Effects of a school readiness intervention on hypothalamus-pituitary-adrenal axis functioning and school adjustment for children in foster care.
Maltreated children in foster care are at high risk for dysregulated hypothalamus-pituitary-adrenal (HPA) axis functioning and educational difficulties. The present study examined the effects of a short-term school readiness intervention on HPA axis functioning in response to the start of kindergarten, a critical transition marking entry to formal schooling, and whether altered HPA axis functioning influenced children's school adjustment. Compared to a foster care comparison group, children in the intervention group showed a steeper diurnal cortisol slope on the first day of school, a pattern previously observed among nonmaltreated children. A steeper first day of school diurnal cortisol slope predicted teacher ratings of better school adjustment (i.e., academic performance, appropriate classroom behaviors, and engagement in learning) in the fall of kindergarten. Furthermore, the children's HPA axis response to the start of school mediated the effect of the intervention on school adjustment. These findings support the potential for ameliorative effects of interventions targeting critical transitional periods, such as the transition of formal schooling. This school readiness intervention appears to influence stress neurobiology, which in turn facilitates positive engagement with the school environment and better school adjustment in children who have experienced significant early adversity.


Nanoscale imaging of whole cells using a liquid enclosure and a scanning transmission electron microscope.
Nanoscale imaging techniques are needed to investigate cellular function at the level of individual proteins and to study the interaction of nanomaterials with biological systems. We imaged whole fixed cells in liquid state with a scanning transmission electron microscope (STEM) using a micrometer-sized liquid enclosure with electron transparent windows providing a wet specimen environment. Wet-STEM images were obtained of fixed E. coli bacteria labeled with gold nanoparticles attached to surface membrane proteins. Mammalian cells (COS7) were incubated with gold-tagged epidermal growth factor and fixed. STEM imaging of these cells resulted in a resolution of 3 nm for the gold nanoparticles. The wet-STEM method has several advantages over conventional imaging techniques. Most important is the capability to image whole fixed cells in a wet environment with nanometer resolution, which can be used, e.g., to map individual protein distributions in/on whole cells. The sample preparation is compatible with that used for fluorescent microscopy on fixed cells for experiments involving nanoparticles. Thirdly, the system is rather simple and involves only minimal new equipment in an electron microscopy (EM) laboratory.


Alpha-tocopherol ameliorates nephrotoxicity associated with the use of colistin in rabbits.
The alarming rise in the rate of multi drug resistant, life threatening gram negative infections has brought renaissance in the use of Colistin for last two decades. The major constraint in its utilization is its nephrotoxicity. Therefore it is being underused which is favoring the development of resistance. This study assesses the prevention of nephrotoxicity associated with high and low toxic doses of Colistin by alpha-tocopherol. Thirty rabbits were randomly divided into five groups. Baseline serum urea, creatinine and electrolytes were estimated. A loading dose of colistin was given in the form of infusion followed by I.M injections for six days. In the preventive groups α-tocopherol was additionally given orally for two weeks. Rabbits were sacrificed 24 hours after the last dose. The kidney slides graded and statistically analyzed using "chi square". The results of serum analysis were compared using one way analysis of variance followed by post hoc tukey test. There was marked nephrotoxicity in high toxic group where as in low toxic group mild nephrotoxicity was evident. Alpha-tocopherol attenuated the renal insult in both the toxic groups. As damage induced by colistin is oxidative in nature, thus it was concluded that the protection offered by α- tocopherol is due to its antioxidant activity.


The secret message of heterochromatin: new insights into the mechanisms and function of centromeric and pericentric repeat sequence transcription.
In the fission yeast, S. Pombe, small dsRNA generated by RNAi-dependent mechanisms are involved in the establishment and maintenance of heterochromatic regions. The existence of conserved features within the general organization of centromeric and pericentromeric repeats in yeast, mouse and human argues in favor of a conserved role for centromeric and pericentromeric-derived transcripts across these species. In support of this, evidence is accumulating that centromeric and pericentromeric sequences are transcriptionally competent in diverse biological contexts in mammalian cells. Given the importance of centromeric and pericentromeric regions, not only with respect to centromere function, but also to gene regulation, this review examines the biological contexts in which mouse and human centromeric and pericentromeric-specific transcripts have been observed. The structure of the transcripts generated, the molecular mechanisms underlying their expression and their supposed functions will be discussed.


Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations.
African Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome-wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA. In this study, we performed the first admixture mapping of DSM-IV alcohol dependence diagnosis, DSM-IV alcohol dependence criterion count, and two scores from the self-rating of effects of ethanol (SRE) as measures of response to alcohol: the first five times of using alcohol (SRE-5) and average of SRE across three times (SRE-T). Findings revealed a region on chromosome 4 that was genome-wide significant for SRE-5 (p value = 4.18E-05). Fine mapping did not identify a single causal variant to be associated with SRE-5; instead, conditional analysis concluded that multiple variants collectively explained the admixture mapping signal. PPARGC1A, a gene that has been linked to alcohol consumption in previous studies, is located in this region. Our finding suggests that admixture mapping is a useful tool to identify genes/variants that may have been missed by current GWAS approaches in admixed populations.


Live Attenuated Influenza H7N3 Vaccine is Safe, Immunogenic and Confers Protection in Animal Models.
In 2003 the outbreak of highly pathogenic H7 avian influenza occurred in the Netherlands. The avian H7 virus causing the outbreak was also detected in humans; one person died of pneumonia and acute respiratory distress syndrome. Our paper describes preclinical studies of a H7N3 live attenuated influenza A vaccine (LAIV) candidate in various animal models. To study safety, immunogenicity and protection of H7N3 LAIV candidate in mice, ferrets and chickens. The vaccine was generated by a classical reassortment between low pathogenicity A/mallard/Netherlands/00 (H7N3) virus and A/Leningrad4/17/57 (H2N2) master donor virus (MDV). Immunogenicity was found that H7N3 LAIV was similar to the MDV in terms of replication in the respiratory organs of mice and failed to replicate in mouse brains. One dose of a H7N3 LAIV elicited measurable antibody response and it was further boosted with a second vaccine dose. Immunization of mice with H7N3 LAIV provided protection against infection following a homologous challenge with wild type H7N3 virus. Attenuated phenotype of H7N3 LAIV has been confirmed in ferrets. Immunogenicity and protective efficacy of H7N3 LAIV in ferrets were also demonstrated. The vaccine protected animals from subsequent infection with wild type H7N3 virus. The results of histopathology study revealed that inoculation of H7N3 LAIV in ferrets did not cause any inflammation or destructive changes in lungs. Lack of H7N3 LAIV replication in chicken demonstrated complete safety of this preparation for poultry. Results of our study suggest that new H7N3 LAIV candidate is safe, immunogenic and protects from homologues influenza virus infection in mice and ferrets.


Predictors of nursing home placement in Huntington disease.
To determine whether motor, behavioral, or psychiatric symptoms in Huntington disease (HD) predict skilled nursing facility (SNF) placement. Subjects were participants in the Huntington Study Group's Unified Huntington Disease Rating Scale Database (Rochester, NY) between January 1994 and September 1999. Specific motor, psychiatric, and behavioral variables in subjects residing at home and in SNF were analyzed using chi2 and Student's t-tests. For a subset of subjects for whom longitudinal data existed, a Cox proportional hazards model controlling for age, sex, and disease duration was used. Among 4,809 subjects enrolled, 3,070 had clinically definite HD. Of these, 228 (7.4%) resided in SNF. The SNF residents' average age was 52 years, average disease duration was 8.6 years, and they were predominantly women (63%). The SNF residents had worse motor function (chorea, bradykinesia, gait abnormality, and imbalance, p < 0.0001); were more likely to have obsessions, compulsions, delusions, and auditory hallucinations; and had more aggressive, disruptive (p < 0.0001), and irritable behaviors (p = 0.0012). For 1,559 subjects, longitudinal data existed (average length of follow-up, 1.9 years), and 87 (5%) moved from home to SNF. In the Cox model, bradykinesia (HR 1.965, 95% CI 1.083 to 3.564), impaired gait (HR 3.004, 95% CI 1.353 to 6.668), and impaired tandem walking (HR 2.546, 95% CI 1.460 to 4.439) were predictive of SNF placement. Institutionalized patients with HD are more motorically, psychiatrically, and behaviorally impaired than their counterparts living at home. However, motor variables alone predicted institutionalization. Treatment strategies that delay the progression of motor dysfunction in HD may postpone the need for institutionalization.


Changes across Cohorts in Wage Returns to Schooling and Early Work Experiences.
This paper investigates the wage returns to schooling and actual early work experiences and how these returns have changed over the past 20 years. Using the NLSY surveys, we develop and estimate a dynamic model of the joint schooling and work decisions that young men make in early adulthood and quantify how they affect wages using a generalized Mincerian specification. Our results highlight the need to account for dynamic selection and changes in composition when analyzing changes in wage returns. In particular, we find that ignoring the selectivity of accumulated work experiences results in overstatement of the returns to education.


Pseudomonas aeruginosa Outer Membrane Vesicles Triggered by Human Mucosal Fluid and Lysozyme Can Prime Host Tissue Surfaces for Bacterial Adhesion.
Pseudomonas aeruginosa is a leading cause of human morbidity and mortality that often targets epithelial surfaces. Host immunocompromise, or the presence of indwelling medical devices, including contact lenses, can predispose to infection. While medical devices are known to accumulate bacterial biofilms, it is not well understood why resistant epithelial surfaces become susceptible to P. aeruginosa. Many bacteria, including P. aeruginosa, release outer membrane vesicles (OMVs) in response to stress that can fuse with host cells to alter their function. Here, we tested the hypothesis that mucosal fluid can trigger OMV release to compromise an epithelial barrier. This was tested using tear fluid and corneal epithelial cells in vitro and in vivo. After 1 h both human tear fluid, and the tear component lysozyme, greatly enhanced OMV release from P. aeruginosa strain PAO1 compared to phosphate buffered saline (PBS) controls (∼100-fold). Transmission electron microscopy (TEM) and SDS-PAGE showed tear fluid and lysozyme-induced OMVs were similar in size and protein composition, but differed from biofilm-harvested OMVs, the latter smaller with fewer proteins. Lysozyme-induced OMVs were cytotoxic to human corneal epithelial cells in vitro and murine corneal epithelium in vivo. OMV exposure in vivo enhanced Ly6G/C expression at the corneal surface, suggesting myeloid cell recruitment, and primed the cornea for bacterial adhesion (∼4-fold, P < 0.01). Sonication disrupted OMVs retained cytotoxic activity, but did not promote adhesion, suggesting the latter required OMV-mediated events beyond cell killing. These data suggest that mucosal fluid induced P. aeruginosa OMVs could contribute to loss of epithelial barrier function during medical device-related infections.


Cardiac myocyte-secreted cAMP exerts paracrine action via adenosine receptor activation.
Acute stimulation of cardiac β-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained β-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues.


Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface.
Trophoblast adhesion to the uterine wall is the requisite first step of implantation and, subsequently, placentation. At the maternal-fetal interface, we investigated the expression of selectin adhesion systems that enable leukocyte capture from the bloodstream. On the maternal side, human uterine epithelial cells up-regulated selectin oligosaccharide-based ligands during the window of receptivity. On the fetal side, human trophoblasts expressed L-selectin. This ligand-receptor system was functional, because beads coated with the selectin ligand 6-sulfo sLe(x) bound to trophoblasts, and trophoblasts bound to ligand-expressing uterine luminal epithelium in tissue sections. These results suggest that trophoblast L-selectin mediates interactions with the uterus and that this adhesion mechanism may be critical to establishing human pregnancy.


Sleep and mood disorders in women with dry eye disease.
The aim of the present study was to evaluate sleep and mood disorders in women aged 30-69 with dry eye disease (DED). All subjects underwent corneal examinations, with 890 completing a questionnaire regarding symptoms of DED and 213 completing both the Pittsburgh Sleep Quality Index (PSQI) and the Hospital Anxiety and Depression Scale (HADS) questionnaires. Subjects were then divided into three groups based on age (younger [30-45 years], perimenopausal [46-55 years], and older [56-69 years]), and comparisons were made among groups in subjects with and without DED. PSQI scores were significantly worse in subjects with (6.1 ± 2.9) than without (4.9 ± 2.7) DED (P = 0.003) and, in the younger group, HADS scores were worse in those with (13.2 ± 6.0) than without DED (9.7 ± 6.0) (P = 0.020). In contrast, there were no differences in mood indices between those with and without DED in the other groups. PSQI score was significantly correlated with HADS rather than ocular findings. In conclusion, sleep quality had deteriorated in women with DED. However, mood problems contributed more to sleep quality than ocular status, especially in those with DED in the younger group.


A comparative evaluation of models of cinnabar moth dynamics.
1. A complex model of cinnabar moth dynamics proposed by Dempster and Lakhani (1979) with 23 parameters is reduced to a single equation with five parameters, and the behaviour of the reduced model shown to explain most features of the full model. 2. The efficiency of the full model is compared with the reduced model and with two even simpler models (the two parameter discrete logistic and a four parameter model based on a step-function for mortality) in their abilities to describe time series data of cinnabar moth population densities from Weeting Heath. Models with more parameters were not significantly better than few-parameter models in describing population trajectories. 3. Models that included a driving variable (in this case observed rainfall data) were no better at describing the data than simpler models without driving variables. It appears, therefore, that the routine inclusion of driving variables may be counterproductive, unless there is compelling empirical or theoretical evidence of their importance and the mode of action of the driving variables can be modelled mechanistically. For example, the regression model used to describe the relationship between rainfall and plant biomass in Dempster and Lakhani (1979), breaks down if rainfall is assumed to be constant, because there is no explicit model for the regulation of plant biomass. 4. The parameter values of the cinnabar-ragwort interaction suggest that cinnabar moth dynamics may be chaotic. Whether or not field data exhibit chaos or environmental stochasticity (or a mixture of both) is impossible to determine from inspection of time series data on population density. There is an urgent need for experimental and theoretical protocols to disentangle these two sources of population fluctuation.


Size-dependent Raman shift of semiconductor nanomaterials determined using bond number and strength.
Significant variations in Raman shifts with decreasing material size, D, have been detected in Raman spectroscopy. In this study, we propose a simple and unified model to determine and explain the size-dependent Raman shift, ω(D), of low-dimensional semiconductor nanomaterials. ω(D) was found to be a function of bond number in a system, with an obvious decline in Raman shift observed when size dropped to the nanoscale. This arose from a decrease in coordination number, Z(D), and increase in single bond strength, ε(D). The predicted results show good agreement with experimental data for a series of semiconductor nanomaterials, showing that bond number can be used to calculate Raman shifts of nanomaterials. Moreover, this theoretical model was successfully applied to both single crystals and some binary semiconductor nanomaterials. Furthermore, bond number, which is directly related to the nanomaterial shape and size, becomes the only parameter required to determine ω(D) in this model, as both Z(D) and ε(D) can be determined from the bond number. This indicates that the established model has the potential to determine Raman shifts of nanomaterials with different shapes and sizes.


Ascl1 controls the number and distribution of astrocytes and oligodendrocytes in the gray matter and white matter of the spinal cord.
Glia constitute the majority of cells in the mammalian central nervous system and are crucial for neurological function. However, there is an incomplete understanding of the molecular control of glial cell development. We find that the transcription factor Ascl1 (Mash1), which is best known for its role in neurogenesis, also functions in both astrocyte and oligodendrocyte lineages arising in the mouse spinal cord at late embryonic stages. Clonal fate mapping in vivo reveals heterogeneity in Ascl1-expressing glial progenitors and shows that Ascl1 defines cells that are restricted to either gray matter (GM) or white matter (WM) as astrocytes or oligodendrocytes. Conditional deletion of Ascl1 post-neurogenesis shows that Ascl1 is required during oligodendrogenesis for generating the correct numbers of WM but not GM oligodendrocyte precursor cells, whereas during astrocytogenesis Ascl1 functions in balancing the number of dorsal GM protoplasmic astrocytes with dorsal WM fibrous astrocytes. Thus, in addition to its function in neurogenesis, Ascl1 marks glial progenitors and controls the number and distribution of astrocytes and oligodendrocytes in the GM and WM of the spinal cord.


Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure.
An increasing number of currently used pesticides are reported to possess oestrogen-like properties or to disturb the endocrine system in other ways. To investigate if xeno-oestrogenic activity in serum can be used as a biomarker of the combined exposure to pesticides with oestrogen-like properties in an occupational setting. Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity. A fraction containing major xeno-oestrogens but without pharmaceutical and endogenously produced oestrogens was isolated from each serum sample by solid-phase extraction and tested for oestrogenic response in a MCF-7 cell proliferation assay. The pesticide exposure for each woman was categorised as low, medium or high based on information collected by detailed interviews of the women and the employers. In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno-oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week. The study illustrates the usefulness of this biomarker for qualitative assessment of the combined exposure to mixtures of oestrogen-like pesticides. Although the individual pesticides responsible for the xeno-oestrogenic response were not identified, the study demonstrates that, even within highly-controlled greenhouse operations, occupational exposure to oestrogen-like pesticides can result in detectable impacts on hormonal activity in the blood.


Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56,419 completely sequenced and manually annotated full-length cDNAs.
We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56,419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37,670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function, which is mediated by the fast expanding universe of alternative splicing variants.


Temporal frequencies of short and evolving pulses in interferometric spectrum analyzers.
The output of an acoustooptic spectrum analyzer contains both spatial and temporal frequencies. In a previous paper, VanderLugt predicted a difference in the temporal frequency as a function of spatial frequency for a cw signal, a pulse evolving into the acoustooptic cell, and an isolated pulse moving through the cell. We provide a more complete analysis for each of the three input signals. An analysis is made of the effects of sidelobe movement in the evolving pulse signal. This analysis, combined with a mixed transform analysis, leads to an accurate prediction of the temporal frequency behavior and to new interpretations of the results presented in the original paper. In particular, our analysis accurately predicts the temporal frequencies associated with the evolving pulse. Experimental results validate the methematical analysis for all three signal types.


A role for cell sex in stem cell-mediated skeletal muscle regeneration: female cells have higher muscle regeneration efficiency.
We have shown that muscle-derived stem cells (MDSCs) transplanted into dystrophic (mdx) mice efficiently regenerate skeletal muscle. However, MDSC populations exhibit heterogeneity in marker profiles and variability in regeneration abilities. We show here that cell sex is a variable that considerably influences MDSCs' regeneration abilities. We found that the female MDSCs (F-MDSCs) regenerated skeletal muscle more efficiently. Despite using additional isolation techniques and cell cloning, we could not obtain a male subfraction with a regeneration capacity similar to that of their female counterparts. Rather than being directly hormonal or caused by host immune response, this difference in MDSCs' regeneration potential may arise from innate sex-related differences in the cells' stress responses. In comparison with F-MDSCs, male MDSCs have increased differentiation after exposure to oxidative stress induced by hydrogen peroxide, which may lead to in vivo donor cell depletion, and a proliferative advantage for F-MDSCs that eventually increases muscle regeneration. These findings should persuade researchers to report cell sex, which is a largely unexplored variable, and consider the implications of relying on cells of one sex.


Element-centric clustering comparison unifies overlaps and hierarchy.
Clustering is one of the most universal approaches for understanding complex data. A pivotal aspect of clustering analysis is quantitatively comparing clusterings; clustering comparison is the basis for many tasks such as clustering evaluation, consensus clustering, and tracking the temporal evolution of clusters. In particular, the extrinsic evaluation of clustering methods requires comparing the uncovered clusterings to planted clusterings or known metadata. Yet, as we demonstrate, existing clustering comparison measures have critical biases which undermine their usefulness, and no measure accommodates both overlapping and hierarchical clusterings. Here we unify the comparison of disjoint, overlapping, and hierarchically structured clusterings by proposing a new element-centric framework: elements are compared based on the relationships induced by the cluster structure, as opposed to the traditional cluster-centric philosophy. We demonstrate that, in contrast to standard clustering similarity measures, our framework does not suffer from critical biases and naturally provides unique insights into how the clusterings differ. We illustrate the strengths of our framework by revealing new insights into the organization of clusters in two applications: the improved classification of schizophrenia based on the overlapping and hierarchical community structure of fMRI brain networks, and the disentanglement of various social homophily factors in Facebook social networks. The universality of clustering suggests far-reaching impact of our framework throughout all areas of science.


Pharmacovigilance in hospice/palliative care: net effect of pregabalin for neuropathic pain.
Real-world effectiveness of many medications has been poorly researched, including in hospice/palliative care. Directly extrapolating findings from other clinical settings may not yield robust clinical advice. Pharmacovigilance studies provide an opportunity to understand better the net impact of medications. The study aimed to examine immediate and short-term benefits and harms of pregabalin in routine practice for neuropathic pain in hospice/palliative care. A consecutive cohort of 155 patients from 62 centres in 5 countries was started on pregabalin and studied prospectively. Data were collected at three time points: baseline; day 7 (immediate, short-term harms); ad hoc reports of any harms ≤21 days; and day 21 (short-term benefits). Median dose for 155 patients at day 21 was 150 mg/24 h. Benefits were reported by 61 patients (39%), of whom 11 (7%) experienced complete pain resolution. Harms were reported by 51 (35%) patients at or before 7 days, the most frequent of which were somnolence, fatigue, cognitive disturbance and dizziness. 10 patients (6%) ceased pregabalin due to harms, but 82 patients (53%) were being treated at 21 days. In regression modelling, people with worse baseline pain derived more benefit (OR=8.5 (95% CI 2.5 to 28.68). Pregabalin delivered benefit to many patients, with 4 of 10 experiencing pain reductions by 21 days. Harms, occurring in 1 in 3 patients, may be difficult to detect in clinical practice, as they mostly involve worsening of symptoms prevalent at baseline.


Treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor.
Mesenchymal stem cells could differentiate into cardiomyocytes in vitro and have been shown to reconstitute the impaired myocardium in vivo. Hepatocyte growth factor, a recognized angiogenic factor and endothelial cell chemoattractant, has been applied in the treatment of myocardial ischemia. In this study, we used a ligation model of proximal left anterior descending coronary artery of rats to evaluate the effect of mesenchymal stem cells overexpressing hepatocyte growth factor in the treatment of myocardial ischemia. Bone marrow-derived mesenchymal stem cells were isolated, expanded, characterized, and infected with adenovirus carrying human hepatocyte growth factor cDNA (Ad-HGF). Mesenchymal stem cells infected by Ad-HGF released soluble HGF protein at a high level, which was maintained at least for 2 weeks. Implantation of mesenchymal stem cells overexpressing hepatocyte growth factor into left anterior descending risk areas improved the functions of impaired myocardium, including diminishing the area of ischemia, increasing the number of capillaries, and reducing collagen content. By using the sry gene as a marker, we also demonstrated that the engrafted cells or their progeny incorporated into ischemic cardiac muscle. These results showed that treatment of myocardial ischemia with bone marrow-derived mesenchymal stem cells overexpressing hepatocyte growth factor could be a novel strategy that can both restore local blood flow and regenerate lost cardiomyocytes.


Investigation of adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents in the iliac vein: insights into developing a better iliac vein stent.
We analyzed the adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents for the treatment of iliac venous thromboembolism and investigated their relationships with the anatomical features of the iliac vein, to gain insights into the development of a better iliac vein stent. Reports of adverse events following the use of stents in the iliac vein were retrieved from the Manufacturer and User Facility Device Experience (MAUDE) database that contain suspected device-associated complications reported to the Food and Drug Administration. Data from 2006 to 2016 were investigated. The literature analysis was also conducted using PubMed, Cochrane Library, EMBASE, and Web of Science focusing on English articles published up to 4 October 2016. The analysis of 88 adverse events from the MAUDE database and 182 articles from the literature revealed that a higher number of adverse events had been reported following the use of arterial stents in the iliac vein compared to CE-marked iliac vein stents. While stent migration and shortening were reported only for the arterial stents, stent fracture and compression occurred regardless of the stent type, even though a vein does not pulsate. A study of the anatomical features of the iliac vein implies that bending, compression, and kink loads are applied to the iliac vein stents in vivo. For designing, developing, and pre-clinical testing of stents intended for use in the iliac vein, the above mechanical load environments induced by the anatomical features should be considered.


Operons in Escherichia coli: genomic analyses and predictions.
The rich knowledge of operon organization in Escherichia coli, together with the completed chromosomal sequence of this bacterium, enabled us to perform an analysis of distances between genes and of functional relationships of adjacent genes in the same operon, as opposed to adjacent genes in different transcription units. We measured and demonstrated the expected tendencies of genes within operons to have much shorter intergenic distances than genes at the borders of transcription units. A clear peak at short distances between genes in the same operon contrasts with a flat frequency distribution of genes at the borders of transcription units. Also, genes in the same operon tend to have the same physiological functional class. The results of these analyses were used to implement a method to predict the genomic organization of genes into transcription units. The method has a maximum accuracy of 88% correct identification of pairs of adjacent genes to be in an operon, or at the borders of transcription units, and correctly identifies around 75% of the known transcription units when used to predict the transcription unit organization of the E. coli genome. Based on the frequency distance distributions, we estimated a total of 630 to 700 operons in E. coli. This step opens the possibility of predicting operon organization in other bacteria whose genome sequences have been finished.


Effects of vehicle-ride exposure on cervical pathology: a meta-analysis.
Research to date on the effect vehicle-ride exposure has on the development of cervical pathologies in mounted Warfighters is conflicting. The purpose of this study was to determine if the literature suggests a definite effect of vehicle-ride exposure on cervical pathology. Databases were searched using multiple combinations of select terms. Twelve studies meeting the inclusion criteria were included in the meta-analysis. The results of the meta-analysis revealed that overall vehicle-ride exposure was likely to increase cervical pathology (p=0.01, odds ratio=1.59, 95% CI=1.16-2.17). Using vehicle type as a moderator it was found that vehicle-ride exposure in ground-based vehicles (p=0.01, odds ratio=2.33, 95% CI=1.41-3.85) and fixed-wing aircraft (p=0.01, odds ratio =1.59, 95% CI=1.13-2.23) were likely to increase cervical pathology. Using operator/other personnel moderator it was found that in the populations tested, fighter pilots or fighter jet weapons systems operators were more likely to develop a cervical pathology (p<0.001, odds ratio=1.78, 95% CI=1.26-2.50). The available studies indicate an increase in cervical pathology for personnel exposed to ground-based vehicles and fixed-wing aircraft.


A fully coupled poroelastic reactive-transport model of cartilage.
Cartilage maintains its integrity in a hostile mechanical environment. This task is made more difficult because cartilage has no blood supply, and so nutrients and growth factors need to be transported greater distances than normal to reach cells several millimetres from the cartilage surface. The chondrocytes embedded within the extracellular matrix (ECM) are essential for maintaining the mechanical integrity of the ECM, through a balance of degradation and synthesis of collagen and proteoglycans. A chondrocyte senses various chemical and mechanical signals in its local microenvironment, responding by appropriate adaption of the local ECM. Clearly a 'systems understanding' of cartilage behaviour is of critical importance in developing an integrated understanding of both normal and abnormal physiology of cartilage. In a series of papers, we have developed a reactive-transport porous-media model to investigate the coupled processes of growth factor transport, mechanical deformation and fluid flow, and in this paper, we extend the model to include biosynthesis and degradation of matrix molecules. The model is validated using three independent experimental data sets, it being found that a single set of parameters described the experimental results remarkably well. The model is then employed to make predictions about changes in proteoglycan content under a variety of conditions. This model may prove useful in predicting the behaviour of tissue engineering constructs, or predicting the outcome of repair processes in cartilage.


Activation of the G protein Gq/11 through tyrosine phosphorylation of the alpha subunit.
Various receptors coupled to the heterotrimeric guanine nucleotide-binding protein Gq/11 stimulate formation of inositol-1,4,5-trisphosphate (IP3). Activation of these receptors also induces protein tyrosine phosphorylation. Formation of IP3 in response to stimulated receptors that couple to Gq/11 was blocked by protein tyrosine kinase inhibitors. These inhibitors appeared to act before activation of Gq/11. Moreover, stimulation of receptors coupled to Gq/11 induced phosphorylation on a tyrosine residue (Tyr356) of the Galphaq/11 subunit, and this tyrosine phosphorylation event was essential for Gq/11 activation. Tyrosine phosphorylation of Galphaq/11 induced changes in its interaction with receptors. Therefore, tyrosine phosphorylation of Galphaq/11 appears to regulate the activation of Gq/11 protein.


The 15N/14N ratios of plants in South Africa and Namibia: relationship to climate and coastal/saline environments.
Data are presented for the 15N/14N ratios of 140 indigenous terrestrial plants from a wide variety of natural habitats in South Africa and Namibia. Over much of the area, from high-rainfall mountains to arid deserts, the δ 15N values of plants lie typically in the range -1 to +6‰; with no evident differences between C3 plants and C4 grasses. There is a slight correlation between δ 15N and aridity, but this is less marked than the correlation between the δ 15N values of animal bones and aridity. At coastal or saline sites, however, the mean δ 15N values for plants are higher than those at nearby inland or non-saline sites-e.g.: arid Namib coast (10‰ higher than inland Namib); wet Natal beach (5‰ higher than inland Natal); saline soils 500 km from coast (4‰ higher than non-saline soils). High values were also found at one site where there were no marked coastal or saline influences. These environmental effects on the isotopic composition of plants will extend upwards to the animals and humans they support. They therefore have important consequences for the use of nitrogen isotope data in the study of the dietary habits and trophic structures of modern and prehistoric communities.


Kinetic analyses of vasculogenesis inform mechanistic studies.
Vasculogenesis is a complex process by which endothelial stem and progenitor cells undergo de novo vessel formation. Quantitative assessment of vasculogenesis is a central readout of endothelial progenitor cell functionality. However, current assays lack kinetic measurements. To address this issue, new approaches were developed to quantitatively assess in vitro endothelial colony-forming cell (ECFC) network formation in real time. Eight parameters of network structure were quantified using novel Kinetic Analysis of Vasculogenesis (KAV) software. KAV assessment of structure complexity identified two phases of network formation. This observation guided the development of additional vasculogenic readouts. A tissue cytometry approach was established to quantify the frequency and localization of dividing ECFCs. Additionally, Fiji TrackMate was used to quantify ECFC displacement and speed at the single-cell level during network formation. These novel approaches were then implemented to identify how intrauterine exposure to maternal diabetes mellitus (DM) impairs fetal ECFC vasculogenesis. Fetal ECFCs exposed to maternal DM form fewer initial network structures, which are not stable over time. Correlation analyses demonstrated that ECFC samples with greater division in branches form fewer closed network structures. Additionally, reductions in average ECFC movement over time decrease structural connectivity. Identification of these novel phenotypes utilizing the newly established methodologies provides evidence for the cellular mechanisms contributing to aberrant ECFC vasculogenesis.


Osteoarthritis.
Osteoarthritis (OA) is the most common joint disorder, is associated with an increasing socioeconomic impact owing to the ageing population and mainly affects the diarthrodial joints. Primary OA results from a combination of risk factors, with increasing age and obesity being the most prominent. The concept of the pathophysiology is still evolving, from being viewed as cartilage-limited to a multifactorial disease that affects the whole joint. An intricate relationship between local and systemic factors modulates its clinical and structural presentations, leading to a common final pathway of joint destruction. Pharmacological treatments are mostly related to relief of symptoms and there is no disease-modifying OA drug (that is, treatment that will reduce symptoms in addition to slowing or stopping the disease progression) yet approved by the regulatory agencies. Identifying phenotypes of patients will enable the detection of the disease in its early stages as well as distinguish individuals who are at higher risk of progression, which in turn could be used to guide clinical decision making and allow more effective and specific therapeutic interventions to be designed. This Primer is an update on the progress made in the field of OA epidemiology, quality of life, pathophysiological mechanisms, diagnosis, screening, prevention and disease management.


IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases.
Inhibitor of apoptosis (IAP) gene products play an evolutionarily conserved role in regulating programmed cell death in diverse species ranging from insects to humans. Human XIAP, cIAP1 and cIAP2 are direct inhibitors of at least two members of the caspase family of cell death proteases: caspase-3 and caspase-7. Here we compared the mechanism by which IAPs interfere with activation of caspase-3 and other effector caspases in cytosolic extracts where caspase activation was initiated by caspase-8, a proximal protease activated by ligation of TNF-family receptors, or by cytochrome c, which is released from mitochondria into the cytosol during apoptosis. These studies demonstrate that XIAP, cIAP1 and cIAP2 can prevent the proteolytic processing of pro-caspases -3, -6 and -7 by blocking the cytochrome c-induced activation of pro-caspase-9. In contrast, these IAP family proteins did not prevent caspase-8-induced proteolytic activation of pro-caspase-3; however, they subsequently inhibited active caspase-3 directly, thus blocking downstream apoptotic events such as further activation of caspases. These findings demonstrate that IAPs can suppress different apoptotic pathways by inhibiting distinct caspases and identify pro-caspase-9 as a new target for IAP-mediated inhibition of apoptosis.


Functional Performance and Discharge Setting Predict Outcomes 3 Months After Rehabilitation Hospitalization for Stroke.
Some clinical features of patients after stroke may be modifiable and used to predict outcomes. Identifying these features may allow for refining plans of care and informing estimates of posthospital service needs. The purpose of this study was to identify key factors that predict functional independence and living setting 3 months after rehabilitation hospital discharge by using a large comprehensive national data set of patients with stroke. The Uniform Data System for Medical Rehabilitation was queried for the records of patients with a diagnosis of stroke who were hospitalized for inpatient rehabilitation from 2005 through 2007. The system includes demographic, administrative, and clinical variables collected at rehabilitation admission, discharge, and 3-month follow-up. Primary outcome measures were the Functional Independence Measure score and living setting 3 months after rehabilitation hospital discharge. The sample included 16,346 patients (80% white; 50% women; mean [SD] age, 70.3 [13.1] years; 97% ischemic stroke). The strongest predictors of Functional Independence Measure score and living setting at 3 months were those same factors at rehabilitation discharge, despite considering multiple other predictor variables including age, lesion laterality, initial neurologic impairment, and stroke-related comorbid conditions. These data can inform clinicians, patients with stroke, and their families about what to expect in the months after hospital discharge. The predictive power of these factors, however, was modest, indicating that other factors may influence postacute outcomes. Future predictive modeling may benefit from the inclusion of educational status, socioeconomic factors, and brain imaging to improve predictive power.


Control of cholesterol synthesis through regulated ER-associated degradation of HMG CoA reductase.
Multiple mechanisms for feedback control of cholesterol synthesis converge on the rate-limiting enzyme in the pathway, 3-hydroxy-3-methylglutaryl coenzyme A reductase. This complex feedback regulatory system is mediated by sterol and nonsterol metabolites of mevalonate, the immediate product of reductase activity. One mechanism for feedback control of reductase involves rapid degradation of the enzyme from membranes of the endoplasmic reticulum (ER). This degradation results from the accumulation of sterols in ER membranes, which triggers binding of reductase to ER membrane proteins called Insig-1 and Insig-2. Insig binding leads to the recruitment of a membrane-associated ubiquitin ligase called gp78 that initiates ubiquitination of reductase. Ubiquitinated reductase then becomes extracted from ER membranes and is delivered to cytosolic 26S proteasomes through an unknown mechanism that is mediated by the gp78-associated ATPase Valosin-containing protein/p97 and appears to be augmented by nonsterol isoprenoids. Here, we will highlight several advances that have led to the current view of mechanisms for sterol-accelerated, ER-associated degradation of reductase. In addition, we will discuss potential mechanisms for other aspects of the pathway such as selection of reductase for gp78-mediated ubiquitination, extraction of the ubiquitinated enzyme from ER membranes, and the contribution of Insig-mediated degradation to overall regulation of reductase in whole animals.


Understanding Variability in Individual Response to Hearing Aid Signal Processing in Wearable Hearing Aids.
Previous work has suggested that individual characteristics, including amount of hearing loss, age, and working memory ability, may affect response to hearing aid signal processing. The present study aims to extend work using metrics to quantify cumulative signal modifications under simulated conditions to real hearing aids worn in everyday listening environments. Specifically, the goal was to determine whether individual factors such as working memory, age, and degree of hearing loss play a role in explaining how listeners respond to signal modifications caused by signal processing in real hearing aids, worn in the listener's everyday environment, over a period of time. Participants were older adults (age range 54-90 years) with symmetrical mild-to-moderate sensorineural hearing loss. We contrasted two distinct hearing aid fittings: one designated as mild signal processing and one as strong signal processing. Forty-nine older adults were enrolled in the study and 35 participants had valid outcome data for both hearing aid fittings. The difference between the two settings related to the wide dynamic range compression and frequency compression features. Order of fittings was randomly assigned for each participant. Each fitting was worn in the listener's everyday environments for approximately 5 weeks before outcome measurements. The trial was double blind, with neither the participant nor the tester aware of the specific fitting at the time of the outcome testing. Baseline measures included a full audiometric evaluation as well as working memory and spectral and temporal resolution. The outcome was aided speech recognition in noise. The two hearing aid fittings resulted in different amounts of signal modification, with significantly less modification for the mild signal processing fitting. The effect of signal processing on speech intelligibility depended on an individual's age, working memory capacity, and degree of hearing loss. Speech recognition with the strong signal processing decreased with increasing age. Working memory interacted with signal processing, with individuals with lower working memory demonstrating low speech intelligibility in noise with both processing conditions, and individuals with higher working memory demonstrating better speech intelligibility in noise with the mild signal processing fitting. Amount of hearing loss interacted with signal processing, but the effects were small. Individual spectral and temporal resolution did not contribute significantly to the variance in the speech intelligibility score. When the consequences of a specific set of hearing aid signal processing characteristics were quantified in terms of overall signal modification, there was a relationship between participant characteristics and recognition of speech at different levels of signal modification. Because the hearing aid fittings used were constrained to specific fitting parameters that represent the extremes of the signal modification that might occur in clinical fittings, future work should focus on similar relationships with more diverse types of signal processing parameters.


Prevalence of faecal carriage of colistin-resistant Gram-negative rods in a university hospital in western France, 2016.
Plasmid-mediated and chromosomally-encoded colistin resistance is increasingly being reported worldwide. We aimed to determine the prevalence of faecal carriage of colistin-resistant Gram-negative rod isolates in a university hospital in western France. From February to May 2016, rectal swabs from 653 patients hospitalized in various clinical settings were recovered and subsequently screened for colistin resistance using the SuperPolymyxin medium. Antimicrobial susceptibilities were determined according to EUCAST guidelines. Genetic detection of plasmid-mediated colistin resistance was performed by PCR. The faecal carriage with intrinsic colistin-resistant isolates was high (23 %), while the faecal carriage with Gram-negative rods showing acquired resistance was low (1.4 %). No isolate carried the plasmid-mediated mcr-1/mcr-2 genes. It was noteworthy that none of the patients carrying isolates with acquired colistin resistance had previously received a colistin-based treatment, while these isolates were not multidrug resistant.


Stem cell-specific epigenetic priming and B cell-specific transcriptional activation at the mouse Cd19 locus.
Low-level expression of multiple lineage-specific genes is a hallmark of hematopoietic stem cells (HSCs). HSCs predominantly express genes specific for the myeloid or megakaryocytic-erythroid lineages, whereas the transcription of lymphoid specific genes appears to begin after lymphoid specification. It has been demonstrated for a number of genes that epigenetic priming occurs before gene expression and lineage specification; however, little is known about how epigenetic priming of lymphoid genes is regulated. To address the question of how B cell-restricted expression is established, we studied activation of the Cd19 gene during hematopoietic development. We identified a B cell-specific upstream enhancer and showed that the developmental regulation of Cd19 expression involves precisely coordinated alterations in transcription factor binding and chromatin remodeling at Cd19 cis-regulatory elements. In multipotent progenitor cells, Cd19 chromatin is first remodeled at the upstream enhancer, and this remodeling is associated with binding of E2A. This is followed by the binding of EBF and PAX5 during B-cell differentiation. The Cd19 promoter is transcriptionally activated only after PAX5 binding. Our experiments give important mechanistic insights into how widely expressed and B lineage-specific transcription factors cooperate to mediate the developmental regulation of lymphoid genes during hematopoiesis.


Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of Pathogenic Mycobacteria.
Mycobacteria possess different type VII secretion (T7S) systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the secretion of multiple substrates. However, the role of ESX-5 substrates in growth and/or virulence is largely unknown. In this study, we show that esx-5 is essential for growth of both Mycobacterium marinum and Mycobacterium bovis. Remarkably, this essentiality can be rescued by increasing the permeability of the outer membrane, either by altering its lipid composition or by the introduction of the heterologous porin MspA. Mutagenesis of the first nucleotide-binding domain of the membrane ATPase EccC5 prevented both ESX-5-dependent secretion and bacterial growth, but did not affect ESX-5 complex assembly. This suggests that the rescuing effect is not due to pores formed by the ESX-5 membrane complex, but caused by ESX-5 activity. Subsequent proteomic analysis to identify crucial ESX-5 substrates confirmed that all detectable PE and PPE proteins in the cell surface and cell envelope fractions were routed through ESX-5. Additionally, saturated transposon-directed insertion-site sequencing (TraDIS) was applied to both wild-type M. marinum cells and cells expressing mspA to identify genes that are not essential anymore in the presence of MspA. This analysis confirmed the importance of esx-5, but we could not identify essential ESX-5 substrates, indicating that multiple of these substrates are together responsible for the essentiality. Finally, examination of phenotypes on defined carbon sources revealed that an esx-5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon sources. Based on these data, we propose a model in which the ESX-5 system is responsible for the transport of cell envelope proteins that are required for nutrient uptake. These proteins might in this way compensate for the lack of MspA-like porins in slow-growing mycobacteria.


ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior.
Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) ATP-dependent chromatin-remodeling complex, occurring in the nucleus accumbens of stress-susceptible mice and depressed humans, is necessary for stress-induced depressive-like behaviors. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the ACF chromatin-remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress-related behaviors.


Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer.
There is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer. We initially conducted a randomized, phase 2 study involving 86 patients to compare cisplatin plus gemcitabine with gemcitabine alone. After we found an improvement in progression-free survival, the trial was extended to the phase 3 trial reported here. We randomly assigned 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer to receive either cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter on days 1 and 8, every 3 weeks for eight cycles) or gemcitabine alone (1000 mg per square meter on days 1, 8, and 15, every 4 weeks for six cycles) for up to 24 weeks. The primary end point was overall survival. After a median follow-up of 8.2 months and 327 deaths, the median overall survival was 11.7 months among the 204 patients in the cisplatin-gemcitabine group and 8.1 months among the 206 patients in the gemcitabine group (hazard ratio, 0.64; 95% confidence interval, 0.52 to 0.80; P<0.001). The median progression-free survival was 8.0 months in the cisplatin-gemcitabine group and 5.0 months in the gemcitabine-only group (P<0.001). In addition, the rate of tumor control among patients in the cisplatin-gemcitabine group was significantly increased (81.4% vs. 71.8%, P=0.049). Adverse events were similar in the two groups, with the exception of more neutropenia in the cisplatin-gemcitabine group; the number of neutropenia-associated infections was similar in the two groups. As compared with gemcitabine alone, cisplatin plus gemcitabine was associated with a significant survival advantage without the addition of substantial toxicity. Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer. (ClinicalTrials.gov number, NCT00262769.)


General or local anesthesia for carotid endarterectomy--the "real-world" experience.
Perioperative complications from carotid endarterectomy (CEA) are the main drawbacks of the procedure. The aim of this study was to assess the complication rates in patients undergoing CEA under general anesthesia (GA) or regional anesthesia (local anesthesia [LA]) at our institution. Patients undergoing CEA at our regional vascular unit between 2000 and 2004 were included. Data were collated retrospectively from a prospective database. Follow-up was up to 62 months. In all, 383 endarterectomies were performed, 260 of which were under LA. Outcome measures included 30-day death (2.1%), stroke (1.8%), and combined stroke and death (2.8%). A 30-day incidence of stroke, death, and combined stroke and death was lower in the LA group. Incidence of myocardial infarction and transient ischemic attacks, and annual mortality were higher in the LA group. No significant difference was found between the 2 groups. In a unit where CEA is preferentially performed under LA, anesthesia technique failed to significantly influence outcome.


Surgical protocol and short-term clinical outcome of immediate placement in molar extraction sockets using a wide body implant.
Implant placement in molar extraction sockets can be difficult due to complex multi-root anatomy and the lack of predictable primary stability. The aim of this study was to evaluate the outcome of an 8 - 9 mm diameter tapered implant, designed to be placed in molar extraction sockets. Patients treated at least 1 year before with a Max(®) implant (Southern Implants, Irene, South Africa) were invited for a clinical examination. Variables collected were surgical and prosthetic protocol, implant dimension and smoking habits. Peri-implant bone level was determined on peri-apical radiographs and compared to baseline, being implant insertion. 98 implants had been placed in 89 patients. One implant had failed. Thirty eight patients representing 47 implants (maxilla 26, mandible 21) were available for clinical examination. Mean bone loss was 0.38 mm (SD 0.48; range - 0.50 - 1.95) after a mean follow-up of 20 months (range 12 - 35). Implant success was 97.9%. Around 30 implants, a bone substitute was used to fill the residual space, but this did not affect the bone loss outcome. Bone loss was only significantly different between maxilla and mandible (0.48 mm vs. 0.27 mm) and between the 8 and 9 mm diameter implants (0.23 mm vs. 0.55 mm). A full papilla was present at 71% of the interproximal sites and irrespective of bone loss. The Max(®) implant demonstrated good primary stability, when placed in molar extraction sockets, with limited bone loss over time.


Spatial layout affects speed discrimination.
We address a surprising result in a previous study of speed discrimination with multiple moving gratings: discrimination thresholds decreased when the number of stimuli was increased, but remained unchanged when the area of a single stimulus was increased [Verghese & Stone (1995). Vision Research, 35, 2811-2823]. In this study, we manipulated the spatial- and phase relationship between multiple grating patches to determine their effect on speed discrimination thresholds. In a fusion experiment, we merged multiple stimulus patches, in stages, into a single patch. Thresholds increased as the patches were brought closer and their phase relationship was adjusted to be consistent with a single patch. Thresholds increased further still as these patches were fused into a single patch. In a fission experiment, we divided a single large patch into multiple patches by superimposing a cross with luminance equal to that of the background. Thresholds decreased as the large patch was divided into quadrants and decreased further as the quadrants were maximally separated. However, when the cross luminance was darker than the background, it was perceived as an occluder and thresholds, on average, were unchanged from that for the single large patch. A control experiment shows that the observed trend in discrimination thresholds is not due to the differences in perceived speed of the stimuli. These results suggest that the parsing of the visual image into entities affects the combination of speed information across space, and that each discrete entity effectively provides a single independent estimate of speed.


Simulation-based inference for non-parametric statistical comparison of biomolecule dynamics.
Numerous models have been developed to account for the complex properties of the random walks of biomolecules. However, when analysing experimental data, conditions are rarely met to ensure model identification. The dynamics may simultaneously be influenced by spatial and temporal heterogeneities of the environment, out-of-equilibrium fluxes and conformal changes of the tracked molecules. Recorded trajectories are often too short to reliably discern such multi-scale dynamics, which precludes unambiguous assessment of the type of random walk and its parameters. Furthermore, the motion of biomolecules may not be well described by a single, canonical random walk model. Here, we develop a two-step statistical testing scheme for comparing biomolecule dynamics observed in different experimental conditions without having to identify or make strong prior assumptions about the model generating the recorded random walks. We first train a graph neural network to perform simulation-based inference and thus learn a rich summary statistics vector describing individual trajectories. We then compare trajectories obtained in different biological conditions using a non-parametric maximum mean discrepancy (MMD) statistical test on their so-obtained summary statistics. This procedure allows us to characterise sets of random walks regardless of their generating models, without resorting to model-specific physical quantities or estimators. We first validate the relevance of our approach on numerically simulated trajectories. This demonstrates both the statistical power of the MMD test and the descriptive power of the learnt summary statistics compared to estimates of physical quantities. We then illustrate the ability of our framework to detect changes in α-synuclein dynamics at synapses in cultured cortical neurons, in response to membrane depolarisation, and show that detected differences are largely driven by increased protein mobility in the depolarised state, in agreement with previous findings. The method provides a means of interpreting the differences it detects in terms of single trajectory characteristics. Finally, we emphasise the interest of performing various comparisons to probe the heterogeneity of experimentally acquired datasets at different levels of granularity (e.g., biological replicates, fields of view, and organelles).


Intravascular papillary endothelial hyperplasia (Masson's tumor) of the scalp with intracranial extension.
Intravascular papillary endothelial hyperplasia (IPEH) (Masson's tumor) is an unusual benign vascular lesion of the skin and subcutaneous tissue, consisting of papillary formations related to a thrombus and covered by a single layer of plump endothelial cells. The lesion is often mistaken with angiosarcoma and a group of other benign and malignant vascular lesions. The clinical and radiological findings are not specific, and the diagnosis is based on the histological examination. Intracranial lesions are extremely rare with only 32 cases been reported in the literature. Only two cases of IPEH presenting as scalp swelling have been reported in the literature. We report a case of a 3-month-old boy with IPEH of scalp in the left parietal region, which was involving the skull bone and extending intracranially.


The Hedgehog response network: sensors, switches, and routers.
The Hedgehog (Hh) signaling pathway is intimately linked to cell growth and differentiation, with normal roles in embryonic pattern formation and adult tissue homeostasis and pathological roles in tumor initiation and growth. Recent advances in our understanding of Hh response have resulted from the identification of new pathway components and new mechanisms of action for old pathway components. The most striking new finding is that signal transmission from membrane to cytoplasm proceeds through recruitment, by the seven-transmembrane protein Smoothened, of an atypical kinesin, which routes pathway activation by interaction with other components of a complex that includes the latent zinc finger transcription factor, Ci.


Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia.
Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date. To determine whether large (>100,000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia. A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray. The Wellcome Trust Case Control Consortium. There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents. Overall load of CNVs and presence of rare CNVs. The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder. Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.


Exendin-4 protected against cognitive dysfunction in hyperglycemic mice receiving an intrahippocampal lipopolysaccharide injection.
Chronic hyperglycemia-associated inflammation plays critical roles in disease initiation and the progression of diabetic complications, including Alzheimer's disease (AD). However, the association of chronic hyperglycemia with acute inflammation of the central nervous system in the progression of AD still needs to be elucidated. In addition, recent evidence suggests that Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damage in the brain. Therefore, the neuroprotective effects of the GLP-1R agonist exendin-4 (EX-4) against hyperglycemia/lipopolysaccharides (LPS) damage were also evaluated in this study. Ten days after streptozotocin (STZ) or vehicle (sodium citrate) treatment in mice, EX-4 treatment (10 µg/kg/day) was applied to the mice before intrahippocampal CA1 injection of LPS or vehicle (saline) and continued for 28 days. This study examined the molecular alterations in these mice after LPS and EX4 application, respectively. The mouse cognitive function was evaluated during the last 6 days of EX-4 treatment. The results showed that the activation of NF-κB-related inflammatory responses induced cognitive dysfunction in both the hyperglycemic mice and the mice that received acute intrahippocampal LPS injection. Furthermore, acute intrahippocampal LPS injection exacerbated the impairment of spatial learning and memory through a strong decrease in monoaminergic neurons and increases in astrocytes activation and apoptosis in the hyperglycemic mice. However, EX-4 treatment protected against the cognitive dysfunction resulting from hyperglycemia or/and intrahippocampal LPS injection. These findings reveal that both hyperglycemia and intrahippocampal LPS injection induced cognitive dysfunction via activation of NF-κB-related inflammatory responses. However, acute intrahippocampal LPS injection exacerbated the progression of cognitive dysfunction in the hyperglycemic mice via a large increase in astrocytes activation-related responses. Furthermore, EX-4 might be considered as a potential adjuvant entity to protect against neurodegenerative diseases.


Progressive resistance training did not improve walking but can improve muscle performance, quality of life and fatigue in adults with multiple sclerosis: a randomized controlled trial.
Few high-quality trials have examined the effects of progressive resistance training (PRT) on people with multiple sclerosis (MS). To determine the effectiveness of PRT for people with MS, focusing on improving the gait deficits common in this population. Using a single blind randomized controlled trial, people with relapsing-remitting MS were randomly allocated to either a PRT program targeting the lower limb muscles twice a week for 10 weeks (n = 36), or usual care plus an attention and social program conducted once a week for 10 weeks (n = 35). Outcomes were recorded at baseline, week 10 and week 22. Participants attended 92% of training sessions, with no serious adverse events. At 10 weeks, no differences were detected in walking performance. However, compared with the comparison group PRT demonstrated increased leg press strength (16.8%, SD 4.5), increased reverse leg press strength (29.8%, SD 12.7), and increased muscle endurance of the reverse leg press (38.7%, SD 32.8). Improvements in favor of PRT were also found for physical fatigue (Mean difference -3.9 units, 95%CI -6.6 to -1.3), and the physical health domain of quality of life (Mean difference 1.5 units, 95%CI 0.1 to 2.9). At week 22 almost no between-group differences remained. PRT is a relatively safe intervention that can have short-term effects on reducing physical fatigue, increasing muscle endurance and can lead to small improvements in muscle strength and quality of life in people with relapsing-remitting MS. However, no improvements in walking performance were observed and benefits do not appear to persist if training is completely stopped.


Cognitive Impairment Is Associated with a Low Omega-3 Index in the Elderly: Results from the KORA-Age Study.
Omega-3 polyunsaturated fatty acids (PUFA) may affect the risk of cognitive decline in older adults. Cross-sectional analysis was conducted among 720 (50.4% women) participants aged 68-92 years (mean age: 77.6, SD ±6.2) of the population-based KORA-Age study. Eicosapentaenoic acid and docosahexaenoic acid (omega-3 index) were measured in erythrocytes as a percentage of total fatty acids. The categories low (<5.7), intermediate (5.7-6.8), and high (>6.8) levels of the omega-3 index were built using tertiles. The association between cognitive status and omega-3 levels was assessed by logistic regression analyses with adjustments for important concurrent risk factors of cognitive decline. In the sex- and age-adjusted model (model 1), subjects with a low omega-3 index were at a significantly higher risk for cognitive impairment (OR: 1.77, 95% CI: 1.15-2.73, p = 0.009). This association remained stable after further adjusting for educational level (model 2; OR: 1.75, 95% CI: 1.13-2.71, p = 0.01) and metabolic risk factors (model 3; OR: 1.77, 95% CI: 1.14-2.75, p = 0.01). After further controlling for affective disorders (model 4), the association did not attenuate (OR: 1.77, 95% CI: 1.14-2.76, p = 0.01). A robust association was found between low omega-3 levels and cognitive impairment in an elderly population. Further research is needed to understand the link between omega-3 PUFA and cognitive functioning.


Comparative analysis of multiple disease resistance in ryegrass and cereal crops.
Ryegrass (Lolium spp.) is among the most important forage crops in Europe and Australia and is also a popular turfgrass in North America. Previous genetic analysis based on a three-generation interspecific (L. perennexL. multiflorum) ryegrass population identified four quantitative trait loci (QTLs) for resistance to gray leaf spot (Magneporthe grisea) and four QTLs for resistance to crown rust (Puccinia coronata). The current analysis based on the same mapping population detected seven QTLs for resistance to leaf spot (Bipolaris sorokiniana) and one QTL for resistance to stem rust (Puccinia graminis) in ryegrass for the first time. Three QTLs for leaf spot resistance on linkage groups (LGs) 2 and 4 were in regions of conserved synteny to the positions of resistance to net blotch (Drechslera teres) in barley (Hordeum vulgare). One ryegrass genomic region spanning 19 cM on LG 4, which contained three QTLs for resistance to leaf spot, gray leaf spot, and stem rust, had a syntenic relationship with a segment of rice chromosome 3, which contained QTLs for resistance to multiple diseases. However, at the genome-wide comparison based on 72 common RFLP markers between ryegrass and cereals, coincidence of QTLs for disease resistance to similar fungal pathogens was not statistically significant.


Adaptive-Fourier-neural-network-based control for a class of uncertain nonlinear systems.
An adaptive Fourier neural network (AFNN) control scheme is presented in this paper for the control of a class of uncertain nonlinear systems. Based on Fourier analysis and neural network (NN) theory, AFNN employs orthogonal complex Fourier exponentials as the activation functions. Due to the clear physical meaning of the neurons, the determination of the AFNN structure as well as the parameters of the activation functions becomes convenient. One salient feature of the proposed AFNN approach is that all the nonlinearities and uncertainties of the dynamical system are lumped together and compensated online by AFNN. It can, therefore, be applied to uncertain nonlinear systems without any a priori knowledge about the system dynamics. Derived from Lyapunov theory, a novel learning algorithm is proposed, which is essentially a frequency domain method and can guarantee asymptotic stability of the closed-loop system. The simulation results of a multiple-input-multiple-output (MIMO) nonlinear system and the experimental results of an X - Y positioning table are presented to show the effectiveness of the proposed AFNN controller.


Radiation Organ Doses Received by U.S. Radiologic Technologists: Estimation Methods and Findings.
Abstract In this paper, we describe recent methodological enhancements and findings from the dose reconstruction component of a study of cancer risks among U.S. radiologic technologists. An earlier version of the dosimetry published in 2006 (Simon et al., Radiat. Res. 166, 174-192, 2006) used physical and statistical models, literature-reported exposure measurements for the years before 1960, and archival personnel monitoring badge data from cohort members through 1984. The data and models were used to estimate unknown occupational radiation doses for 90,000 radiological technologists, incorporating information about each individual's employment practices based on a survey conducted in the mid-1980s. The dosimetry methods presented here, while using many of the same methods as before, now estimate annual and cumulative occupational badge doses (personal dose equivalent) to about 110,000 technologists for each year worked from 1916 to 2006, but with numerous methodological improvements. This dosimetry, using much more comprehensive information on individual use of protection aprons, estimates radiation absorbed doses to 12 organs and tissues (red bone marrow, ovary, colon, brain, lung, heart, female breast, skin of trunk, skin of head and neck and arms, testes, thyroid and lens of the eye). Every technologist's annual dose is estimated as a probability density function (pdf) to account for shared and unshared uncertainties. Major improvements in the dosimetry methods include a substantial increase in the number of cohort member annual badge dose measurements, additional information on individual apron use obtained from surveys conducted in the 1990s and 2005, refined modeling to develop annual badge dose pdfs using Tobit regression, refinements of cohort-based annual badge pdfs to delineate exposures of highly and minimally exposed individuals and to assess minimal detectable limits more accurately, and extensive refinements in organ dose conversion coefficients to account for uncertainties in radiographic techniques employed. For organ dose estimation, we rely on well-researched assumptions about critical exposure-related variables and their changes over the decades, including the peak kilovoltage and filtration typically used in conducting radiographic examinations and the usual body location for wearing radiation monitoring badges. We have derived organ dose conversion coefficients based on air-kerma weighting of photon fluences from published X-ray spectra and derived energy-dependent transmission factors for protective aprons of different thicknesses. We tailor bone marrow dose estimates to individual cohort members by using an individual-specific body mass index correction factor. To our knowledge the models and reconstructed doses presented herein represent the most comprehensive dose reconstructions undertaken for a cohort of medical radiation workers.


Prevalence of household-level food insecurity and its determinants in an urban resettlement colony in north India.
An adequate food intake, in terms of quantity and quality, is a key to healthy life. Malnutrition is the most serious consequence of food insecurity and has a multitude of health and economic implications. India has the world's largest population living in slums, and these have largely been underserved areas. The State of Food Insecurity in the World (2012) estimates that India is home to more than 217 million undernourished people. Various studies have been conducted to assess food insecurity at the global level; however, the literature is limited as far as India is concerned. The present study was conducted with the objective of documenting the prevalence of food insecurity at the household level and the factors determining its existence in an urban slum population of northern India. This cross-sectional study was conducted in an urban resettlement colony of South Delhi, India. A pre-designed, pre-tested, semi-structured questionnaire was used for collecting socioeconomic details and information regarding dietary practices. Food insecurity was assessed using Household Food Insecurity Access Scale (HFIAS). Logistic regression analysis was performed to determine the factors associated with food insecurity. A total of 250 women were interviewed through house-to-house survey. Majority of the households were having a nuclear family (61.6%), with mean family-size being 5.5 (SD +/- 2.5) and the mean monthly household income being INR 9,784 (SD +/- 631). Nearly half (53.3%) of the mean monthly household income was spent on food. The study found that a total of 77.2% households were food-insecure, with 49.2% households being mildly food-insecure, 18.8% of the households being moderately food-insecure, and 9.2% of the households being severely food-insecure. Higher education of the women handling food (OR 0.37, 95% CI 0.15-0.92; p < or = 0.03) and number of earning members in the household (OR 0.68, 95% CI 0.48-0.98; p < or = 0.04) were associated with lesser chance/odds of being food-insecure. The study demonstrated a high prevalence of food insecurity in the marginalized section of the urban society. The Government of India needs to adopt urgent measures to combat this problem.


Moderate Echinostoma trivolvis infection has no effects on physiology and fitness-related traits of larval pickerel frogs (Rana palustris).
High intensity infections of Echinostoma trivolvis metacercariae decrease survival and growth of young amphibian larvae. However, in nature, parasites are highly aggregated, which results in a large proportion of the amphibian population being only moderately infected. Survival and growth responses at these more-common, low-infection levels remain poorly studied. Thus, we investigated the effects of moderate Echinostoma trivolvis metacercariae infection (following exposure to 0, 10, 30, or 90 cercariae) on the growth and development of pickerel frog (Rana palustris) tadpoles. We measured metabolism to determine whether increased energy expenditure is a potential physiological mechanism underlying previously documented reduced growth. Furthermore, we quantified tadpole intestine size, which can exhibit plasticity in response to changing metabolic demands, and we characterized metacercariae distribution in tadpole kidneys. Metacercariae encysted in the pronephros significantly more than in the mesonephros, but tended to occur equally in right and left kidneys. Two mo post-infection (PI), there were no changes in tadpole survival, development, intestine size, or growth related to metacercariae infection. Similarly, metacercariae did not significantly increase metabolic rates during encystment or at 1 mo PI. Our study demonstrated that modest E. trivolvis infections, representative of a large proportion of the host population, had no detectable effects on fitness-related traits in laboratory isolation from other ecological variables.


A new protocol for evaluating putative causes for multiple variables in a spatial setting, illustrated by its application to European cancer rates.
We introduce a statistical protocol for analyzing spatially varying data, including putative explanatory variables. The procedures comprise preliminary spatial autocorrelation analysis (from an earlier study), path analysis, clustering of the resulting set of path diagrams, ordination of these diagrams, and confirmatory tests against extrinsic information. To illustrate the application of these methods, we present incidence and mortality rates of 31 organ- and sex-specific cancers in Europe; these rates vary markedly with geography and type of cancer. Additionally, we investigated three factors (ethnohistory, genetics, and geography) putatively affecting these rates. The five variables were correlated separately for the 31 cancers over European reporting stations. We analyzed the correlations by path analysis, k-means clustering, and nonmetric multidimensional scaling; coefficients of the 31 path diagrams modeling the correlations vary substantially. To simplify interpretation, we grouped the diagrams into five clusters, for which we describe the differential effects of the three putative causes on incidence and mortality. When scaled, the path coefficients intergrade without marked gaps between clusters. Ethnic differences make for differences in cancer rates, even when the populations tested are ancient and complex mixtures. Path analysis usefully decomposes a structural model involving effects and putative causes, and estimates the magnitude of the model's components. Smooth intergradation of the path coefficients suggests the putative causes are the results of multiple forces. Despite this continuity of the path diagrams of the 31 cancers, clustering offers a useful segmentation of the continuum. Etiological and other extrinsic information on the cancers map significantly into the five clusters, demonstrating their epidemiological relevance.


Ethnomethodological studies of nurse-patient and nurse-relative interactions: A scoping review.
Researchers in nursing science interested in the study of nurse-patient and nurse-relative interactions have displayed an ever increasing interest in ethnomethodology and conversation analysis. This review assesses the scope of this literature. We categorize the papers in thematic categories determined both inductively and deductively and synthesize the main findings of this literature within category. Finally we discuss the interactional determinants of the lack patient participation, the limitations of the field, and focus on implications. A scoping review on nurse-patient and nurse-relative interactions. Forty articles focusing on nurse-patient interactions and nurse-relative interactions. All the articles relied on ethnomethodology and/or conversation analysis. A literature search has been carried out on Medline (all articles until June 2016; keywords were: nurs*.ab. and "conversation analysis"; nurs*.ab. and ethnomethodology). A similar search was performed on other platforms. The scope of the literature was identified by inductively and deductively analyzing the themes of the relevant articles. Six thematic categories emerged: Organization of nurse-patient interaction (eleven articles); Organization of mediated nurse-patient interaction (seven articles); Information, explanation and advice (eight articles); Negotiation and influence asymmetry (six articles); Managing emotions in critical illness (two articles); and Interacting with patients presenting reduced interactional competences (six articles). Across most thematic categories it appeared that patient participation is far from ideal as interactional asymmetry was most observed in favor of nurses. When the encounters occurred at the patients' homes this pattern was reversed. Computer-mediated interactions were often reported as non-optimal as the standardized process constrained communication and delayed patients' presentation of their ailments. Micro-analyses of interaction present a clear potential for the development of guidelines for nurse-patient interactions. Implications for practice are described.


Antimicrobial resistance and genetic diversity of Shigella sonnei isolates from western Ireland, an area of low incidence of infection.
Shigella sonnei is a significant cause of gastroenteritis in both developing and industrialized countries. Definition of the diversity and antimicrobial susceptibility of S. sonnei isolates may be helpful in the management of individual cases and outbreaks. Antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE) were performed with 67 isolates of S. sonnei predominantly (n = 59) from three counties in the west of Ireland. Phage typing (n = 17), plasmid profiling (n = 28), and integron analysis (n = 24) were performed with subsets of strains. PFGE typing permitted recognition of two major clusters: PFGE type A (n = 53) and PFGE type B (n = 14). PFGE type A was associated with resistance to ampicillin, streptomycin, and sulfonamides (51 of 53 isolates), and those that were phage typed (n = 6) were phage type 3. PFGE type B was associated with resistance to streptomycin, sulfonamides, tetracycline, and trimethoprim (11 of 14 isolates) and phage type 6 (9 of 11 isolates). Fifteen different plasmid profiles were identified among the 28 isolates analyzed. A class 2 integron was present in all 14 PFGE type B isolates. One of these isolates also contained a class 1 integron and showed a unique variant of the PFGE type B pattern. Sequence analysis of the gene cassette structures contained within these integrons identified distinct open reading frames that encoded determinants of resistance to trimethoprim, streptomycin, and streptothricin. Our data demonstrate two predominant PFGE types among S. sonnei isolates circulating in this region. The limited diversity of the S. sonnei isolates in this region means that detection of isolates indistinguishable by PFGE and according to their antibiograms in two or more patients is not persuasive evidence of a common-source food- or waterborne outbreak. Indistinguishable plasmid profiles in addition to indistinguishable PFGE and antibiogram types may be more suggestive of an epidemiologically relevant link between cases.


Tranexamic acid in the prevention of periventricular haemorrhage.
Increased fibrinolytic activity in the ganglionic eminence of the preterm human brain has been proposed as a factor in the aetiology of periventricular haemorrhage. The effect of tranexamic acid in preventing periventricular haemorrhage was evaluated in 100 infants in a double blind, randomised controlled trial. Haemorrhages developed in 22 infants who received tranexamic acid and in 20 of those who received placebo. A significant reduction in fibrin degradation products in treated infants was seen. Our study suggests that excessive fibrinolytic activity is not an important factor in the aetiology of periventricular haemorrhage and that treatment with tranexamic acid will not prevent its occurrence.


Statistical fluctuations of transmission in slow light photonic-crystal waveguides.
We report statistical fluctuations for the transmissions of a series of photonic-crystal waveguides (PhCWs) that are supposedly identical and that only differ because of statistical structural fabrication-induced imperfections. For practical PhCW lengths offering tolerable -3dB attenuation with moderate group indices (n(g) approximately 60), the transmission spectra contains very narrow peaks (Q approximately 20,000) that vary from one waveguide to another. The physical origin of the peaks is explained by calculating the actual electromagnetic-field pattern inside the waveguide. The peaks that are observed in an intermediate regime between the ballistic and localization transports are responsible for a smearing of the local density of states, for a rapid broadening of the probability density function of the transmission, and bring a severe constraint on the effective use of slow light for on-chip optical information processing. The experimental results are quantitatively supported by theoretical results obtained with a coupled-Bloch-mode approach that takes into account multiple scattering and localization effects.


Association mapping of seed oil and protein content in Sesamum indicum L. using SSR markers.
Sesame is an important oil crop for the high oil content and quality. The seed oil and protein contents are two important traits in sesame. To identify the molecular markers associated with the seed oil and protein contents in sesame, we systematically performed the association mapping among 369 worldwide germplasm accessions under 5 environments using 112 polymorphic SSR markers. The general linear model (GLM) was applied with the criteria of logP ≥ 3.0 and high stability under all 5 environments. Among the 369 sesame accessions, the oil content ranged from 27.89%-58.73% and the protein content ranged from 16.72%-27.79%. A significant negative correlation of the oil content with the protein content was found in the population. A total of 19 markers for oil content were detected with a R2 value range from 4% to 29%; 24 markers for protein content were detected with a R2 value range from 3% to 29%, of which 19 markers were associated with both traits. Moreover, partial markers were confirmed using mixed linear model (MLM) method, which suggested that the oil and protein contents are controlled mostly by major genes. Allele effect analysis showed that the allele associated with high oil content was always associated with low protein content, and vice versa. Of the 19 markers associated with oil content, 17 presented near the locations of the plant lipid pathway genes and 2 were located just next to a fatty acid elongation gene and a gene encoding Stearoyl-ACP Desaturase, respectively. The findings provided a valuable foundation for oil synthesis gene identification and molecular marker assistant selection (MAS) breeding in sesame.


Sleep disturbances and predictors of nondeployability among active-duty Army soldiers: an odds ratio analysis of medical healthcare data from fiscal year 2018.
The impact of sleep disorders on active-duty soldiers' medical readiness is not currently quantified. Patient data generated at military treatment facilities can be accessed to create research reports and thus can be used to estimate the prevalence of sleep disturbances and the role of sleep on overall health in service members. The current study aimed to quantify sleep-related health issues and their impact on health and nondeployability through the analysis of U.S. military healthcare records from fiscal year 2018 (FY2018). Medical diagnosis information and deployability profiles (e-Profiles) were queried for all active-duty U.S. Army patients with a concurrent sleep disorder diagnosis receiving medical care within FY2018. Nondeployability was predicted from medical reasons for having an e-Profile (categorized as sleep, behavioral health, musculoskeletal, cardiometabolic, injury, or accident) using binomial logistic regression. Sleep e-Profiles were investigated as a moderator between other e-Profile categories and nondeployability. Out of 582,031 soldiers, 48.4% (n = 281,738) had a sleep-related diagnosis in their healthcare records, 9.7% (n = 56,247) of soldiers had e-Profiles, and 1.9% (n = 10,885) had a sleep e-Profile. Soldiers with sleep e-Profiles were more likely to have had a motor vehicle accident (pOR (prevalence odds ratio) =4.7, 95% CI 2.63-8.39, P ≤ 0.001) or work/duty-related injury (pOR = 1.6, 95% CI 1.32-1.94, P ≤ 0.001). The likelihood of nondeployability was greater in soldiers with a sleep e-Profile and a musculoskeletal e-Profile (pOR = 4.25, 95% CI 3.75-4.81, P ≤ 0.001) or work/duty-related injury (pOR = 2.62, 95% CI 1.63-4.21, P ≤ 0.001). Nearly half of soldiers had a sleep disorder or sleep-related medical diagnosis in 2018, but their sleep problems are largely not profiled as limitations to medical readiness. Musculoskeletal issues and physical injury predict nondeployability, and nondeployability is more likely to occur in soldiers who have sleep e-Profiles in addition to these issues. Addressing sleep problems may prevent accidents and injuries that could render a soldier nondeployable.