IMPAIRED FERTILITY AND PERCEIVED DIFFICULTIES CONCEIVING IN GHANA: MEASUREMENT PROBLEMS AND PROSPECTS.
What is the most appropriate measure of impaired fertility for understanding its social consequences in sub-Saharan Africa? The dearth of subjective measures in surveys in the region has prevented comparisons of subjective and objective measures. Perceived difficulties conceiving may have a greater impact than objective measures for social outcomes such as divorce, stigmatization and distress. This study compares 12- (clinical) and 24- (epidemiological) month measures from biomedicine and 5- and 7-year measures from demography with a subjective measure of impaired fertility using correlations, random effects models and test-retest models to assess relationships between measures, their association with sociodemographic characteristics and the stability of measures across time. Secondary panel data (1998-2004) from 1350 Ghanaian women aged 15-49 of all marital statuses are used. Longer waiting times to identification of impaired fertility required by demographic measures result in more stable measures, but perceived difficulties conceiving are most closely aligned with clinical infertility (r=0.61; p<0.05). Epidemiological infertility is also closely aligned with the subjective measure. A large proportion of those identified as having impaired fertility based purely on waiting times are successful contraceptors. Where subjective measures are not available, epidemiological (24-month) measures may be most appropriate for studies of the social consequences of impaired fertility. Accounting for contraceptive use is important in order to avoid false positives. Future research should consider a variety of measures of perceived difficulties conceiving and self-identified infertility to assess which is most valid; in order to accomplish this, it is imperative that subjective measures of infertility be included in social surveys in sub-Saharan Africa.


Award for Distinguished Professional Contributions to Applied Research.
This award is given to a psychologist whose research has led to important discoveries or developments in the field of applied psychology. To be eligible, this research should have led to innovative applications in an area of psychological practice, including but not limited to assessment, consultation, instruction, or intervention (either direct or indirect). Research involving the original development of procedures, methodologies, or technical skills that significantly improve the application of psychological knowledge and provide direct and immediate solutions to practical problem areas will be considered, as will research that has informed psychologists on how better to observe, define, predict, or control behavior. Original integration of existing theories or knowledge is also eligible for consideration. In previous years, this award was called the Award for Distinguished Professional Contributions to Knowledge. The name was changed in 2003 to better describe this award. The 2020 recipients of the APA Professional Contributions Awards were selected by the 2019 Board of Professional Affairs (BPA). (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Does the milk of Callitrichid monkeys differ from that of larger anthropoids?
The generalization that anthropoid primates produce dilute milks that are low in protein and energy is based primarily on data from large monkeys of the families Cebidae and Cercopithecidae, as well as humans. The marmosets and tamarins (Callitrichidae) are not only much smaller in body size, but also typically raise multiple offspring during a relatively brief lactation. We hypothesized that selection for small body size and high reproductive rate might favor secretion of milk of higher energy and protein concentrations. To test this hypothesis, 46 milk samples collected from 10 common marmosets (Callithrix jacchus, ca. 350 g) were assayed for dry matter (DM), crude protein (CP), fat, and sugar; and gross energy (GE) was calculated from these constituents. We also assayed five samples collected from three golden lion tamarins (Leontopithecus rosalia, ca. 700 g) and six samples collected from a single pygmy marmoset (Cebuella pygmaea, ca. 150 g) over two lactation periods. All samples were collected between days 10 and 57 post partum, representing mid lactation for these species. The milks of these three species were similar, containing 14.0%, 16.1%, and 13.7% DM; 2.7%, 2.6%, and 2.9% CP; 3.6%, 5.2%, and 3.7% fat; 7.4%, 7.2%, and 7.8% sugar; and 0.76, 0.90, and 0.82 kcal/g for common marmosets, golden lion tamarins, and the pygmy marmoset, respectively. These species produced milks with energy values that were within the range reported for large anthropoids, albeit with slightly higher protein concentration. However, milk composition did vary substantially among individual common marmoset females, especially in the proportion of milk energy derived from fat. In contrast, CP as expressed as a percent of GE was remarkably constant among common marmoset females. Callitrichid milk appeared to be similar to that of larger anthropoid primates in GE, but was higher in CP and in the proportion of GE from CP. However, the small sample sizes for the golden lion tamarin and the pygmy marmoset, and the wide variation in milk composition found among common marmoset females cautions against definitively characterizing the milks of callitrichids from these data.


Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction.
Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.


Large adjustments in visually guided reaching do not depend on vision of the hand or perception of target displacement.
When we reach towards an object that suddenly appears in our peripheral visual field, not only does our arm extend towards the object, but our eyes, head and body also move in such a way that the image of the object falls on the fovea. Popular models of how reaching movements are programmed have argued that while the first part of the limb movement is ballistic, subsequent corrections to the trajectory are made on the basis of dynamic feedback about the relative positions of the hand and the target provided by central vision. These models have assumed that the adjustments are dependent on seeing the hand moving with respect to the target. Here we present evidence that a change in the position of a visual target during a reaching movement can modify the trajectory even when vision of the hand is prevented. Moreover, these dynamic corrections to the trajectory of the moving limb occur without the subject perceiving the change in target location. These findings demonstrate that visual feedback about the relative position of the hand and target is not necessary for visually driven corrections in reaching to occur, and the mechanisms that maintain the apparent stability of a target in space are dissociable from those that mediate the visuomotor output directed at that target.


A confocal Raman microscopy study of the distribution of a carotene-containing yeast in a living Pseudomonas aeruginosa biofilm.
The distribution of a carotene-containing yeast (CCY) in a biofilm formed by a small colony variant (SCV) of Pseudomonas aeruginosa PA01 was followed by confocal Raman microspectroscopy (CRM). SCV PA01 and CCY cells were distinguished by their spectral signatures, and the distribution of the overall biomass was monitored by the C-H bending or stretching signal. The distributions of total biomass, PA01, and CCY cells were compared at various times and positions within the biofilm. The distribution of the CCY was very heterogeneous. It was found in the water channels as well as in regions within biofilm colonies. Many of the yeast cells observed within the biofilm colonies under conditions of low or stopped flow were removed when medium was flowing, suggesting that the yeast was not held in the matrix as tightly as were the bacteria.


Aminoglutethimide--a new endocrine therapy in breast cancer. A cancer research review.
Aminoglutethimide is an effective treatment for advanced postmenopausal breast cancer, acting in a novel way. It inhibits peripheral and tumour aromatase, which converts androgens to oestrogens. Marked suppression of oestrone and oestradiol is produced. Aminoglutethimide was used as an inhibitor of adrenal steroid biosynthesis, but the concentrations required to inhibit aromatase in vitro are 10 times lower. This has led to its clinical evaluation in much lower doses. Doses of 125 mg twice daily produce oestrogen suppression equivalent to conventional doses of 1 g daily, and also similar tumour responses. Toxicity is much reduced by the lower dose.


Schizont transcriptome variation among clinical isolates and laboratory-adapted clones of the malaria parasite Plasmodium falciparum.
Malaria parasites are genetically polymorphic and phenotypically plastic. In studying transcriptome variation among parasites from different infections, it is challenging to overcome potentially confounding technical and biological variation between samples. We investigate variation in the major human parasite Plasmodium falciparum, generating RNA-seq data on multiple independent replicate sample preparations of merozoite-containing intra-erythrocytic schizonts from a panel of clinical isolates and from long-term laboratory-adapted clones, with a goal of robustly identifying differentially expressed genes. Analysis of biological sample replicates shows that increased numbers improve the true discovery rate of differentially expressed genes, and that six independent replicates of each parasite line allowed identification of most differences that could be detected with larger numbers. For highly expressed genes, focusing on the top quartile at schizont stages, there was more power to detect differences. Comparing cultured clinical isolates and laboratory-adapted clones, genes more highly expressed in the laboratory-adapted clones include those encoding an AP2 transcription factor (PF3D7_0420300), a ubiquitin-binding protein and two putative methyl transferases. In contrast, higher expression in clinical isolates was seen for the merozoite surface protein gene dblmsp2, proposed to be a marker of schizonts forming merozoites committed to sexual differentiation. Variable expression was extremely strongly, but not exclusively, associated with genes known to be targeted by Heterochromatin Protein 1. Clinical isolates show variable expression of several known merozoite invasion ligands, as well as other genes for which new RT-qPCR assays validate the quantitation and allow characterisation in samples with more limited material. Expression levels of these genes vary among schizont preparations of different clinical isolates in the first ex vivo cycle in patient erythrocytes, but mean levels are similar to those in continuously cultured clinical isolates. Analysis of multiple biological sample replicates greatly improves identification of genes variably expressed between different cultured parasite lines. Clinical isolates recently established in culture show differences from long-term adapted clones in transcript levels of particular genes, and are suitable for analyses requiring biological replicates to understand parasite phenotypes and variable expression likely to be relevant in nature.


In vivo analysis reveals that the interdomain region of the yeast proliferating cell nuclear antigen is important for DNA replication and DNA repair.
To identify the regions of the proliferating cell nuclear antigen (PCNA) that are important for function in vivo, we used random mutagenesis to isolate 10 cold-sensitive (Cs-) and 31 methyl methanesulfonate-sensitive (Mmss) mutations of the PCNA gene (POL30) in Saccharomyces cerevisiae. Unlike the Mmss mutations, the Cs- mutations are strikingly clustered in the interdomain region of the three-dimensional PCNA monomer structure. At the restrictive temperature, the Cs- pol30 mutants undergo a RAD9-dependent arrest as large-budded cells with a 2c DNA content. Defects in DNA synthesis are suggested by a significant delay in the progression of synchronized pol30 cells through S phase at the restrictive temperature. DNA repair defects are revealed by the observation that Cs- pol30 mutants are very sensitive to the alkylating agent MMS and mildly sensitive to ultraviolet radiation, although they are not sensitive to gamma radiation. Finally, analysis of the chromosomal DNA in pol30 cells by velocity sedimentation gradients shows that pol30 cells accumulate single-stranded DNA breaks at the restrictive temperature. Thus, our results show that PCNA plays an essential role in both DNA replication and DNA repair in vivo.


Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing.
Thyroid-stimulating hormone receptor (TSHR) expression is frequently silenced in epithelial thyroid cancers associated with decreased or absent TSH-promoted iodine uptake. To study the underlying molecular mechanism of decreased TSHR expression, we examined the methylation status of the TSHR gene promoter by sequencing bisulfite-treated DNA from thyroid tumors. After identification of methylated sites by sequencing bisulfite-treated DNA, we used methylation-specific polymerase chain reaction and found frequent CpG methylation in papillary thyroid cancer (23 of 39 patients; 59%) and follicular thyroid cancers (7 of 15 patients; 47%). In contrast, we saw no methylation in normal thyroid tissues and benign adenomas (0 of 8 patients; 0%). In human thyroid tumor cell lines, we observed that TSHR was normally expressed at the protein and mRNA level in cells where the TSHR gene was unmethylated, whereas it was silenced in cell lines where the TSHR promoter was hypermethylated. Treatment of the latter cells with a demethylating agent partially restored TSHR expression. We thus demonstrate aberrant methylation of human TSHR as a likely molecular pathway responsible for the silencing of this gene in thyroid cancers. We propose that methylation of TSHR may provide a novel diagnostic marker of malignancy and a basis for potential use of demethylating agents in conjunction with TSH-promoted radioiodine therapy for epithelial thyroid cancers.


Widespread RNA and DNA sequence differences in the human transcriptome.
The transmission of information from DNA to RNA is a critical process. We compared RNA sequences from human B cells of 27 individuals to the corresponding DNA sequences from the same individuals and uncovered more than 10,000 exonic sites where the RNA sequences do not match that of the DNA. All 12 possible categories of discordances were observed. These differences were nonrandom as many sites were found in multiple individuals and in different cell types, including primary skin cells and brain tissues. Using mass spectrometry, we detected peptides that are translated from the discordant RNA sequences and thus do not correspond exactly to the DNA sequences. These widespread RNA-DNA differences in the human transcriptome provide a yet unexplored aspect of genome variation.


Variable Pulse Duration From a New Holmium:YAG Laser: The Effect on Stone Comminution, Fiber Tip Degradation, and Retropulsion in a Dusting Model.
To more clearly define the efficiency and potential benefits of variable pulse-width laser technology for ureteroscopic lithotripsy, we performed comparative in vitro evaluations assessing stone comminution, laser fiber tip degradation, and stone retropulsion. All experiments were conducted using a Swiss LaserClast Holmium:YAG laser (Electro Medical Systems, Nyon, Switzerland) with adjustable pulse duration (300 µs-1500 µs). To assess comminution efficiency and fiber tip degradation, a "dusting" model was employed; the laser fiber tip was moved by a 3-dimensional positioning system in a spiral motion across a flat BegoStone surface submerged in water. Comminution efficiency was measured as the loss of stone mass while fiber tip degradation was measured simultaneously. The same laser and fiber were used in a pendulum model to measure stone retropulsion with a high-speed resolution camera. In our dusting model, comminution was significantly greater at high energy (2 J/5 Hz). At the high energy setting, comminution was significantly greater with long pulse duration than short pulse, although this difference was not seen at the high frequency setting (1 J/10 Hz). Tip degradation was increased at high energy settings and was even more pronounced with short pulse duration than long pulse. Short pulse duration caused far more retropulsion than the long pulse setting. In an in vitro dusting model, a longer laser pulse duration provides effective stone comminution with the advantage of reducing laser fiber tip degradation and stone retropulsion.


Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis.
There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases. To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA. Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane-Armitage trend test implemented in PLINK. One SNP in the LPP gene, rs1464510, showed significant association with JIA (p(trend)=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (p(trend)=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (p(trend)=0.005, OR=1.88, 95% CI 1.2 to 2.94). Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts.


Functional characterization and sex differences in small mesenteric arteries of the estrogen receptor-beta knockout mouse.
The role of the estrogen receptor (ER) subtypes in the modulation of vascular function is poorly understood. The aim of this study was to characterize ex vivo the functional properties of small arteries and their response to estrogens in the mesenteric circulation of female and male ER-beta knockout mice (beta-ERKO) and their wild-type (WT) littermates. Responses to changes in intraluminal flow and pressure were obtained before and after incubation with 17beta-estradiol or ER-alpha agonist propyl-pyrazole-triol (3 h; 10 nM). Cumulative concentration-response curves to acetylcholine, norepinephrine, and passive distensibility were compared with respect to sex and genotype. The collagen and elastin content within the vascular wall and ER expression were also determined. Endothelial morphology was visualized by scanning electron microscopy. 17beta-Estradiol and propyl-pyrazole-triol-treated arteries from female beta-ERKO and WT mice showed enhanced flow-mediated dilation, but this was not evident in males. Distensibility was decreased in arteries from beta-ERKO females. Sex differences in myogenic tone were observed in 17beta-estradiol-treated arteries, but were similar between beta-ERKO and WT mice. Acetylcholine- and norepinephrine-induced responses were similar between groups and sexes. ER-alpha was similarly expressed in the endothelium and media of arteries from all groups studied, as well as ER-beta in WT animals. Endothelial morphology was similar in arteries from animals of both sexes and genotype; however, arterial elastin content was decreased, and collagen content was increased in beta-ERKO male compared with WT male and with beta-ERKO female. We suggest that ERs play a sex-specific role in estrogen-mediated flow responses and distensibility, and that deletion of ER-beta affects artery structure but only in male animals. Further studies in beta-ERKO mice with established hypertension and in alpha-ERKO mice are warranted.


Hand classification of fMRI ICA noise components.
We present a practical "how-to" guide to help determine whether single-subject fMRI independent components (ICs) characterise structured noise or not. Manual identification of signal and noise after ICA decomposition is required for efficient data denoising: to train supervised algorithms, to check the results of unsupervised ones or to manually clean the data. In this paper we describe the main spatial and temporal features of ICs and provide general guidelines on how to evaluate these. Examples of signal and noise components are provided from a wide range of datasets (3T data, including examples from the UK Biobank and the Human Connectome Project, and 7T data), together with practical guidelines for their identification. Finally, we discuss how the data quality, data type and preprocessing can influence the characteristics of the ICs and present examples of particularly challenging datasets.


The undue burden of paying for abortion: An exploration of abortion fund cases.
The results of a secondary data analysis of 3,999 administrative cases from a national abortion fund, representing patients who received pledges for financial assistance to pay for an abortion from 2010 to 2015, are presented. Case data from the fund's national call center was analyzed to assess the impact of the fund and examine sample demographics which were compared to the demographics of national abortion patients. Procedure costs, patient resources, funding pledges, additional aid, and changes over time in financial pledges for second-trimester procedures were also examined. Results indicate that the fund sample differed from national abortion patients in that fund patients were primarily single, African American, and seeking funding for second trimester abortions. Patients were also seeking to fund expensive procedures, costing an average of over $2,000; patients were receiving over $1,000 per case in pledges and other aid; and funding pledges for second trimester procedures were increasing over time. Abortion funding assistance is essential for women who are not able to afford abortion costs, and it is particularly beneficial for patients of color and those who are younger and single. Repeal of policy banning public funding of abortion would help to eliminate financial barriers that impede abortion access.


Characteristics of peripapillary retinal nerve fiber layer thickness in eyes with myopic optic disc tilt and rotation.
The purpose of the study was to investigate the effects of myopic optic disc tilt and rotation on peripapillary retinal nerve fiber layer (RNFL) thickness characteristics measured by Cirrus HD spectral-domain optical coherence tomography (Cirrus HD OCT). A total of 93 right eyes from 93 healthy young male individuals with myopia underwent ophthalmic examinations, including refractive error, axial length, and optic disc area measurements. The superior/inferior peak locations, RNFL thickness, and horizontal/vertical optic disc tilt were evaluated using the Cirrus HD OCT. The optic disc rotation was assessed by the angle between the long axis of the optic disc and the vertical meridian. The patients were divided into the tilted group and the non-tilted group; the tilted group was further divided into the rotated group and the nonrotated group. The eyes in the tilted group (n=47) had a greater axial length and thicker temporal RNFL and more temporally positioned superior/inferior peak locations than the non-tilted group (n=46) (all P <0.05). Among the eyes in the tilted group, the eyes in the rotated group (n=23) had a thicker temporal RNFL and a more temporally positioned superior peak location than the eyes in the nonrotated group (n=24) (all P <0.05). The eyes with a myopic temporal optic disc tilt and counterclockwise rotation had a thicker temporal RNFL and more temporally positioned superior peak location. The characteristics of the RNFL thickness in eyes with myopic optic disc tilt and rotation should be considered when interpreting the RNFL thickness measured by the Cirrus HD OCT.


Modulated zero-area solitary pulses: properties and applications.
This paper investigates a specific kind of solitary pulse, the modulated zero-area (MZA) solitary pulse, when propagating within MgO photonic bandgap medium doped with silver nanoparticles (NPs). It will be shown that two coupled MZA pulses do propagate unattenuated within this medium but for a certain combination of the dipole moments and the density of the NPs. More important, and in contrast to the other kinds of solitary pulses, one of the two MZA pulses exhibits a slowing in its group velocity in comparison to the other one, depending on the amplitudes of the components of the dipole moments of the NPs that are in resonance with the two MZA pulses. With this particular feature, the system has the potential of working as an all-optical switch.


Amplification of natural regulatory immune mechanisms for transplantation tolerance.
There is a need to derive donor-specific tolerance in clinical organ transplantation, where potential benefits remain overshadowed by chronic rejection and side effects of continual immunosuppressive therapy. It is known that the mature immune system in mice can be reprogrammed to accept a foreign graft as if it were "self." Here we show that, once generated, this state of operational tolerance becomes self-sustaining, imposing itself on new cohorts of lymphocytes as they arise. These new cohorts retain specificity for the tolerizing antigen and can be selectively amplified to tolerate new antigens that have linked expression with the original tolerogen. Regulation is critically dependent upon the continuous presence of tolerizing antigen and is mediated by the CD4+ lymphocyte population. We propose that such natural mechanisms of immune regulation may eventually be exploited for transplantation tolerance, even in fully immune-competent recipients.


A simple way to identify non-viable cells within living plant tissue using confocal microscopy.
Plant cell death is a normal process during plant development. Mutant plants may exhibit misregulation of this process, which can lead to severe growth defects. Simple ways of visualising cell death in living plant tissues can aid the study of plant development and physiology. Spectral variants of the fluorescent SYTOX dyes were tested for their usefulness for the detection of non-viable cells within plant embryos and roots using confocal laser-scanning microscopy. The dyes were selective for non-viable cells and showed very little background staining in living cells. Simultaneous detection of SYTOX dye and fluorescent protein (e.g. GFP) fluorescence was possible. The fluorescent SYTOX dyes are useful for an easy and quick first assay of plant cell viability in living plant samples using fluorescence and confocal laser-scanning microscopy.


Spatio-spectral color filter array design for optimal image recovery.
In digital imaging applications, data are typically obtained via a spatial subsampling procedure implemented as a color filter array-a physical construction whereby only a single color value is measured at each pixel location. Owing to the growing ubiquity of color imaging and display devices, much recent work has focused on the implications of such arrays for subsequent digital processing, including in particular the canonical demosaicking task of reconstructing a full color image from spatially subsampled and incomplete color data acquired under a particular choice of array pattern. In contrast to the majority of the demosaicking literature, we consider here the problem of color filter array design and its implications for spatial reconstruction quality. We pose this problem formally as one of simultaneously maximizing the spectral radii of luminance and chrominance channels subject to perfect reconstruction, and-after proving sub-optimality of a wide class of existing array patterns-provide a constructive method for its solution that yields robust, new panchromatic designs implementable as subtractive colors. Empirical evaluations on multiple color image test sets support our theoretical results, and indicate the potential of these patterns to increase spatial resolution for fixed sensor size, and to contribute to improved reconstruction fidelity as well as significantly reduced hardware complexity.


A Ninhydrin-Type Urea Sorbent for the Development of a Wearable Artificial Kidney.
The aim of this study is to develop polymeric chemisorbents with a high density of ninhydrin groups, able to covalently bind urea under physiological conditions and thus potentially suitable for use in a wearable artificial kidney. Macroporous beads are prepared by suspension polymerization of 5-vinyl-1-indanone (vinylindanone) using a 90:10 (v/v) mixture of toluene and nitrobenzene as a porogen. The indanone groups are subsequently oxidized in a one-step procedure into ninhydrin groups. Their urea absorption kinetics are evaluated under both static and dynamic conditions at 37 °C in simulated dialysate (urea in phosphate buffered saline). Under static conditions and at a 1:1 molar ratio of ninhydrin: urea the sorbent beads remove ≈0.6-0.7 mmol g-1 and under dynamic conditions and at a 2:1 molar excess of ninhydrin ≈0.6 mmol urea g-1 sorbent in 8 h at 37 °C, which is a step toward a wearable artificial kidney.


Protective Effect of Probiotic Bacteria and Estrogen in Preventing HIV-1-Mediated Impairment of Epithelial Barrier Integrity in Female Genital Tract.
Approximately 40% of global HIV-1 transmission occurs in the female genital tract (FGT) through heterosexual transmission. Epithelial cells lining the FGT provide the first barrier to HIV-1 entry. Previous studies have suggested that certain hormonal contraceptives or a dysbiosis of the vaginal microbiota can enhance HIV-1 acquisition in the FGT. We examined the effects of lactobacilli and female sex hormones on the barrier functions and innate immune responses of primary endometrial genital epithelial cells (GECs). Two probiotic strains, Lactobacillus reuteri RC-14 and L. rhamnosus GR-1, were tested, as were sex hormones estrogen (E2), progesterone (P4), and the hormonal contraceptive medroxyprogesterone acetate (MPA). Our results demonstrate that probiotic lactobacilli enhance barrier function without affecting cytokines. Treatment of GECs with MPA resulted in reduced barrier function. In contrast, E2 treatment enhanced barrier function and reduced production of proinflammatory cytokines. Comparison of hormones plus lactobacilli as a pre-treatment prior to HIV exposure revealed a dominant effect of lactobacilli in preventing loss of barrier function by GECs. In summary, the combination of E2 and lactobacilli had the best protective effect against HIV-1 seen by enhancement of barrier function and reduction in proinflammatory cytokines. These studies provide insights into how probiotic lactobacilli in the female genital microenvironment can alter HIV-1-mediated barrier disruption and how the combination of E2 and lactobacilli may decrease susceptibility to primary HIV infection.


Large outbreak of mumps virus genotype G among vaccinated students in Norway, 2015 to 2016.
From 6 September 2015-May 2016, a large mumps outbreak occurred among vaccinated students in Norway. A case was defined as a person presenting with a clinical mumps infection, notified between 1 September 2015 and 30 June 2016. Confirmed cases had positive laboratory confirmation and probable cases had an epidemiological link; PCR-positive specimens were genotyped. A total of 232 cases were notified (230 confirmed) with median age of 23 years (range 4-81) and 61% were male. Of 68 (30%) confirmed cases that were genotyped, 66 were genotype G and associated with the outbreak. Cases that had received two doses of the measles-mumps-rubella (MMR) vaccine had reduced risk of hospitalisation (adjusted relative risk (aRR): 0.14; 95%CI: 0.03-0.57), mumps-related orchitis (aRR: 0.21; 95% CI: 0.08-0.55) and severe outcome (aRR: 0.25; 95% CI: 0.10-0.62) compared with those unvaccinated. A third dose of the vaccine was offered to approximately 1,300 fully vaccinated close contacts and subsequently reported cases decreased. This large outbreak, occurring among predominately vaccinated students, suggests the current genotype A vaccine offers suboptimal protection against mumps genotype G. We recommend maintaining high vaccination coverage and offering the vaccine to all unvaccinated individuals.


Understanding the complexity of glycaemic health: systematic bio-psychosocial modelling of fasting glucose in middle-age adults; a DynaHEALTH study.
The prevention of the risk of type 2 diabetes (T2D) is complicated by multidimensional interplays between biological and psychosocial factors acting at the individual level. To address the challenge we took a systematic approach, to explore the bio-psychosocial predictors of blood glucose in mid-age. Based on the 31-year and 46-year follow-ups (5,078 participants, 43% male) of Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio-psychosocial variables at 31 years to enable a data-driven approach. As selection criteria, the variable must be (i) a component of the metabolic syndrome or an indicator of psychosocial health using WHO guidelines, (ii) easily obtainable in general health check-ups and (iii) associated with fasting blood glucose at 46 years (P < 0.10). Exploratory and confirmatory factor analysis were used to derive latent factors, and stepwise linear regression allowed exploration of relationships between factors and fasting glucose. Of all 26 variables originally considered, 19 met the selection criteria and were included in an exploratory factor analysis. Two variables were further excluded due to low loading (<0.3). We derived four latent factors, which we named as socioeconomic, metabolic, psychosocial and blood pressure status. The combination of metabolic and psychosocial factors, adjusted for sex, provided best prediction of fasting glucose at 46 years (explaining 10.7% of variation in glucose; P < 0.001). Regarding different bio-psychosocial pathways and relationships, the importance of psychosocial factors in addition to established metabolic risk factors was highlighted. The present study supports evidence for the bio-psychosocial nature of adult glycemic health and exemplifies an evidence-based approach to model the bio-psychosocial relationships. The factorial model may help further research and public health practice in focusing also on psychosocial aspects in maintaining normoglycaemia in the prevention of cardio-metabolic diseases.


Vocal Health and Vocal Health Knowledge Among Occupational Voice Users in the Province of Quebec.
Voice disorders are frequent among occupational voice users such as teachers. Although these disorders can have serious personal and professional consequences, they are not often recognized as occupational diseases and little attention is paid to their prevention. This study aimed to provide a portrait of the self-reported vocal health and vocal health knowledge of occupational voice users in Quebec, Canada, and to identify risk factors associated with voice disorder symptoms. We conducted an online survey targeting occupational voice users in the province of Quebec, Canada, with a focus on those involved in teaching or training. The final sample, after excluding incomplete surveys, included 808 respondents (665 women, M = 41.5 ± 10.4 years old). The survey responses were analyzed using descriptive and inferential statistics. Results indicated that 9.8% of the respondents had a history of a diagnosed voice disorder and 68.8% of the respondents experienced at least one voice symptom on a regular basis. Ordinal logistic regressions revealed that several personal and environmental factors are associated with an increased risk of developing voice disorders symptoms: being a woman, suffering from a breathing disorder, allergies, acid reflux and/or hearing impairment, having less work experience, working with elementary school children and/or with continuous or speech noise in the background. Most of the respondents (94.6%) had never received information regarding voice disorders during their academic training and less than half of them (47.7%) knew which professionals can treat voice disorders. These findings highlight the need for formal vocal health education among both occupational voice users and their employers to improve prevention and treatment for voice disorders in an at-risk population.


Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea.
Chewing areca nut (AN), also known as betel nut, is common in Asia and the South Pacific and the habit has been linked to a number of serious health problems including oral cancer. Use of AN in pregnancy has been associated with a reduction in mean birthweight in some studies, but this association and the relationship between AN chewing and other adverse pregnancy outcomes remain poorly understood. We assessed the impact of AN chewing on adverse outcomes including stillbirth, low birthweight (LBW, <2,500 g) and anaemia at delivery (haemoglobin <11.0 g/dL) in a longitudinal cohort of 2,700 pregnant women residing in rural lowland Papua New Guinea (PNG) from November 2009 until February 2013. Chewing habits and participant characteristics were evaluated at first antenatal visit and women were followed until delivery. 83.3% [2249/2700] of pregnant women used AN, and most chewed on a daily basis (86.2% [1939/2249]. Smoking and alcohol use was reported by 18.9% (511/2700) and 5.0% (135/2688) of women, respectively. AN use was not associated with pregnancy loss or congenital abnormalities amongst women with a known pregnancy outcome (n = 2215). Analysis of 1769 birthweights did not demonstrate an association between AN and LBW (chewers: 13.7% [200/1459] vs. non-chewers: 14.5% [45/310], P = 0.87) or reduced mean birthweight (2957 g vs. 2966 g; P = 0.76). Women using AN were more likely to be anaemic (haemoglobin <11 g/dL) at delivery (75.2% [998/1314] vs. 63.9% [182/285], adjusted odds ratio [95% CI]: 1.67 [1.27, 2.20], P < 0.001). Chewers more commonly had male babies than non-chewers (46.1% [670/1455] vs. 39.8% [123/309], P = 0.045). AN chewing may contribute to anaemia. Although not associated with other adverse pregnancy outcome in this cohort gestational AN use should be discouraged, given the potential adverse effects on haemoglobin and well-established long-term health risk including oral cancer. Future research evaluating the potential association of AN use and anaemia may be warranted. ClinicalTrials.gov NCT01136850 (06 April 2010).


Changes in the provision of implant-supported prostheses at the Academic Centre for Dentistry Amsterdam (ACTA) from 1989 to 1995.
Over the last decade, oral implantology has become a major treatment modality to aid the restoration of reduced dentitions. The present study monitored and quantified changes within a 5-year interval (1989-1991 [denoted as 1990*] to 1995) in the provision of different types of implant-supported superstructures and characteristics of recipient patients at the Academic Centre for Dentistry Amsterdam (ACTA). All patients who received oral implants in 1990* and in 1995 were selected, and their files (95 and 105, respectively) were consulted. Data of interest were retrieved retrospectively, compared, and statistically analyzed using Chi-squared tests. A number of statistically significant differences was apparent between these 2 periods. By 1995 there was a threefold increase in both the number of patients and the number of implants placed per year. The patient group of < or = 40 years of age had significantly increased, from 7% to 23%. Also, in 1995 more maxillae were implanted than in 1990* (44% vs 26%). Whereas the majority of implanted patients was edentulous in 1990* (64%), the majority in 1995 was partially edentulous (60%). By 1995, the new technique of guided bone regeneration (GBR) using membranes was evidenced (no GBR in 1990* vs 33% of all patients in 1995 receiving some form of local GBR therapy). With respect to the type of superstructures, there was a strong increase in the number of single-tooth replacements (from 4% to 23%). In the edentulous group, the majority of superstructures in 1990 was fixed prostheses (64%), whereas in 1995 the majority was overdentures (71%). Major changes in oral implantology treatments were noticed between the 1990* and 1995 periods at ACTA. There is a trend toward implanting younger patients for partial implant-supported reconstructions using more regenerative procedures and with a more equal distribution in the maxilla and mandible.


Road traffic noise and annoyance--an increasing environmental health problem.
Traffic noise, which is steadily increasing, is considered to be an important environmental health problem. The aim of this study was to estimate the degree of annoyance and sleep disturbance related to road traffic noise in residential settings in an urban community. The study is based on a questionnaire on environmentally related health effects distributed to a stratified random sample of 1000 individuals, 19-80 years old, in a municipality with heavy traffic in the county of Stockholm. The response rate was 76%. The individual noise exposure was estimated using evaluated noise dispersion models and local noise assessments. Frequent annoyance was reported by 13% of subjects exposed to Leq 24 hr >50 dBA compared to 2% among those exposed to <50 dBA, resulting in a difference of 11% (95% Confidence Interval (CI) 7%, 15%). Sometimes or frequently occurring sleep disturbance was reported by 23% at Leq 24 hr >50 dBA and by 13% at levels <50 dBA, a difference of 11% (95% CI 4%, 18%). A positive exposure- response relation was indicated for annoyance as well as for sleep disturbances when classifying the individuals into four different exposure categories (< 45, 46- 50, 51-55 and >55 dBA Leq 24 hr). There was some habituation to noise for problems related to sleep but not for annoyance. The prevalence of both annoyance and sleep problems was higher when bedroom windows were facing streets. People living in apartments had more sleep problems compared to people living in detached or semi-detached houses. In conclusion traffic noise exposure, even at low levels, was associated with annoyance and sleep disturbance. Access to a quiet side seemed to be a major protective factor for noise related problems.


Strategies to facilitate integrated care for people with alcohol and other drug problems: a systematic review.
There is a growing body of research highlighting the potential benefits of integrated care as a way of addressing the needs of people with alcohol and other drug (AOD) problems, given the broad range of other issues clients often experience. However, there has been little academic attention on the strategies that treatment systems, agencies and clinicians could implement to facilitate integrated care. We synthesised the existing evidence on strategies to improve integrated care in an AOD treatment context by conducting a systematic review of the literature. We searched major academic databases for peer-reviewed articles that evaluated strategies that contribute to integrated care in an AOD context between 1990 and 2014. Over 2600 articles were identified, of which 14 met the study inclusion criteria of reporting on an empirical study to evaluate the implementation of integrated care strategies. The types of strategies utilised in included articles were then synthesised. We identified a number of interconnected strategies at the funding, organisational, service delivery and clinical levels. Ensuring that integrated care is included within service specifications of commissioning bodies and is adequately funded was found to be critical in effective integration. Cultivating positive inter-agency relationships underpinned and enabled the implementation of most strategies identified. Staff training in identifying and responding to needs beyond clinicians' primary area of expertise was considered important at a service level. However, some studies highlight the need to move beyond discrete training events and towards longer term coaching-type activities focussed on implementation and capacity building. Sharing of client information (subject to informed consent) was critical for most integrated care strategies. Case-management was found to be a particularly good approach to responding to the needs of clients with multiple and complex needs. At the clinical level, screening in areas beyond a clinician's primary area of practice was a common strategy for facilitating referral and integrated care, as was joint care planning. Despite considerable limitations and gaps in the literature in terms of the evaluation of integrated care strategies, particularly between AOD services, our review highlights several strategies that could be useful at multiple levels. Given the interconnectedness of integrated care strategies identified, implementation of multi-level strategies rather than single strategies is likely to be preferable.


Real-time monitoring of progression towards renal failure in primary care patients.
Chronic renal failure is a progressive condition that, typically, is asymptomatic for many years. Early detection of incipient kidney failure enables ameliorative treatment that can slow the rate of progression to end-stage renal failure, at which point expensive and invasive renal replacement therapy (dialysis or transplantation) is required. We use routinely collected clinical data from a large sample of primary care patients to develop a system for real-time monitoring of the progression of undiagnosed incipient renal failure. Progression is characterized as the rate of change in a person's kidney function as measured by the estimated glomerular filtration rate, an adjusted version of serum creatinine level in a blood sample. Clinical guidelines in the UK suggest that a person who is losing kidney function at a relative rate of at least 5% per year should be referred to specialist secondary care. We model the time-course of a person's underlying kidney function through a combination of explanatory variables, a random intercept and a continuous-time, non-stationary stochastic process. We then use the model to calculate for each person the predictive probability that they meet the clinical guideline for referral to secondary care. We suggest that probabilistic predictive inference linked to clinical criteria can be a useful component of a real-time surveillance system to guide, but not dictate, clinical decision-making.


Revision in previously satisfied knee arthroplasty patients is the result of their call on the physician, not on pre-planned follow-up: a retrospective study of 181 patients who underwent revision within 2 years.
Degree of satisfaction with a knee arthroplasty is said to be correlated to reduced pain and better function. During a validation of the Swedish Knee Arthroplasty Register in 1997, previously operated patients were asked how satisfied they were with their knee. A subgroup of "satisfied" patients was identified who underwent revision within 2 years of having expressed satisfaction. Our aim was to study the revision diagnosis, to determine whether the problem leading to revision had been discovered as a result of routine follow-up, and also to find out when the symptoms leading to revision had started. We retrospectively studied the medical records of 181 patients (181 knees), with a median age of 74 (31-88) years. 68% were women and the median time between primary operation and revision was 8 (3-21) years. Aseptic loosening (74/181) was the most common diagnosis. 2 cases were revised as a result of routine follow-up. 44% of the medical records included reports of pain in the replaced knee prior to answering the satisfaction questionnaire. Few patients were admitted to knee revision surgery due to medical findings discovered during routine follow-up. The term "satisfaction" must be interpreted with care, as it seems to have a more complex meaning for the patients than absence of knee pain.


A morphometric analysis of vegetation patterns in dryland ecosystems.
Vegetation in dryland ecosystems often forms remarkable spatial patterns. These range from regular bands of vegetation alternating with bare ground, to vegetated spots and labyrinths, to regular gaps of bare ground within an otherwise continuous expanse of vegetation. It has been suggested that spotted vegetation patterns could indicate that collapse into a bare ground state is imminent, and the morphology of spatial vegetation patterns, therefore, represents a potentially valuable source of information on the proximity of regime shifts in dryland ecosystems. In this paper, we have developed quantitative methods to characterize the morphology of spatial patterns in dryland vegetation. Our approach is based on algorithmic techniques that have been used to classify pollen grains on the basis of textural patterning, and involves constructing feature vectors to quantify the shapes formed by vegetation patterns. We have analysed images of patterned vegetation produced by a computational model and a small set of satellite images from South Kordofan (South Sudan), which illustrates that our methods are applicable to both simulated and real-world data. Our approach provides a means of quantifying patterns that are frequently described using qualitative terminology, and could be used to classify vegetation patterns in large-scale satellite surveys of dryland ecosystems.


Extracellular nucleotides stimulate Cl- currents in biliary epithelia through receptor-mediated IP3 and Ca2+ release.
Extracellular ATP regulates bile formation by binding to P2 receptors on cholangiocytes and stimulating transepithelial Cl(-) secretion. However, the specific signaling pathways linking receptor binding to Cl(-) channel activation are not known. Consequently, the aim of these studies in human Mz-Cha-1 biliary cells and normal rat cholangiocyte monolayers was to assess the intracellular pathways responsible for ATP-stimulated increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) and membrane Cl(-) permeability. Exposure of cells to ATP resulted in a rapid increase in [Ca(2+)](i) and activation of membrane Cl(-) currents; both responses were abolished by prior depletion of intracellular Ca(2+). ATP-stimulated Cl(-) currents demonstrated mild outward rectification, reversal at E(Cl(-)), and a single-channel conductance of approximately 17 pS, where E is the equilibrium potential. The conductance response to ATP was inhibited by the Cl(-) channel inhibitors NPPB and DIDS but not the CFTR inhibitor CFTR(inh)-172. Both ATP-stimulated increases in [Ca(2+)](i) and Cl(-) channel activity were inhibited by the P2Y receptor antagonist suramin. The PLC inhibitor U73122 and the inositol 1,4,5-triphosphate (IP3) receptor inhibitor 2-APB both blocked the ATP-stimulated increase in [Ca(2+)](i) and membrane Cl(-) currents. Intracellular dialysis with purified IP3 activated Cl(-) currents with identical properties to those activated by ATP. Exposure of normal rat cholangiocyte monolayers to ATP increased short-circuit currents (I(sc)), reflecting transepithelial secretion. The I(sc) was unaffected by CFTR(inh)-172 but was significantly inhibited by U73122 or 2-APB. In summary, these findings indicate that the apical P2Y-IP3 receptor signaling complex is a dominant pathway mediating biliary epithelial Cl(-) transport and, therefore, may represent a potential target for increasing secretion in the treatment of cholestatic liver disease.


The impact of minimum legal drinking age laws on alcohol consumption, smoking, and marijuana use: evidence from a regression discontinuity design using exact date of birth.
This paper uses a regression discontinuity design to estimate the impact of the minimum legal drinking age laws on alcohol consumption, smoking, and marijuana use among young adults. Using data from the National Longitudinal Survey of Youth (1997 Cohort), we find that granting legal access to alcohol at age 21 leads to an increase in several measures of alcohol consumption, including an up to a 13 percentage point increase in the probability of drinking. Furthermore, this effect is robust under several different parametric and non-parametric models. We also find some evidence that the discrete jump in alcohol consumption at age 21 has negative spillover effects on marijuana use but does not affect the smoking habits of young adults. Our results indicate that although the change in alcohol consumption habits of young adults following their 21st birthday is less severe than previously known, policies that are designed to reduce drinking among young adults may have desirable impacts and can create public health benefits.


Nutritional performance and activity of some digestive enzymes of the cotton bollworm, Helicoverpa armigera, in response to seven tested bean cultivars.
Nutritional performance and activity of some digestive enzymes (protease and α-amylase) of Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) in response to feeding on bean (Phaseolus vulgaris L. (Fabales: Fabaceae)) cultivars (Shokufa, Akhtar, Sayyad, Naz, Pak, Daneshkadeh, and Talash) were evaluated under laboratory conditions (25 ± 1°C, 65 ± 5% RH, and a 16:8 L:D photoperiod). The highest and lowest respective values of approximate digestibility were observed when fourth, fifth, and sixth larval instar H. armigera were fed red kidney bean Akhtar and white kidney bean Daneshkadeh. The efficiency of conversion of ingested and digested food was highest when H. armigera was fed red kidney beans Akhtar and Naz and lowest when they were fed white kidney bean Pak. The highest protease activity of fifth instars was observed when they were fed red kidney bean Naz, and the highest amylase activity of fifth instars was observed when they were fed red kidney bean Sayyad. Sixth instar larvae that fed on red kidney bean Sayyad showed the highest protease activity. Larvae reared on common bean Talash and white kidney bean Pak showed the highest amylase activity. Among bean cultivars tested, red kidney bean Sayyad was the most unsuitable host for feeding H. armigera.


Patient Preferences for Doctor Attire: The White Coat's Place in the Medical Profession.
The white coat's place in the medical profession is a heavily debated topic. Five years after the bare-below-the-elbow policy took effect in England, we reexamined the evidence about coats' potential to transmit infection, reviewed previous studies, and explored our patients' opinions on doctor attire. We administered a survey at 3 locations in the Ochsner Health System (hospital clinic, satellite clinic, and inpatient ward) in 2013. The survey assessed patient preference for doctors to wear white coats and included 4 images of the same doctor in different attire: traditional white coat, bare-below-the-elbow attire, a white coat with scrubs, and scrubs alone. Respondents rated images head-to-head for their preferences and individually for their confidence in the physician's skills and for their comfort level with the physician based upon the displayed attire. Participants' attitudes were then reassessed after they were given information about potential disease transmission. Overall, 69.9% of the 153 patients surveyed preferred doctors to wear white coats. When locations were compared, a statistically higher proportion of outpatients preferred coats (P=0.001), a trend most pronounced between hospital clinic (84%) and ward inpatients (51.9%). Patients disliked bare-below-the-elbow attire, scoring it lowest on the comfort and confidence scales (0.05 and 0.09, respectively). Information regarding risks of coat-carried infections did not influence respondents' opinions; 86.9% would still feel comfortable with a doctor who wore one. These findings suggest patients prefer white coats, and they contribute to greater comfort and confidence in their physicians, despite knowledge of theoretic concerns of disease transmission.


Metabolic Implications of Exposure to Light at Night: Lessons from Animal and Human Studies.
Lately, the incidence of overweight, obesity, and type 2 diabetes has shown a staggering increase. To prevent and treat these conditions, one must look at their etiology. As life on earth has evolved under the conditions of nature's 24-hour light/dark cycle, it seems likely that exposure to artificial light at night (LAN) would affect physiology. Indeed, ample evidence has shown that LAN impacts many metabolic parameters, at least partly via the biological clock in the suprachiasmatic nucleus of the hypothalamus. This review focuses on the impact of chronic and acute effects of LAN of different wavelengths on locomotor activity, food intake, the sleep/wake cycle, body temperature, melatonin, glucocorticoids, and glucose and lipid metabolism. While chronic LAN disturbs daily rhythms in these parameters, experiments using short-term LAN exposure also have shown acute negative effects in metabolically active peripheral tissues. Experiments using LAN of different wavelengths not only have indicated an important role for melanopsin, the photopigment found in intrinsically photosensitive retinal ganglion cells, but also provided evidence that each wavelength may have a specific impact on energy metabolism. Importantly, exposure to LAN has been shown to impact glucose homeostasis also in humans and to be associated with an increased incidence of overweight, obesity, and atherosclerosis.


A survey of new temperature-sensitive, embryonic-lethal mutations in C. elegans: 24 alleles of thirteen genes.
To study essential maternal gene requirements in the early C. elegans embryo, we have screened for temperature-sensitive, embryonic lethal mutations in an effort to bypass essential zygotic requirements for such genes during larval and adult germline development. With conditional alleles, multiple essential requirements can be examined by shifting at different times from the permissive temperature of 15°C to the restrictive temperature of 26°C. Here we describe 24 conditional mutations that affect 13 different loci and report the identity of the gene mutations responsible for the conditional lethality in 22 of the mutants. All but four are mis-sense mutations, with two mutations affecting splice sites, another creating an in-frame deletion, and one creating a premature stop codon. Almost all of the mis-sense mutations affect residues conserved in orthologs, and thus may be useful for engineering conditional mutations in other organisms. We find that 62% of the mutants display additional phenotypes when shifted to the restrictive temperature as L1 larvae, in addition to causing embryonic lethality after L4 upshifts. Remarkably, we also found that 13 out of the 24 mutations appear to be fast-acting, making them particularly useful for careful dissection of multiple essential requirements. Our findings highlight the value of C. elegans for identifying useful temperature-sensitive mutations in essential genes, and provide new insights into the requirements for some of the affected loci.


Inhibition of neutral endopeptidase, the degradative enzyme for natriuretic peptides, in rat kidney after oral SCH 42495.
1. Inhibition of neutral endopeptidase (NEP), the degradative enzyme for atrial natriuretic peptide, was studied in vitro and in vivo using a previously characterized NEP inhibitor radioligand, 125I-labelled RB104. 2. SCH 42354, the active di-acid of the ethylester prodrug, SCH 42495, caused a concentration-dependent displacement of 125I-labelled RB104 from rat renal NEP. The concentration of SCH 42354 that displaced 50% of radioligand bound to the enzyme NEP (IC50) was 3.3 +/- 0.1 nmol/l (mean +/- SEM). Enalaprilat, an angiotensin converting enzyme inhibitor, did not displace 125I-labelled RB104 in concentrations up to 10 mumol/l. 3. In adult normotensive Sprague-Dawley rats, oral SCH 42495 (3-300 mg/kg) caused significant inhibition of renal NEP (P < 0.001). SCH 42495 had no effect on renal or plasma angiotensin converting enzyme activity, but high-dose SCH 42495 (300 mg/kg) caused a significant increase in plasma renin activity (P < 0.01). 4. In a time course study, oral SCH 42495 (30 mg/kg) caused rapid (within 30 min) and significant inhibition of renal NEP for up to 48 h (P < 0.001). No changes in plasma atrial natriuretic peptide or plasma angiotensin converting enzyme activity were seen. 5. These data provide evidence that short-term administration of the NEP inhibitor SCH 42495 results in inhibition of renal NEP and does not inhibit the circulating or the tissue renin-angiotensin system. The NEP inhibitor radioligand 125I-labelled RB104, is a useful tool to study tissue NEP inhibition after administration of NEP inhibitors.


Current surgical results with low-grade brain arteriovenous malformations.
Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs-the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process. A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period. Of the 232 surgical patients included, 120 (52%) presented with hemorrhage, 33% had Spetzler-Martin Grade I, and 67% had Grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (modified Rankin Scale [mRS] score 0-1) were found in 78% of patients, with 97% improved or unchanged from their preoperative mRS scores. Patients with unruptured AVMs had better functional outcomes (91% good outcome vs 65% in the ruptured group, p = 0.0008), while relative outcomes were equivalent (98% improved/unchanged in patients with ruptured AVMs vs 96% in patients with unruptured AVMs). Surgery should be regarded as the "gold standard" therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in patients with both ruptured and unruptured AVMs support a dominant surgical posture for low-grade AVMS, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate, lowest risk profile, and greatest protection against hemorrhage for low-grade AVMs. ARUBA results are influenced by a low randomization rate, bias toward nonsurgical therapies, a shortage of surgical expertise, a lower rate of complete AVM obliteration, a higher rate of delayed hemorrhage, and short study duration. Another randomized trial is needed to reestablish the role of surgery in unruptured AVM management.


Comparative analysis of kinetic realizations of insulin signaling.
Several studies have developed dynamical models to understand the underlying mechanisms of insulin signaling, a signaling cascade that leads to the translocation of glucose, the human body's main source of energy. Fortunately, reaction network analysis allows us to extract properties of dynamical systems without depending on their model parameter values. This study focuses on the comparison of insulin signaling in healthy state (INSMS or INSulin Metabolic Signaling) and in type 2 diabetes (INRES or INsulin RESistance) using reaction network analysis. The analysis uses network decomposition to identify the different subsystems involved in insulin signaling (e.g., insulin receptor binding and recycling, GLUT4 translocation, and ERK signaling pathway, among others). Furthermore, results show that INSMS and INRES are similar with respect to some network, structo-kinetic, and kinetic properties. Their differences, however, provide insights into what happens when insulin resistance occurs. First, the variation in the number of species involved in INSMS and INRES suggests that when irregularities occur in the insulin signaling pathway, other complexes (and, hence, other processes) get involved, characterizing insulin resistance. Second, the loss of concordance exhibited by INRES suggests less restrictive interplay between the species involved in insulin signaling, leading to unusual activities in the signaling cascade. Lastly, GLUT4 losing its absolute concentration robustness in INRES may signify that the transporter has lost its reliability in shuttling glucose to the cell, inhibiting efficient cellular energy production. This study also suggests possible applications of the equilibria parametrization and network decomposition, resulting from the analysis, to potentially establish absolute concentration robustness in a species.


Classification and treatment of pooling of contrast material on computed tomographic scan of blunt hepatic trauma.
Pooling of contrast material on computed tomographic (CT) scan represents free extravasation of blood as a result of active bleeding. For patients with blunt hepatic injury, aggressive management such as angiography or celiotomy is usually indicated if this sign is detected. The purposes of this study were to further categorize this CT scan finding and to correlate its characteristics with clinical outcomes. This CT scan classification might be helpful for the selection of appropriate management. During a 42-month period, 276 patients with blunt hepatic injury were treated. Two hundred twelve of them were hemodynamically stable after initial resuscitation and underwent abdominal CT scan examination. Pooling of contrast material was detected on the CT scans of 15 patients. The CT scans and medical records were reviewed. Special attention was paid to the presence, location, and character of the extravasated contrast material. The finding of pooling of contrast material on CT scan was categorized into three types according to its location and character. Type I showed extravasation and pooling of contrast material in the peritoneal cavity (six patients). All patients with type I CT scan findings became hemodynamically unstable soon after CT scan examination and required emergent laparotomy. Type II findings showed simultaneous presence of hemoperitoneum and intraparenchymal contrast material pooling (six patients). Four patients with type II CT scan findings required laparotomy for hemostasis. Type III findings showed intraparenchymal contrast material pooling without hemoperitoneum (three patients). All patients with type III CT scan signs remained hemodynamically stable. With the use of a high-speed spiral CT scanner, it is possible to predict the necessity of operative management or angiography for patients with blunt hepatic injury before deterioration of hemodynamic status. The presence of pooling of contrast material within the peritoneal cavity indicates active and massive bleeding. Patients with this CT scan finding show rapid deterioration of hemodynamic status. Most of these patients might require emergent surgery. Pooling of contrast material in a ruptured hepatic parenchyma indicates active bleeding. Close monitoring and emergent angiography should be performed. Deterioration of hemodynamic status in these patients usually requires prompt surgical intervention. Intraparenchymal pooling of contrast material with unruptured liver capsule often indicates a self-limited hemorrhage. Patients with this CT scan finding have a high possibility of successful nonoperative treatment.


[Cirrhotic cardiomyopathy].
Most patients with liver cirrhosis have hyperdynamic circulatory alterations with increased cardiac output, and decreased systemic vascular resistance and arterial pressure. But, in spite of the increased resting cardiac output, ventricular contractile response to stressful stimuli is attenuated in cirrhotic patients which is termed as cirrhotic cardiomyopathy. The prevalence of cirrhotic cardiomyopathy remains unknown at present. Clinical features include structural, histological, electrophysiological, systolic and diastolic dysfunction. Multiple factors are considered as responsible, including impaired beta-adrenergic receptor signal transduction, abnormal membrane biophysical characteristics, and increased activity of cardiodepressant systems mediated by cGMP. Generally, cirrhotic cardiomyopathy with overt severe heart failure is rare. However, major stresses on the cardiovascular system such as liver transplantation, infections and insertion of transjugular intrahepatic portosystemic shunts (TIPS) can unmask the presence of cirrhotic cardiomyopathy and thereby convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome and circulatory failure in liver cirrhosis. Because of the marked paucity of treatment studies, current recommendations for management are empirical, nonspecific measures. Further studies for pathogenesis and new therapeutic strategies in this area are required.


Magnetic fields at uranus.
The magnetic field experiment on the Voyager 2 spacecraft revealed a strong planetary magnetic field of Uranus and an associated magnetosphere and fully developed bipolar masnetic tail. The detached bow shock wave in the solar wind supersonic flow was observed upstream at 23.7 Uranus radii (1 R(U) = 25,600 km) and the magnetopause boundary at 18.0 R(U), near the planet-sun line. A miaximum magnetic field of 413 nanotesla was observed at 4.19 R(U ), just before closest approach. Initial analyses reveal that the planetary magnetic field is well represented by that of a dipole offset from the center of the planet by 0.3 R(U). The angle between Uranus' angular momentum vector and the dipole moment vector has the surprisingly large value of 60 degrees. Thus, in an astrophysical context, the field of Uranus may be described as that of an oblique rotator. The dipole moment of 0.23 gauss R(3)(U), combined with the large spatial offset, leads to minimum and maximum magnetic fields on the surface of the planet of approximately 0.1 and 1.1 gauss, respectively. The rotation period of the magnetic field and hence that of the interior of the planet is estimated to be 17.29+/- 0.10 hours; the magnetotail rotates about the planet-sun line with the same period. Thelarge offset and tilt lead to auroral zones far from the planetary rotation axis poles. The rings and the moons are embedded deep within the magnetosphere, and, because of the large dipole tilt, they will have a profound and diurnally varying influence as absorbers of the trapped radiation belt particles.


Investigation of strategies for the introduction and transportation of replacement gilts on southern Ontario sow farms.
Porcine reproductive and respiratory syndrome (PRRS) is of major concern to the swine industry; infection with the virus can lead to production losses, morbidity, and mortality within swine operations. Biosecurity practices related to the management of replacement animals are important for the prevention and control of the PRRS virus, as well as other diseases. The objectives of this study were: (i) to describe individual biosecurity practices related to the introduction and transportation of replacement gilts on southern Ontario sow farms, and (ii) to understand patterns in the implementation of these practices. The second objective was accomplished using multiple correspondence analysis (MCA), which allows visualization of the relationships between individual practices and provides information about which practices frequently occur together, and which practices rarely occur together. These patterns constitute strategies for the implementation of biosecurity practices related to the introduction and transportation of replacement gilts. Data were collected using version 2 of the Production Animal Disease Risk Assessment Program's survey for the breeding herd. Two subsets of variables were retained for analysis; one subset pertained to how replacements were managed upon arrival to the farm, and the other pertained to the transportation of genetic animals. For both subsets of variables, the results of the MCA procedure were similar; in both solutions the 1st dimension separated herds that were closed with respect to replacement animals from herds that were open, and the 2nd dimension described how open herds managed replacements. The most interesting finding of this study was that, in some cases where a risky practice was being implemented, it was closely associated with other biosecurity practices that may mitigate that risk. The findings from this approach suggest that one cannot always examine biosecurity on a variable-by-variable basis. Even if a practice that is generally considered high-risk is being implemented, it may be balanced by other practices that mitigate that risk. Thus, the overall biosecurity strategy on a farm must be considered instead of only examining the implementation of individual practices.


Knockdown of sestrin2 increases pro-inflammatory reactions and ER stress in the endothelium via an AMPK dependent mechanism.
Sestrin2 (sesn2) has recently gained attention as an important regulator for various metabolic disorders. Sesn2 is involved in AMP-activated protein kinase (AMPK) activation, which leads to anti-inflammatory and anti-oxidative responses. However, the role of sesn2 in the endothelium has not yet been clarified. To evaluate sesn2-mediated anti-atherosclerotic effects, siRNA to silence sesn2 expression was introduced to human umbilical vein endothelial cells (HUVECs), THP-1 cells and C57BL/6 mice. Lipopolysaccharide (LPS) was administrated to sesn2-knockdown cells and mice to induce atherosclerotic signals. Knockdown of sesn2 was involved with atherosclerotic reactions caused by LPS treatment through decrease of AMPK phosphorylation. In sesn2-knockdown HUVECs and THP-1 cells, LPS-mediated nuclear factor kappa B (NF-κB) phosphorylation and secretion of pro-inflammatory cytokines were both significantly increased. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly increased after sesn2-knockdown. Furthermore, LPS-induced reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and cell toxicity were all significantly elevated after sesn2-knockdown in HUVECs. Interestingly, all these pro-atherosclerotic effects were fully abrogated by treatment with an AMPK activator. In aortic tissue samples from C57BL/6 mice, sesn2-knockdown using siRNA oligomers resulted in reduced AMPK phosphorylation and induction of LPS-mediated NF-κB phosphorylation, leading to up-regulation of adhesion molecules and ER stress-related signaling. Knockdown of sesn2 aggravates atherosclerotic processes by increasing pro-inflammatory reactions and ER stress in the endothelium via an AMPK-dependent mechanism, suggesting that sesn2 might be a novel therapeutic target for atherosclerosis.


CRISPR-Cas: From the Bacterial Adaptive Immune System to a Versatile Tool for Genome Engineering.
The field of biology has been revolutionized by the recent advancement of an adaptive bacterial immune system as a universal genome engineering tool. Bacteria and archaea use repetitive genomic elements termed clustered regularly interspaced short palindromic repeats (CRISPR) in combination with an RNA-guided nuclease (CRISPR-associated nuclease: Cas) to target and destroy invading DNA. By choosing the appropriate sequence of the guide RNA, this two-component system can be used to efficiently modify, target, and edit genomic loci of interest in plants, insects, fungi, mammalian cells, and whole organisms. This has opened up new frontiers in genome engineering, including the potential to treat or cure human genetic disorders. Now the potential risks as well as the ethical, social, and legal implications of this powerful new technique move into the limelight.


Two distinct modes of PERIOD recruitment onto dCLOCK reveal a novel role for TIMELESS in circadian transcription.
Negative transcriptional feedback loops are a core feature of eukaryotic circadian clocks and are based on rhythmic interactions between clock-specific repressors and transcription factors. In Drosophila, the repression of dCLOCK (dCLK)-CYCLE (CYC) transcriptional activity by dPERIOD (dPER) is critical for driving circadian gene expression. Although growing lines of evidence indicate that circadian repressors such as dPER function, at least partly, as molecular bridges that facilitate timely interactions between other regulatory factors and core clock transcription factors, how dPER interacts with dCLK-CYC to promote repression is not known. Here, we identified a small conserved region on dPER required for binding to dCLK, termed CBD (for dCLK binding domain). In the absence of the CBD, dPER is unable to stably associate with dCLK and inhibit the transcriptional activity of dCLK-CYC in a simplified cell culture system. CBD is situated in close proximity to a region that interacts with other regulatory factors such as the DOUBLETIME kinase, suggesting that complex architectural constraints need to be met to assemble repressor complexes. Surprisingly, when dPER missing the CBD (dPER(ΔCBD)) was evaluated in flies the clock mechanism was operational, albeit with longer periods. Intriguingly, the interaction between dPER(ΔCBD) and dCLK is TIM-dependent and modulated by light, revealing a novel and unanticipated in vivo role for TIM in circadian transcription. Finally, dPER(ΔCBD) does not provoke the daily hyperphosphorylation of dCLK, indicating that direct interactions between dPER and dCLK are necessary for the dCLK phosphorylation program but are not required for other aspects of dCLK regulation.


Precision pointing and tracking through random media by exploitation of the enhanced backscatter phenomenon.
The active illumination of a target through a turbulent medium with a monostatic transmitter-receiver results in a naturally occurring conjugate wave caused by reciprocal scattering paths that experience identical phase variations. This reciprocal path-scattering phenomenon produces an enhanced backscatter in the retroverse direction (precisely along the boresight of the pointing telescope). A dual aperture causes this intensity enhancement to take the form of Young's interference fringes. Interference fringes produced by the reciprocal path-scattering phenomenon are temporally stable even in the presence of time-varying turbulence. Choosing the width-to-separation ratio of the dual apertures appropriately and utilizing orthogonal polarizations to suppress the time-varying common-path scattered radiation allow one to achieve interferometric sensitivity in pointing accuracy through a random medium or turbulent atmosphere. Computer simulations are compared with laboratory experimental data. This new precision pointing and tracking technique has potential applications in ground-to-space laser communications, laser power beaming to satellites, and theater missile defense scenarios.


Design and numerical evaluation of a volume coil array for parallel MR imaging at ultrahigh fields.
In this work, we propose and investigate a volume coil array design method using different types of birdcage coils for MR imaging. Unlike the conventional radiofrequency (RF) coil arrays of which the array elements are surface coils, the proposed volume coil array consists of a set of independent volume coils including a conventional birdcage coil, a transverse birdcage coil, and a helix birdcage coil. The magnetic fluxes of these three birdcage coils are intrinsically cancelled, yielding a highly decoupled volume coil array. In contrast to conventional non-array type volume coils, the volume coil array would be beneficial in improving MR signal-to-noise ratio (SNR) and also gain the capability of implementing parallel imaging. The volume coil array is evaluated at the ultrahigh field of 7T using FDTD numerical simulations, and the g-factor map at different acceleration rates was also calculated to investigate its parallel imaging performance.


Variation in Older Adult Characteristics by Residence Type and Use of Home- and Community-Based Services.
Background: The majority of older adults prefer to remain in their homes, or to "age-in-place." To accomplish this goal, many older adults will rely upon home- and community-based services (HCBS) for support. However, the availability and accessibility of HCBS may differ based on whether the older adult lives in the community or in a senior housing apartment facility. Methods: This paper reports findings from the Pathways to Life Quality study of residential change and stability among seniors in upstate New York. Data were analyzed from 663 older adults living in one of three housing types: service-rich facilities, service-poor facilities, and community-dwelling in single-family homes. A multinomial logistic regression model was used to examine factors associated with residence type. A linear regression model was fitted to examine factors associated with HCBS utilization. Results: When compared to community-dwelling older adults, those residing in service-rich and service-poor facilities were more likely to be older, report more activity limitations, and provide less instrumental assistance to others. Those in service-poor facilities were more likely to have poorer mental health and lower perceived purpose in life. The three leading HCBS utilized were senior centers (20%), homemaker services (19%), and transportation services (18%). More HCBS utilization was associated with participants who resided in service-poor housing, were older, were female, and had more activity limitations. More HCBS utilization was also associated with those who received instrumental support, had higher perceived purpose in life, and poorer mental health. Conclusions: Findings suggest that older adults' residential environment is associated with their health status and HCBS utilization. Building upon the Person-Environment Fit theories, dedicated efforts are needed to introduce and expand upon existing HCBS available to facility residents to address physical and mental health needs as well as facilitate aging-in-place.


Mycoplasma genitalium coinfection in men with symptomatic gonococcal urethritis.
International guidelines recommend Mycoplasma genitalium testing, preferably using an assay to detect macrolide resistance-associated mutations, for men presenting with non-gonococcal urethritis, but there is no specific guidance on such testing for men with gonococcal urethritis. This study aimed to estimate the proportion of men with gonococcal urethritis who have coinfection with M. genitalium through a retrospective analysis of cases of symptomatic urethral gonorrhoea at Western Sydney Sexual Health Centre in 2017 and 2018. Fourteen of 184 (7.6%, 95% CI 3.7 to 11.5) men with gonococcal urethritis had M. genitalium detected in the urine at the time of presentation. No demographic or behavioural factors predicted M. genitalium coinfection. Coinfection with urethral Chlamydia trachomatis was detected in 29 of 184 (15.8%, 95% CI 10.5 to 21.1). All five men with macrolide-resistant M. genitalium detected returned for treatment with moxifloxacin at a median of 8 days (range 5-16 days) after presentation and treatment of gonorrhoea; three of five were documented to remain symptomatic at this visit. Although M. genitalium coinfection is less common than chlamydia among men with symptomatic gonococcal urethritis, M. genitalium testing, using an assay to detect macrolide resistance, will potentially reduce symptom duration particularly for men with macrolide-resistant infections, but may not be justifiable on cost-benefit analysis.


Overview of mathematical approaches used to model bacterial chemotaxis II: bacterial populations.
We review the application of mathematical modeling to understanding the behavior of populations of chemotactic bacteria. The application of continuum mathematical models, in particular generalized Keller-Segel models, is discussed along with attempts to incorporate the microscale (individual) behavior on the macroscale, modeling the interaction between different species of bacteria, the interaction of bacteria with their environment, and methods used to obtain experimentally verified parameter values. We allude briefly to the role of modeling pattern formation in understanding collective behavior within bacterial populations. Various aspects of each model are discussed and areas for possible future research are postulated.


[Natalizumab and reduction of carbonylated proteins in patients with multiple sclerosis].
The sensitivity of the central nervous system to oxidative damage and its relationship with inflammatory response are well known. Recent studies have shown that oxidative stress is present in the establishment and development of multiple sclerosis (MS). One of the most recent treatments in this process is natalizumab, a monoclonal antibody. To evaluate whether the therapeutic effect of natalizumab is associated with the severity of the disease and the oxidative damage. Researchers recruited twenty patients with relapsing-remitting MS (RRMS) undergoing therapy with natalizumab and distributed, according to the Expanded Disability Status Scale (EDSS), in two groups: RRMS-1 (EDSS < 5) and RRMS-2 (EDSS ≥ 5). Blood samples were taken for an oxidative profile study. Data showed a decrease in carbonylated proteins following treatment with natalizumab. The reduction in oxidative damage rated as protein oxidation is significant between the previous (baseline) situation of the patient and after 14 months' treatment. The most significant decrease coincided with the patients with the highest levels of severity in the process. Although it has not been possible to establish a correlation, the statistical significance is higher for patients in the RRMS-2 group treated with natalizumab. The antioxidant systems, on the other hand, did not display any statistically significant changes. Natalizumab brings about a reduction in carbonylated protein levels.


A randomized controlled trial assessing the health economics of realtime teledermatology compared with conventional care: an urban versus rural perspective.
A randomized controlled trial was carried out to measure the cost-effectiveness of realtime teledermatology compared with conventional outpatient dermatology care for patients from urban and rural areas. One urban and one rural health centre were linked to a regional hospital in Northern Ireland by ISDN at 128 kbit/s. Over two years, 274 patients required a hospital outpatient dermatology referral--126 patients (46%) were randomized to a telemedicine consultation and 148 (54%) to a conventional hospital outpatient consultation. Of those seen by telemedicine, 61% were registered with an urban practice, compared with 71% of those seen conventionally. The clinical outcomes of the two types of consultation were similar--almost half the patients were managed after a single consultation with the dermatologist. The observed marginal cost per patient of the initial realtime teledermatology consultation was 52.85 Pounds for those in urban areas and 59.93 Pounds per patient for those from rural areas. The observed marginal cost of the initial conventional consultation was 47.13 Pounds for urban patients and 48.77 Pounds for rural patients. The total observed costs of teledermatology were higher than the costs of conventional care in both urban and rural areas, mainly because of the fixed equipment costs. Sensitivity analysis using a real-world scenario showed that in urban areas the average costs of the telemedicine and conventional consultations were about equal, while in rural areas the average cost of the telemedicine consultation was less than that of the conventional consultation.


VLAT: Development of a Visualization Literacy Assessment Test.
The Information Visualization community has begun to pay attention to visualization literacy; however, researchers still lack instruments for measuring the visualization literacy of users. In order to address this gap, we systematically developed a visualization literacy assessment test (VLAT), especially for non-expert users in data visualization, by following the established procedure of test development in Psychological and Educational Measurement: (1) Test Blueprint Construction, (2) Test Item Generation, (3) Content Validity Evaluation, (4) Test Tryout and Item Analysis, (5) Test Item Selection, and (6) Reliability Evaluation. The VLAT consists of 12 data visualizations and 53 multiple-choice test items that cover eight data visualization tasks. The test items in the VLAT were evaluated with respect to their essentialness by five domain experts in Information Visualization and Visual Analytics (average content validity ratio = 0.66). The VLAT was also tried out on a sample of 191 test takers and showed high reliability (reliability coefficient omega = 0.76). In addition, we demonstrated the relationship between users' visualization literacy and aptitude for learning an unfamiliar visualization and showed that they had a fairly high positive relationship (correlation coefficient = 0.64). Finally, we discuss evidence for the validity of the VLAT and potential research areas that are related to the instrument.


Global status and conservation potential of reef sharks.
Decades of overexploitation have devastated shark populations, leaving considerable doubt as to their ecological status1,2. Yet much of what is known about sharks has been inferred from catch records in industrial fisheries, whereas far less information is available about sharks that live in coastal habitats3. Here we address this knowledge gap using data from more than 15,000 standardized baited remote underwater video stations that were deployed on 371 reefs in 58 nations to estimate the conservation status of reef sharks globally. Our results reveal the profound impact that fishing has had on reef shark populations: we observed no sharks on almost 20% of the surveyed reefs. Reef sharks were almost completely absent from reefs in several nations, and shark depletion was strongly related to socio-economic conditions such as the size and proximity of the nearest market, poor governance and the density of the human population. However, opportunities for the conservation of reef sharks remain: shark sanctuaries, closed areas, catch limits and an absence of gillnets and longlines were associated with a substantially higher relative abundance of reef sharks. These results reveal several policy pathways for the restoration and management of reef shark populations, from direct top-down management of fishing to indirect improvement of governance conditions. Reef shark populations will only have a high chance of recovery by engaging key socio-economic aspects of tropical fisheries.


The contribution of vision to asymmetries in manual aiming.
An experiment was conducted to examine the hypothesis that the right hand system is superior in the processing of visual information. A manual aiming task utilizing four visual conditions was employed. In the full-vision (FV) condition subjects were afforded vision of both the hand and the target throughout the course of the movement. In the ambient-illumination-off (AO) condition, the room lights were extinguished at movement initiation, thus preventing vision of the moving limb. The target remained illuminated. In the target-off (TO) condition, the target was extinguished upon initiation of the movement. Ambient illumination and thus vision of the hand remained present. Finally there was a no-vision (NV) condition in which ambient illumination was removed and the target was extinguished upon initiation of the response movement. Although the manipulation of vision had potent effects upon terminal accuracy, and influenced reaction and movement time measures, the hands did not differ in the extent to which these characteristics were expressed. A left hand advantage for reaction time was observed. This may reflect a relative increase in right hemisphere involvement prior to aiming movements which are spatially complex.


Cost-Effectiveness of Tight Control of Inflammation in Early Psoriatic Arthritis: Economic Analysis of a Multicenter Randomized Controlled Trial.
Treat-to-target approaches have proved to be effective in rheumatoid arthritis, but have not been studied in psoriatic arthritis (PsA). This study was undertaken to examine the cost-effectiveness of tight control (TC) of inflammation in early PsA compared to standard care. Cost-effectiveness analyses were undertaken alongside a UK-based, open-label, multicenter, randomized controlled trial. Taking the perspective of the health care sector, effectiveness was measured using the 3-level EuroQol 5-domain, which allows for the calculation of quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) are presented, which represent the additional cost per QALY gained over a 48-week time horizon. Sensitivity analyses are presented assessing the impact of variations in the analytical approach and assumptions on the cost-effectiveness estimates. The mean cost and QALYs were higher in the TC group: £4,198 versus £2,000 and 0.602 versus 0.561. These values yielded an ICER of £53,948 per QALY. Bootstrapped uncertainty analysis suggests that the TC has a 0.07 probability of being cost-effective at a £20,000 threshold. Stratified analysis suggests that with certain costs being controlled, an ICER of £24,639 can be calculated for patients with a higher degree of disease severity. A tight control strategy to treat PsA is an effective intervention in the treatment pathway; however, this study does not find tight control to be cost-effective in most analyses. Lower drug prices, targeting polyarthritis patients, or reducing the frequency of rheumatology visits may improve value for money metrics in future studies.


[Basic Studies on the Mechanism, Prevention, and Treatment of Osteonecrosis of the Jaw Induced by Bisphosphonates].
Since the first report in 2003, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been increasing, without effective clinical strategies. Osteoporosis is common in elderly women, and bisphosphonates (BPs) are typical and widely used anti-osteoporotic or anti-bone-resorptive drugs. BRONJ is now a serious concern in dentistry. As BPs are pyrophosphate analogues and bind strongly to bone hydroxyapatite, and the P-C-P structure of BPs is non-hydrolysable, they accumulate in bones upon repeated administration. During bone-resorption, BPs are taken into osteoclasts and exhibit cytotoxicity, producing a long-lasting anti-bone-resorptive effect. BPs are divided into nitrogen-containing BPs (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). N-BPs have far stronger anti-bone-resorptive effects than non-N-BPs, and BRONJ is caused by N-BPs. Our murine experiments have revealed the following. N-BPs, but not non-N-BPs, exhibit direct and potent inflammatory/necrotic effects on soft-tissues. These effects are augmented by lipopolysaccharide (the inflammatory component of bacterial cell-walls) and the accumulation of N-BPs in jawbones is augmented by inflammation. N-BPs are taken into soft-tissue cells via phosphate-transporters, while the non-N-BPs etidronate and clodronate inhibit this transportation. Etidronate, but not clodronate, has the effect of expelling N-BPs that have accumulated in bones. Moreover, etidronate and clodronate each have an analgesic effect, while clodronate has an anti-inflammatory effect via inhibition of phosphate-transporters. These findings suggest that BRONJ may be induced by phosphate-transporter-mediated and infection-promoted mechanisms, and that etidronate and clodronate may be useful for preventing and treating BRONJ. Our clinical trials support etidronate being useful for treating BRONJ, although additional clinical trials of etidronate and clodronate are needed.