Is Hip Arthroscopy Effective in Patients With Combined Excessive Femoral Anteversion and Borderline Dysplasia? A Match-Controlled Study.
Appropriate patient selection is critical when hip arthroscopy is considered in the setting of borderline dysplasia (BD). It is presumable that excessive femoral anteversion (EFA) and BD may contraindicate arthroscopy. Patients with combined EFA and BD (EFABD) demonstrate significantly inferior short-term outcomes after arthroscopic labral preservation and capsular closure when compared with a similar control group with normal lateral coverage and femoral anteversion. Cohort study; Level of evidence, 3. Data were prospectively collected and retrospectively reviewed on patients undergoing hip arthroscopy between April 2010 and November 2014. The EFABD group's inclusion criteria were BD (lateral center-edge angle, 18°-25°), labral tear, capsular closure, and femoral version ≥20°, as well as preoperative modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score-Sports Specific Subscale, and visual analog scale. Exclusion criteria were workers' compensation, preoperative Tönnis grade >1, microfracture, abductor pathology, or previous ipsilateral hip surgery or conditions. Patients in the EFABD group were matched 1:2 to a similar control group with normal coverage and femoral anteversion by age at surgery ± 6 years, sex, body mass index ± 5, acetabular Outerbridge grade (0, 1 vs 2, 3, 4), and iliopsoas fractional lengthening. Sixteen EFABD cases were eligible for inclusion, and 100% follow-up was obtained at ≥2 years postoperatively. Twelve EFABD cases were matched to 24 control cases. Mean femoral version was 22.4° in the EFABD group and 10.2° in the control group ( P = .01). Mean lateral center-edge angle was 22.1° in the EFABD group and 31.5° in the control group ( P < .0001). Acetabuloplasty was performed significantly more frequently in the control group ( P = .0006). No other significant differences were found regarding demographics, findings, procedures, or preoperative scores. At latest follow-up, the EFABD group demonstrated significantly lower mean modified Harris Hip Score (76.1 vs 85.9; P = .005), Nonarthritic Hip Score (74.8 vs 88.5; P < .0001), Hip Outcome Score-Sports Specific Subscale (58.3 vs 78.4; P = .02), and patient satisfaction (7.1 vs 8.3; P = .005). There were 4 secondary surgical procedures (33.3%) in the EFABD group and 1 (4.2%) in the control group ( P = .03). One patient in each group required arthroplasty. Patients treated with arthroscopic labral preservation and capsular closure in the setting of EFABD demonstrated significant improvements from presurgery to latest follow-up. However, their results are significantly inferior when compared with a matched-controlled group. Consideration of periacetabular osteotomy or femoral osteotomy may be warranted in the setting of EFABD to achieve optimal benefit.


Polymorphisms in the F Pocket of HLA-B27 Subtypes Strongly Affect Assembly, Chaperone Interactions, and Heavy-Chain Misfolding.
HLA-B27 is associated with the inflammatory spondyloarthritides (SpA), although subtypes HLA-B*27:06 and HLA-B*27:09 are not. These subtypes differ from the HLA-B*27:05 disease-associated allele primarily at residues 114 and 116 of the heavy chain, part of the F pocket of the antigen-binding groove. Dimerization of HLA-B27 during assembly has been implicated in disease onset. The purpose of this study was to investigate the factors that influence differences in dimerization between disease-associated and non-disease-associated HLA-B27 alleles. HLA-B*27:05 and mutants resembling the HLA-B*27:06 and 09 subtypes were expressed in the rat C58 T cell line, the human CEM T cell line and its calnexin-deficient variant CEM.NKR. Immunoprecipitation, pulse-chase experiments, flow cytometry, and immunoblotting were performed to study the assembly kinetics, heavy-chain dimerization, and chaperone associations. By expressing HLA-B*27:05, 06-like, and 09 alleles on a restrictive rat transporter associated with antigen processing background, we demonstrate that a tyrosine expressed at p116, either alone or together with an aspartic acid residue at p114, inhibited HLA-B27 dimerization and increased the assembly rate. F-pocket residues altered the associations with chaperones of the early major histocompatibility complex class I folding pathway. Calnexin was demonstrated to participate in endoplasmic reticulum (ER) stress-mediated degradation of dimers, whereas the oxidoreductase ERp57 does not appear to influence dimerization. Residues within the F pocket of the peptide-binding groove, which differ between disease-associated and non-disease-associated HLA-B27 subtypes, can influence the assembly process and heavy-chain dimerization, events which have been linked to the initiation of disease pathogenesis.


Characteristics of the genioglossus and musculus uvulae in sleep apnea hypopnea syndrome and in snorers.
Genioglossus (GG) activity has been extensively studied by electromyographic recordings in the investigation of the pathophysiology of sleep apnea-hypopnea syndrome (SAHS). However, the effective force developed by this upper airway (UA) dilator muscle depends on its metabolic and histochemical characteristics. The aim of this study was to compare the metabolic and fiber type characteristics of two UA dilator muscles, musculus uvulae (MU) and GG, in 17 patients with SAHS and in 11 nonapneic snorers. MU and GG samples were obtained during uvulopalatopharyngoplasty. Anthropomorphic characteristics were similar in snorers and patients with SAHS, who differed only in the presence of sleep-related breathing abnormalities. MU glycolytic, glycogenolytic, and anaerobic enzyme activities were significantly greater in patients with SAHS than in snorers. These differences were not observed for GG. MU and GG enzyme activities differed only in snorers. The proportion of type I muscle fiber was greater in GG than in MU, but it was similar in patients with SAHS and snorers for each muscle. Type IIA and IIB muscle fibers were, respectively, in greater and smaller proportions in patients with SAHS than in snorers. We conclude that (1) the differences in metabolic characteristics between patients with SAHS and snorers are not observed in all UA muscles, and (2) similar histochemical differences are observed in GG and MU between these two groups, thus suggesting that these differences may be implicated in the pathophysiology of SAHS.


A synaptic and circuit basis for corollary discharge in the auditory cortex.
Sensory regions of the brain integrate environmental cues with copies of motor-related signals important for imminent and ongoing movements. In mammals, signals propagating from the motor cortex to the auditory cortex are thought to have a critical role in normal hearing and behaviour, yet the synaptic and circuit mechanisms by which these motor-related signals influence auditory cortical activity remain poorly understood. Using in vivo intracellular recordings in behaving mice, we find that excitatory neurons in the auditory cortex are suppressed before and during movement, owing in part to increased activity of local parvalbumin-positive interneurons. Electrophysiology and optogenetic gain- and loss-of-function experiments reveal that motor-related changes in auditory cortical dynamics are driven by a subset of neurons in the secondary motor cortex that innervate the auditory cortex and are active during movement. These findings provide a synaptic and circuit basis for the motor-related corollary discharge hypothesized to facilitate hearing and auditory-guided behaviours.


Design and baseline participant characteristics of the Human Immunodeficiency Virus Epidemiology Research (HER) Study: a prospective cohort study of human immunodeficiency virus infection in US women.
The prospective, multisite human immunodeficiency (HIV) Epidemiology Research Study was established to define the biologic, psychologic, and social effects of HIV infection on the health of US women. From 1993 to 1995, a total of 871 HIV-infected women and 439 demographically matched, uninfected women aged 16-55 years, half of whom reported injection drug use and half of whom reported only sexual risk behaviors, were recruited in four US cities. Two sites recruited primarily from medical/drug therapy care settings, and two recruited from community sources. Women consented to biannual interviews; physical examination; blood, urine, and cervicovaginal specimen collection and repository; laboratory assays; and abstraction of outpatient and inpatient medical records to document HIV and acquired immunodeficiency syndrome-related diagnoses. Retention was greater than 88% at the third 6-month follow-up. Lower retention was associated with currently injecting drugs, not having dependent children, and not being infected with HIV at enrollment. In addition to the core study, a variety of nested studies are under way, some in collaboration with other HIV cohorts and various Public Health Service agencies. This cohort is distinct from other HIV longitudinal cohorts in the diversity of its participants and the comprehensive range of measures to study prospectively the biomedical, social, and emotional effects of the HIV epidemic on infected women and those whose behavior puts them at high risk of infection.


Ultrastructural localization of immunoglobulin G and complement C9 in the brain stem and spinal cord following peripheral nerve injury: an immunoelectron microscopic study.
The ultrastructural localization of immunoreactivity for immunoglobulin G (IgG), F(ab')2 and complement C9 was examined with preembedding immunoelectron microscopy in the hypoglossal nucleus and gracile nucleus as well as in the L4 spinal cord dorsal horn 1 week following hypoglossal or sciatic nerve transection, respectively. Only a few scattered immunoreactive profiles were observed on the unoperated side. On the operated side, IgG and F(ab')2 immunoreactivity was present in the membranes of all reactive microglial cells observed. In addition, the cell membrane of some hypoglossal motoneurons showed IgG immunoreactivity. Complement C9 immunoreactivity was present in the cytoplasm of all reactive microglial cells examined. In addition, there was diffuse C9 immunoreactivity in motoneuron perikarya ipsilateral to nerve injury as well as in cell membranes in the neuropil, some of which could be identified as neuronal. Our interpretation of these findings is (1) that peripheral nerve injury results in binding of IgG to reactive microglia, as well as to some axotomized neurons, and (2) that C9 is synthesized by reactive microglia in response to axon injury and is also associated with axotomized motoneurons. These findings suggest that IgG and complement C9 are involved in microglia-neuron interactions after peripheral nerve injury.


CCR5-Dependent Homing of T Regulatory Cells to the Tumor Microenvironment Contributes to Skin Squamous Cell Carcinoma Development.
Squamous cell carcinoma (SCC) is one of the most common human cancers worldwide. Recent studies show that regulatory T cells (Treg) have a critical role in the modulation of an antitumor immune response, and consequently the SCC development. Because the accumulation of Tregs at the tumor site is, in part, due to selective recruitment through CCR5- and CCR5-associated chemokines, we investigated the role of CCR5 in the SCC development. Our findings showed that CCR5-deficient mice (CCR5KO) were efficient in controlling papilloma's incidence when compared with wild-type mice. Analysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Tregs and increased of CD4 T cells into the tumors. Moreover, the adoptive transfer of naturally occurring Tregs CD4+CD25+CCR5+, CD4+CD25-CCR5+ or CD8+CCR5+ conventional T cells to CCR5KO mice resulted in an increased papilloma incidence. Interestingly, adoptive transfer of WT CD4+CD25+CCR5+ cells to CCR5KO mice induced more undifferentiated SCC lesions, characterized by higher infiltration of macrophages and dendritic cells. In this study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of antitumor cells such as cytotoxic CD8+ T cells. Our findings reinforce the therapeutic potential of CCR5 inhibition for cancer treatment, and indicate an attractive approach for SCC treatment. Mol Cancer Ther; 16(12); 2871-80. ©2017 AACR.


Antigenic characterization of Tettnang virus: complications caused by passage of the virus in mice from a colony enzootically infected with mouse hepatitis virus.
Neutralization assays were undertaken for the purpose of antigenically characterizing three strains of Tettnang virus from two geographic regions. The previously reported relationship of Tettnang virus strains to mouse hepatitis virus (MHV) was confirmed. However, the precise relationship of the Tettnang strains to prototype MHV strains was obscured in our study by the finding that the isolates had been passaged in mice from a colony subclinically infected with MHV. An Egyptian strain of Tettnang which had not been passaged in that colony was reciprocally related to the neurotropic JHM strain of MHV. Our data stress the importance of microbiological monitoring of apparently healthy laboratory animals used for virologic research.


On the formation of concentrated stable w/o emulsions.
The conditions for the formation of concentrated w/o emulsions based on Aerosol OT and aliphatic hydrocarbons were studied. It was found that high stability is obtained if the attraction between the emulsion droplets is kept to a minimum. This is achieved by matching the refractive index of the dispersed phase and the organic phase. Furthermore, it is shown that the mere presence of salt does not render any stability. Hence, the speculated mechanism that salt stabilises against Ostwald ripening does not hold for these emulsions.


Trends in medical students' stress, physical, and emotional health throughout training.
Background: Medical student wellness, including physical health, emotional health, and levels of perceived stress, appears to decline during training, with students reporting high levels of depression, anxiety, and burnout as early as the first year of medical school. The impact of curricular changes on health and stress remains unclear, and a modified curriculum that compresses training of the foundational sciences and its effect on wellness has not been studied. Oregon Health & Science University School of Medicine has recently instituted a unique competency-based model, which provides an important opportunity to assess the effects of curricular change on student wellness.Objective: Assess the effects of curricular change on student wellness.Design: Medical students at a single institution were administered the SF-8, an 8-item health-related quality of life survey, as well as the Perceived Stress Scale, a 10-item scale that measures the degree to which life situations are appraised as stressful, at baseline (matriculation) and at the end of Year 1, 2 and 3. Individual variables were assessed over time, as well as a trend analysis of summary domain scores over the 4 time periods.Results: Physical, emotional, and overall health were highest at baseline and lowest at the end of Year 1, after which they improved but never again reached baseline levels. Physical health declined less than emotional health. Perceived stress levels did not change over time but remained moderately high. There were no differences in health or perceived stress based on demographic variables.Conclusions: In a competency-based curriculum, physical, emotional and overall health significantly worsened during Year 1 but improved thereafter, while perceived stress remained unchanged. Early in training, stress and poor overall health may be related to concerns about self-efficacy and workload. Although advanced students show improved wellness, concerns remained about emotional difficulties, such as anxiety and irritability, and feeling a lack of control.


Effective density and morphology of particles emitted from small-scale combustion of various wood fuels.
The effective density of fine particles emitted from small-scale wood combustion of various fuels were determined with a system consisting of an aerosol particle mass analyzer and a scanning mobility particle sizer (APM-SMPS). A novel sampling chamber was combined to the system to enable measurements of highly fluctuating combustion processes. In addition, mass-mobility exponents (relates mass and mobility size) were determined from the density data to describe the shape of the particles. Particle size, type of fuel, combustion phase, and combustion conditions were found to have an effect on the effective density and the particle shape. For example, steady combustion phase produced agglomerates with effective density of roughly 1 g cm(-3) for small particles, decreasing to 0.25 g cm(-3) for 400 nm particles. The effective density was higher for particles emitted from glowing embers phase (ca. 1-2 g cm(-3)), and a clear size dependency was not observed as the particles were nearly spherical in shape. This study shows that a single value cannot be used for the effective density of particles emitted from wood combustion.


Human telomerase contains two cooperating telomerase RNA molecules.
Telomerase uses a short stretch of its intrinsic RNA molecule as template for telomere repeat synthesis. Reverse transcription of the RNA template is catalyzed by the telomerase reverse transcriptase (TERT) protein subunit. We demonstrate that human telomerase reconstituted from recombinant TERT and telomerase RNA runs as a dimer on a gel filtration column and that it contains two telomerase RNA molecules. Significantly, a telomerase heterodimer reconstituted from wild-type and mutant telomerase RNA is barely active when compared with the wild-type homodimer. We conclude that the telomerase RNA templates in the active enzyme are interdependent and functionally cooperate with each other. We discuss models that may explain the biological and enzymatic roles of telomerase dimerization.


Effect of different extracting solutions on the electrodialytic remediation of CCA-treated wood waste Part I. Behaviour of Cu and Cr.
Removal of Cu and Cr from chromated copper arsenate (CCA)-treated wood waste under batch electrodialytic conditions was studied. The effect of different types of extracting solutions, such as deionised water or aqueous solutions of NaCl, formic acid, oxalic acid, and EDTA, on the magnitude and direction of the fluxes of Cu- and Cr-containing species in the electrodialytic cell was investigated. Oxalic acid was found to have the best performance if simultaneous removal of the two elements is required (removal efficiencies of 80.5% for Cu and 87.4% for Cr, respectively). A mixture of oxalic acid and formic acid also led to similar removal efficiencies. In these experiments, the target elements were accumulated in both the anode and cathode compartments of the electrodialytic cell due to the formation of negatively charged complexes with the organic acids used besides the free cationic forms. The latter were not present if EDTA was the extracting solution resulting in directing the Cu and Cr fluxes to the anode compartment. Contrary, these fluxes were exclusively to the cathode compartment if deionised water or an aqueous solution of NaCl were used. These extracting solutions proved suitable for solubilising (re-mobilisation) of Cu but were less efficient for Cr removal (less than 20% removal). Overall, the results obtained show the important role of the proper selection of the type and composition of the extracting solution for the success of subsequent electrodialytic removal of Cu and Cr from CCA-treated wood waste.


Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.
Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.


Transmissibility of novel H7N9 and H9N2 avian influenza viruses between chickens and ferrets.
Previous studies have shown that the H7N9 avian influenza virus cannot be transmitted efficiently between ferrets via respiratory droplets. Here, we studied the infectivity of the H7N9 avian influenza virus in chickens and its transmissibility from infected to naïve chickens and ferrets. The H7N9 virus (A/Anhui/1/2013) replicated poorly in chickens and could not be transmitted efficiently from infected chickens to naïve chickens and ferrets. H7N9 virus was shed from chicken tracheae for only 2 days after infection and from chicken cloacae for only 1 day after infection, while the H9N2 avian influenza virus, which is endemic in chickens in many Asian countries, was shed from tracheae and cloacae for 8 days after infection. Taken together, our results suggest that chickens may be a poor agent of transmission for the H7N9 virus to other chickens and to mammals, including humans.


Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C.
Nuclear events of mitosis are initiated when the protein kinase cyclin-B1-Cdk1 is translocated into the nucleus during prophase. Recent work has unveiled many of the mechanisms that govern the localization of cyclin-B1-Cdk1 and its regulator Cdc25C. Phosphorylation-dependent changes in the rate of nuclear import and export of these proteins help to control the onset of mitosis both in normal cells and in cells delayed before mitosis by DNA damage.


Telomere-independent cellular senescence in human fetal cardiomyocytes.
Fetal cardiomyocytes have been proposed as a potential source of cell-based therapy for heart failure. This study examined cellular senescence in cultured human fetal ventricular cardiomyocytes (HFCs). HFCs were isolated and identified by immunocytochemistry and RT-PCR. Cells were found to senesce after 20-25 population doublings, as determined by growth arrest, morphological changes and senescence-associated beta-galactosidase activity. Using the telomeric repeat amplification protocol assay, telomerase activity was undetectable in primary HFCs. Cells were transduced to express the human reverse transcriptase subunit (hTERT) of telomerase. This resulted in greatly increased telomerase activity, but no significant lifespan extension. Analysis of telomere length in primary HFCs revealed that the senescent phenotype was not accompanied by telomere shortening. Telomeres in hTERT-positive cells were elongated in comparison with primary cells, and elongation was retained in senescent cells. Levels of the tumor suppressor protein p16INK4A increased in all senescent cells whether telomerase-positive or -negative. Senescence was accompanied by a decline in transcript levels of the polycomb gene Bmi-1, Ets1 and Ets2 transcription factors, and Id1, Id2 and Id3 helix-loop-helix proteins, suggesting roles for these genes in maintenance of cardiomyocyte proliferative capacity. In addition to offering novel insights into the behavior of human fetal cardiomyocytes in culture, these findings have implications for the development of a cell-based therapy for cardiac injury using primary fetal heart tissue.


Genome-wide integration on transcription factors, histone acetylation and gene expression reveals genes co-regulated by histone modification patterns.
N-terminal tails of H2A, H2B, H3 and H4 histone families are subjected to posttranslational modifications that take part in transcriptional regulation mechanisms, such as transcription factor binding and gene expression. Regulation mechanisms under control of histone modification are important but remain largely unclear, despite of emerging datasets for comprehensive analysis of histone modification. In this paper, we focus on what we call genetic harmonious units (GHUs), which are co-occurring patterns among transcription factor binding, gene expression and histone modification. We present the first genome-wide approach that captures GHUs by combining ChIP-chip with microarray datasets from Saccharomyces cerevisiae. Our approach employs noise-robust soft clustering to select patterns which share the same preferences in transcription factor-binding, histone modification and gene expression, which are all currently implied to be closely correlated. The detected patterns are a well-studied acetylation of lysine 16 of H4 in glucose depletion as well as co-acetylation of five lysine residues of H3 with H4 Lys12 and H2A Lys7 responsible for ribosome biogenesis. Furthermore, our method further suggested the recognition of acetylated H4 Lys16 being crucial to histone acetyltransferase ESA1, whose essential role is still under controversy, from a microarray dataset on ESA1 and its bypass suppressor mutants. These results demonstrate that our approach allows us to provide clearer principles behind gene regulation mechanisms under histone modifications and detect GHUs further by applying to other microarray and ChIP-chip datasets. The source code of our method, which was implemented in MATLAB (http://www.mathworks.com/), is available from the supporting page for this paper: http://www.bic.kyoto-u.ac.jp/pathway/natsume/hm_detector.htm.


Effect of Final Monomer Deposition Steps on Molecular Layer-by-Layer Polyamide Surface Properties.
A current challenge to desalination membrane technology is the inability to precisely control the properties of the polyamide selective layer due to the complexity of interfacial polymerization. In this study, we investigate the ability of molecular layer-by-layer (mLbL) assembly, an alternative polyamide fabrication technique, to create polyamide surfaces with tunable chemistry. We explore the influence of terminating monomer, monomer deposition time, monomer size, and the presence of underlying ionizable functional groups on mLbL-derived polyamide surface properties. AFM colloidal probe measurements, contact angle titrations, QCM cesium adsorption experiments, and XPS data show that polyamide films terminated with m-phenylenediamine or trimesoyl chloride for 20-30 s are chemically similar. Increasing terminating monomer deposition time or using a smaller, more reactive monomer results in more distinct colloidal-probe adhesive interactions, contact angle titration curves, negative charge densities, and near surface atomic compositions. By optimizing the final monomer deposition steps, both amine-rich and carboxyl-rich polyamide surfaces can be fabricated, which has implications for the application of mLbL assembly to membrane-based desalination.


Influence of Nd:Zn codoping in near-stoichiometric lithium niobate.
Near-stoichiometric lithium niobate (SLN) crystals doped with up to 1.6 mol % Zn and codoped with various Nd concentrations in the melt (0.2, 0.5, 0.9, and 1.5 mol %) (Nd:Zn:SLN) are grown from 58.6 mol % Li(2)O using conventional Czochralski technique. Crystals are pulled at the rate of 0.35 mmh with seed rotation at 9 rpm. Concentrations of Zn and Nd in the crystal are varied by adding appropriate amounts of ZnO and Nd(2)O(3) to the starting composition. Unit cell parameters of the grown crystals are calculated by Rietveld refinement method using FULLPROFF software. Domain structure studies are carried out by chemical etching followed by microscopic examination. Dielectric studies reveal the existence of piezoelectric resonance at high frequencies. Enhancement in dielectric constant and tan delta in Nd doped samples has been attributed to the space charge polarization. Nd doped samples exhibit reduction in the relative permittivity after oxygen annealing. Transmission spectra of Nd:Zn:SLN crystals in the UV region exhibit blueshift in the cutoff wavelength. In Mid Infrared (MIR) region crystals doped with 1.6 mol % Zn have shift in the OH absorption peak from 2873 to 2833 nm. Judd-Ofelt analysis carried out on the absorption spectra of codoped crystal yields the lifetime of 104 mus for the metastable state (4)F(32). The branching ratio for the electronic transition from (4)F(32) to (4)I(112) is high compared to that for (4)F(32) to (4)I(132), indicating a higher emission cross section for the former transition. Laser damage threshold evaluated using 532 nm, 5 ns pulsed neodymium doped yttrium aluminum garnet laser, shows an increase by two orders of magnitude for crystals doped with 1.6 mol % Zn. Photorefractive damage threshold for these crystals shows an enhancement of four orders of magnitude due to increase in the photoconductivity.


Asymmetric syntheses of the homalium alkaloids (-)-(S,S)-homaline and (-)-(R,R)-hopromine.
The highly diastereoselective conjugate additions of the novel lithium amide reagents lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)amide and lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to α,β-unsaturated esters were used as the key steps in syntheses of the homalium alkaloids (-)-(S,S)-homaline and (-)-(R,R)-hopromine. The asymmetric synthesis of (-)-(S,S)-homaline was achieved in 8 steps and 18% overall yield, and the asymmetric synthesis of (-)-(R,R)-hopromine was achieved in 9 steps and 23% overall yield, from commercially available starting materials in each case. These syntheses therefore represent by far the most efficient total asymmetric syntheses of these alkaloids reported to date. A sample of the (4'R,4''S)-epimer of hopromine was also produced using this approach, which provided the first unambiguous confirmation of its absolute configuration and therefore that of natural (-)-(R,R)-hopromine.


Network flux analysis: impact of 13C-substrates on metabolism in Arabidopsis thaliana cell suspension cultures.
The aim of this study was to test the assumption that (13)C-enrichment of respiratory substrate does not perturb metabolism. Cell suspension cultures of Arabidopsis thaliana were grown in MS medium containing unlabelled glucose (with (13)C at natural abundance), 100% [1-(13)C]glucose, 100% [U-(13)C(6)]glucose or 10% [U-(13)C(6)]glucose plus 90% unlabelled glucose. There was no significant difference in the metabolism of [U-(14)C]glucose between the cultures. Similarly, the pattern of (14)CO(2) release from specifically labelled [(14)C]-substrates was unaffected. Principal component analysis of (13)C-decoupled (1)H NMR metabolite fingerprints of cell extracts was unable to discriminate between the different culture conditions. It is concluded that (13)C-enrichment of the growth substrate has no effect on flux through the central pathways of carbon metabolism in higher plants. This conclusion supports the implicit assumption in metabolic flux analysis that steady-state (13)C-labelling does not perturb fluxes through the reactions of the metabolic network it seeks to quantify.


Appropriate and inappropriate electrical therapies delivered by an implantable cardioverter-defibrillator: effect on intracardiac electrogram.
Local injury current (LIC) seen after induced ventricular fibrillation rescue implantable cardioverter-defibrillator (ICD) shock predicts heart failure progression. We sought to determine the frequency of LIC after spontaneous events in patients receiving ICD therapies. Near-field (NF) right ventricular (RV) EGM during 10 seconds after delivered ICD therapy was compared with baseline EGM in 420 events that occurred in 134 patients (mean age 60.8 ± 14.8, 106 [79%] male). The magnitude of elevated or depressed potential immediately after the major fast EGM deflection was defined as LIC, and its ratio to the peak-to-peak EGM amplitude was defined as relative LIC. LIC of at least 1 mV or relative LIC of at least 15% was considered significant. LIC was observed in 121 events (28.8%) and was detected more frequently after appropriate (43 [60.6%] events) and inappropriate (56 [64.4%] events) ICD shocks, as compared with appropriate (8 [9.2%] events) and inappropriate (3 [4.7%] events) antitachycardia pacing (ATP) or nonsustained ventricular tachycardia (11 [9.9%] events) [ANOVA P < 0.0001]. Type of ICD therapy (ICD shock vs ATP) was the most significant predictor of LIC (ATP β coefficient -0.81; 95%CI-1.19 to 0.44); P < 0.0001), along with cycle length of tachycardia (β coefficient -0.0117; 95%CI -0.0167 to -0.0068, P < 0.00001) and shock energy (β coefficient 0.024; 95%CI 0.003-0.045, P = 0.025). Appropriate and inappropriate ICD shocks are frequently characterized by the development of LIC in patients with structural heart disease. Type of electrical ICD therapy, shock energy and cycle length of ventricular arrhythmia are important determinants of LIC.


Tracking Changes in Frontal Lobe Hemodynamic Response in Individual Adults With Developmental Language Disorder Following HD tDCS Enhanced Phonological Working Memory Training: An fNIRS Feasibility Study.
Background: Current research suggests a neurobiological marker of developmental language disorder (DLD) in adolescents and young adults may be an atypical neural profile coupled with behavioral performance that overlaps with that of normal controls. Although many imaging techniques are not suitable for the study of speech and language processing in DLD populations, fNIRS may be a viable option. In this study we asked if fNIRS can be used to identify atypical cortical activation patterns in individual adults with DLD and track potential changes in cortical activation patterns following a phonological working memory training protocol enhanced with anodal HD tDCS stimulation to the presupplementary motor area (preSMA). Objective/Hypothesis: The purpose of this study was two-fold: (1) to determine if fNIRS can be used to identify atypical hemodynamic responses in individual young adults with DLD during active spoken word processing and, (2) to determine if fNIRS can detect changes in hemodynamic response in these same adults with DLD following anodal HD tDCS enhanced phonological working memory training. Methods: Two adult subjects with DLD (female, age 25) completed a total of two sessions of fNIRs working memory task prior to and following one session of a non-word repetition task paired with anodal HD tDCS (1.0 mA tDCS; 20 min) to the preSMA. Standardized z-scores of behavioral measures (accuracy and reaction time) and changes in hemodynamic response during an n-back working memory task for the two participants with DLD was compared to that of a normative sample of 21 age- and gender- matched normal controls (ages 18 to 25) prior to and following phonological working memory training. Results: Individual standardized z-scores for each participant with DLD indicated that prior to training, hemoglobin response in the prefrontal lobe for both participants was markedly different from each other and normal controls. Following training, standard scores showed that the hemodynamic response for both participants moved within normal limits for ROIs. Conclusion: These findings highlight the feasibility of fNIRS to establish individual differences in the link between behavior and neural patterns in single subjects with DLD, as well as track individual differences in changes in brain activity following working memory training.


A functional organization of ON and OFF pathways in the rabbit retina.
Intracellular electrophysiological recordings were obtained from amacrine and ganglion cells in an isolated, superfused retina-eyecup preparation of the rabbit. Cells were characterized physiologically, after which cell-staining was accomplished by intracellular iontophoresis of HRP. A computer-assisted image-processing system was used to study the dendritic stratification pattern of HRP-labeled neurons within the inner plexiform layer (IPL). Our results support the concept that the IPL is functionally divided into a distal OFF region and proximal ON layer. ON and OFF ganglion and amacrine cells show dendritic arborizations consistent with this division and ON-OFF ganglion cells have processes in both portions of the IPL. It appears that these functional subdivisions of the IPL reflect excitatory, but not necessarily inhibitory, inputs. Thus, the pattern of dendritic arborization of a cell appears to predict its physiological response polarity, regardless of the type of inhibition it receives.


Contextualizing gender differences and methamphetamine use with HIV prevalence within a South African community.
This study was conducted in a large Black African township outside of Cape Town, South Africa, where HIV infection has been endemic at extremely high levels for years. Problems associated with high HIV prevalence are compounded by gender inequality and high rates of gender-based violence exacerbated by heavy alcohol use and increasing methamphetamine use. Informal drinking establishments (known as shebeens) were geocoded and mapped. Based on visual examination, we identified 36 neighbourhoods, each of which contained between three to seven drinking venues clustered together. Neighbourhoods were separated from each other by at least 200m. We randomly selected 30 of the 36 neighbourhoods. Outreach workers screened males in shebeens and screened their female partners. This analysis includes 580 study participants recruited from 30 neighbourhoods between 2010 and 2012. All participants completed a baseline questionnaire that included individual-level, couple-level, and neighbourhood-level measures of alcohol and other drug use, HIV infection, and HIV risk behaviours. Multilevel fixed effects regression analyses stratified by gender were conducted to examine correlates of HIV infection. Women were twice as likely as men to be HIV infected, yet they reported fewer sex partners. Neighbourhood prevalence of HIV was correlated with greater likelihood of HIV infection among women, but not men. Neighbourhood methamphetamine use was marginally associated with HIV among women but not among men. At the individual level, heavy alcohol use was marginally associated with HIV infection among men but not among women. Having an HIV positive partner was the strongest correlate of being HIV positive among both men and women. Findings from this study underscore the need for policy makers to direct scarce resources to the communities, places within communities, and populations, especially vulnerable women, where the impact on HIV prevention and onward transmission will be greatest.


Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial.
It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI-AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One-hundred thirty-one subjects were randomized into a multicenter, double-blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent-to-treat population). Both orlistat-and placebo-treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (-15.7% vs. -9.4%, P < 0.05). In addition, orlistat-treated subjects had significantly greater weight loss (-5.93 kg vs. -3.94 kg, P < 0.05), total fat mass loss (-4.65 kg vs. -3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue and content of liver fat compared with placebo-treated subjects. This is the first study to demonstrate that orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.


Dopamine transporter imaging is associated with long-term outcomes in Parkinson's disease.
Dopamine (DA) transporter (DAT) imaging has been studied as a diagnostic tool for degenerative parkinsonism. Our aim was to measure the prognostic value of imaging for motor and nonmotor outcomes in Parkinson's disease (PD). We prospectively evaluated a Parkinson's cohort after enrollment in a de novo clinical trial with a battery of motor (UPDRS), cognitive (Montreal Cognitive Assessment), and behavioral measures. DAT imaging with [(123)I][β]-CIT and single-photon emission computerized tomography (SPECT) was performed at baseline and after 22 months. In total, 491 (91%) of the 537 subjects had evidence of DA deficiency on their baseline scan, consistent with PD, and were included in the analyses. The cohort was followed for 5.5 (0.8) years, with a mean duration of diagnosis of 6.3 (1.2). Lower striatal binding at baseline was independently associated with higher risk for clinical milestones and measures of disease severity, including motor-related disability, falling and postural instability, cognitive impairment, psychosis, and clinically important depressive symptoms. Subjects in the bottom quartile for striatal binding, compared to the top quartile, had an odds ratio (95% confidence interval) of 3.3 (1.7, 6.7) for cognitive impairment and 12.9 (2.6, 62.4) for psychosis. Change from baseline in imaging after 22 months was also independently associated with motor, cognitive, and behavioral outcomes. DAT imaging with [(123)I][β]-CIT and SPECT, shortly after the diagnosis of PD, was independently associated with clinically important long-term motor and nonmotor outcomes. These results should be treated as hypothesis generating and require confirmation.


Accuracy and interlaboratory reliability of human papillomavirus DNA testing by hybrid capture.
Epidemiologists and clinicians wishing to introduce human papillomavirus (HPV) testing into cervical cancer prevention programs need standardized, reliable, and accurate HPV DNA tests that can detect the full spectrum of pathogenic HPV types. The Hybrid Capture System assay from Digene (hybrid capture assay) is a nonradioactive kit designed to detect 14 HPV types in two groups: a mix of 9 high-risk types associated with anogenital cancer (HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56) and another group of 5 low-risk types associated with condyloma acuminatum (HPV types 6, 11, 42, 43, and 44). The assay yields quantitative data meant to reflect viral concentration. In a study of 199 cervical specimens from women with concurrent Pap smears, we assessed the reliability of the new assay by comparing the hybrid capture assay results from three laboratories. We assessed the accuracy of the hybrid capture assay in comparison with a reference standard of HPV DNA content (multiple testing by several methods in two reference laboratories). We also compared the hybrid capture assay results with the concurrent cytologic diagnoses on the basis of an independent review of each smear by five pathologists. Pairwise interlaboratory agreement rates on HPV positivity for either high-risk or low-risk types ranged from 87 to 94%, and kappa values ranged from 0.61 to 0.83. Among specimens positive for high-risk types (the most important clinical outcome), the interlaboratory correlations of the quantitative data ranged from 0.60 to 0.90. Test results from all three laboratories were strongly associated with those of the HPV DNA reference standard and with the concurrent cytopathologic diagnoses. The most common errors were sporadic, apparently false-positive results.


Efficacy of right unilateral ultrabrief pulse width ECT: a preliminary report.
Ultrabrief (right unilateral) electroconvulsive therapy (UB-RU ECT) is a newer form of ECT, which uses a shorter pulse width than the standard ECT (0.3 vs 1.0 millisecond, respectively). As a result, the use of UB ECT may provide a means of further decreasing ECT-related cognitive adverse effects. In 2011, the University of Texas Southwestern Department of ECT in Austin adopted a UB ECT protocol. The purpose of this study was to perform a preliminary evaluation of the effectiveness and efficiency of UB-RU ECT. This study also examined whether sex, age, or diagnosis affected response rates. This retrospective chart review identified 62 patients treated with the UB ECT protocol. An analysis of ECT response rates and demographic characteristics was conducted based on the data from clinical evaluations and Patient Health Questionnaire 9. Sixty-eight percent of patients in the study responded to ECT; 55% responded to UB pulse width RU ECT with another 13% responding when switched to standard pulse width bilateral ECT. The mean number of treatments in an index ECT series was 12.5. There was no statistically significant difference in response rates between bipolar and unipolar depressed patients. Men required progression to bilateral treatment more than women. This UB ECT protocol demonstrated a similar response rate when compared to standard ECT protocols; however, an increase in the number of treatments was required. Ultrabrief protocols are a viable option for both bipolar and unipolar depression. In men, UB ECT protocols may be less advantageous due to a need to overcome a potentially higher seizure threshold in men; however, additional research is needed to confirm this finding.


Biochemical analysis of the interactions of IQGAP1 C-terminal domain with CDC42.
To understand the interaction of human IQGAP1 and CDC42, especially the effects of phosphorylation and a cancer-associated mutation. Recombinant CDC42 and a novel C-terminal fragment of IQGAP1 were expressed in, and purified from, Escherichia coli. Site directed mutagenesis was used to create coding sequences for three phosphomimicking variants (S1441E, S1443D and S1441E/S1443D) and to recapitulate a cancer-associated mutation (M1231I). These variant proteins were also expressed and purified. Protein-protein crosslinking using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide was used to investigate interactions between the C-terminal fragment and CDC42. These interactions were quantified using surface plasmon resonance measurements. Molecular modelling was employed to make predictions about changes to the structure and flexibility of the protein which occur in the cancer-associated variant. The novel, C-terminal region of human IQGAP1 (residues 877-1558) is soluble following expression and purification. It is also capable of binding to CDC42, as judged by crosslinking experiments. Interaction appears to be strongest in the presence of added GTP. The three phosphomimicking mutants had different affinities for CDC42. S1441E had an approximately 200-fold reduction in affinity compared to wild type. This was caused largely by a dramatic reduction in the association rate constant. In contrast, both S1443D and the double variant S1441E/S1443D had similar affinities to the wild type. The cancer-associated variant, M1231I, also had a similar affinity to wild type. However, in the case of this variant, both the association and dissociation rate constants were reduced approximately 10-fold. Molecular modelling of the M1231I variant, based on the published crystal structure of part of the C-terminal region, revealed no gross structural changes compared to wild type (root mean square deviation of 0.564 Å over 5556 equivalent atoms). However, predictions of the flexibility of the polypeptide backbone suggested that some regions of the variant protein had greatly increased rigidity compared to wild type. One such region is a loop linking the proposed CDC42 binding site with the helix containing the altered residue. It is suggested that this increase in rigidity is responsible for the observed changes in association and dissociation rate constants. The consequences of introducing negative charge at Ser-1441 or Ser-1443 in IQGAP1 are different. The cancer-associated variant M1231I exerts its effects partly by rigidifying the protein.


Investigation of the impact of feeding Lactobacillus plantarum CRL 1815 encapsulated in microbially derived polymers on the rat faecal microbiota.
The aim of this study was to evaluate the impact of the administration of microencapsulated Lactobacillus plantarum CRL 1815 with two combinations of microbially derived polysaccharides, xanthan : gellan gum (1%:0·75%) and jamilan : gellan gum (1%:1%), on the rat faecal microbiota. A 10-day feeding study was performed for each polymer combination in groups of 16 rats fed either with placebo capsules, free or encapsulated Lact. plantarum or water. The composition of the faecal microbiota was analysed by fluorescence in situ hybridization and temporal temperature gradient gel electrophoresis. Degradation of placebo capsules was detected, with increased levels of polysaccharide-degrading bacteria. Xanthan : gellan gum capsules were shown to reduce the Bifidobacterium population and increase the Clostridium histolyticum group levels, but not jamilan : gellan gum capsules. Only after administration of jamilan : gellan gum-probiotic capsules was detected a significant increase in Lactobacillus-Enterococcus group levels compared to controls (capsules and probiotic) as well as two bands were identified as Lact. plantarum in two profiles of ileum samples. Exopolysaccharides constitute an interesting approach for colon-targeted delivery of probiotics, where jamilan : gellan gum capsules present better biocompatibility and promising results as a probiotic carrier. This study introduces and highlights the importance of biological compatibility in the encapsulating material election, as they can modulate the gut microbiota by themselves, and the use of bacterial exopolysaccharides as a powerful source of new targeted-delivery coating material.


Cognitive vulnerability to depressive symptoms in adolescents in urban and rural Hunan, China: a multiwave longitudinal study.
The current multiwave longitudinal study examined the applicability of two cognitive vulnerability-stress models of depression-Beck's (1967, 1983) cognitive theory and the hopelessness theory (Abramson, Metalsky, & Alloy, 1989)-in two independent samples of adolescents from Hunan Province, China (one rural and one urban). During an initial assessment, participants completed measures assessing dysfunctional attitudes (Beck, 1967, 1983), negative cognitive style (Abramson et al., 1989), neuroticism (Costa & McCrae, 1992), depressive symptoms, and anxiety symptoms. Once a month for the subsequent 6 months, participants completed measures assessing the occurrence of different types of negative events, depressive symptoms, and anxiety symptoms. Results provided support for cognitive vulnerability factors as predictors of increases in depressive symptoms following the occurrence of higher than average levels of negative events in Chinese adolescents. The results also supported the specificity of these two cognitive vulnerability factors as predictors of depressive versus anxiety symptoms following the occurrence of higher than average levels of negative events (i.e., symptom specificity), and the ability of cognitive vulnerability factors to predict prospective change in depressive symptoms above and beyond the effects of trait neuroticism (i.e., etiological specificity).


Sperry versus Hebb: topographic mapping in Isl2/EphA3 mutant mice.
In wild-type mice, axons of retinal ganglion cells establish topographically precise projection to the superior colliculus of the midbrain. This means that axons of neighboring retinal ganglion cells project to the proximal locations in the target. The precision of topographic projection is a result of combined effects of molecular labels, such as Eph receptors and ephrins, and correlated neural activity. In the Isl2/EphA3 mutant mice the expression levels of molecular labels are changed. As a result the topographic projection is rewired so that the neighborhood relationships between retinal cell axons are disrupted. Here we study the computational model for retinocollicular connectivity formation that combines the effects of molecular labels and correlated neural activity. We argue that the effects of correlated activity presenting themselves in the form of Hebbian learning rules can facilitate the restoration of the topographic connectivity even when the molecular labels carry conflicting instructions. This occurs because the correlations in electric activity carry information about retinal cells' origin that is independent on molecular labels. We argue therefore that partial restoration of the topographic property of the retinocollicular projection observed in Isl2/EphA3 heterozygous knockin mice may be explained by the effects of correlated neural activity. We address the maps observed in Isl2/EphA3 knockin/EphA4 knockout mice in which the levels of retinal labels are uniformly reduced. These maps can be explained by either the saturation of EphA receptor mapping leading to the relative signaling model or by the reverse signaling conveyed by ephrin-As expressed by retinal axons. According to our model, experiments in Isl2/EphA3 knock-in mice test the interactions between effects of molecular labels and correlated activity during the development of neural connectivity. Correlated activity can partially restore topographic order even when molecular labels carry conflicting information.


Synthesis and characterization of uranyl ion-imprinted microspheres based on amidoximated modified alginate.
Surface ion-imprinting technique was utilized for the preparation of surface ion-imprinted chelating microspheres based on amidoximated modified alginate (U-AOX) in presence of uranyl ions as a template and glutaraldehyde cross-linker. Different instrumental techniques such as elemental analysis, scanning electron microscope (SEM), FTIR, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction spectra were employed for full investigation of the manufactured materials. The synthesized microspheres displayed a higher ability for selective extraction of UO2(2+) when compared to the non-imprinted microspheres (NI-AOX). In addition, the essential parameters such as pH, temperature, time and initial uranyl ion concentration were evaluated in order to optimize the conditions of the adsorption process. The results indicated that pH 5 was the best for the UO2(2+) removal, also, the adsorption was endothermic in nature, follows the second-order kinetics and the adsorption isotherm showed the best fit with Langmuir model with maximum adsorption capacity of 155 ± 1 and 64 ± 1 mg/g for both U-AOX and NI-AOX respectively. Desorption and regeneration had been carried out using 0.5M HNO3 solution and the results indicated that the microspheres maintained about 96% of its original efficiency after five consecutive adsorption-desorption cycles.


Online prevention of disordered eating in at-risk young-adult women: a two-country pragmatic randomized controlled trial.
Disordered eating (DE) is a widespread, serious problem. Efficacious prevention programs that can be delivered at-scale are needed. A pragmatic randomized controlled trial of two online programs was conducted. Participants were young-adult women from Australia and New Zealand seeking to improve their body image. Media Smart-Targeted (MS-T) and Student Bodies (SB) were both 9-module interventions released weekly, whilst control participants received positive body image information. Primary [Eating Disorder Examination-Questionnaire (EDE-Q) Global], secondary (DE risk factors) and tertiary (DE) outcome measures were completed at baseline, post-program, 6- and 12-month follow-up. Baseline was completed by 608 women (M age = 20.71 years); 33 were excluded leaving 575 randomized to: MS-T (N = 191); SB (N = 190) or control (N = 194). Only 66% of those randomized to MS-T or SB accessed the intervention and were included in analyses with controls; 78% of this sample completed measures subsequent to baseline. Primary intent-to-treat (ITT) analyses revealed no differences between groups, while measure completer analyses found MS-T had significantly lower EDE-Q Global than controls at 12-month follow-up. Secondary ITT analyses found MS-T participants reported significantly higher quality of life-mental relative to both SB and controls (6-month follow-up), while MS-T and controls had lower clinical impairment relative to SB (post-program). Amongst measure completers, MS-T scored significantly lower than controls and SB on 5 variables. Of those with baseline DE, MS-T participants were significantly less likely than controls to have DE at 12-month follow-up. Given both programs were not therapist-moderated, MS-T has potential to achieve reductions in DE risk at low implementation costs.


Habitat fragmentation, tree diversity, and plant invasion interact to structure forest caterpillar communities.
Habitat fragmentation and invasive species are two of the most prominent threats to terrestrial ecosystems. Few studies have examined how these factors interact to influence the diversity of natural communities, particularly primary consumers. Here, we examined the effects of forest fragmentation and invasion of exotic honeysuckle (Lonicera maackii, Caprifoliaceae) on the abundance and diversity of the dominant forest herbivores: woody plant-feeding Lepidoptera. We systematically surveyed understory caterpillars along transects in 19 forest fragments over multiple years in southwestern Ohio and evaluated how fragment area, isolation, tree diversity, invasion by honeysuckle and interactions among these factors influence species richness, diversity and abundance. We found strong seasonal variation in caterpillar communities, which responded differently to fragmentation and invasion. Abundance and richness increased with fragment area, but these effects were mitigated by high levels of honeysuckle, tree diversity, landscape forest cover, and large recent changes in area. Honeysuckle infestation was generally associated with decreased caterpillar abundance and diversity, but these effects were strongly dependent on other fragment traits. Effects of honeysuckle on abundance were moderated when fragment area, landscape forest cover and tree diversity were high. In contrast, negative effects of honeysuckle invasion on caterpillar diversity were most pronounced in fragments with high tree diversity and large recent increases in area. Our results illustrate the complex interdependencies of habitat fragmentation, plant diversity and plant invasion in their effects on primary consumers and emphasize the need to consider these processes in concert to understand the consequences of anthropogenic habitat change for biodiversity.


Magnetic structure of UO2 and NpO2 by first-principle methods.
The magnetic structure of the actinide dioxides (AnO2) remains a field of intense research. A low-temperature experimental investigation of the magnetic ground-state is complicated by thermal energy released from the radioactive decay of the actinide nuclei. To establish the magnetic ground-state, we have employed high-accuracy computational methods to systematically probe different magnetic structures. A transverse 1k antiferromagnetic ground-state with Fmmm (No. 69) crystal symmetry has been established for UO2, whereas a ferromagnetic (111) ground-state with R3[combining macron]m (No. 166) has been established for NpO2. Band structure calculations have been performed to analyse these results.


Response calculations based on an independent particle system with the exact one-particle density matrix: excitation energies.
Adiabatic response time-dependent density functional theory (TDDFT) suffers from the restriction to basically an occupied → virtual single excitation formulation. Adiabatic time-dependent density matrix functional theory allows to break away from this restriction. Problematic excitations for TDDFT, viz. bonding-antibonding, double, charge transfer, and higher excitations, are calculated along the bond-dissociation coordinate of the prototype molecules H(2) and HeH(+) using the recently developed adiabatic linear response phase-including (PI) natural orbital theory (PINO). The possibility to systematically increase the scope of the calculation from excitations out of (strongly) occupied into weakly occupied ("virtual") natural orbitals to larger ranges of excitations is explored. The quality of the PINO response calculations is already much improved over TDDFT even when the severest restriction is made, to virtually the size of the TDDFT diagonalization problem (only single excitation out of occupied orbitals plus all diagonal doubles). Further marked improvement is obtained with moderate extension to allow for excitation out of the lumo and lumo+1, which become fractionally occupied in particular at longer distances due to left-right correlation effects. In the second place the interpretation of density matrix response calculations is elucidated. The one-particle reduced density matrix response for an excitation is related to the transition density matrix to the corresponding excited state. The interpretation of the transition density matrix in terms of the familiar excitation character (single excitations, double excitations of various types, etc.) is detailed. The adiabatic PINO theory is shown to successfully resolve the problematic cases of adiabatic TDDFT when it uses a proper PI orbital functional such as the PILS functional.


Mechanisms of genotoxin-induced transcription and hypermutation in p53.
It is widely assumed that genotoxin-induced damage (e.g., G-to-T transversions) to the tumor suppressor gene, p53, is a direct cause of cancer. However, genotoxins also induce the stress response, which upregulates p53 transcription and the formation of secondary structures from ssDNA. Since unpaired bases are thermodynamically unstable and intrinsically mutable, increased transcription could be the cause of hypermutation, and thus cancer. Support for this hypothesis has been obtained by analyzing 6662 mutations in all types of cancer compared to lung and colon cancers, using the p53 mutation database. The data suggest that genotoxins have two independent effects: first, they induce p53 transcription, which increases the number of mutable bases that determine the incidence of cancer. Second, genotoxins may alter the fate, or ultimate mutation of a mutable base, for example, by causing more of the available mutable Gs to mutate to T, leaving fewer to mutate to A. Such effects on the fate of mutable bases have no impact on the incidence of cancer, as both types of mutations lead to cancer.


Advantages of closed-loop calibration in intracortical brain-computer interfaces for people with tetraplegia.
Brain-computer interfaces (BCIs) aim to provide a means for people with severe motor disabilities to control their environment directly with neural activity. In intracortical BCIs for people with tetraplegia, the decoder that maps neural activity to desired movements has typically been calibrated using 'open-loop' (OL) imagination of control while a cursor automatically moves to targets on a computer screen. However, because neural activity can vary across contexts, a decoder calibrated using OL data may not be optimal for 'closed-loop' (CL) neural control. Here, we tested whether CL calibration creates a better decoder than OL calibration even when all other factors that might influence performance are held constant, including the amount of data used for calibration and the amount of elapsed time between calibration and testing. Two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial performed a center-out-back task using an intracortical BCI, switching between decoders that had been calibrated on OL versus CL data. Even when all other variables were held constant, CL calibration improved neural control as well as the accuracy and strength of the tuning model. Updating the CL decoder using additional and more recent data resulted in further improvements. Differences in neural activity between OL and CL contexts contribute to the superiority of CL decoders, even prior to their additional 'adaptive' advantage. In the near future, CL decoder calibration may enable robust neural control without needing to pause ongoing, practical use of BCIs, an important step toward clinical utility.


Do opiates affect the clinical evaluation of patients with acute abdominal pain?
Clinicians have traditionally withheld opiate analgesia from patients with acute abdominal pain until after evaluation by a surgeon, out of concern that analgesia may alter the physical findings and interfere with diagnosis. To determine the impact of opiate analgesics on the rational clinical examination and operative decision for patients with acute abdominal pain. MEDLINE (through May 2006), EMBASE, and hand searches of article bibliographies to identify placebo-controlled randomized trials of opiate analgesia reporting changes in the history, physical examination findings, or diagnostic errors (those resulting in "management errors," defined as the performance of unnecessary surgery or failure to perform necessary surgery in a timely fashion). Two authors independently reviewed each study, abstracted data, and classified study quality. A third reviewer independently resolved discrepancies. Studies both in adults (9 trials) and in children (3 trials) showed trends toward increased risks of altered findings on the abdominal examination due to opiate administration, with risk ratios for changes in the examination of 1.51 (95% confidence interval [CI], 0.85 to 2.69) and 2.11 (95% CI, 0.60 to 7.35), respectively. When the analysis was restricted to the 8 adult and pediatric trials that reported significantly greater analgesia for patients who received opiates compared with those who received placebo, the risk of physical examination changes became significant (risk ratio, 2.13; 95% CI, 1.14 to 3.98). These trials exhibited significant heterogeneity (I2 = 68.6%; P = .002), and only 2 trials distinguished clinically significant changes such as loss of peritoneal signs from all other changes; consequently, we analyzed risk of management errors as a marker for important changes in the physical examination. Opiate administration had no significant association with management errors (+0.3% absolute increase; 95% CI, -4.1% to +4.7%). The 3 pediatric trials showed a nonsignificant absolute decrease in management errors (-0.8%; 95% CI, -8.6% to +6.9%). Across adult and pediatric trials with adequate analgesia, opiate administration was associated with a nonsignificant absolute decrease in the risk of management errors (-0.2%; 95% CI, -4.0% to +3.6%). Opiate administration may alter the physical examination findings, but these changes result in no significant increase in management errors. The existing literature does not rule out a small increase in errors, but this error rate reflects a conservative definition in which surgeries labeled as either delayed or unnecessary may have met appropriate standards of care. In published research reports, no patient experienced major morbidity or mortality attributable to opiate administration.


Pneumococcal infection in patients with coeliac disease.
Some patients with coeliac disease are hyposplenic. Splenectomy is a risk factor for pneumococcal infection. Our objective was to determine the risk of invasive pneumococcal disease - septicaemia, pneumonia or meningitis - in patients with coeliac disease. We analysed routinely collected, linked statistical records of hospital admission to study the risk of pneumococcal infection in patients with coeliac disease, in patients who underwent splenectomy and in a comparison cohort. The main outcome measure was the rate ratio for pneumococcal infection in the coeliac and splenectomized cohorts, compared with the comparison cohort. We undertook the study using linked records in two temporally and geographically distinct populations: the Oxford region (1963-1999) and the whole of England (1998-2003). The rate ratio of pneumococcal infection in patients with coeliac disease was 2.06 (95% confidence interval, 1.27-3.15) in the Oxford population and 1.61 (1.36-1.90) in England as a whole. As a comparison, the rate ratios in splenectomized patients were 3.40 (2.44-4.60) and 3.32 (2.80-3.90) in the Oxford and England populations, respectively. The increased rate ratio in coeliac patients persisted beyond the first year after diagnosis of the coeliac disease. The period covered by the Oxford study was mainly before the widespread availability of pneumococcal vaccination; but the availability of pneumococcal vaccine was widespread during the time of the English study. Some patients with coeliac disease have an elevated risk of invasive pneumococcal disease.


Mining and biodiversity: key issues and research needs in conservation science.
Mining poses serious and highly specific threats to biodiversity. However, mining can also be a means for financing alternative livelihood paths that, over the long-term, may prevent biodiversity loss. Complex and controversial issues associated with mining and biodiversity conservation are often simplified within a narrow frame oriented towards the negative impacts of mining at the site of extraction, rather than posed as a series of challenges for the conservation science community to embrace. Here, we synthesize core issues that, if better understood, may ensure coexistence between mining and conservation agendas. We illustrate how mining impacts biodiversity through diverse pathways and across spatial scales. We argue that traditional, site-based conservation approaches will have limited effect in preventing biodiversity loss against an increasing mining footprint, but opportunities to improve outcomes (e.g. through long-term strategic assessment and planning) do exist. While future mineral supply is uncertain, projections suggest demand will grow for many metals and shift mining operations towards more dispersed and biodiverse areas. Initiating dialogue between mining companies, policy-makers and conservation organizations is urgent, given the suite of international agendas simultaneously requiring more minerals but less biodiversity loss.


Responding to Young People's Health Risks in Primary Care: A Cluster Randomised Trial of Training Clinicians in Screening and Motivational Interviewing.
To evaluate the effectiveness of a complex intervention implementing best practice guidelines recommending clinicians screen and counsel young people across multiple psychosocial risk factors, on clinicians' detection of health risks and patients' risk taking behaviour, compared to a didactic seminar on young people's health. Pragmatic cluster randomised trial where volunteer general practices were stratified by postcode advantage or disadvantage score and billing type (private, free national health, community health centre), then randomised into either intervention or comparison arms using a computer generated random sequence. Three months post-intervention, patients were recruited from all practices post-consultation for a Computer Assisted Telephone Interview and followed up three and 12 months later. Researchers recruiting, consenting and interviewing patients and patients themselves were masked to allocation status; clinicians were not. General practices in metropolitan and rural Victoria, Australia. General practices with at least one interested clinician (general practitioner or nurse) and their 14-24 year old patients. This complex intervention was designed using evidence based practice in learning and change in clinician behaviour and general practice systems, and included best practice approaches to motivating change in adolescent risk taking behaviours. The intervention involved training clinicians (nine hours) in health risk screening, use of a screening tool and motivational interviewing; training all practice staff (receptionists and clinicians) in engaging youth; provision of feedback to clinicians of patients' risk data; and two practice visits to support new screening and referral resources. Comparison clinicians received one didactic educational seminar (three hours) on engaging youth and health risk screening. Primary outcomes were patient report of (1) clinician detection of at least one of six health risk behaviours (tobacco, alcohol and illicit drug use, risks for sexually transmitted infection, STI, unplanned pregnancy, and road risks); and (2) change in one or more of the six health risk behaviours, at three months or at 12 months. Secondary outcomes were likelihood of future visits, trust in the clinician after exit interview, clinician detection of emotional distress and fear and abuse in relationships, and emotional distress at three and 12 months. Patient acceptability of the screening tool was also described for the intervention arm. Analyses were adjusted for practice location and billing type, patients' sex, age, and recruitment method, and past health risks, where appropriate. An intention to treat analysis approach was used, which included multilevel multiple imputation for missing outcome data. 42 practices were randomly allocated to intervention or comparison arms. Two intervention practices withdrew post allocation, prior to training, leaving 19 intervention (53 clinicians, 377 patients) and 21 comparison (79 clinicians, 524 patients) practices. 69% of patients in both intervention (260) and comparison (360) arms completed the 12 month follow-up. Intervention clinicians discussed more health risks per patient (59.7%) than comparison clinicians (52.7%) and thus were more likely to detect a higher proportion of young people with at least one of the six health risk behaviours (38.4% vs 26.7%, risk difference [RD] 11.6%, Confidence Interval [CI] 2.93% to 20.3%; adjusted odds ratio [OR] 1.7, CI 1.1 to 2.5). Patients reported less illicit drug use (RD -6.0, CI -11 to -1.2; OR 0.52, CI 0.28 to 0.96), and less risk for STI (RD -5.4, CI -11 to 0.2; OR 0.66, CI 0.46 to 0.96) at three months in the intervention relative to the comparison arm, and for unplanned pregnancy at 12 months (RD -4.4; CI -8.7 to -0.1; OR 0.40, CI 0.20 to 0.80). No differences were detected between arms on other health risks. There were no differences on secondary outcomes, apart from a greater detection of abuse (OR 13.8, CI 1.71 to 111). There were no reports of harmful events and intervention arm youth had high acceptance of the screening tool. A complex intervention, compared to a simple educational seminar for practices, improved detection of health risk behaviours in young people. Impact on health outcomes was inconclusive. Technology enabling more efficient, systematic health-risk screening may allow providers to target counselling toward higher risk individuals. Further trials require more power to confirm health benefits. ISRCTN.com ISRCTN16059206.


In vivo molecular MRI of cell survival and teratoma formation following embryonic stem cell transplantation into the injured murine myocardium.
Embryonic stem cells (ESCs) have shown the potential to restore cardiac function after myocardial injury. Superparamagnetic iron oxide nanoparticles (SPIO) have been widely employed to label ESCs for cellular MRI. However, nonspecific intracellular accumulation of SPIO limits long-term in vivo assessment of the transplanted cells. To overcome this limitation, a novel reporter gene (RG) has been developed to express antigens on the ESC surface. By employing SPIO-conjugated monoclonal antibody against these antigens (SPIO-MAb), the viability of transplanted ESCs can be detected in vivo. This study aims to develop a new molecular MRI method to assess in vivo ESC viability, proliferation, and teratoma formation. The RG is designed to express 2 antigens (hemagglutinin A and myc) and luciferase on the ESC surface. The two antigens serve as the molecular targets for SPIO-MAb. The human and mouse ESCs were transduced with the RG (ESC-RGs) and transplanted into the peri-infarct area using the murine myocardial injury model. In vivo MRI was performed following serial intravenous administration of SPIO-MAb. Significant hypointense signal was generated from the viable and proliferating ESCs and subsequent teratoma. This novel molecular MRI technique enabled in vivo detection of early ESC-derived teratoma formation in the injured murine myocardium.


Felbamate monotherapy for partial-onset seizures: an active-control trial.
We evaluated felbamate (FBM) monotherapy in 111 patients with uncontrolled partial-onset seizures in a multicenter, double-blind, parallel-group trial. During the 56-day baseline period, patients had at least eight partial-onset seizures and received one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients received either FBM 3,600 mg/d or valproate (VPA) 15 mg/kg/d. The baseline AED at therapeutic levels was discontinued by one-third decrements on study days 1, 14, and 28 and the sub-therapeutic AED, if any, was discontinued completely on study day 1. Study endpoints were completion of 112 study days or fulfilling one or more escape criteria. Criteria for escape relative to baseline were (1) twofold increase in monthly seizure frequency, (2) twofold increase in highest 2-day seizure frequency, (3) single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or (4) significant prolongation of GTCs. The primary efficacy variable was the number of patients in each treatment group who met escape criteria. Thirty-seven patients on VPA and 18 on FBM met escape criteria (p < 0.001). Even when we considered FBM dropouts to have fulfilled escape criteria and VPA dropouts to have completed the 112-day trial, the treatment difference remained statistically significant (p = 0.039) in favor of FBM. Adverse experiences with FBM were all mild or moderate in severity. The frequency of adverse experiences was much lower during monotherapy. FBM monotherapy was effective in the treatment of partial-onset seizures with or without secondarily generalized seizures and demonstrated a favorable safety profile.


Evaluation of saliva as an alternative matrix for monitoring plasma Zidovudine, Lamivudine and nevirapine concentrations in Rwanda.
Saliva may provide interesting advantages as matrix for compliance measurements, pharmacokinetic studies and therapeutic drug monitoring in resource limited countries. We investigated the feasibility of using saliva for compliance monitoring of zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP) in 29 HIV-1 infected patients from Rwanda. ZDV, 3TC and NVP drug levels were quantified by an LC/MS-MS method in plasma and stimulated saliva samples and compared using Bland-Altman analysis. Seven patients demonstrated undetectable saliva ZDV levels while five out of these seven also showed no 3TC salivary concentrations. For the other samples, we observed a good agreement between salivary and plasma concentrations of each antiretroviral drug. A significant relation between the difference in saliva and plasma ZDV concentrations and the average ZDV concentration in the two matrices was deduced as follow: y = -380.15 + 1.79 x. The log saliva and plasma concentration difference of both 3TC and NVP was consistent across the range of average log concentration. Overall, we showed large agreement limits suggesting a wide inter patient variability that may result to non-reliable plasma level predictions from saliva drug measurements. Therefore, our results indicate that saliva may serve as a valuable tool only for NVP compliance testing because of its high salivary concentration.


The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks.
All mammalian hepadnaviruses possess a gene, termed X, that encodes a protein capable of transactivating virus gene expression. The X gene overlaps the polymerase and precore genes as well as two newly identified open reading frames (ORFs) termed ORF5 and ORF6. In this investigation, we examined whether ORF5, ORF6, and the X gene were important for the replication of woodchuck hepatitis virus (WHV) in susceptible woodchucks. First, we investigated whether proteins were produced from ORF5 and ORF6 by in vitro translation of appropriate viral transcripts, searched for antibodies against the putative proteins in the sera of animals infected with wild-type virus, and looked for an antisense WHV transcript, necessary for expression of a protein from ORF6, in the livers of acutely or chronically infected woodchucks. All such experiments yielded negative results. Next, we used oligonucleotide-directed mutagenesis to introduce termination codons into ORF5 and ORF6 at two locations within each ORF. Adult woodchucks in groups of three were transfected with one of the four mutant genomes. All of these woodchucks developed WHV infections that were indistinguishable from those of animals transfected with the wild-type WHV recombinant. Polymerase chain reaction amplification and direct DNA sequencing confirmed that reversion of the mutants to a wild-type genotype did not occur. Taken together, these data indicate that ORF5 and ORF6 are not essential for virus replication and are unlikely to represent authentic genes. Finally, we generated five WHV X-gene mutants that either removed the initiation codon for protein synthesis or truncated the carboxyl terminus of the protein by 3, 16, 31, or 52 amino acids. Groups of three adult woodchucks were transfected with one of the five X-gene mutants. Only the mutant that possessed an X gene lacking 3 amino acids from the carboxyl terminus was capable of replication within the 6-month time frame of the experiment. In contrast, all seven woodchucks transfected with wild-type WHV DNA developed markers consistent with viral infection. Thus, it is likely (P < 0.01) that the WHV X gene is important for virus replication in the natural host.


Activating mutation in MET oncogene in familial colorectal cancer.
In developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The MET proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility. MET exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies). Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C >T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors. Here we report a germline non-synonymous change in the MET proto-oncogene at amino acid position T992I (also reported as MET p.T1010I) in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in <1% in the general population. The threonine at amino acid position 992 lies in the tyrosine kinase domain of MET and a change to isoleucine at this position has been shown to promote metastatic behavior in cell-based models. The average age of CRC diagnosis in patients in this study is 63 years in mutation carriers, which is 8 years earlier than the general population average for CRC. Although the MET p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this MET genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will be an important extension of this work to define the clinical significance.


Preventing opportunistic infections in human immunodeficiency virus-infected persons: implications for the developing world.
More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases.


Intensity-based modified Doppler variance algorithm: application to phase instable and phase stable optical coherence tomography systems.
The traditional phase-resolved Doppler method demonstrates great success for in-vivo imaging of blood flow and blood vessels. However, the phase-resolved method always requires high phase stability of the system. In phase instable situations, the performance of the phase-resolved methods will be degraded. We propose a modified Doppler variance algorithm that is based on the intensity or amplitude value. Performances of the proposed algorithm are compared with traditional phase-resolved Doppler variance and color Doppler methods for both phase stable and phase instable systems. For the phase instable situation, the proposed algorithm demonstrates images without phase instability induced artifacts. In-vivo imaging of window-chamber hamster skin is demonstrated for phase instable situation with a spectrometer-based Fourier domain OCT system. A microelectromechanical systems (MEMS) based swept source OCT (SSOCT) system is also used to demonstrate the performance of the proposed method in a phase instable situation. The phase stability of the SSOCT system is analyzed. In-vivo imaging of the blood vessel of human skin is demonstrated with the proposed method and the SSOCT system. For the phase stable situation, the proposed algorithm also demonstrates comparable performance with traditional phase-resolved methods. In-vivo imaging of the human choroidal blood vessel network is demonstrated with the proposed method under the phase stable situation. Depth-resolved fine choroidal blood vessel networks are shown.


Impact of Dietary Protein Concentration and Quality on Immune Function of Cats.
Protein levels and quality in cat food can vary significantly and might affect immune function in various ways. In the present study, 3 diets with a low protein quality (LQ) and 3 diets with a high protein quality (HQ) were offered to 10 healthy adult cats for 6 weeks each, using a randomized cross-over design. The LQ and HQ diets differed in the collagen content and had low (36.7% and 36.2%), medium (45.0% and 43.3%) and high (56.1% and 54.9%) protein levels. At the end of each feeding period, blood was collected for phenotyping of leukocyte subsets, lymphocyte proliferation assay and cytokine measurements, phagocytosis assay and differential blood count. The results demonstrated no group differences for numbers of CD4+CD8-, CD4+CD8+, CD4-CD8+, MHCII+, CD21+, SWC3+ and CD14+ cells in the blood of the cats. Proliferative activity of lymphocytes when stimulated with pokeweed mitogen, Concanavalin A and Phytohemagglutinin, M form did not differ depending on the dietary protein concentration and quality. Concentrations of tumor necrosis factor alpha and interferon gamma in the supernatant of the proliferation assay were also not affected by the dietary treatment. Blood monocyte phagocytic activity was higher (P = 0.048) and cell numbers of eosinophilic granulocytes in the blood were lower (P = 0.047) when cats were fed the low protein diets. In conclusion, only a few differences in feline immune cell populations and activity depending on dietary protein supply could be detected. However, the observed increase of eosinophilic granulocytes by a higher protein intake indicates an activation of immunological mechanisms and requires further investigation.


Prediction of cognitive decline in healthy older adults using fMRI.
Few studies have examined the extent to which structural and functional MRI, alone and in combination with genetic biomarkers, can predict future cognitive decline in asymptomatic elders. This prospective study evaluated individual and combined contributions of demographic information, genetic risk, hippocampal volume, and fMRI activation for predicting cognitive decline after an 18-month retest interval. Standardized neuropsychological testing, an fMRI semantic memory task (famous name discrimination), and structural MRI (sMRI) were performed on 78 healthy elders (73% female; mean age = 73 years, range = 65 to 88 years). Positive family history of dementia and presence of one or both apolipoprotein E (APOE) ε4 alleles occurred in 51.3% and 33.3% of the sample, respectively. Hippocampal volumes were traced from sMRI scans. At follow-up, all participants underwent a repeat neuropsychological examination. At 18 months, 27 participants (34.6%) declined by at least 1 SD on one of three neuropsychological measures. Using logistic regression, demographic variables (age, years of education, gender) and family history of dementia did not predict future cognitive decline. Greater fMRI activity, absence of an APOE ε4 allele, and larger hippocampal volume were associated with reduced likelihood of cognitive decline. The most effective combination of predictors involved fMRI brain activity and APOE ε4 status. Brain activity measured from task-activated fMRI, in combination with APOE ε4 status, was successful in identifying cognitively intact individuals at greatest risk for developing cognitive decline over a relatively brief time period. These results have implications for enriching prevention clinical trials designed to slow AD progression.


Crop improvement using life cycle datasets acquired under field conditions.
Crops are exposed to various environmental stresses in the field throughout their life cycle. Modern plant science has provided remarkable insights into the molecular networks of plant stress responses in laboratory conditions, but the responses of different crops to environmental stresses in the field need to be elucidated. Recent advances in omics analytical techniques and information technology have enabled us to integrate data from a spectrum of physiological metrics of field crops. The interdisciplinary efforts of plant science and data science enable us to explore factors that affect crop productivity and identify stress tolerance-related genes and alleles. Here, we describe recent advances in technologies that are key components for data driven crop design, such as population genomics, chronological omics analyses, and computer-aided molecular network prediction. Integration of the outcomes from these technologies will accelerate our understanding of crop phenology under practical field situations and identify key characteristics to represent crop stress status. These elements would help us to genetically engineer "designed crops" to prevent yield shortfalls because of environmental fluctuations due to future climate change.


Quantitative, three-dimensional imaging of aluminum drop combustion in solid propellant plumes via digital in-line holography.
Burning aluminized propellants eject reacting molten aluminum drops with a broad size distribution. Prior to this work, in situ measurement of the drop size statistics and other quantitative flow properties was complicated by the narrow depth-of-focus of microscopic videography. Here, digital in-line holography (DIH) is demonstrated for quantitative volumetric imaging of the propellant plume. For the first time, to the best of our knowledge, in-focus features, including burning surfaces, drop morphologies, and reaction zones, are automatically measured through a depth spanning many millimeters. By quantifying all drops within the line of sight, DIH provides an order of magnitude increase in the effective data rate compared to traditional imaging. This enables rapid quantification of the drop size distribution with limited experimental repetition.


OdoCapsule: next-generation wireless capsule endoscopy with accurate lesion localization and video stabilization capabilities.
In this paper, we propose a platform to achieve accurate localization of small-bowel lesions and endoscopic video stabilization in wireless capsule endoscopy. Current research modules rely on the use of external magnetic fields and triangulation methods to calculate the position vector of the capsule, leading to considerable error margins. Our platform, entitled OdoCapsule (a synthesis of the words Odometer and Capsule), provides real-time distance information from the point of duodenal entry to the point of exit from the small bowel. To achieve this, OdoCapsule is equipped with three miniature legs. Each leg carries a soft rubber wheel, which is made with human-compliant material. These legs are extendable and retractable thanks to a micromotor and three custom-made torsion springs. The wheels are specifically designed to function as microodometers: each rotation they perform is registered. Hence, the covered distance is measured accurately in real time. Furthermore, with its legs fully extended, OdoCapsule can stabilize itself inside the small-bowel lumen thus offering smoother video capture and better image processing. Recent ex vivo testing of this concept, using porcine small bowel and a commercially available (custom-modified) capsule endoscope, has proved its viability.


Get out of here, quick! Problems with transparent labels on glass doors.
We studied the case of transparent word labels (e.g., "push") placed on glass doors, when viewed from the other side as mirror-reversed script, hence requiring an action opposite to word meaning. As compared with a regular view, labels seen "from the other side" in the glass door situation caused strong delays of actions and a tripling of error rates. This problem is unrelated to mirror reading but is at least partially due to the need to act opposite to word meaning. The glass door effect was not related to practice and age and showed no adaptation effect after incompatible trials. Distribution analyses showed an increased correct reaction time (RT) effect for slower responses, whereas accuracy effects were specific for fast responses. In the literature, problems with such mixed mappings have often been interpreted in the sense of competing action tendencies. Experiments 1 to 4, however, demonstrated that this might merely be a task difficulty effect due to the necessity for a mental transformation in case of mirror-reversed labels. Moreover, our results strongly advocate against using transparent labels because they may pose a considerable risk.