Production, characterisation, utilisation, and beneficial soil application of steel slag: A review.
Slags are a co-product produced by the steel manufacturing industry and have mainly been utilised for aggregates in concreting and road construction. The increased utilisation of slag can increase economic growth and sustainability for future generations by creating a closed-loop system, circular economy within the metallurgical industries. Slags can be used as a soil amendment, and slag characteristics may reduce leachate potential of heavy metals, reduce greenhouse gas emissions, as well as contain essential nutrients required for agricultural use and environmental remediation. This review aims to examine various slag generation processes in steel plants, their physicochemical characteristics in relation to beneficial utilisation as a soil amendment, and environmental implications and risk assessment of their utilisation in agricultural soils. In relation to enhancing recycling of these resources, current and emerging techniques to separate iron and phosphorus slag compositions are also outlined in this review. Although there are no known immediate direct threats posed by slag on human health, the associated risks include potential heavy metal contamination, leachate contamination, and bioaccumulation of heavy metals in plants, thereby reaching the food chain. Further research in this area is required to assess the long-term effects of slag in agricultural soils on animal and human health.


Long-term trends in Medicare payments in the last year of life.
To update research on Medicare payments in the last year of life. Continuous Medicare History Sample, containing annual summaries of claims data on a 5 percent sample from 1978 to 2006. Analyses were based on elderly beneficiaries in fee for service. For each year, Medicare payments were assigned either to decedents (persons in their last year) or to survivors (all others). The share of Medicare payments going to persons in their last year of life declined slightly from 28.3 percent in 1978 to 25.1 percent in 2006. After adjustment for age, sex, and death rates, there was no significant trend. Despite changes in the delivery of medical care over the last generation, the share of Medicare expenditures going to beneficiaries in their last year has not changed substantially.


Evidence for proactive interference in the focus of attention of working memory.
Proactive interference (PI) occurs when an earlier item interferes with memory for a newer item. Whereas some researchers (e.g., Surprenant & Neath, 2009a) argue that PI can be observed in all memory systems, some multiple systems theorists (e.g., Cowan, 1999) propose that items in the focus of attention of working memory are immune to PI. Two experiments tested whether PI occurs when the to-be-remembered items are assumed, by multiple-systems theorists, to be held in the focus of attention. In each experiment, subjects saw four trials in a row with the same type of to-be-remembered items, followed by four trials in a row with a different type of material. On each trial, only 3 stimuli were shown, which is below the capacity limit of the focus of attention, and subjects were asked if a probe item was one of those 3 items seen. In both experiments, response time increased from Trial 1 to Trial 4, suggesting that items from the earlier trials interfered with memory on the later trials. In addition, release from PI was shown in that response times decreased with a change of materials. The results replicate those first reported by Hanley and Scheirer (1975), and pose a problem for theorists who argue that parts of short-term memory are immune to PI.


The interaction of attention and action: from seeing action to acting on perception.
We discuss evidence indicating that human visual attention is strongly modulated by the potential of objects for action. The possibility of action between multiple objects enables the objects to be attended as a single group, and the fit between individual objects in a group and the action that can be performed influences responses to group members. In addition, having a goal state to perform a particular action affects the stimuli that are selected along with the features and area of space that is attended. These effects of action may reflect statistical learning between environmental cues that are linked by action and/or the coupling between perception and action systems in the brain. The data support the argument that visual selection is a flexible process that emerges as a need to prioritize objects for action.


SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing.
The Polycomb-group (PcG) repressive complex-1 (PRC1) forms microscopically visible clusters in nuclei; however, the impact of this cluster formation on transcriptional regulation and the underlying mechanisms that regulate this process remain obscure. Here, we report that the sterile alpha motif (SAM) domain of a PRC1 core component Phc2 plays an essential role for PRC1 clustering through head-to-tail macromolecular polymerization, which is associated with stable target binding of PRC1/PRC2 and robust gene silencing activity. We propose a role for SAM domain polymerization in this repression by two distinct mechanisms: first, through capturing and/or retaining PRC1 at the PcG targets, and second, by strengthening the interactions between PRC1 and PRC2 to stabilize transcriptional repression. Our findings reveal a regulatory mechanism mediated by SAM domain polymerization for PcG-mediated repression of developmental loci that enables a robust yet reversible gene repression program during development.


Role of cysteine62 in DNA recognition by the P50 subunit of NF-kappa B.
A powerful chemical modification procedure has been developed to define determinants of DNA recognition by the p50 subunit of NF-kappa B. Differential labelling with [14C] iodoacetate has identified a conserved cysteine residue, Cys62, that was protected from modification by the presence of an oligonucleotide containing the specific recognition site of the protein. To determine the importance of this cysteine residue, each of the conserved cysteines in p50 was changed to serine and the DNA binding properties of the mutant proteins determined. Scatchard analysis indicated that the C62S mutant bound to its DNA recognition site with a 10-fold larger dissociation constant than the wild type protein, while the other two mutants bound with an intermediate affinity. Dissociation rate constant measurements correlated well with the dissociation constants for the wild type, C119S, and C273S p50 proteins, whereas the p50 C62S-DNA complex dissociated anomalously quickly. Competition analyses with oligonucleotide variants of the DNA recognition site and nonspecific E. coli DNA revealed that the C62S p50 mutant had an altered DNA binding site specificity and was impaired in its ability to discriminate between specific and non-specific DNA. Thus the sulphydryl group of Cys62 is an important determinant of DNA recognition by the p50 subunit of NF-kappa B.


Coupled-cavity mode locking of a KCl:Tl laser using an erbium-doped optical fiber.
An erbium-doped monomode fiber that exhibits enhanced optical nonlinearity has been incorporated into a coupled-cavity mode-locked (CCM) KCl:Tl laser, from which stable, sub-100-fsec pulses have been produced near 1.5 microm. Spectral measurements of the CCM laser output also indicate the existence of a self-frequency shift that can provide pulse generation in two distinct wavelength regimes.


Effect of vitamin D on the recurrence rate of rheumatoid arthritis.
Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by chronic inflammation affecting target tissues including the joints, bones, and synovial membrane. However, the etiology and pathogenesis of RA remains to be determined, and investigations into the treatment of RA are imperative. Vitamin D (Vit D) was previously found to be associated with the activity of RA and exerts therapeutic benefits. The aim of the present study was to investigate the effect of Vit D on the recurrence rate of RA. A total of 377 patients with RA at remission stage were divided into the normal Vit D group and the Vit D-deficient group according to their Vit D levels at baseline. The patients in the Vit D-deficient group were further randomly allocated to receive treatment with or without Vit D. The patients were followed up for 24 months, and the visual analogue scale, as well as the number of pain and swelling joints were recorded every 2-3 months. In addition, C-reactive protein and the blood sedimentation rate were measured every 2-3 months to assess the recurrence of RA based on disease activity score 28 (DAS28). The recurrence rate of RA was 16.7, 19.0 and 29.5% for the normal Vit D group (n=168), Vit D treatment subgroup (n=84), and non-Vit D treatment subgroup (n=88), respectively. The recurrence rate of the normal Vit D group was lower, compared to the non-Vit D treatment subgroup, and the difference was statistically significant. However, the difference was not statistically significant between the Vit D treatment subgroup and non-Vit D treatment subgroup. In conclusion, a decreased level of Vit D is a risk factor for the recurrence of RA.


Epidemic bacteremia due to Acinetobacter baumannii in five intensive care units.
From March 5, 1986 to September 4, 1987, Acinetobacter baumannii (AB) was isolated from blood or vascular catheter-tip cultures of 75 patients in five intensive care units at a hospital in New Jersey. To identify risk factors for AB bacteremia in the intensive care units, a case-control study was conducted. Characteristics of 72 case-patients were compared with those of 37 controls. Case-patients were more likely than controls to have had peripheral arterial catheters (odds ratio (OR) = 7.0, p less than 0.001), mechanical ventilation (OR = 5.8, p less than 0.001), hyperalimentation (OR = 5.7, p less than 0.001), or pulmonary arterial catheters (OR = 3.9, p less than 0.001). Arterial catheters were used with reusable pressure transducers for intravascular pressure monitoring. A logistic regression analysis identified four independent risk factors: transducers, ventilation, hyperalimentation, and days of transducer use at an insertion site. The strongest influence on the risk of AB bacteremia was exerted by number of days of transducer usage. Cultures of 70 transducer diaphragms or domes, 42 in-use and 28 in-storage, were positive for AB in 21% and 46%, respectively. Plasmid analysis showed that patient blood cultures and transducer isolates were identical. Transducers were wiped with alcohol in the units between patient uses. Since reusable transducers appeared to be the source of this outbreak, it is recommended that reusable transducers receive either high level disinfection or sterilization between patient uses.


A Bayesian mathematical model of motor and cognitive outcomes in Parkinson's disease.
There are few established predictors of the clinical course of PD. Prognostic markers would be useful for clinical care and research. To identify predictors of long-term motor and cognitive outcomes and rate of progression in PD. Newly diagnosed PD participants were followed for 7 years in a prospective study, conducted at 55 centers in the United States and Canada. Analyses were conducted in 244 participants with complete demographic, clinical, genetic, and dopamine transporter imaging data. Machine learning dynamic Bayesian graphical models were used to identify and simulate predictors and outcomes. The outcomes rate of cognition changes are assessed by the Montreal Cognitive Assessment scores, and rate of motor changes are assessed by UPDRS part-III. The most robust and consistent longitudinal predictors of cognitive function included older age, baseline Unified Parkinson's Disease Rating Scale (UPDRS) parts I and II, Schwab and England activities of daily living scale, striatal dopamine transporter binding, and SNP rs11724635 in the gene BST1. The most consistent predictor of UPDRS part III was baseline level of activities of daily living (part II). Key findings were replicated using long-term data from an independent cohort study. Baseline function near the time of Parkinson's disease diagnosis, as measured by activities of daily living, is a consistent predictor of long-term motor and cognitive outcomes. Additional predictors identified may further characterize the expected course of Parkinson's disease and suggest mechanisms underlying disease progression. The prognostic model developed in this study can be used to simulate the effects of the prognostic variables on motor and cognitive outcomes, and can be replicated and refined with data from independent longitudinal studies.


A long-lived fusogenic state is induced in erythrocyte ghosts by electric pulses.
Treatment of erythrocyte ghosts in random positions in a suspension with membrane fusion-inducing direct current electric field pulses causes the membranes to become fusogenic. Significant fusion yields are observed if the membranes are dielectrophoretically aligned into membrane-membrane contact with a weak alternating electric field as much as 5 min after the application of the pulses. This demonstrates that a long-lived membrane structural alteration is involved in this fusion mechanism. Other experiments indicate that the areas on the membrane which become fusogenic after treatment with the pulses may be very highly localized. The locations of these fusogenic areas coincide with where the trans-membrane electric field strength was greatest during the pulse. The fusogenic membrane alteration, or components thereof, in these areas laterally diffuses very slowly or not at all, or, to be fusogenic, must be present at concentrations in the membrane above a certain threshold. The loss of soluble 0.9-3-nm-diameter fluorescent probes from resealed cytoplasmic compartments of randomly positioned erythrocyte ghosts occurs through electric field pulse-induced pores only during a pulse but not between pulses or after a train of pulses if the probe diameter is 1.2 nm or greater. For a given pulse treatment of membranes in random positions in suspensions, an increase in ionic strength of the medium results in (a) a decrease in loss during the pulse, (b) no difference in loss between pulses, and (c) an increase in fusion yield when membrane-membrane contact is established. The latter two results (b and c) are incompatible with a fusion mechanism that proposes a simple relationship between electric field-induced pores and fusion.


The incidence of sudden death syndrome in a cohort of infants.
To quantify the incidence of sudden infant death syndrome in the town of Passo Fundo, in Rio Grande do Sul, Brazil, and to describe the profile of the deaths observed. A population-based cohort study of the live births from February 2003 to January 2004 to parents resident in the urban area. Infants were excluded if they had been hospitalized since birth, were in the process of being adopted or had died before data collection. 2,411 children were included from the total of 2,634 live births and 2,285 (94.8%) of these were followed-up. Data were obtained from the Live Births Information System (Sistema de Informações Sobre Nascidos Vivos), death registers, records of the Committee on Infant Mortality and from interviews with the social mother during home visits. Data collection instruments were adapted from previously validated forms. Data were analyzed on Epi-Info with descriptive statistics. Ten deaths were registered (0.4%). Four deaths of unknown causes could be included in sudden infant death syndrome category III. These deaths took place at home, between 4 and 6 months of age. The children slept on their sides, sharing a bed with adults, and had soft mattresses, pillows and diapers on the surface. They were the children of young mothers, smokers, with incomplete prenatal care and previous births from underprivileged economic classes. The incidence of suspicion of this syndrome was 1.75/1,000. The incidence rate of suspected sudden infant death syndrome in Passo Fundo is comparable with the highest international coefficients, which suggests the need for vigilance and risk prevention measures.


Real-time fingerprint sensor using a hologram.
A holographic fingerprint sensor has been developed for a system that identifies a person by his or her fingerprints. The sensor uses a laser as its light source and consists of a light-conducting plate, which is a transparent glass plate with a plain grating-type hologram, and a focusing lens system just under the hologram. Since the sensor uses a plane-parallel plate, all the optical paths from each point of a fingerprint to the hologram are equal, and a bright fingerprint can be created without the trapezoidal distortion that is inherent in conventional prism-type sensors.


Development and Validation of Single Nucleotide Polymorphisms (SNPs) Markers from Two Transcriptome 454-Runs of Turbot (Scophthalmus maximus) Using High-Throughput Genotyping.
The turbot (Scophthalmus maximus) is a commercially valuable flatfish and one of the most promising aquaculture species in Europe. Two transcriptome 454-pyrosequencing runs were used in order to detect Single Nucleotide Polymorphisms (SNPs) in genes related to immune response and gonad differentiation. A total of 866 true SNPs were detected in 140 different contigs representing 262,093 bp as a whole. Only one true SNP was analyzed in each contig. One hundred and thirteen SNPs out of the 140 analyzed were feasible (genotyped), while Ш were polymorphic in a wild population. Transition/transversion ratio (1.354) was similar to that observed in other fish studies. Unbiased gene diversity (He) estimates ranged from 0.060 to 0.510 (mean = 0.351), minimum allele frequency (MAF) from 0.030 to 0.500 (mean = 0.259) and all loci were in Hardy-Weinberg equilibrium after Bonferroni correction. A large number of SNPs (49) were located in the coding region, 33 representing synonymous and 16 non-synonymous changes. Most SNP-containing genes were related to immune response and gonad differentiation processes, and could be candidates for functional changes leading to phenotypic changes. These markers will be useful for population screening to look for adaptive variation in wild and domestic turbot.


Functional consequences of the interactions among the neural cell adhesion molecule NCAM, the receptor tyrosine kinase TrkB, and the inwardly rectifying K+ channel KIR3.3.
Cell adhesion molecules and neurotrophin receptors are crucial for the development and the function of the nervous system. Among downstream effectors of neurotrophin receptors and recognition molecules are ion channels. Here, we provide evidence that G protein-coupled inwardly rectifying K(+) channel Kir3.3 directly binds to the neural cell adhesion molecule (NCAM) and neurotrophin receptor TrkB. We identified the binding sites for NCAM and TrkB at the C-terminal intracellular domain of Kir3.3. The interaction between NCAM, TrkB, and Kir3.3 was supported by immunocytochemical co-localization of Kir3.3, NCAM, and/or TrkB at the surface of hippocampal neurons. Co-expression of TrkB and Kir3.1/3.3 in Xenopus oocytes increased the K(+) currents evoked by Kir3.1/3.3 channels. This current enhancement was reduced by the concomitant co-expression with NCAM. Both surface fluorescence measurements of microinjected oocytes and cell surface biotinylation of transfected CHO cells indicated that the cell membrane localization of Kir3.3 is regulated by TrkB and NCAM. Furthermore, the level of Kir3.3, but not of Kir3.2, at the plasma membranes was reduced in TrkB-deficient mice, supporting the notion that TrkB regulates the cell surface expression of Kir3.3. The premature expression of developmentally late appearing Kir3.1/3.3 in hippocampal neurons led to a reduction of NCAM-induced neurite outgrowth. Our observations indicate a decisive role for the neuronal K(+) channel in regulating NCAM-dependent neurite outgrowth and attribute a physiologically meaningful role to the functional interplay of Kir3.3, NCAM, and TrkB in ontogeny.


Metabolism of sulphonated anthraquinones in rhubarb, maize and celery: the role of cytochromes P450 and peroxidases.
Sulphonated anthraquinones are precursors of many synthetic dyes and pigments, recalcitrant to biodegradation, and thus contaminating many industrial effluents and rivers. In the development of a phytotreatment to remove sulphonated aromatic compounds, rhubarb (Rheum rhaponticum), a plant producing natural anthraquinones, as well as maize (Zea mays) and celery (Apium graveolens), plants not producing anthraquinones, were tested for their ability to metabolise these xenobiotics. Plants were cultivated under hydroponic conditions, with or without sulphonated anthraquinones, and were harvested at different times. Either microsomal or cytosolic fractions were prepared. The monooxygenase activity of cytochromes P450 towards several sulphonated anthraquinones was tested using a new method based on the fluorimetric detection of oxygen consumed during cytochromes P450-catalysed reactions. The activity of cytosolic peroxidases was measured by spectrophotometry, using guaiacol as a substrate. Results indicated that the activity of cytochromes P450 and peroxidases significantly increased in rhubarb plants cultivated in the presence of sulphonated anthraquinones. A higher activity of cytochromes P450 was also detected in maize and celery exposed to the pollutants. In these two plants, a peroxidase activity was also detected, but without a clear difference between the control plants and the plants exposed to the organic contaminants. This research demonstrated the existence in rhubarb, maize and celery of biochemical mechanisms involved in the metabolism and detoxification of sulphonated anthraquinones. Taken together, results confirmed that rhubarb might be the most appropriate plant for the phytotreatment of these organic pollutants.


Adult emergency department patients with sickle cell pain crisis: results from a quality improvement learning collaborative model to improve analgesic management.
The aims of this study were to 1) estimate differences in pain management process and patient-reported outcomes, pre- and postimplementation of analgesic protocols for adults with sickle cell disease (SCD), and 2) examine the effects of site and visit frequency on changes in pain scores and time to analgesic. A multicenter, prospective, longitudinal study enrolled patients from three academic medical centers between October 2007 and September 2009. All ED patients 18 years or older with a chief complaint of a sickle cell pain episode were enrolled. Sites formed a SCD quality improvement (QI) team and implemented standard nurse-initiated emergency department (ED) analgesic protocols; outcomes were compared between study periods defined as pre- and postimplementation of protocols. Medical record review was conducted to measure time to administration of initial analgesic, opioids used, route of opioid administration, the change in pain scores from arrival to discharge (negative numbers reflect a decrease in pain scores), and the number of ED visits per individual patient during the study period at each site. On day 7 after the ED visit, a follow-up phone interview was conducted. Patients were queried about their ED pain management using a scale from 1 to 10 (1 = outstanding, 10 = worst). Descriptive statistics are used to report the results. Ordinary least-squares regression models were constructed to measure the effect of time period, site, and number of visits per patient on change in pain score. During the study period, 342 unique patients (57% female, mean ± SD age = 32 ± 11 years) were enrolled and had a total of 2,934 visits. There was no difference in time to administration of the initial analgesic between study periods. Overall, there was a significant decrease in pain scores from arrival to discharge between the pre- and postintervention study periods: the average difference in arrival to discharge pain scores (cm) was greater during the postimplementation period than during the preintervention period (-4.1 vs. -3.6, t = 2.6, p < 0.01). Site 1 had significant improvement between study periods (mean difference = -0.87, t = 2.63, p < 0.01; F = 14.3, p < 0.01). Patients with few ED visits (one to six annual visits, mean difference = -1.55, t = 2.1, p = 0.04) and those with frequent ED visits (7 to 19 annual visits, mean difference = -1.65, t = 3.52, p < 0.01) had a significant decrease in pain scores compared to patients with very frequent ED visits (>19 visits). There was an overall decrease in the use of morphine sulfate (MS) and increase in the use of hydromorphone (χ(2) = 105.67, p < 0.001) between study periods and a significant increase in the use of oral (PO) and subcutaneous (SC) routes, with a corresponding decrease in the intravenous (IV) route (χ(2) = 13.67, p < 0.001). There were no statistically significant differences in patient-reported satisfaction with the attempt to manage pain in the ED between study periods (p = 0.54). While the use of a learning collaborative and implementation of nurse-initiated analgesic protocols was not associated with improvement in time to administration of the initial analgesic, improvements in the decrease in the arrival to discharge pain score and increased use of hydromorphone and the SC route were noted in adults with SCD in the ED.


Does the probability of DWI arrest fall following participation in DWI and hybrid drug treatment court programs?
Using North Carolina administrative data, this study examined recidivism following participation in specialty hybrid drug and driving while intoxicated (DWI) court programs. Three court program participation levels were considered-being referred to, enrolling in, and completing a specialty court program. Measures of DWI recidivism were: arrest and total number of arrests for DWI, and being convicted of DWI during follow-up periods of two and, alternatively, four years. Propensity score matching was used to obtain comparable control groups. Using a four-year follow-up, persons convicted of a DWI who completed a specialty court program were associated with a greater reduction in DWI re-arrests and re-convictions than did matched individuals who were never referred to a specialty court program. DWI courts were more effective in reducing re-arrests than hybrid drug courts were. Although promising from the vantage point of participants, few persons convicted of a DWI were referred to either court type, thus limiting this strategy's potential effectiveness in reducing DWI.


Clouds and Convective Self-Aggregation in a Multimodel Ensemble of Radiative-Convective Equilibrium Simulations.
The Radiative-Convective Equilibrium Model Intercomparison Project (RCEMIP) is an intercomparison of multiple types of numerical models configured in radiative-convective equilibrium (RCE). RCE is an idealization of the tropical atmosphere that has long been used to study basic questions in climate science. Here, we employ RCE to investigate the role that clouds and convective activity play in determining cloud feedbacks, climate sensitivity, the state of convective aggregation, and the equilibrium climate. RCEMIP is unique among intercomparisons in its inclusion of a wide range of model types, including atmospheric general circulation models (GCMs), single column models (SCMs), cloud-resolving models (CRMs), large eddy simulations (LES), and global cloud-resolving models (GCRMs). The first results are presented from the RCEMIP ensemble of more than 30 models. While there are large differences across the RCEMIP ensemble in the representation of mean profiles of temperature, humidity, and cloudiness, in a majority of models anvil clouds rise, warm, and decrease in area coverage in response to an increase in sea surface temperature (SST). Nearly all models exhibit self-aggregation in large domains and agree that self-aggregation acts to dry and warm the troposphere, reduce high cloudiness, and increase cooling to space. The degree of self-aggregation exhibits no clear tendency with warming. There is a wide range of climate sensitivities, but models with parameterized convection tend to have lower climate sensitivities than models with explicit convection. In models with parameterized convection, aggregated simulations have lower climate sensitivities than unaggregated simulations.


Population genomics reveals additive and replacing horizontal gene transfers in the emerging pathogen Dickeya solani.
Dickeya solani is an emerging pathogen that causes soft rot and blackleg diseases in several crops including Solanum tuberosum, but little is known about its genomic diversity and evolution. We combined Illumina and PacBio technologies to complete the genome sequence of D. solani strain 3337 that was used as a reference to compare with 19 other genomes (including that of the type strain IPO2222(T)) which were generated by Illumina technology. This population genomic analysis highlighted an unexpected variability among D. solani isolates since it led to the characterization of two distinct sub-groups within the D. solani species. This approach also revealed different types of variations such as scattered SNP/InDel variations as well as replacing and additive horizontal gene transfers (HGT). Infra-species (between the two D. solani sub-groups) and inter-species (between D. solani and D. dianthicola) replacing HGTs were observed. Finally, this work pointed that genetic and functional variation in the motility trait could contribute to aggressiveness variability in D. solani. This work revealed that D. solani genomic variability may be caused by SNPs/InDels as well as replacing and additive HGT events, including plasmid acquisition; hence the D. solani genomes are more dynamic than that were previously proposed. This work alerts on precautions in molecular diagnosis of this emerging pathogen.


Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans.
We have used whole genome paired-end Illumina sequence data to identify tandem duplications in 20 isofemale lines of Drosophila yakuba and 20 isofemale lines of D. simulans and performed genome wide validation with PacBio long molecule sequencing. We identify 1,415 tandem duplications that are segregating in D. yakuba as well as 975 duplications in D. simulans, indicating greater variation in D. yakuba. Additionally, we observe high rates of secondary deletions at duplicated sites, with 8% of duplicated sites in D. simulans and 17% of sites in D. yakuba modified with deletions. These secondary deletions are consistent with the action of the large loop mismatch repair system acting to remove polymorphic tandem duplication, resulting in rapid dynamics of gain and loss in duplicated alleles and a richer substrate of genetic novelty than has been previously reported. Most duplications are present in only single strains, suggesting that deleterious impacts are common. Drosophila simulans shows larger numbers of whole gene duplications in comparison to larger proportions of gene fragments in D. yakuba. Drosophila simulans displays an excess of high-frequency variants on the X chromosome, consistent with adaptive evolution through duplications on the D. simulans X or demographic forces driving duplicates to high frequency. We identify 78 chimeric genes in D. yakuba and 38 chimeric genes in D. simulans, as well as 143 cases of recruited noncoding sequence in D. yakuba and 96 in D. simulans, in agreement with rates of chimeric gene origination in D. melanogaster. Together, these results suggest that tandem duplications often result in complex variation beyond whole gene duplications that offers a rich substrate of standing variation that is likely to contribute both to detrimental phenotypes and disease, as well as to adaptive evolutionary change.


Mathematical modelling of ethanol metabolism in normal subjects and chronic alcohol misusers.
The time course of ethanol disappearance from the blood has been examined in normal males and females and in alcohol misusers. Blood alcohol estimations were made over a period of 3 hr, following an oral dose of ethanol (0.8 g/kg body weight) administered in the form of whisky. Attempts were made to fit the data to zero order, first order and mixed zero + first order kinetics. In the majority (75%) of normal females the blood ethanol concentrations was still increasing at 30 min. This was only seen in 50% of normal males and in 50% of non-dependent alcohol misusers, but not in dependent alcohol misusers. In all of the normal females the disappearance of ethanol could be adequately described by zero order kinetics. However, in the normal male group only 20% could be described by zero order kinetics, 10% fitted first order kinetics and the remainder required a mixed model of zero + first order. The rate constant for the zero order component of the control male group was identical to zero order rate constant obtained for the female control group. In the female alcohol misuser group, 40% of the curves could not be described by zero order kinetics and fitted best to a mixed model. The zero order component of the entire group was significantly increased (by 35%) compared to that obtained for the female control group. In the male dependent and non-dependent alcohol misuser groups, all blood alcohol concentration curves fitted best to mixed zero and first order kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)


Methods to investigate intrathecal adaptive immunity in neurodegeneration.
Cerebrospinal fluid (CSF) provides basic mechanical and immunological protection to the brain. Historically, analysis of CSF has focused on protein changes, yet recent studies have shed light on cellular alterations. Evidence now exists for involvement of intrathecal T cells in the pathobiology of neurodegenerative diseases. However, a standardized method for long-term preservation of CSF immune cells is lacking. Further, the functional role of CSF T cells and their cognate antigens in neurodegenerative diseases are largely unknown. We present a method for long-term cryopreservation of CSF immune cells for downstream single cell RNA and T cell receptor sequencing (scRNA-TCRseq) analysis. We observe preservation of CSF immune cells, consisting primarily of memory CD4+ and CD8+ T cells. We then utilize unbiased bioinformatics approaches to quantify and visualize TCR sequence similarity within and between disease groups. By this method, we identify clusters of disease-associated, antigen-specific TCRs from clonally expanded CSF T cells of patients with neurodegenerative diseases. Here, we provide a standardized approach for long-term storage of CSF immune cells. Additionally, we present unbiased bioinformatic approaches that will facilitate the discovery of target antigens of clonally expanded T cells in neurodegenerative diseases. These novel methods will help improve our understanding of adaptive immunity in the central nervous system.


A two-part measure of degree of invasion for cross-community comparisons.
Invasibility is a critical feature of ecological communities, especially for management decisions. To date, invasibility has been measured in numerous ways. Although most researchers have used the richness (or number) of exotic species as a direct or indirect measure of community invasibility, others have used alternative measures such as the survival, density, or biomass of either a single or all exotic species. These different measures, even when obtained from the same communities, have produced inconsistent results and have made comparisons among communities difficult. Here, we propose a measure of the degree of invasion (DI) of a community as a surrogate for community invasibility. The measure is expressed as 2 independent components: exotic proportion of total species richness and exotic proportion of total species abundance (biomass or cover). By including richness and abundance, the measure reflects that the factors that control invasibility affect both of these components. Expressing exotic richness and abundance relative to the richness and abundance of all species in a community makes comparisons across communities of different sizes and resource availability possible and illustrates the importance of dominance of exotic species relative to natives, which is a primary management concern associated with exotic species.


A brain-based pain facilitation mechanism contributes to painful diabetic polyneuropathy.
The descending pain modulatory system represents one of the oldest and most fundamentally important neurophysiological mechanisms relevant to pain. Extensive work in animals and humans has shown how a functional imbalance between the facilitatory and inhibitory components is linked to exacerbation and maintenance of persistent pain states. Forward translation of these findings into clinical populations is needed to verify the relevance of this imbalance. Diabetic polyneuropathy is one of the most common causes of chronic neuropathic pain; however, the reason why ∼25-30% of patients with diabetes develop pain is not known. The current study used a multimodal clinical neuroimaging approach to interrogate whether the sensory phenotype of painful diabetic polyneuropathy involves altered function of the ventrolateral periaqueductal grey-a key node of the descending pain modulatory system. We found that ventrolateral periaqueductal grey functional connectivity is altered in patients suffering from painful diabetic polyneuropathy; the magnitude of which is correlated to their spontaneous and allodynic pain as well as the magnitude of the cortical response elicited by an experimental tonic heat paradigm. We posit that ventrolateral periaqueductal grey-mediated descending pain modulatory system dysfunction may reflect a brain-based pain facilitation mechanism contributing to painful diabetic polyneuropathy.


Coexistence of racemic and homochiral two-dimensional lattices formed by a prochiral molecule: dicarboxystilbene on Cu(110).
Dicarboxystilbene, a molecule that becomes chiral in the adsorbed state through the loss of its improper axis of rotation, forms long-range "handed" structures when adsorbed on Cu(110) as revealed by scanning tunnelling microscopy. We show that these structures are created from chiral "adsorption complex" building blocks, giving rise to a complete set of racemic and enantiomerically pure structural assemblies. We interpret the formation of these structures in terms of a balance between hydrogen bond mediated intermolecular interactions and the adsorbate-surface structural relationship and discuss the reasons for temperature-induced conversion from the metastable enantiomerically pure to the racemic structure.


Comparative point prevalence survey of antimicrobial consumption between a hospital in Northern Ireland and a hospital in Jordan.
To assess antimicrobial prescribing in a Northern Ireland hospital (Antrim Area Hospital (AAH)) and compare them with those of a hospital in Jordan (Specialty Hospital). Using the Global-PPS approach, the present study surveyed patients admitted to the hospital in 2015, the prescribed antibiotics, and a set of quality control indicators related to antibiotics. Ultimately, 444 and 112 inpatients in the AAH and the Specialty Hospital, respectively, were surveyed. For the medical group, 165 inpatients were prescribed 239 antibiotics in the AAH, while 44 patients in the Specialty Hospital were prescribed 65 antibiotics. In relation to the surgical group, 34 inpatients treated for infection were prescribed 66 antibiotics in the AAH, while 41 patients in the Specialty Hospital treated for infection were prescribed 56 antibiotics. For the medical patients, the most frequently prescribed antibiotics in the AAH were a combination of penicillins (18.8%) and penicillins with extended spectrum (18.8%). For the surgical patients, the most frequently prescribed antibiotics in the AAH were imidazole derivatives (24.2%). For the medical and surgical patients in the Specialty Hospital, the most frequently prescribed antibiotics were third-generation cephalosporins (26.2 and 37.5%, respectively). In medical patients, compliance to guidelines was 92.2% in the Specialty Hospital compared to 72.0% in the AAH (p < 0.001). In surgical patients, compliance to guidelines was 92.7% in the Specialty Hospital compared to 81.8% in the AAH (p = 0.012). The present study highlighted differences in the utilisation of antimicrobials between two hospitals in two distinct regions and benchmarked antibiotic prescriptions across two hospitals.


A metric for the evaluation of dense vector field visualizations.
In this work, we present an intuitive image-quality metric that is derived from the motivation of DVF visualization. It utilizes the features of the resulting image and effectively measures the similarity between the output of the visualization method and the input flow data. We use the angle between the gradient direction and the original vector field as a measure of such similarity and the gradient magnitude as an importance measure. Our metric enables the automatic evaluation of images for a given vector field and allows the comparison of different methods, parameters sets, and quality improvement strategies for a specific vector field. By integrating the metric into the image-computation process, our approach can be used to generate improved images by choosing the best parameter set. To verify the effectiveness of our method, we conducted an extensive user study that demonstrated the metric's applicability to various situations. For instance, our approach elucidated the robustness of a DVF visualization in the presence of data-altering filters, such as resampling.


Assessment of branched-chain amino Acid status and potential for biomarkers.
BCAAs are not synthesized in the body in humans, but they are crucial in protein and neurotransmitter synthesis. The protein anabolic role of BCAAs seems to be mediated not only by their important role as a promoter of the translation process (and possibly acting at the transcription level) but also by inhibition of protein degradation. Leucine may play a critical role in these signaling pathways. Supplementation with BCAAs spares lean body mass during weight loss, promotes wound healing, may decrease muscle wasting with aging, and may have beneficial effects in renal and liver disease. BCAA supplementation is extensively used in the athletic field with the assumption of improved performance and muscle mass. Measuring serum BCAAs has limited clinical utility beyond the controlled setting because levels are affected by a variety of clinical states, and optimal levels in these scenarios have not been completely elucidated. We discuss the effects diet, hormones, stress, aging, and renal or liver dysfunction have on BCAA levels and how understanding the biological effects of BCAAs may help to develop biomarkers of BCAA status. We also discuss potential biomarkers of BCAA status.


Kombucha: a systematic review of the clinical evidence.
Kombucha has become a popular complementary remedy. The aim of this systematic review was to critically evaluate the evidence related to its efficacy and safety. Computerised literature searches were carried out to locate all human medical investigations of kombucha regardless of study design. Data were extracted and validated by the present author and are reported in narrative form. No clinical studies were found relating to the efficacy of this remedy. Several case reports and case series raise doubts about the safety of kombucha. They include suspected liver damage, metabolic acidosis and cutaneous anthrax infections. One fatality is on record. On the basis of these data it was concluded that the largely undetermined benefits do not outweigh the documented risks of kombucha. It can therefore not be recommended for therapeutic use.


Antagonistic coevolution between hosts and sexually transmitted infections.
Sexually transmitted infections (STIs) are predicted to play an important role in the evolution of host mating strategies, and vice versa, yet our understanding of host-STI coevolution is limited. Previous theoretical work has shown mate choice can evolve to prevent runaway STI virulence evolution in chronic, sterilizing infections. Here, I generalize this theory to examine how a broader range of life-history traits influence coevolution; specifically, how host preferences for healthy mates and STI virulence coevolve when infections are acute and can cause mortality or sterility, and hosts do not form long-term sexual partnerships. I show that mate choice reduces both mortality and sterility virulence, with qualitatively different outcomes depending on the mode of virulence, costs associated with mate choice, recovery rates, and host lifespan. For example, fluctuating selection-a key finding in previous work-is most likely when hosts have moderate lifespans, STIs cause sterility and long infections, and costs of mate choice are low. The results reveal new insights into the coevolution of mate choice and STI virulence as different life-history traits vary, providing increased support for parasite-mediated sexual selection as a potential driver of host mate choice, and mate choice as a constraint on the evolution of virulence.


Medial femoral head border is a reliable and reproducible reference for axis determination for femoral component of unicompartmental knee arthroplasty.
The femoral component should be implanted parallel to the mechanical axis in unicompartmental knee arthroplasty. It was hypothesised that a line between medial femoral condyle centres and medial border of femoral head will be parallel to the mechanical axis; this study set out to examine this hypothesis. One hundred X-rays in fifty patients were included for this study. Long-leg standing X-rays including hip and ankle with patellae facing forwards were obtained. On these films, we measured the angle, α, between mechanical axis and the line between the femoral head centre and knee centre (medial mechanical axis), and the angle, β, between the medial mechanical axis and a line between medial femoral condyle and femoral head centre. The average value of α was 0.1 ± 0.5° and the average value of β 3.0° ± 0.3°. These data indicate that mechanical axis and medial mechanical axis are virtually parallel to each other. As medial femoral head border is easily identified fluoroscopically, it is a reliable landmark for orientating the femoral component of medial UKA.


[Posttraumatic Growth after Profession-Related Traumatization in Rescue Workers].
This study aims to explore the association between self-reported secondary traumatization and personal growth in a sample of Belarusians rescue workers, focusing on the mediating role of 2 socio-interpersonal processes (disclosure and co-rumination). In a cross-sectional survey, self-reported posttraumatic growth and secondary traumatization were assessed in a sample of 168 rescue workers. Posttraumatic growth was positively linked to the extent of secondary traumatization, likewise disclosure and co-rumination were positively linked to posttraumatic growth. Mediation analyses revealed that the association between secondary traumatization and posttraumatic personal growth was mediated by disclosure and co-rumination. The results thus are in favor of a socio-interpersonal perspective on posttraumatic adjustment.


Host subversion of bacterial metallophore usage drives copper intoxication.
Microorganisms can acquire metal ions in metal-limited environments using small molecules called metallophores. While metals and their importers are essential, metals can also be toxic, and metallophores have limited ability to discriminate between metals. The impact of metallophore-mediated non-cognate metal uptake on bacterial metal homeostasis and pathogenesis remains to be defined. The globally significant pathogen Staphylococcus aureus uses the Cnt system to secrete the metallophore staphylopine in zinc-limited host niches. Here, we show that staphylopine and the Cnt system facilitate bacterial copper uptake, potentiating the need for copper detoxification. During in vivo infection, staphylopine usage increased S. aureus susceptibility to host-mediated copper stress, indicating that the innate immune response can harness the antimicrobial potential of altered elemental abundances in host niches. Collectively, these observations show that while the broad-spectrum metal-chelating properties of metallophores can be advantageous, the host can exploit these properties to drive metal intoxication and mediate antibacterial control. IMPORTANCE During infection, bacteria must overcome the dual threats of metal starvation and intoxication. This work reveals that the zinc-withholding response of the host sensitizes S. aureus to copper intoxication. In response to zinc starvation, S. aureus utilizes the metallophore staphylopine. The current work revealed that the host can leverage the promiscuity of staphylopine to intoxicate S. aureus during infection. Significantly, staphylopine-like metallophores are produced by a wide range of pathogens, suggesting that this is a conserved weakness that the host can leverage to toxify invaders with copper. Moreover, it challenges the assumption that the broad-spectrum metal binding of metallophores is inherently beneficial to bacteria.


Global genome diversity of the Leishmania donovani complex.
Protozoan parasites of the Leishmania donovani complex - L. donovani and L. infantum - cause the fatal disease visceral leishmaniasis. We present the first comprehensive genome-wide global study, with 151 cultured field isolates representing most of the geographical distribution. L. donovani isolates separated into five groups that largely coincide with geographical origin but vary greatly in diversity. In contrast, the majority of L. infantum samples fell into one globally-distributed group with little diversity. This picture is complicated by several hybrid lineages. Identified genetic groups vary in heterozygosity and levels of linkage, suggesting different recombination histories. We characterise chromosome-specific patterns of aneuploidy and identified extensive structural variation, including known and suspected drug resistance loci. This study reveals greater genetic diversity than suggested by geographically-focused studies, provides a resource of genomic variation for future work and sets the scene for a new understanding of the evolution and genetics of the Leishmania donovani complex.


Impact of microbial count distributions on human health risk estimates.
Quantitative microbiological risk assessment (QMRA) is influenced by the choice of the probability distribution used to describe pathogen concentrations, as this may eventually have a large effect on the distribution of doses at exposure. When fitting a probability distribution to microbial enumeration data, several factors may have an impact on the accuracy of that fit. Analysis of the best statistical fits of different distributions alone does not provide a clear indication of the impact in terms of risk estimates. Thus, in this study we focus on the impact of fitting microbial distributions on risk estimates, at two different concentration scenarios and at a range of prevalence levels. By using five different parametric distributions, we investigate whether different characteristics of a good fit are crucial for an accurate risk estimate. Among the factors studied are the importance of accounting for the Poisson randomness in counts, the difference between treating "true" zeroes as such or as censored below a limit of quantification (LOQ) and the importance of making the correct assumption about the underlying distribution of concentrations. By running a simulation experiment with zero-inflated Poisson-lognormal distributed data and an existing QMRA model from retail to consumer level, it was possible to assess the difference between expected risk and the risk estimated with using a lognormal, a zero-inflated lognormal, a Poisson-gamma, a zero-inflated Poisson-gamma and a zero-inflated Poisson-lognormal distribution. We show that the impact of the choice of different probability distributions to describe concentrations at retail on risk estimates is dependent both on concentration and prevalence levels. We also show that the use of an LOQ should be done consciously, especially when zero-inflation is not used. In general, zero-inflation does not necessarily improve the absolute risk estimation, but performance of zero-inflated distributions in QMRA tends to be more robust to changes in prevalence and concentration levels, and to the use of an LOQ to interpret zero values, compared to that of their non-zero-inflated counterparts.


Early osteolysis following second-generation metal-on-metal hip replacement.
Total hip arthroplasty with use of metal-on-metal bearings has been reintroduced as an alternative to the use of metal-on-polyethylene bearings because of theoretical advantages such as reduced wear and a lower prevalence of osteolysis. However, we observed early osteolysis in a cohort of patients who had been managed with second-generation metal-on-metal hip replacements and investigated the possible etiologic role of metal hypersensitivity. We retrospectively analyzed 165 patients (169 hips) who had undergone primary cementless total hip replacement with a contemporary metal-on-metal total hip design between 2000 and 2002. After a minimum duration of follow-up of twenty-four months, nine patients (ten hips) had an osteolytic lesion localized to the greater trochanter. Skin-patch tests for hypersensitivity to metals were performed on the nine patients and on nine randomly selected patients with total hip replacements who did not have osteolytic changes and who were matched to the study cohort for age and gender. Microbiological cultures, histopathologic examinations, and immunohistochemical analysis were performed on samples of periprosthetic tissue that were collected during revision arthroplasty on two hips with early osteolysis. The patients with early osteolysis had a significantly higher rate of hypersensitivity reaction to cobalt compared with controls (p = 0.031). The retrieved periprosthetic tissues showed no evidence of metallic staining, but histologic analysis revealed a perivascular accumulation of CD3-positive T-cells and CD68-positive macrophages and an absence of both particle-laden macrophages and polymorphonuclear cells. Immunohistochemical analysis demonstrated that bone-resorbing cytokines such as IL-1beta and TNF-alpha were produced mainly by infiltrating lymphocytes and activated macrophages. These findings raise the possibility that early osteolysis in patients with this second-generation metal-on-metal hip replacement is associated with abnormalities consistent with delayed-type hypersensitivity to metal. A prospective study in which a large group of patients is evaluated with multiple diagnostic methods is needed in order to establish whether there is a causal relationship between metal hypersensitivity and osteolysis.


An efficient parameterless quadrilateral-based image segmentation method.
This paper proposes a general quadrilateral-based framework for image segmentation, in which quadrilaterals are first constructed from an edge map, where neighboring quadrilaterals with similar features of interest are then merged together to form regions. Under the proposed framework, the quadrilaterals enable the elimination of local variations and unnecessary details for merging from which each segmented region is accurately and completely described by a set of quadrilaterals. To illustrate the effectiveness of the proposed framework, we derived an efficient and high-performance parameterless quadrilateral-based segmentation algorithm from the framework. The proposed algorithm shows that the regions obtained under the framework are segmented into multiple levels of quadrilaterals that accurately represent the regions without severely over or undersegmenting them. When evaluated objectively and subjectively, the proposed algorithm performs better than three other segmentation techniques, namely, seeded region growing, K-means clustering and constrained gravitational clustering, and offers an efficient description of the segmented objects conducive to content-based applications.


Time sequence of nuclear pore formation in phytohemagglutinin-stimulated lymphocytes and in HeLa cells during the cell cycle.
The time sequence of nuclear pore frequency changes was determined for phytohemagglutinin (PHA)-stimulated human lymphocytes and for HeLa S-3 cells during the cell cycle. The number of nuclear pores/nucleus was calculated from the experimentally determined values of nuclear pores/micro(2) and the nuclear surface. In the lymphocyte system the number of pores/nucleus approximately doubles during the 48 hr after PHA stimulation. The increase in pore frequency is biphasic and the first increase seems to be related to an increase in the rate of protein synthesis. The second increase in pores/nucleus appears to be correlated with the onset of DNA synthesis. In the HeLa cell system, we could also observe a biphasic change in pore formation. Nuclear pores are formed at the highest rate during the first hour after mitosis. A second increase in the rate of pore formation corresponds in time with an increase in the rate of nuclear acidic protein synthesis shortly before S phase. The total number of nuclear pores in HeLa cells doubles from approximately 2000 in G(1) to approximately 4000 at the end of the cell cycle. The doubling of the nuclear volume and the number of nuclear pores might be correlated to the doubling of DNA content. Another correspondence with the nuclear pore number in S phase is found in the number of simultaneously replicating replication sites. This number may be fortuitous but leads to the rather speculative possibility that the nuclear pore might be the site of initiation and/or replication of DNA as well as the site of nucleocytoplasmic exchange. That is, the nuclear pore complex may have multiple functions.


Long-term safety of biologics in dermatology.
The use of biologics in dermatology has increased rapidly. Although most are relatively safe when correctly used and monitored, there are known side effects and adverse events that occur. Selection of patients should be done on a case-by-case basis. Severity of disease, comorbidity profile, drug profile, and cost-effectiveness should be all taken into consideration while deciding to start and/or maintain one of these therapies. Dermatologists should be aware of the benefits and limitations of this class of drugs, as well as the appropriate monitoring. The authors propose a concise overview of the safety profiles of some of the biologics currently used in the dermatologic field.


Monitoring hybrid process specifications with conflict management: An automata-theoretic approach.
Complexity of medical treatments can vary from prescribing medicine for a specific ailment to managing a complex set of simultaneous medical issues. In the latter case, doctors are assisted by clinical guidelines which outline standard medical procedures, tests, treatments, etc. To facilitate the use of such guidelines, they can be digitized as processes and adopted in complex process engines offering additional help to health providers such as decision support while monitoring active treatments so as to detect flaws in treatment procedures and suggest possible reactions on them. For example, a patient may present symptoms of multiple diseases simultaneously (requiring multiple clinical guidelines to be followed), while also being allergic to some often-used drugs (requiring additional constraints to be respected). This can easily lead to treating a patient based on a set of process specifications which are not fully compatible with each other. While a scenario like that commonly occurs in practice, research in that direction has thus far given little consideration to how to specify multiple clinical guidelines and how to automatically combine their specifications in the context of the monitoring task. In our previous work (Alman et al., 20222), we presented a conceptual framework for handling the above cases in the context of monitoring. In this paper, we present the algorithms necessary for implementing key components of this conceptual framework. More specifically, we provide formal languages for representing clinical guideline specifications and formalize a solution for monitoring the interplay of such specifications expressed as a combination of (data-aware) Petri nets and temporal logic rules. The proposed solution seamlessly handles combination of the input process specifications and provides both early conflict detection and decision support during process execution. We also discuss a proof-of-concept implementation of our approach and present the results of extensive scalability experiments.


Mitochondrial and Endoplasmic Reticulum Stress Trigger Triglyceride Accumulation in Models of Parkinson's Disease Independent of Mutations in MAPT.
The metabolic basis of Parkinson's disease pathology is poorly understood. However, the involvement of mitochondrial and endoplasmic reticulum stress in dopamine neurons in disease aetiology is well established. We looked at the effect of rotenone- and tunicamycin-induced mitochondrial and ER stress on the metabolism of wild type and microtubule-associated protein tau mutant dopamine neurons. Dopamine neurons derived from human isolated iPSCs were subjected to mitochondrial and ER stress using RT and TM, respectively. Comprehensive metabolite profiles were generated using a split phase extraction analysed by reversed phase lipidomics whilst the aqueous phase was measured using HILIC metabolomics. Mitochondrial and ER stress were both shown to cause significant dysregulation of metabolism with RT-induced stress producing a larger shift in the metabolic profile of both wild type and MAPT neurons. Detailed analysis showed that accumulation of triglycerides was a significant driver of metabolic dysregulation in response to both stresses in both genotypes. Whilst the consequence is similar, the mechanisms by which triglyceride accumulation occurs in dopamine neurons in response to mitochondrial and ER stress are very different. Thus, improving our understanding of how these mechanisms drive the observed triglyceride accumulation can potentially open up new therapeutic avenues.


CSF proteins and resting-state functional connectivity in Parkinson disease.
The purpose of this study was to investigate the relationship between disruption of MRI-measured resting-state functional connectivity (rs-fcMRI) brain networks and CSF levels of potentially pathogenic proteins that reflect brain pathology in Parkinson disease (PD). PD participants without dementia (n = 43) and age-matched controls (n = 22) had lumbar punctures to measure CSF protein levels, Pittsburgh compound B (PiB)-PET imaging, and rs-fcMRI while off medication. Imaging analyses focused on 5 major resting-state networks as well as the striatum. Participants with PD had significantly reduced sensorimotor functional connectivity, which correlated with reduced CSF levels of α-synuclein. The PD group also had significantly stronger default mode network functional connectivity that did not correlate with CSF β-amyloid (Aβ)42 or PiB uptake. In contrast, default mode network functional connectivity in the control group did correlate with CSF Aβ42 levels. Functional connectivity was similar between groups in the dorsal attention, control, and salience networks. These results suggest that abnormal α-synuclein accumulation, but not Aβ, contributes to the disruption of motor-related functional connectivity in PD. Furthermore, correlating CSF protein measures with the strength of resting-state networks provides a direct link between abnormal α-synuclein metabolism and disrupted brain function in PD.


Multimorbidity is common among young workers and related to increased work absenteeism and presenteeism: results from the population-based Raine Study cohort.
Objectives This study aimed to determine the extent of both multimorbidity and work productivity loss among young adults with paid work and to analyze their association. Methods We included 604 participants from a follow-up of the Raine Study that comprised a cohort who were 22 years at the time (Gen2-22). Information on 36 health conditions, grouped into 10 condition categories, was collected through questionnaires and physical assessments (for body mass index only). Quarterly questionnaires about work productivity, including total absenteeism, sickness absenteeism, and total presenteeism, were distributed electronically over the subsequent 12 months. Descriptive statistics were used to determine the prevalence of health conditions, condition categories, multimorbidity, and work productivity. Zero-inflated negative binomial regression analyses were used to assess the association of multimorbidity with productivity loss. Results Multimorbidity prevalence was substantially higher in females (63%) compared to males (41%). Productivity loss increased as the number of condition categories increased. For example, total absenteeism was associated with an increase in the number of health condition categories in males [incidence rate ratio (IRR) 1.20, 95% confidence interval (CI) 1.05-1.36] and females (IRR 1.13, 95% CI 1.04-1.24). Similar results were found for sickness absenteeism and presenteeism. The highest burden of productivity loss was found for musculoskeletal disorders (42 444 hours/1000 workers/year), sleep problems (33 581 hours/1000 workers/year), mental and neurological conditions (15 650 hours/1000 workers/year), and 'other' medical conditions (22 519 hours/1000 workers/year). Conclusions Multimorbidity appears to be highly prevalent among young adults with paid work and is strongly related to work productivity loss. Therefore, young workers should be targeted in interventions aiming to reduce multimorbidity and its impact on work productivity.


Anterior tooth growth periods in Neandertals were comparable to those of modern humans.
A longstanding controversy in paleoanthropology surrounds the question of whether Neandertals shared the prolonged growth periods of modern humans. To address this question, this investigation compares the duration of enamel formation in Neandertals with that of three comparative modern human groups. Because dental and somatic growth are correlated with each other, dental growth periods are indicative of overall periods of growth. Growth increments on the anterior teeth of Neandertals, modern Inuit, and modern people from Newcastle and southern Africa were counted and their means compared. In addition, potential variation in the time spans represented by growth increments was considered and incorporated into the analysis of enamel formation times. These analyses show that Neandertal imbricational enamel formation times, although likely to have been faster than those of the Inuit, are not likely to have been faster than those of the Newcastle sample and for some teeth are clearly slower than those of the southern African sample. Thus, Neandertal tooth growth and, by extension, somatic growth, appears to be encompassed within the modern human range of interpopulation variation.


Fetal macrosomia--an obstetrician's nightmare?
Fetal macrosomia is defined as a fetus that is of large size for gestational age, i.e. equal to or greater than the 90th percentile of weight. There is some evidence of increased perinatal mortality and morbidity rates in cases of macrosomia. This is a retrospective study of patients with term pregnancy. We analyzed the deliveries of 508 infants born with birth weight ≥ 4 200 grams and considered them as a study group. The deliveries of newborns with birth weight less than 4 000 g constituted the control group (330 cases). Maternal and neonatal medical records were retrospectively reviewed for clinical data. The study was conducted in Second Department of Obstetrics and Gynecology Warsaw Medical University from January 2004 to December 2007. Maternal age, parity, BMI and pregnancy weight gain were positively related to fetal macrosomia. Prolonged first stage of labor, cesarean section rate and increased blood loss were observed more frequent in macrososmia. There were no differences between both groups according to Apgar score and neonatal birth trauma. Macrosomia was observed more frequent in male fetuses. Our data showed that careful qualification to way of delivery let us achieve the same good outcome in macrosomia. Older obese multiparas are at increased risk of having macrosomic baby. The increased incidence of cesarean section in these women is due to cephalo-pelvic disproportion or obstructed labor. Macrosomia is more often in male fetuses.


Complete DNA barcode reference library for a country's butterfly fauna reveals high performance for temperate Europe.
DNA barcoding aims to accelerate species identification and discovery, but performance tests have shown marked differences in identification success. As a consequence, there remains a great need for comprehensive studies which objectively test the method in groups with a solid taxonomic framework. This study focuses on the 180 species of butterflies in Romania, accounting for about one third of the European butterfly fauna. This country includes five eco-regions, the highest of any in the European Union, and is a good representative for temperate areas. Morphology and DNA barcodes of more than 1300 specimens were carefully studied and compared. Our results indicate that 90 per cent of the species form barcode clusters allowing their reliable identification. The remaining cases involve nine closely related species pairs, some whose taxonomic status is controversial or that hybridize regularly. Interestingly, DNA barcoding was found to be the most effective identification tool, outperforming external morphology, and being slightly better than male genitalia. Romania is now the first country to have a comprehensive DNA barcode reference database for butterflies. Similar barcoding efforts based on comprehensive sampling of specific geographical regions can act as functional modules that will foster the early application of DNA barcoding while a global system is under development.


Individual and mixture effects of caffeine and sulfamethoxazole on the daggerblade grass shrimp Palaemonetes pugio following maternal exposure.
Pharmaceuticals and personal care products (PPCPs) such as caffeine and sulfamethoxazole have been detected in the estuarine environment. The present study characterized effects of a maternal exposure of these compounds on the development of the daggerblade grass shrimp Palaemonetes pugio from embryo to juvenile life stage. Ovigerous females were exposed to either caffeine (20 mg/L), sulfamethoxazole (60 mg/L), or a mixture of both (20 mg/L caffeine and 60 mg/L sulfamethoxazole). Embryos were then removed from the females and the effects of the PPCPs on hatching, metamorphosis, juvenile growth, and overall mortality were determined. No significant effect was observed on gravid female survival after 5 d of exposure to caffeine, sulfamethoxazole, or the mixture; however, development of the embryos on the female shrimp was delayed in the mixture. Caffeine and sulfamethoxazole in the mixture significantly reduced embryo survival. There was a significant effect of caffeine, sulfamethoxazole, and the mixture on embryo hatching time. Exposure to sulfamethoxazole alone significantly delayed larval metamorphosis. Exposure to caffeine and sulfamethoxazole separately led to significantly smaller length of juvenile shrimp. Maternal exposure to caffeine and sulfamethoxazole, individually and in mixture, resulted in negative effects on P. pugio offspring survival and development; however, the concentrations tested in the present study were well above maximum detected field concentrations. These results may be incorporated into PPCP risk assessments to protect sensitive estuarine ecosystems more effectively.


Steady-state catalytic wave-shapes for 2-electron reversible electrocatalysts and enzymes.
Using direct electrochemistry to learn about the mechanism of electrocatalysts and redox enzymes requires that kinetic models be developed. Here we thoroughly discuss the interpretation of electrochemical signals obtained with adsorbed enzymes and molecular catalysts that can reversibly convert their substrate and product. We derive analytical relations between electrochemical observables (overpotentials for catalysis in each direction, positions, and magnitudes of the features of the catalytic wave) and the characteristics of the catalytic cycle (redox properties of the catalytic intermediates, kinetics of intramolecular and interfacial electron transfer, etc.). We discuss whether or not the position of the wave is determined by the redox potential of a redox relay when intramolecular electron transfer is slow. We demonstrate that there is no simple relation between the reduction potential of the active site and the catalytic bias of the enzyme, defined as the ratio of the oxidative and reductive limiting currents; this explains the recent experimental observation that the catalytic bias of NiFe hydrogenase depends on steps of the catalytic cycle that occur far from the active site [Abou Hamdan et al., J. Am. Chem. Soc. 2012, 134, 8368]. On the experimental side, we examine which models can best describe original data obtained with various NiFe and FeFe hydrogenases, and we illustrate how the presence of an intramolecular electron transfer chain affects the voltammetry by comparing the data obtained with the FeFe hydrogenases from Chlamydomonas reinhardtii and Clostridium acetobutylicum, only one of which has a chain of redox relays. The considerations herein will help the interpretation of electrochemical data previously obtained with various other bidirectional oxidoreductases, and, possibly, synthetic inorganic catalysts.


Transcriptional profiling of epidermal keratinocytes: comparison of genes expressed in skin, cultured keratinocytes, and reconstituted epidermis, using large DNA microarrays.
Epidermal keratinocytes are complex cells that create a unique three-dimensional (3-D) structure, differentiate through a multistage process, and respond to extracellular stimuli from nearby cells. Consequently, keratinocytes express many genes, i.e., have a relatively large "transcriptome." To determine which of the expressed genes are innate to keratinocytes, which are specific for the differentiation and 3-D architecture, and which are induced by other cell types, we compared the transcriptomes of skin from human subjects, differentiating 3-D reconstituted epidermis, cultured keratinocytes, and nonkeratinocyte cell types. Using large oligonucleotide microarrays, we analyzed five or more replicates of each, which yielded statistically consistent data and allowed identification of the differentially expressed genes. Epidermal keratinocytes, unlike other cells, express many proteases and protease inhibitors and genes that protect from UV light. Skin specifically expresses a higher number of receptors, secreted proteins, and transcription factors, perhaps influenced by the presence of nonkeratinocyte cell types. Surprisingly, mitochondrial proteins were significantly suppressed in skin, suggesting a low metabolic rate. Three-dimensional samples, skin and reconstituted epidermis, are similar to each other, expressing epidermal differentiation markers. Cultured keratinocytes express many cell-cycle and DNA replication genes, as well as integrins and extracellular matrix proteins. These results define innate, architecture-specific, and cell-type-regulated genes in epidermis.


Tuning the Dzyaloshinskii-Moriya interaction in Pt/Co/MgO heterostructures through the MgO thickness.
The interfacial Dzyaloshinskii-Moriya interaction (DMI) in ferromagnetic/heavy metal ultra-thin film structures has attracted a lot of attention thanks to its capability to stabilize Néel-type domain walls (DWs) and magnetic skyrmions for the realization of non-volatile memory and logic devices. In this study, we demonstrate that magnetic properties in perpendicularly magnetized Ta/Pt/Co/MgO/Pt heterostructures, such as magnetization and DMI, can be significantly influenced by the MgO thickness. To avoid the excessive oxidation of Co, an ultrathin Mg layer is inserted to improve the quality of the Co-MgO interface. By using field-driven domain wall expansion in the creep regime, we find that non-monotonic tendencies of the DMI field appear when changing the thickness of MgO. With the insertion of a monatomic Mg layer, the strength of the DMI could reach a high level and saturate. We conjecture that the efficient control of the DMI is a result of subtle changes of both Pt/Co and Co/MgO interfaces, which provides a method to optimize the design of ultra-thin structures achieving skyrmion electronics.


What is a mammalian omnivore? Insights into terrestrial mammalian diet diversity, body mass and evolution.
Mammalian omnivores are a broad group of species that are often treated uniformly in ecological studies. Here, we incorporate omnivorous dietary differences to investigate previously found mammalian macroevolutionary and macroecological trends. We investigate the frequency with which vertebrate prey, invertebrate prey, fibrous plant material and non-fibrous plant material co-occur in the diets of terrestrial mammals. We quantify the body size distributions and phylogenetic signal of different omnivorous diets and use multistate reversible jump Markov chain Monte Carlo methods to assess the transition rates between diets on the mammalian phylogenetic tree. We find omnivores that consume all four food types are relatively rare, as most omnivores consume only invertebrate prey and non-fibrous plants. In addition, omnivores that only consume invertebrate prey, many of which are from Rodentia, are on average smaller than omnivores that incorporate vertebrate prey. Our transition models have high rates from invertivorous omnivory to herbivory, and from vertivory to prey mixing and ultimately invertivory. We suggest prey type is an important aspect of omnivore macroevolution and macroecology, as it is correlated with body mass, evolutionary history and diet-related evolutionary transition rates. Future work should avoid lumping omnivores into one category given the ecological variety of omnivore diets and their strong evolutionary influence.


Secondary predation constrains DNA-based diet reconstruction in two threatened shark species.
Increasing fishing effort, including bycatch and discard practices, are impacting marine biodiversity, particularly among slow-to-reproduce taxa such as elasmobranchs, and specifically sharks. While some fisheries involving sharks are sustainably managed, collateral mortalities continue, contributing towards > 35% of species being threatened with extinction. To effectively manage shark stocks, life-history information, including resource use and feeding ecologies is pivotal, especially among those species with wide-ranging distributions. Two cosmopolitan sharks bycaught off eastern Australia are the common blacktip shark (Carcharhinus limbatus; globally classified as Near Threatened) and great hammerhead (Sphyrna mokarran; Critically Endangered). We opportunistically sampled the digestive tracts of these two species (and also any whole prey; termed the 'Russian-doll' approach), caught in bather-protection gillnets off northern New South Wales, to investigate the capacity for DNA metabarcoding to simultaneously determine predator and prey regional feeding ecologies. While sample sizes were small, S. mokkaran fed predominantly on stingrays and skates (Myliobatiformes and Rajiformes), but also teleosts, while C. limbatus mostly consumed teleosts. Metabarcoding assays showed extensive intermixing of taxa from the digestive tracts of predators and their whole prey, likely via the predator's stomach chyme, negating the opportunity to distinguish between primary and secondary predation. This Russian-doll effect requires further investigation in DNA metabarcoding studies focussing on dietary preferences and implies that any outcomes will need to be interpreted concomitant with traditional visual approaches.


Investigations of anti-inflammatory and antinociceptive activities of Piper cubeba, Physalis angulata and Rosa hybrida.
The anti-inflammatory activities of Piper cubeba (fruit), Physalis angulata (flower) and Rosa hybrida (flower) were determined by carrageenan-induced paw edema, arachidonic acid-induced ear edema and formaldehyde-induced arthritis in mice. The anti-allergic and analgesic activities of these plants were also studied by using 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reaction (type IV) and hot plate test in mice, respectively. These plant extracts clearly exhibited inhibitory effects against acute and subacute inflammation by oral administration (200 mg/kg). Also, administration (200 mg/kg, p.o.) of plant extracts for 1 week significantly inhibited type IV allergic reaction in mice (P<0.05). Rosa hybrida showed an analgesic effect against hot plate-induced thermal stimulation at a dose of 200 mg/kg. These results provide support for the use of Rosa hybrida in relieving inflammatory pain, and insight into the development of new agents for treating inflammatory diseases.


Chapter 31: Common in vitro tests for allergy and immunology.
Allergen-specific IgE antibody is the most commonly ordered in vitro test in the practice of allergy and is used to diagnose type I hypersensitivity reactions to foods or reactivity to aeroallergens in patients with relative contraindications to skin-prick testing such as dermatographism. The Phadebas radioallergosorbent test (RAST; Pharmacia, Uppsala, Sweden) was the first assay reported for the detection of the allergen-specific IgE antibody. In a RAST, antigen (allergen) is bound to a solid phase, such as a paper disk, and then incubated with human serum. A buffer wash removes unbound serum proteins, and radiolabeled anti-human IgE is added to detect bound IgE, if present. The results are reported in arbitrary units of IgE per milliliter of serum. The term RAST was originally a brand name but it is now often used colloquially (and incorrectly) to describe any in vitro assay for allergen-specific IgE. Total serum IgE can be measured and is helpful in determining atopic presentations such as in allergic bronchopulmonary aspergillosis or in patients with persistent asthma who are candidates for monoclonal anti-IgE antibody therapy with, omalizumab. In patients with recurrent bacterial infections of the sinopulmonary tract, the basic humoral immune system testing includes measuring quantitative immunoglobulins (IgG, IgA, and IgM) and comparing them to age-matched normal ranges. Most clinical laboratories use nephelometry to measure immunoglobulin levels quantitatively. Nephelometry detects either the rate or the end point of soluble immune complex formation (the IgG in sera complexes with an anti-IgG antibody forming a classic immunoprecipitation reaction) by monitoring the scatter of transmitted light. The most common method for the screening of cellular immunodeficiency involved the measurement of the absolute and relative representation of the major lymphocyte subsets, T-cells, T-helper cells, T-cytotoxic cells, B-cells and NK-cells.


Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005-2012 in Turkey. A multicenter prospective surveillance study.
Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey.


A score to predict early risk of recurrence after ischemic stroke.
There is currently no instrument to stratify patients presenting with ischemic stroke according to early risk of recurrent stroke. We sought to develop a comprehensive prognostic score to predict 90-day risk of recurrent stroke. We analyzed data on 1,458 consecutive ischemic stroke patients using a Cox regression model with time to recurrent stroke as the response and clinical and imaging features typically available to physician at admission as covariates. The 90-day risk of recurrent stroke was calculated by summing up the number of independent predictors weighted by their corresponding beta-coefficients. The resultant score was called recurrence risk estimator at 90 days or RRE-90 score (available at: http://www.nmr.mgh.harvard.edu/RRE-90/). Sixty recurrent strokes (54 had baseline imaging) occurred during the follow-up period. The risk adjusted for time to follow-up was 6.0%. Predictors of recurrence included admission etiologic stroke subtype, prior history of TIA/stroke, and topography, age, and distribution of brain infarcts. The RRE-90 score demonstrated adequate calibration and good discrimination (area under the ROC curve [AUC] = 0.70-0.80), which was maintained when applied to a separate cohort of 433 patients (AUC = 0.70-0.76). The model's performance was also maintained for predicting early (14-day) risk of recurrence (AUC = 0.80). The RRE-90 is a Web-based, easy-to-use prognostic score that integrates clinical and imaging information available in the acute setting to quantify early risk of recurrent stroke. The RRE-90 demonstrates good predictive performance, suggesting that, if validated externally, it has promise for use in creating individualized patient management algorithms and improving clinical practice in acute stroke care.


Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory.
Two extant evolutionary models, biological sensitivity to context theory (BSCT) and differential susceptibility theory (DST), converge on the hypothesis that some individuals are more susceptible than others to both negative (risk-promoting) and positive (development-enhancing) environmental conditions. These models contrast with the currently dominant perspective on personal vulnerability and environmental risk: diathesis stress/dual risk. We review challenges to this perspective based on emerging theory and data from the evolutionary, developmental, and health sciences. These challenges signify the need for a paradigm shift in conceptualizing Person x Environment interactions in development. In this context we advance an evolutionary--neurodevelopmental theory, based on DST and BSCT, of the role of neurobiological susceptibility to the environment in regulating environmental effects on adaptation, development, and health. We then outline current thinking about neurogenomic and endophenotypic mechanisms that may underpin neurobiological susceptibility, summarize extant empirical research on differential susceptibility, and evaluate the evolutionary bases and implications of BSCT and DST. Finally, we discuss applied issues including methodological and statistical considerations in conducting differential susceptibility research; issues of ecological, cultural, and racial--ethnic variation in neurobiological susceptibility; and implications of differential susceptibility for designing social programs. We conclude that the differential susceptibility paradigm has far-reaching implications for understanding whether and how much child and adult development responds, for better and for worse, to the gamut of species-typical environmental conditions.


Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial.
AIMS More intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study. METHODS AND RESULTS PLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either ticagrelor, a non-thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or clopidogrel in addition to aspirin. Patients randomized to ticagrelor and clopidogrel had similar rates of PLATO major bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related bleeding rates were also similar. Non-CABG major bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major bleeding (3.1 vs. 2.3%, P = 0.05) were more common in ticagrelor-treated patients, primarily after 30 days on treatment. Fatal bleeding and transfusion rates did not differ between groups. There were no significant interactions for major bleeding or combined minor plus major bleeding between treatment groups and age ≥75 years, weight <60 kg, region, chronic kidney disease, creatinine clearance <60 mL/min, aspirin dose >325 mg on the day of randomization, pre-randomization clopidogrel administration, or clopidogrel loading dose. CONCLUSION Ticagrelor compared with clopidogrel was associated with similar total major bleeding but increased non-CABG and non-procedure-related major bleeding, primarily after 30 days on study drug treatment. Fatal bleeding was low and did not differ between groups.


Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus Erythematosus.
Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging of cerebral small vessel disease (SVD), a risk factor for stroke. Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sex- and age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration. Fifty-one SLE patients (age: 48.8 years; SD: 14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher perivascular spaces and deep white matter hyperintensity scores and more superficial brain atrophy in SLE patients versus healthy controls. Despite fewer vascular risk factors than similarly aged stroke patients, SLE patients had similar or more of some SVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure. In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications.


Neural correlates of telling lies: a functional magnetic resonance imaging study at 4 Tesla.
Intentional deception (ie, lying) is a complex cognitive act, with important legal, moral, political, and economic implications. Prior studies have identified activation of discrete anterior frontal regions, such as the ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), dorsal medial prefrontal cortex (DMPFC), and anterior cingulate cortex (ACC) during deception. To extend these findings, we used novel real-time functional magnetic resonance imaging (fMRI) technology to simulate a polygraph experience in order to evoke performance anxiety about generating lies, and sought to ascertain the neural correlates of deception. In this investigational fMRI study done with a 4-T scanner, we examined the neural correlates of lying in 14 healthy adult volunteers while they performed a modified card version of the Guilty Knowledge Test (GKT), with the understanding that their brain activity was being monitored in real time by the investigators conducting the study. The volunteers were instructed to attempt to generate Lies that would not evoke changes in their brain activity, and were told that their performance and brain responses were being closely monitored. Subjects reported performance anxiety during the task. Deceptive responses were specifically associated with activation of the VLPFC, DLPFC, DMPFC, and superior temporal sulcus. These findings suggest the involvement of discrete regions of the frontal cortex during lying, and that the neural substrates responsible for cognitive control of behavior may also be engaged during deception.


Upper-extremity emboli secondary to axillofemoral graft thrombosis.
Four episodes of upper-extremity arterial emboli following axillofemoral bypass graft thrombosis are described. The source of the embolus was the blind stump of the proximal portion of the graft limb that remained patent after graft occlusion. With axillofemoral graft thrombosis, management requires treatment of the lower-limb ischemia and an awareness of the embolic potential of the acutely thrombotic graft limb. Patient evaluation and the surgical management of axillofemoral graft thrombosis with and without the complication of upper-extremity ischemia are discussed, as well as the etiology and prevention of this complication.


Optical retarder system with programmable spectral retardance.
An optical system that works as a retarder waveplate with programmable spectral retardance is proposed. The system is based on a pixelated liquid crystal on silicon (LCoS) spatial light modulator (SLM). The input light beam is spectrally dispersed and different spectral components are projected onto different pixels of the LCoS-SLM. A different retardance is then addressed for each pixel, adapted to the incoming wavelength. Light reflected from the SLM is then recombined by the same setup. In this way a programmable polarization spectrum can be encoded. We illustrate the broadband characterization that is required for proper use of the system. Then several examples are shown, including spectral compensation to yield retarders with constant retardance, retarders with abrupt changes in the spectral retardance function, or bandpass variable retarder filters. The system is also demonstrated to provide programmable light spectrum generation.


Magnetorotational Turbulence and Dynamo in a Collisionless Plasma.
We present results from the first 3D kinetic numerical simulation of magnetorotational turbulence and dynamo, using the local shearing-box model of a collisionless accretion disk. The kinetic magnetorotational instability grows from a subthermal magnetic field having zero net flux over the computational domain to generate self-sustained turbulence and outward angular-momentum transport. Significant Maxwell and Reynolds stresses are accompanied by comparable viscous stresses produced by field-aligned ion pressure anisotropy, which is regulated primarily by the mirror and ion-cyclotron instabilities through particle trapping and pitch-angle scattering. The latter endow the plasma with an effective viscosity that is biased with respect to the magnetic-field direction and spatiotemporally variable. Energy spectra suggest an Alfvén-wave cascade at large scales and a kinetic-Alfvén-wave cascade at small scales, with strong small-scale density fluctuations and weak nonaxisymmetric density waves. Ions undergo nonthermal particle acceleration, their distribution accurately described by a κ distribution. These results have implications for the properties of low-collisionality accretion flows, such as that near the black hole at the Galactic center.


From single cells to complex tissues in applications of surface-enhanced Raman scattering.
As surface-enhanced Raman scattering (SERS) continues to grow in popularity, more work needs to be done to evaluate its compatibility with a wider scope of applications. With such a strong emphasis on SERS being used for biosensing, it is important to examine how SERS is used in bioanalytical nanoscience, and more importantly, look towards where SERS is heading. For many, the initial steps involve demonstrating in vivo sensing by SERS using cultures of live cells. To further and better demonstrate the capabilities of SERS as a technique in bioanalytical nanoscience, it is necessary to transition away from studies involving single cells or small quantities of cells. This means working with tissue, typically as an ex vivo slice or a spheroid, before moving onto in vivo animal models. Although working with tissue as opposed to single cells introduces new challenges, the types of approaches developed for single cell studies serve as the foundation for the more complex biomaterials. The aim of this tutorial review is to better facilitate the transition from single cells to complex tissues by demonstrating the similarities in the methodologies that have been used and how to overcome some of the challenges of working with tissue. Specifically, we explore how three of the most common methods of working with nanoparticles and cells have been adapted and incorporated for experiments involving different types of tissues. Overall, this review highlights a variety of methods that can be readily implemented for those wishing to perform SERS measurements with or in complex tissues.