the upper visual field (UVF). Here we test whether this asymmetry is linked to an interaction between differences in spatial resolution across the visual field and the specific stimuli used in previous studies. We measured visual evoked potentials in response to task-irrelevant, high-contrast textures of different densities in a comparatively large sample of healthy volunteers (N = 31) using high-density electroencephalogram. Our results show differential response profiles for upper and lower hemifields, with UVF responses saturating at higher stimulus densities. In contrast, lower visual field responses did not increase, and even showed a tendency toward a decrease at the highest density tested. We propose that these findings reflect feature- and task-specific pooling of signals from retinotopic regions with different sensitivity profiles. Such complex interactions between anatomic and functional asymmetries need to be considered to resolve whether human early visual cortex activity is modulated by top-down factors.


Provision of leucocyte poor blood at the bedside.
The Imugard IG 500 cotton wool filter and the Cellselect cellulose acetate filter were adapted for filtration of leucocytes from packed cell transfusions at the bedside. Sixty five transfusions were given via the Imugard IG 500 filter and 54 transfusions were given via the Cellselect filter. Packed red cell concentrates from the National Blood Transfusion Service provided for routine blood transfusions were used in all cases. No patient in either group of multitransfused patients experienced a febrile blood transfusion reaction during the study. The Imugard IG 500 removed 91% +/- 9 (SEM) leucocytes; the Cellselect removed 96% +/- 7 (SEM) leucocytes. In the Imugard IG 500 group one patient received greater than 0.5 X 10(9) leucocytes. In the Imugard IG 500 group one patient received greater than 0.5 X 10(9) leucocytes, but no patient in the Cellselect group received greater than 0.5 X 10(9) leucocytes in any single transfusion. This is a safe method of providing leucocyte poor blood at the bedside.


The Swedish validation of Edinburgh Postnatal Depression Scale (EPDS) during pregnancy.
Around 10-15% of women suffer from depressive illness during pregnancy or the first year postpartum. Depression during pregnancy constitutes a risk for prenatal stress and preterm birth. No validated screening instrument for detecting depression during pregnancy was available in Swedish. We aimed to validate the Edinburgh Postnatal Depression Scale (EPDS) against DSM-IV criteria for depression during pregnancy, establish a reliable cut-off and estimate the correlation between the EPDS and HAD-S (Hospital Anxiety and Depression Scale). In a population-based community sample of 1175 pregnant women, 918 women (78%) answered questionnaires with the EPDS and HAD-S. In all, 121 were interviewed using the PRIME-MD (Primary Care Evaluation of Mental disorders) for diagnosing depression. Women were interviewed in mean gestational week 13 (range 8-21). For the EPDS, a receiver operating characteristic (ROC) curve was calculated for prediction of depression. Pearson's correlation coefficient was used to investigate the association between EPDS and HAD-S scores. The optimal cut-off score on the EPDS scale for detecting depression was ≥13 (standard error coefficient of 1.09 and c-statistics of 0.84) giving a sensitivity of 77% and specificity of 94%. The EPDS scores correlated strongly with the HAD-S, Pearson's correlation was 0.83 (P < 0.0001). This study confirms that the EPDS is a valid screening instrument for detection of depressive symptoms during pregnancy. The EPDS shows persuasive measuring outcomes with an optimal cut-off at ≥13. Healthcare for pregnant women should consider screening procedures and follow-up routines for depressive symptoms.


Natural Polyphenols in Cancer Chemoresistance.
Resistance to chemotherapy remains a major impediment to the management of most types of cancer. Both intrinsic and acquired drug resistance are mediated by several cellular and molecular mechanisms, including alternative growth-signaling pathways unaffected by specific therapies, alterations in the tumor microenvironment (e.g., hypoxia and angiogenesis), and active transport of drugs out of the cell. Epidemiological studies have validated an inverse correlation between the consumption of dietary polyphenols and the risk of cancer, which has been attributed to polyphenol antioxidant capacity and their potential to inhibit activation of procarcinogens, cancer cell proliferation, metastasis, and angiogenesis, and inhibition or downregulation of active drug efflux transporters. Moreover, polyphenols can induce apoptosis in cancer cells and modulate immune responses and inflammatory cascades. Augmentation of the efficacy of chemotherapy and prevention of multidrug resistance are other important effects of dietary polyphenols that deserve further research, especially after the discovery of tight "crosstalk" between aberrant growth signaling and metabolic dysfunction in cancer cells. In this review, we cover what is currently known about the role of natural polyphenolic compounds in overcoming cancer drug resistance mediated by diverse primary and secondary resistance mechanisms.


Mapping the use of simulation in prehospital care - a literature review.
High energy trauma is rare and, as a result, training of prehospital care providers often takes place during the real situation, with the patient as the object for the learning process. Such training could instead be carried out in the context of simulation, out of danger for both patients and personnel. The aim of this study was to provide an overview of the development and foci of research on simulation in prehospital care practice. An integrative literature review were used. Articles based on quantitative as well as qualitative research methods were included, resulting in a comprehensive overview of existing published research. For published articles to be included in the review, the focus of the article had to be prehospital care providers, in prehospital settings. Furthermore, included articles must target interventions that were carried out in a simulation context. The volume of published research is distributed between 1984- 2012 and across the regions North America, Europe, Oceania, Asia and Middle East. The simulation methods used were manikins, films, images or paper, live actors, animals and virtual reality. The staff categories focused upon were paramedics, emergency medical technicians (EMTs), medical doctors (MDs), nurse and fire fighters. The main topics of published research on simulation with prehospital care providers included: Intubation, Trauma care, Cardiac Pulmonary Resuscitation (CPR), Ventilation and Triage. Simulation were described as a positive training and education method for prehospital medical staff. It provides opportunities to train assessment, treatment and implementation of procedures and devices under realistic conditions. It is crucial that the staff are familiar with and trained on the identified topics, i.e., intubation, trauma care, CPR, ventilation and triage, which all, to a very large degree, constitute prehospital care. Simulation plays an integral role in this. The current state of prehospital care, which this review reveals, includes inadequate skills of prehospital staff regarding ventilation and CPR, on both children and adults, the lack of skills in paediatric resuscitation and the lack of knowledge in assessing and managing burns victims. These circumstances suggest critical areas for further training and research, at both local and global levels.


Propofol for Treatment-Resistant Depression: A Pilot Study.
We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression. Ten participants with moderate-to-severe medication-resistant depression (age 18-45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy. Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0-45 points), corresponding to a mean 58% improvement from baseline (range 0-100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol. These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol's antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.


Improving the learning needs survey by using four approaches.
Learning needs analyses are often undertaken to plan continuing education programs. They usually use questionnaires that have shortcomings regarding validity, relevance, breadth and detail. We tested a questionnaire using four questioning strategies to approximately 1762 general practitioners. Our questionnaire listing 104 topics asked open ended questions and specific information about desired topics. It was distributed by The Royal Australian College of General Practitioners and divisions of general practice in South Australia and the Northern Territory. The survey yielded 578 responses (33%). The different survey strategies highlighted different areas of learning need. Overall, the highest ranked topics were dermatology, complementary medicine, psychiatry, and business and practice management. Participating divisions were generally satisfied with the feedback. Despite a poor response rate, the survey provided interesting information, and a set of broad learning topics.


Etherification of Wood-Based Hemicelluloses for Interfacial Activity.
We present wetting, hygroscopicity, and interfacial activity of hemicellulose with respect to etherification and contrast it to their potential as interfacial modifiers, which is demonstrated by oil-in-water emulsification containing up to 60 vol% of the oil phase. Tunable amphiphilicity of hardwood and softwood hemicelluloses, xylans, and galactoglucomannans, respectively, was accomplished via controlled etherification. A series of degree of substitution (DS) of hydroxypropylated and 3-butoxy-2-hydroxypropylated ("butylated") grades was synthesized. The hemicellulose ethers were characterized by gel permeation chromatography, spectroscopic techniques, such as NMR, and contact angle measurements. An attenuated total reflectance infrared method was developed for fast identification of the DS. Near infrared analysis was utilized to explore the hygroscopicity of the material and to perform principle component analysis. The modification to butylated grades decreased the hygroscopicity, whereas the hydroxypropylated grades bound moisture. All of the hemicellulose ethers were water-soluble. The interfacial tension of the aqueous hemicellulose solutions was determined by pendant-drop tensiometer, and it was demonstrated to be dependent on the degree of modification.


Effect of weather and time on trauma events determined using emergency medical service registry data.
Trauma admissions are associated with weather and temporal factors; however, previous study results regarding these factors are contradictory. We hypothesised that weather and temporal factors have different effects on specific trauma events in an emergency medical service (EMS) system. EMS data from January 1, 2009, to December 31, 2010, were obtained from the fire department of Taipei City and associated with the local weather data. EMS trauma events were categorised into total trauma, traffic accidents (TAs), motorbike accidents (MBAs), and falls. Hourly data on trauma patients were analysed using the zero-inflated Poisson model. The hourly incidence of total trauma increased with the magnitude of precipitation (incidence rate ratio [IRR]=1.06, 1.09, and 1.11 in light, moderate, and heavy rain, respectively), and this effect was more prominent in fall patients than in patients with other injuries (IRR=1.07, 1.21, and 1.32). However, the hourly incidence of TAs and MBAs was associated only with light rain (IRR=1.11 and 1.06, respectively). An hour of sunshine exposure was associated with an increase in the hourly incidence of all groups, and higher temperatures were associated with an increased hourly incidence of total trauma, TAs, and MBAs, but not falls. The hourly incidence of falls increased only in late fall and winter. Compared with the hourly incidence between 3 am and 7 am, the hourly incidence of all groups plateaued between 7 am and 11 pm and declined from 11 pm to 3 am. During the plateau period, 2 peaks in the incidence of TAs (IRR=5.03 and 5.07, respectively) and MBAs (IRR=5.81 and 5.51, respectively) were observed during 7-11 am and 3-7 pm. The hourly incidence of total trauma, TAs, and MBAs plateaued during workdays, peaked on Fridays, declined on Saturdays, and troughed on Sundays. The incidence of falls increased only on Mondays (IRR=1.09). Weather and temporal factors had different impacts on the incidence of traffic-related accidents and falls. Therefore, EMS data may have implications in preventing injuries and planning resource use for prehospital trauma rescue.


[Resistance to second-line anti-tuberculosis drugs among peruvian multidrug resistant Mycobacterium tuberculosis strains].
To determine the drug resistance profiles for quinolones: ciprofloxacin (CFX), ofloxacin (OFX), moxifloxacin (MFX), and gatifloxacin (GFX); and for injectables: kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) in multidrug resistant (MDR) strains. We also investigated the correlation between mutations in rrs, tlyA and gyrA/B genes, and the in vitro resistance to the second-line anti-tuberculosis drugs. In this pilot study we selected MDR clinical isolates collected from June-December 2004 in the Tropical Medicine Institute "Alexander von Humboldt" (Lima, Perú). The Minimum Inhibitory Concentration (MIC) of CFX, OFX, MFX, GFX, KAN, AMK and CAP for 14 clinical isolates were determined and the sequences of rrs, tlyA and gyrA/B genes were analyzed by conventional PCR followed by sequencing. We obtained valid results for 11 samples. Four isolates were resistant to injectable drugs, and in all the cases the MICs were; >120 µg/mL for KAN and >160 µg/mL for AMK and CAP. Only 2 isolates were resistant to OFX with MIC = 4 µg/mL. Sequencing results suggested that the mutation A1401T in rrs gene could be the molecular cause of the resistance to injectable drugs. In this study we did not find any mutation in tlyA and gyrA/B associated to resistance. Our study suggests a possible association between the mutation A1401T in rrs and resistance to injectable drugs. However further studies should be done to confirm this hypothesis in Perú.


Primary school students' mental health in Uganda and its association with school violence, connectedness, and school characteristics: a cross-sectional study.
Few studies have explored risk factors for poor mental health in Ugandan primary schools. This study investigated whether individual- and contextual-level school-related factors including violence from school staff and other students, connectedness to school and peers, as well as school size and urban/rural location, were associated with mental health difficulties in Ugandan children. We also examined whether associations between violence exposure at school and mental health were mediated by connectedness as well as whether associations were different for boys and girls. The analytic sample consisted of 3,565 students from 42 primary schools participating in the Good Schools Study. Data were collected through individual interviews conducted in June and July 2012. Mental health was measured using the Strengths and Difficulties Questionnaire. Multilevel logistic regression was applied to investigate factors associated with mental health difficulties. Experiences of violence from school staff and other students in the past week were strongly associated with mental health difficulties (OR = 1.58, 95 % CI 1.31 to 1.90 and 1.81, 1.47 to 2.23, respectively). Children with a low school connectedness had 1.43 times (1.11 to 1.83) the odds of mental health difficulties compared to those with a high school connectedness. The OR comparing children never feeling close to other students at their school with those always feeling close was 1.86 (1.18 to 2.93). The effect of violence on mental health was not mediated through the connectedness variables. School size was not related to mental health difficulties, but attending an urban school increased the odds of mental health difficulties after accounting for other factors. We did not find evidence that the effect of one or more of the exposures on the outcome differed between boys and girls. These findings suggest that violence in school and low connectedness to school and peers are independently associated with mental health difficulties and interventions should address both concurrently. Extra support may be needed for students in urban schools. Clinicaltrials.gov NCT01678846 . Registered 24 August 2012.


Fatigue in COPD and the impact of respiratory symptoms and heart disease--a population-based study.
Fatigue is reported in COPD and in heart disease; however, there are hardly any population based data on the relationship between these conditions. To describe fatigue in relation to COPD by disease severity and to evaluate the impact of respiratory symptoms and heart disease. Data were collected in 2007 from the OLIN COPD study; 564 subjects with COPD (FEV1/FVC < 0.70) and a distribution of disease severity representative for the general population, and 786 subjects without COPD. The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale was used to assess fatigue (0-52); lower scores represent worse fatigue. Median FACIT-F score was 44.0 in COPD defined by merely spirometric criteria and 42.0 in COPD also reporting respiratory symptoms, significantly lower compared to 46.0 in non-COPD (p = 0.006 and p < 0.001), and decreased by disease severity. The score was lower in COPD stage ≥ II and in COPD with respiratory symptoms already from stage I when compared to non-COPD. Subjects with heart disease reported lower scores than those without heart disease in COPD by all stages and in non-COPD. COPD with respiratory symptoms stage ≥II remained a significant risk factor for clinically significant fatigue also when adjusted for gender, age, heart disease and smoking habits (stage II OR 1.65, CI 1.17-2.31 and stage III-IV OR 2.66, CI 1.11-6.36). Fatigue is common in COPD, and is affected by respiratory symptoms and concomitant heart disease. In COPD with respiratory symptoms stage ≥ II, there is an increased risk for clinically significant fatigue.


Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.
Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm-related genes (CRY2 and MTNR1B) associated with glucose homeostasis. We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial. The variants CRY2 rs11605924 (n = 721) and MTNR1B rs10830963 (n = 722) were genotyped in overweight or obese adults who were randomly assigned to 1 of 4 weight-loss diets that differed in their proportions of macronutrients. Respiratory quotient (RQ) and resting metabolic rate (RMR) were measured. By 2 y of diet intervention, the A allele of CRY2 rs11605924 was significantly associated with a greater reduction in RQ (P = 0.03) and a greater increase in RMR and RMR/kg (both P = 0.04). The G allele of MTNR1B rs10830963 was significantly associated with a greater increase in RQ (P = 0.01) but was not related to changes in RMR and RMR/kg. In addition, we found significant gene-diet fat interactions for both CRY2 (P-interaction = 0.02) and MTNR1B (P-interaction < 0.001) in relation to 2-y changes in RQ. Our data indicate that variants in the circadian-related genes CRY2 and MTNR1B may affect long-term changes in energy expenditure, and dietary fat intake may modify the genetic effects. This trial was registered at www.clinicaltrials.gov as NCT00072995.


The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers.
Experimental evidences have demonstrated that Nigella sativa Linn. seed (NS) has positive modulation effects on aged rats with memory impairments, prevents against hippocampal pyramidal cell loss and enhances consolidation of recall capability of stored information and spatial memory in rats. NS has neuroprotective, nephroprotective, lung protective, cardioprotective, hepatoprotective activities as established by previous studies on animals. Several clinical trials with NS on human have also demonstrated beneficial effect. The present study was designed to investigate the effects of NS on memory, attention and cognition in healthy elderly volunteers. Furthermore, safety profile of NS was assessed during the nine-week study period. Forty elderly volunteers were recruited and divided randomly into group A and group B--each consisting of 20 volunteers. The treatment procedure for group A was 500 mg NS capsule twice daily for nine weeks and Group B received placebo instead of NS in the similar manner. All the volunteers were assessed for neuropsychological state and safety profile twice before treatment and after nine weeks. The neuropsychological tests were logical memory test, digit span test, Rey-Osterrieth complex figure test, letter cancellation test, trail making test and stroop test. Safety profile was assessed by measuring biochemical markers of Cardiac (total cholesterol, triglycerides and high density lipoprotein cholesterol, very low density lipoprotein, low density lipoprotein cholesterol, creatine kinase-MB); Liver (aspartate aminotransferase, alanin aminotransferase, alkaline phosphatase, total protein, albumin, bilirubin) and Kidney (creatinine and blood urea nitrogen) through using commercial kits. There was significant difference (p<0.05) in the score of logical memory test-I and II, total score of digit span, 30 min delayed-recall, percent score in Rey-Osterrieth complex figure test, time taken to complete letter cancellation test, time taken in trail making test-A and test-B, score in part C of stroop test due to ingestion of NS for nine weeks. There were not statistically significant changes (p>0.05) in any of the biochemical markers of cardiac, liver, kidney function during this nine-week study period. The current study demonstrates the role of NS in enhancing memory, attention and cognition. Therefore, whether NS could be considered as potential food supplement for preventing or slow progressing of Alzheimer disease needs further investigations. However, study with Alzheimer's patients with large population size for longer period of time is recommended before using NS daily and extensive phytochemical investigations are recommended for novel drug discovery from NS for treating cognitive disorders.


Obese Kidney Donors in the Laparoscopic Living Nephrectomy Era: How Safe?
BACKGROUND Obesity is a major worldwide health problem, causing up to 3.4 million deaths per year. It is considered to be a relative contraindication for laparoscopic surgery. Laparoscopic living donor nephrectomy is the criterion standard procedure for kidney procurement in many transplant centers. However, the selection of the obese donors undergoing laparoscopic nephrectomies is still debatable. The objective of this study was to compare short-term results of obese donors and non-obese donors undergoing laparoscopic living donor nephrectomies. MATERIAL AND METHODS A retrospective analysis of 259 live donors between November 2011 and August 2015 was performed. Body mass index equal to or more than 30 kg/m2 was categorized as obese. Twenty subjects were categorized as obese donors. We randomly assigned for 30 non-obese donors to the control group. Intra-operative and post-operative data were compared between these 2 groups. A p-value ≤0.05 was considered a significant difference. RESULTS Donor characteristics were the same in the 2 groups. No significant differences were found in the first warm ischemic time, estimated blood loss, or postoperative pain. The operative time in the obese group was significantly longer than in the control group (270 vs. 245 min, p≤0.05). The hospital stay was also significantly longer in the obese group (4 vs. 3 days, p≤0.05). CONCLUSIONS At our hospital, obese donors had short-term results comparable to those of non-obese donors in laparoscopic living nephrectomy. While longer operative time and length of stay were found, there were no significant complications observed. Long-term outcomes should be evaluated to justify use of obese donors.


Association of the presence of bone bars on radiographs and hip fracture in postmenopausal Caucasian women.
To determine whether the presence of bone bars (BB) identified on anteroposterior hip radiographs are more prevalent in patients that have had a hip fracture as compared to patients without a fracture. Ninety-two Caucasian women with a unilateral proximal femur fracture were retrospectively evaluated and randomly selected using radiology database records to comprise the investigational group. Ninety-eight age-matched Caucasian women without hip fracture were selected as a control group. Anteroposterior hip radiographs were evaluated for the presence of BBs by two musculoskeletal radiologists. Chi-square tests were used to assess whether fractures were more prevalent in patients with BB than those without BB. The patient population was comprised Caucasian women with a mean age of 79.8 ± 6.4 years in the control group and 79.9 ± 6.6 years in the investigational group. Regardless of the reader, BB were identified in a significantly higher percentage of women with a fracture (75 versus 39%, p < 0.001 or 53 versus 38%, p = 0.041) as compared to those without a fracture. BB are associated with hip fracture. Their presence is a trigger for requesting a dual-energy x-ray absorptiometry (DXA) examination to confirm or refute a diagnosis of low bone mineral density (BMD) and a subsequent increased risk of fracture.


QUANTITATIVE DISTRIBUTION OF PARTICULATE MATERIAL (MANGANESE DIOXIDE) ADMINISTERED INTRAVENOUSLY TO THE CAT.
1. Manganese dioxide suspended in an acacia-sodium chloride solution provides a non-toxic injection which in the present experiments has contained no particles larger than 1micro and which, when deposited in the body, can be determined quantitatively and seen microscopically. 2. Intravenous injections have been made under precautions which preclude removal from the blood or deposition in organs through simple capillary blockage. 3. In nine experiments out of thirteen the circulating blood contained no manganese after 18 minutes. In the four remaining instances there was a steady slight elimination which was incomplete at the end of 1 hour. Within certain limits the rate of removal from the circulating blood and the sites of deposition in the animal are not influenced by the concentration of the suspension, the blood pressure, or antecedent introduction of acacia or histamine. 4. In the cat amounts of manganese dioxide varying between 9.8 and 3.9 mg. of manganese and containing from 50,000,000,000 to 10,000,000,000 particles, if injected intravenously, permit recovery at the end of 1 hour of 90 per cent of the material in the lungs, liver, and spleen in the following proportions: lungs 47 per cent; liver 38.3 per cent; spleen 4.3 per cent. 5. These experiments, coupled with correlative results by other investigators, make it clear that in certain organs-the lungs, liver, and spleen of the cat-the vascular endothelium possesses phagocytic power rendering the capillaries permeable to particulate material as well as to gases, liquids, and dissolved substances.


Racemic crystallography of synthetic protein enantiomers used to determine the X-ray structure of plectasin by direct methods.
We describe the use of racemic crystallography to determine the X-ray structure of the natural product plectasin, a potent antimicrobial protein recently isolated from fungus. The protein enantiomers L-plectasin and D-plectasin were prepared by total chemical synthesis; interestingly, L-plectasin showed the expected antimicrobial activity, while D-plectasin was devoid of such activity. The mirror image proteins were then used for racemic crystallization. Synchrotron X-ray diffraction data were collected to atomic resolution from a racemic plectasin crystal; the racemate crystallized in the achiral centrosymmetric space group P1 with one L-plectasin molecule and one D-plectasin molecule forming the unit cell. Dimer-like intermolecular interactions between the protein enantiomers were observed, which may account for the observed extremely low solvent content (13%-15%) and more highly ordered nature of the racemic crystals. The structure of the plectasin molecule was well defined for all 40 amino acids and was generally similar to the previously determined NMR structure, suggesting minimal impact of the crystal packing on the plectasin conformation.


Stromal cell regulation of lymphoid and myeloid differentiation.
In vitro microenvironmental influences seem to be critical for both B lymphocyte and myeloid differentiation. Studies on murine Dexter cultures and Whitlock-Witte lymphocyte cultures suggest the presence of two critical stromal regulatory cells: an alkaline-phosphatase-positive epithelioid cell and a macrophage. Further data suggest that these cells are capable of producing colony stimulating factor-1, granulocyte-macrophage CSF, a myeloid synergizing activity, and probably separate B cell growth factors. Isolation of a cell line from Dexter stroma was accomplished and this line produced CSF-1, GM-CSF, a pre-B cell and myeloid synergizing activity, and an activity acting on differentiated B cells. We speculate that the Dexter and Whitlock-Witte in vitro culture systems are regulated by factors produced by the two adherent cell types. A lineage nonspecific factor capable of inducing cells into the B lineage or synergizing with interleukin-3, GM-CSF, and CSF-1 is produced, which presumably acts on early stem cells. In addition, the cell line produces GM-CSF, CSF-1, and a factor acting on differentiated B cells. We speculate that in these culture systems, these "terminal differentiating hormones" regulate the final pathway of differentiation, whereas the pre-B-synergizing activity supports early stem cells that can then respond to the other differentiating hormones.


Nonlocal model for nematic liquid-crystal elastomers.
We have developed a fully nonlocal model to describe the dynamic behavior of nematic liquid-crystal elastomers. The free energy, incorporating both elastic and nematic contributions, is a function of the material displacement vector and the orientational order parameter tensor. The free energy cost of spatial variations of these order parameters is taken into account through nonlocal interactions rather than through the use of gradient expansions. We also give an expression for the Rayleigh dissipation function. The equations of motion for displacement and orientational order are obtained from the free energy and the dissipation function by the use of a Lagrangian approach. We examine the free energy and the equations of motion in the limit of long-wavelength and small-amplitude variations of the displacement and the orientational order parameter. We compare our results with those in the literature. If the scalar order parameter is held fixed, we recover the usual viscoelastic theory for nematic liquid crystals.


Perceptual learning.
Perceptual learning involves relatively long-lasting changes to an organism's perceptual system that improve its ability to respond to its environment. Four mechanisms of perceptual learning are discussed: attention weighting, imprinting, differentiation, and unitization. By attention weighting, perception becomes adapted to tasks and environments by increasing the attention paid to important dimensions and features. By imprinting, receptors are developed that are specialized for stimuli or parts of stimuli. By differentiation, stimuli that were once indistinguishable become psychologically separated. By unitization, tasks that originally required detection of several parts are accomplished by detecting a single constructed unit representing a complex configuration. Research from cognitive psychology, psychophysics, neuroscience, expert/novice differences, development, computer science, and cross-cultural differences is described that relates to these mechanisms. The locus, limits, and applications of perceptual learning are also discussed.


Quantification of aortic regurgitant fraction and volume with multi-detector computed tomography comparison with echocardiography.
Evaluate quantification of the aortic regurgitant fraction and volume with computed tomography (CT). Fifty-three patients with aortic regurgitation (AR) and 29 controls were examined with 64-multi-detector CT coronary angiography and transthoracic echocardiography (TTE). A dedicated software algorithm employing three-dimensional segmentation of left ventricle (LV) and right ventricle (RV) volumes and LV mass was applied. AR volume and fraction was calculated based on RV and LV stroke volumes (SV) and compared with echocardiography. The aortic regurgitant orifice area (ROA) was measured by CT. A good correlation of the AR fraction and AR volume determined by CT compared to echocardiography was found for mild, moderate, and severe AR with 14.2% ± 9, 28.8% ± 8, and 57.9% ± 9 (r = 0.95, P < .001) for AR fraction, and 15.7 mL ± 11.33 mL ± 14, and 98.9 mL ± 36 for AR volume (r = 0.92, P < .0001), respectively. CT correctly classified severity of AR in 93% of patients based of AR-fraction, and in 89% based on AR volume. The sensitivity and specificity of CT were 98% and specificity 90.3%. The specificity improved to 97%, if the ROA by CT was added as diagnostic criterion. Aortic regurgitation fraction and volume can be accurately quantified from CT coronary angiography datasets. These parameters can assist clinical management, e.g. in case of pending cardiac surgery decision.


Pseudomonas brassicacearum subsp. neoaurantiaca subsp. nov., orange-pigmented bacteria isolated from soil and the rhizosphere of agricultural plants.
A large group of 38 strains of saprophytic bacteria was isolated from soil and the rhizosphere of agricultural plants. The novel organisms were Gram-negative, aerobic, rod-shaped bacteria that produced a green fluorescent pigment, a red-orange diffusible pigment and a complex mixture of phloroglucinol derivates with antimicrobial activity. The latter have not been found in other bacteria, but are peculiar to ferns. The bacteria were vigorous denitrifiers that synthesized levan from sucrose and liquefied gelatin, but were found not to degrade aesculin, starch, agar, Tween 80 or DNA. Bacterial growth was found to occur at 4 degrees C but not at 40 degrees C. The predominant cellular fatty acids were 16 : 0, 16 : 1(n-7), 18 : 1(n-7) and 17 : 0 cyclo. The G+C content of the novel bacteria was 61.0-62.9 mol%. 16S rRNA gene sequence analysis indicated that the representative strain CIP 109457(T) had a clear affiliation with Pseudomonas sensu stricto groups, with the nearest relatives being Pseudomonas brassicacearum, P. thivervalensis, P. corrugata, P. mediterranea and P. kilonensis. DNA-DNA hybridization experiments showed that the group of isolated strains exhibited high levels of genetic relatedness (81-100 %), confirming that they are representatives of the same species. At the same time, they bound at low levels (4-46 %) with DNA of the type strains of their nearest relatives with the exception of P. brassicacearum; DNA binding of 90 % with the DNA of P. brassicacearum CIP 107059(T) suggested that the bacteria studied belong to this species. Analysis of taxonomic data indicated that the group of novel bacteria maintain a distinct phenotypic profile, allowing the description of novel subspecies within P. brassicacearum, for which the following names are proposed: Pseudomonas brassicacearum subsp. brassicacearum subsp. nov. (type strain DBK11(T) =CFBP 11706(T) =CIP 107059(T) =DSM 13227(T) =JCM 11938(T)) and Pseudomonas brassicacearum subsp. neoaurantiaca subsp. nov., with the type strain CIP 109457(T) (=ATCC 49054(T) =IMV 387(T) =VKM B-1524(T)).


Empirical versus modelling approaches to the estimation of measurement uncertainty caused by primary sampling.
Measurement uncertainty is a vital issue within analytical science. There are strong arguments that primary sampling should be considered the first and perhaps the most influential step in the measurement process. Increasingly, analytical laboratories are required to report measurement results to clients together with estimates of the uncertainty. Furthermore, these estimates can be used when pursuing regulation enforcement to decide whether a measured analyte concentration is above a threshold value. With its recognised importance in analytical measurement, the question arises of 'what is the most appropriate method to estimate the measurement uncertainty?'. Two broad methods for uncertainty estimation are identified, the modelling method and the empirical method. In modelling, the estimation of uncertainty involves the identification, quantification and summation (as variances) of each potential source of uncertainty. This approach has been applied to purely analytical systems, but becomes increasingly problematic in identifying all of such sources when it is applied to primary sampling. Applications of this methodology to sampling often utilise long-established theoretical models of sampling and adopt the assumption that a 'correct' sampling protocol will ensure a representative sample. The empirical approach to uncertainty estimation involves replicated measurements from either inter-organisational trials and/or internal method validation and quality control. A more simple method involves duplicating sampling and analysis, by one organisation, for a small proportion of the total number of samples. This has proven to be a suitable alternative to these often expensive and time-consuming trials, in routine surveillance and one-off surveys, especially where heterogeneity is the main source of uncertainty. A case study of aflatoxins in pistachio nuts is used to broadly demonstrate the strengths and weakness of the two methods of uncertainty estimation. The estimate of sampling uncertainty made using the modelling approach (136%, at 68% confidence) is six times larger than that found using the empirical approach (22.5%). The difficulty in establishing reliable estimates for the input variable for the modelling approach is thought to be the main cause of the discrepancy. The empirical approach to uncertainty estimation, with the automatic inclusion of sampling within the uncertainty statement, is recognised as generally the most practical procedure, providing the more reliable estimates. The modelling approach is also shown to have a useful role, especially in choosing strategies to change the sampling uncertainty, when required.


Clinical characteristics and corticosteroid treatment of acute eosinophilic pneumonia.
The clinical characteristics and optimal duration of corticosteroid treatment for acute eosinophilic pneumonia (AEP) have not been fully evaluated. This was a retrospective study of prospectively collected data from 137 patients with AEP, treated with standardised protocol, to clarify the clinical characteristics and compare the efficacies of 2 weeks versus 4 weeks of corticosteroid treatment for AEP. The majority of the patients altered their smoking habits within a median (interquartile range) of 17 (13-26) days prior to development of AEP. 80 (58%) patients presented with acute respiratory failure. A total of 127 (92%) patients were treated with corticosteroids: 4 weeks, n=42; 2 weeks, n=85. Major symptoms were resolved in 3 days and the severity of respiratory failure was inversely correlated with clinical outcomes. After adjusting for differences in baseline characteristics between the groups, the differences in adjusted mean (95% confidence interval) for resolution of dyspnoea and disappearance of all symptoms were 0.57 (-0.71-1.86) and -0.04 (-1.91-1.83) days, respectively. The difference in adjusted proportion of resolution of radiological abnormalities was 6.92% (-8.19-22.02). In conclusion, the duration of corticosteroid treatment could be shortened to 2 weeks, even in patients with respiratory failure.