Moving forward with dignity: Exploring health awareness in an isolated Deaf community of Australia.
Those within the Deaf community are disadvantaged in a number of aspects of day-to-day life including their access to health care. At times, they may encounter barriers to health care even before they reach the consultation room. As a consequence, they may receive insufficient and inappropriate health care which may lead to poorer health outcomes. A study was conducted to explore health awareness and access to health information and services of Deaf people living in Tasmania, Australia and identify ways of enhancing the interaction between the Deaf and the wider community. A questionnaire was administered, including a number of demographic, health awareness and health service usage questions. In addition, semi-structured interviews and focus groups were conducted with service providers and the Deaf community between March and August 2014. An interpreter was present to translate the questions into Auslan and who then translated the Deaf participant's discussion into English for the researcher. Data were then analyzed using research software SPSS v20.0 and NVivo 10.0. Health as a concept was poorly understood, including mental health, sexual health and health concerning alcohol and drug abuse. Regarding health care resources, due to a sense of security, trust and confidence, the family physician or general practitioner was the single most important health care provider among the Deaf. The Deaf remain underserved by the current health care system; however, through resourcefulness and life experiences, the Deaf have developed coping and management strategies to move forward with dignity in education, meaningful employment and health access.


Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1.
Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.


The prevalence and identity of Chlamydia-specific IgE in children with asthma and other chronic respiratory symptoms.
Recent studies have confirmed the presence of viable Chlamydia in the bronchoalveolar lavage (BAL) fluid of pediatric patients with airway hyperresponsiveness. While specific IgG and IgM responses to C. pneumoniae are well described, the response and potential contribution of Ag-specific IgE are not known. The current study sought to determine if infection with Chlamydia triggers the production of pathogen-specific IgE in children with chronic respiratory diseases which might contribute to inflammation and pathology. We obtained BAL fluid and serum from pediatric respiratory disease patients who were generally unresponsive to corticosteroid treatment as well as sera from age-matched control patients who saw their doctor for wellness checkups. Chlamydia-specific IgE was isolated from BAL and serum samples and their specificity determined by Western blot techniques. The presence of Chlamydia was confirmed by species-specific PCR and BAL culture assays. Chlamydial DNA was detected in the BAL fluid of 134/197 (68%) patients. Total IgE increased with age until 15 years old and then decreased. Chlamydia-specific IgE was detected in the serum and/or BAL of 107/197 (54%) patients suffering from chronic respiratory disease, but in none of the 35 healthy control sera (p < 0.0001). Of the 74 BAL culture-positive patients, 68 (91.9%, p = 0.0001) tested positive for Chlamydia-specific IgE. Asthmatic patients had significantly higher IgE levels compared to non-asthmatics (p = 0.0001). Patients who were positive for Chlamydia DNA or culture had significantly higher levels of serum IgE compared to negative patients (p = 0.0071 and p = 0.0001 respectively). Only 6 chlamydial antigens induced Chlamydia-specific IgE and patients with C. pneumoniae-specific IgE had significantly greater levels of total IgE compared to C. pneumoniae-specific IgE negative ones (p = 0.0001). IgE antibodies play a central role in allergic inflammation; therefore production of Chlamydia-specific IgE may prove significant in the exacerbation of chronic, allergic airway diseases, thus highlighting a direct role for Chlamydia in asthma pathogenesis.


Effects of changes in experimental design on PET studies of isometric force.
Based on single-cell recordings in primates, the relationship between neuronal activity and force magnitude is thought to be monotonic, at least for a subset of pyramidal cells in the motor cortex. Functional neuroimaging studies have also suggested a monotonic relationship between cerebral activation and force magnitude. In order to more precisely define this relationship and to characterize the activation pattern(s) associated with the modulation of static force, we studied 40 normal subjects using [(15)O]water PET and a simple visuomotor task-application of static force on a micro force sensor with the thumb and index finger of the right hand. When our experimental design did not produce the expected result (evidence of a relationship between cerebral activation and force magnitude in ten subjects), we made serial changes in the experimental protocol, including the addition of control (baseline) trials, and increased the number of subjects in an effort to increase our sensitivity to variations in force magnitude. We compared univariate and multivariate data-analytic strategies, but we relied on our multivariate results to elucidate the interaction of attentional and motor networks. We found that increasing the number of subjects from 10 to 20 resulted in an increase in statistical power and a more stable (i.e., more replicable) but qualitatively similar result, and that the inclusion of control trials in a 10-subject group did not enhance our ability to discern significant brain-behavior relationships. Our results suggest that sample sizes greater than 20 may be required to detect parametric variation in some instances and that failure to detect such variation may result from unanticipated neurobehavioral effects.


Foot orthoses for people with rheumatoid arthritis, involving quantitative and qualitative outcomes: protocol for a randomised controlled trial.
Rheumatoid arthritis (RA) involves changes to foot structure and function, and there is an association between RA and foot pain. This pain affects those patient's physical activity and experience of daily living. While there is clinical evidence for the value of foot orthoses (FO) on foot pain, there is a wide range of FO available and there is little evidence on the relative benefits of one orthoses type over another, especially in terms of their impact on physical activity and associated well-being. The aim of this study is to compare physical activity, general and foot health and foot health experiences in people with RA when wearing three different types of FO. A randomised controlled trial with three arms will compare the effects of (1) custom FO made using a direct adaptation technique, (2) custom FO made through a digital design and production process and (3) prefabricated orthoses. The primary outcome is physical activity measured using a GENEActiv bracelet. Secondary outcomes will be pain, function and disability and associated foot and general health evaluated using existing questionnaires. Semistructured interviews will identify patients' experiences of the orthoses and living with RA. The study has been approved by the Portal de Ética de la Investigación Biomédica de Andalucía ethical committee (SPAR-001). The results will be disseminated regardless of the magnitude or direction of effect. NCT03170947; Pre-results.


Quantitative Adverse Outcome Pathways and Their Application to Predictive Toxicology.
A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose-response, and time-course predictions that can support regulatory decision-making. Herein we describe several facets of qAOPs, including (a) motivation for development, (b) technical considerations, (c) evaluation of confidence, and (d) potential applications. The qAOP used as an illustrative example for these points describes the linkage between inhibition of cytochrome P450 19A aromatase (the MIE) and population-level decreases in the fathead minnow (FHM; Pimephales promelas). The qAOP consists of three linked computational models for the following: (a) the hypothalamic-pitutitary-gonadal axis in female FHMs, where aromatase inhibition decreases the conversion of testosterone to 17β-estradiol (E2), thereby reducing E2-dependent vitellogenin (VTG; egg yolk protein precursor) synthesis, (b) VTG-dependent egg development and spawning (fecundity), and (c) fecundity-dependent population trajectory. While development of the example qAOP was based on experiments with FHMs exposed to the aromatase inhibitor fadrozole, we also show how a toxic equivalence (TEQ) calculation allows use of the qAOP to predict effects of another, untested aromatase inhibitor, iprodione. While qAOP development can be resource-intensive, the quantitative predictions obtained, and TEQ-based application to multiple chemicals, may be sufficient to justify the cost for some applications in regulatory decision-making.


Healthcare Costs, School Performance, and Health-related Quality of Life in Adolescence Following Psychotic Experiences in Preadolescence: A Longitudinal Cohort Study.
Psychotic experiences (PEs) are common in the general population in preadolescence. The implications of PEs on socioeconomic outcomes, including educational attainment, are scarcely described. We aimed to estimate how preadolescent PEs were associated with later healthcare costs, school performance, and health-related quality of life (HRQoL) in adolescence. A total of 1607 preadolescents from the general population Copenhagen Child Cohort 2000 were assessed for PEs at age 11-12 years and followed up over 5 years using register-based data on mental and somatic healthcare costs, and school performance at age 16. Furthermore, HRQoL was assessed for a subsample of the children at age 16-17. We adjusted for perinatal and family sociodemographic adversities, prior parental mental illness and healthcare use, child IQ-estimate at age 11-12, and parent-rated general psychopathology of their child. PEs were associated with slightly poorer school performance. However, preadolescents with PEs more often reported HRQoL within the lowest 10th percentile (OR = 2.74 [95% CI 1.71-4.37]). Preadolescents who reported PEs had higher average total healthcare costs over the following 5 years. The costs for individuals with PEs were higher for mental healthcare services across primary to tertiary care, but not for somatic care. After adjustments, PEs remained independently associated with higher costs and poorer HRQoL, but not with poorer school performance. In conclusion, PEs are important in mental health screening of preadolescents and identify a group of young people with increased healthcare service-use throughout adolescence and who report poorer HRQoL in adolescence, over and above parent-rated general psychopathology of their child.


Microindentation for in vivo measurement of bone tissue material properties in atypical femoral fracture patients and controls.
Atypical femoral fractures (AFF) associated with long-term bisphosphonates (LTB) are a growing concern. Their etiology is unknown, but bone material properties might be deteriorated. In an AFF series, we analyzed the bone material properties by microindentation. Four groups of patients were included: 6 AFF, 38 typical osteoporotic fractures, 6 LTB, and 20 controls without fracture. Neither typical osteoporotic fractures nor controls have received any antiosteoporotic medication. A general laboratory workup, bone densitometry by dual-energy X-ray absorptiometry (DXA), and microindentation testing at the tibia were done in all patients. Total indentation distance (Total ID), indentation distance increase (IDI), and creep indentation distance (Creep ID) were measured (microns). Age-adjusted analysis of covariance (ANCOVA) was used for comparisons. Controls were significantly younger than fracture groups. Bisphosphonate exposure was on average 5.5 years (range 5 to 12 years) for the AFF and 5.4 years (range 5 to 8 years) for the LTB groups. Total ID (microns) showed better material properties (lower Total ID) for controls 36 (± 6; mean ± SD) than for AFF 46 (± 4) and for typical femoral fractures 47 (± 13), respectively. Patients on LTB showed values between controls and fractures, 38 (± 4), although not significantly different from any of the other three groups. IDI values showed a similar pattern 13 (± 2), 16 (± 6), 19 (± 3), and 18 (± 5). After adjusting by age, significant differences were seen between controls and typical (p < 0.001) and atypical fractures (p = 0.03) for Total ID and for IDI (p < 0.001 and p < 0.05, respectively). There were no differences in Creep ID between groups. Our data suggest that patients with AFF have a deep deterioration in bone material properties at a tissue level similar to that for the osteoporotic fracture group. The LTB group shows levels that are in between controls and both type of fractures, although not statistically different. These results suggest that bisphosphonate therapy probably does not put the majority of patients at risk for AFF.


Protective effect of Curcuma longa L. extract on CCl4-induced acute hepatic stress.
The Curcuma longa L. (CLL) rhizome has long been used to treat patients with hepatic dysfunction. CLL is a member of the ginger family of spices that are widely used in China, India, and Japan, and is a common spice, coloring, flavoring, and traditional medicine. This study was performed to evaluate the hepatoprotective activity of CLL extract and its active component curcumin in an acute carbon tetrachloride (CCl4)-induced liver stress model. Acute hepatic stress was induced by a single intraperitoneal injection of CCl4 (0.1 ml/kg body weight) in rats. CLL extract was administered once a day for 3 days at three dose levels (100, 200, and 300 mg/kg/day) and curcumin was administered once a day at the 200 mg/kg/day. We performed alanine transaminase (ALT) and aspartate transaminase (AST). activity analysis and also measured total lipid, triglyceride, and cholesterol levels, and lipid peroxidation. At 100 g CLL, the curcuminoid components curcumin (901.63 ± 5.37 mg/100 g), bis-demethoxycurcumin (108.28 ± 2.89 mg/100 g), and demethoxycurcumin (234.85 ± 1.85 mg/100 g) were quantified through high liquid chromatography analysis. In CCl4-treated rats, serum AST and ALT levels increased 2.1- and 1.2-fold compared with the control. AST but not ALT elevation induced by CCl4 was significantly alleviated in CLL- and curcumin-treated rats. Peroxidation of membrane lipids in the liver was significantly prevented by CLL (100, 200, and 300 mg/kg/day) on tissue lipid peroxidation assay and immunostaining with anti-4HNE antibody. We found that CLL extract and curcumin exhibited significant protection against liver injury by improving hepatic superoxide dismutase (p < 0.05) and glutathione peroxidase activity, and glutathione content in the CCl4-treated group (p < 0.05), leading to a reduced lipid peroxidase level. Our data suggested that CLL extract and curcumin protect the liver from acute CCl4-induced injury in a rodent model by suppressing hepatic oxidative stress. Therefore, CLL extract and curcumin are potential therapeutic antioxidant agents against acute hepatotoxicity.


Verbal and spatial analogical reasoning in deaf and hearing children: the role of grammar and vocabulary.
The extent to which cognitive development and abilities are dependent on language remains controversial. In this study, the analogical reasoning skills of deaf and hard of hearing children are explored. Two groups of children (deaf and hard of hearing children with either cochlear implants or hearing aids and hearing children) completed tests of verbal and spatial analogical reasoning. Their vocabulary and grammar skills were also assessed to provide a measure of language attainment. Results indicated significant differences between the deaf and hard of hearing children (regardless of type of hearing device) and their hearing peers on vocabulary, grammar, and verbal reasoning tests. Regression analyses revealed that in the group of deaf and hard of hearing children, but not in the hearing group, the language measures were significant predictors of verbal analogical reasoning, when age and spatial analogical reasoning ability were controlled for. The implications of these findings are discussed.


Measuring the residual stress in dental composites using a ring slitting method.
The objective of this experiment was to employ the ring slitting method for the measurement of the residual stress (RS) produced in dental composite materials after polymerization. This study was designed to determine the effect of slitting and measuring time on the residual stress. Rings were made in a split brass mold from three composites (Z100/3MESPE; Herculite/Kerr; Heliomolar/Ivoclar) and cured in a Triad II (Dentsply). Two points were scribed, and the rings were slit at either 1 h (Early-group) or 24 h (Delayed-group) after curing the composite. The change in the distance between the scribed points was measured using an image analyzer system at both 1 and 24 h after slitting. From the measured change, circumferential RS was calculated and statistically analyzed with ANOVA/Tukey's (P<0.05). The degree of conversion of each composite at 1 and 24 h was measured with FTIR and analyzed using Student's t-test (P<0.05). In general, the residual stress (range=0.42-2.84 MPa) was highest for Z100 and lowest for Heliomolar, but this depended upon the test conditions. The early cut (1 h slitting), 24 h measurement groups showed the highest residual stress values. This study, describes a ring slitting method to measure residual stress generated in dental composites during and after curing. The stress of composite can be affected by the cutting and measurement time.


Comprehensive Profiling of the Androgen Receptor in Liquid Biopsies from Castration-resistant Prostate Cancer Reveals Novel Intra-AR Structural Variation and Splice Variant Expression Patterns.
Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy. We performed profiling of circulating tumour DNA via low-pass whole-genome sequencing and targeted sequencing of the entire AR gene, including introns. Targeted RNA sequencing was performed on enriched circulating tumour cell fractions to assess the expression levels of seven AR splice variants (ARVs). Somatic AR variations, including copy-number alterations, structural variations, and point mutations, were combined with ARV expression patterns and correlated to clinicopathologic parameters. Collectively, any AR perturbation, including ARV, was detected in 25/30 patients. Surprisingly, intra-AR structural variation was present in 15/30 patients, of whom 14 expressed ARVs. The majority of ARV-positive patients expressed multiple ARVs, with AR-V3 the most abundantly expressed. The presence of any ARV was associated with progression-free survival after second-line endocrine treatment (hazard ratio 4.53, 95% confidence interval 1.424-14.41; p=0.0105). Six out of 17 poor responders were AR-V7-negative, but four carried other AR perturbations. Comprehensive AR profiling, which is feasible using liquid biopsies, is necessary to increase our understanding of the mechanisms underpinning resistance to endocrine treatment. Alterations in the androgen receptor are associated with endocrine treatment outcomes. This study demonstrates that it is possible to identify different types of alterations via simple blood draws. Follow-up studies are needed to determine the effect of such alterations on hormonal therapy.


Stronger feelings of loneliness among Moroccan and Turkish older adults in the Netherlands: in search for an explanation.
The prevalence of loneliness among Turkish-Dutch and Moroccan-Dutch older adults is higher than among Dutch older adults of non-migrant origin. Three explanations may account for this difference: (1) differential item functioning might result in scores that vary in intensity and in meaning across categories; (2) the position of migrants is much more vulnerable than that of non-migrants; (3) the lack of protective factors has more severe consequences for older migrants. The Longitudinal Aging Study Amsterdam interviewed 176 persons born in Morocco and 235 born in Turkey, aged 55-66 and living in urban areas. They are compared with a matched sample of 292 Dutch persons. The psychometric properties of the loneliness scale are satisfying, although there is some differential item functioning. Older migrants have more frequent social contacts but are at a disadvantage in other domains. Taking into account differences in social participation, satisfaction with income, mastery and depressive symptoms, the difference between older migrants' and non-migrants' loneliness is reduced by more than half. Protective factors are equally important for older migrants and non-migrants. Exceptions are marriage (less protective for Moroccans), frequent contact with children/children-in-law (mostly for Turks), a higher educational level (protects Moroccans and Turks) and better physical functioning (less for Turks). Being an older migrant and belonging to a minority might further contribute to feelings of loneliness. Interventions can be directed at stimulating social contact, but also at aspects like enhancing the appreciation of their social status and avoiding negative interpretations of a situation.


OxyR-dependent formation of DNA methylation patterns in OpvABOFF and OpvABON cell lineages of Salmonella enterica.
Phase variation of the Salmonella enterica opvAB operon generates a bacterial lineage with standard lipopolysaccharide structure (OpvAB(OFF)) and a lineage with shorter O-antigen chains (OpvAB(ON)). Regulation of OpvAB lineage formation is transcriptional, and is controlled by the LysR-type factor OxyR and by DNA adenine methylation. The opvAB regulatory region contains four sites for OxyR binding (OBSA-D), and four methylatable GATC motifs (GATC1-4). OpvAB(OFF) and OpvAB(ON) cell lineages display opposite DNA methylation patterns in the opvAB regulatory region: (i) in the OpvAB(OFF) state, GATC1 and GATC3 are non-methylated, whereas GATC2 and GATC4 are methylated; (ii) in the OpvAB(ON) state, GATC2 and GATC4 are non-methylated, whereas GATC1 and GATC3 are methylated. We provide evidence that such DNA methylation patterns are generated by OxyR binding. The higher stability of the OpvAB(OFF) lineage may be caused by binding of OxyR to sites that are identical to the consensus (OBSA and OBSc), while the sites bound by OxyR in OpvAB(ON) cells (OBSB and OBSD) are not. In support of this view, amelioration of either OBSB or OBSD locks the system in the ON state. We also show that the GATC-binding protein SeqA and the nucleoid protein HU are ancillary factors in opvAB control.


Ring currents in icosahedral c60.
A new formulation of the current within the London approximation allows the calculation of ring currents in topologically complex molecules. Application of this theory to C(60) demonstrates the existence of remarkable pi electron ring currents. Paramagnetic currents, in size comparable to the ones in benzene, flow within the pentagons, whereas weaker diamagnetic currents flow all around the C.(60) molecule. The overall vanishing ring-current magnetic susceptibility results from a cancellation of diamagnetic and paramagnetic contributions. The presence of ring currents significantly affects chemical shifts as measured in nuclear magnetic resonance experiments. In contrast to the magnetic susceptibility, which is a property of the molecule as a whole, chemical shifts are sensitive to the local magnetic field and the effect of ring currents does not vanish.


Spatial distribution of doubly scattered polarized laser radiation in the focal plane of a lidar receiver.
Depolarization lidars are widely used to study clouds and aerosols because of their ability to discriminate between spherical particles and particles of irregular shape. Depolarization of cloud backscattered radiation can be caused also by multiple scattering events. One of the ways to gain information about particle parameters in the presence of strong multiple scattering is the measurement of radial and azimuthal dependence of the polarization patterns in the focal plane of receiver. We present an algorithm for the calculation of corresponding polarized patterns in the frame of double scattering approximation. Computations are performed for various receiver field of views, for different parameters of the scattering geometry, e.g., cloud base and sounding depth, as well as for different values of cloud particle size and refractive index. As the spatial distribution of cross-polarized radiation is of cross shape and rotated at 45 degrees with respect to laser polarization, the use of a properly oriented cross-shaped mask in the receiver focal plane allows the removal of a significant portion of the depolarized component of the backscattered radiation produced by double scattering. This has been verified experimentally based on cloud depolarization measurements performed at different orientations of the cross-shaped mask. Results obtained from measurements are in agreement with model predictions.


The impact of a Post-Take Ward Round Pharmacist on the Risk Score and Enactment of Medication-Related Recommendations.
There is a scarcity of published research describing the impact of a pharmacist on the post-take ward round (PTWR) in addition to ward-based pharmacy services. The aim of this paper was to evaluate the impact of clinical pharmacists' participation on the PTWR on the risk assessment scores of medication-related recommendations with and without a pharmacist. This includes medication-related recommendations occurring on the PTWR and those recommendations made by the ward-based pharmacist on the inpatient ward. A pre-post intervention study was undertaken that compared the impact of adding a pharmacist to the PTWR compared with ward-based pharmacist services alone. A panel reviewed the risk of not acting on medication recommendations that was made on the PTWR and those recorded by the ward-based pharmacist. The relationship between the risk scores and the number and proportion of recommendations that led to action were compared between study groups. There were more medication-related recommendations on the PTWR in the intervention group when a pharmacist was present. Proportionately fewer were in the 'very high and extreme' risk category. Although there was no difference in the number of ward pharmacist recommendations between groups, there was a significantly higher proportion of ward pharmacist recommendations in the "very high and extreme" category in those patients who had been seen on a PTWR attended by a pharmacist than when a pharmacist was not present. There were a greater proportion of "low and medium" risk actionable medication recommendations actioned on the PTWR in the intervention group; and no difference in the risk scores in ward pharmacist recommendations actioned between groups. Overall, the proportion of recommendations that were actioned was higher for those made on the PTWR compared with the ward. The addition of a pharmacist to the PTWR resulted in an increase in low, medium, and high risk recommendations on the PTWR, more very high and extreme risk recommendations made by the ward-based pharmacist, plus an increased number of recommendations being actioned during the patients' admission.


Transgene and immune gene expression following intramuscular injection of Atlantic salmon (Salmo salar L.) with DNA-releasing PLGA nano- and microparticles.
The use of poly-(D,L-lactic-co-glycolic) acid (PLGA) particles as carriers for DNA delivery has received considerable attention in mammalian studies. DNA vaccination of fish has been shown to elicit durable transgene expression, but no reports exist on intramuscular administration of PLGA-encapsulated plasmid DNA (pDNA). We injected Atlantic salmon (Salmo salar L.) intramuscularly with a plasmid vector containing a luciferase (Photinus pyralis) reporter gene as a) naked pDNA, b) encapsulated into PLGA nano- (~320 nm) (NP) or microparticles (~4 μm) (MP), c) in an oil-based formulation, or with empty particles of both sizes. The ability of the different pDNA-treatments to induce transgene expression was analyzed through a 70-day experimental period. Anatomical distribution patterns and depot effects were determined by tracking isotope labeled pDNA. Muscle, head kidney and spleen from all treatment groups were analyzed for proinflammatory cytokines (TNF-α, IL-1β), antiviral genes (IFN-α, Mx) and cytotoxic T-cell markers (CD8, Eomes) at mRNA transcription levels at days 1, 2, 4 and 7. Histopathological examinations were performed on injection site samples from days 2, 7 and 30. Injection of either naked pDNA or the oil-formulation was superior to particle treatments for inducing transgene expression at early time-points. Empty particles of both sizes were able to induce proinflammatory immune responses as well as degenerative and inflammatory pathology at the injection site. Microparticles demonstrated injection site depots and an inflammatory pathology comparable to the oil-based formulation. In comparison, the distribution of NP-encapsulated pDNA resembled that of naked pDNA, although encapsulation into NPs significantly elevated the expression of antiviral genes in all tissues. Together the results indicate that while naked pDNA is most efficient for inducing transgene expression, the encapsulation of pDNA into NPs up-regulates antiviral responses that could be of benefit to DNA vaccination.


Deliberate self-harm in children and adolescents: a research update.
We outline research developments in 2004 and early 2005 published in English language journals on deliberate self-harm among children and adolescents up to the age of 18 years. The main issue of concern in recent times has been the risk/benefit profile of using antidepressants, especially selective serotonin reuptake inhibitors, in depressed children and adolescents. Other important topics include treatment approaches, particularly cognitive behaviour therapy, dialectical behaviour therapy and multisystemic therapy, barriers to help seeking, the Internet and prevention. Rates of deliberate self-harm appear to be rising among young people. Risk factors associated with deliberate self-harm are becoming clearer and the evaluation of treatments is progressing. However, the recent conflicting evidence and guidelines regarding selective serotonin reuptake inhibitors and suicidality are presenting major difficulties for clinicians. The role of the Internet and initiatives to prevent suicidal behaviour in adolescents require further research.


Investigating the Use of a Dynamic Physical Bar Chart for Data Exploration and Presentation.
Physical data representations, or data physicalizations, are a promising new medium to represent and communicate data. Previous work mostly studied passive physicalizations which require humans to perform all interactions manually. Dynamic shape-changing displays address this limitation and facilitate data exploration tasks such as sorting, navigating in data sets which exceed the fixed size of a given physical display, or preparing "views" to communicate insights about data. However, it is currently unclear how people approach and interact with such data representations. We ran an exploratory study to investigate how non-experts made use of a dynamic physical bar chart for an open-ended data exploration and presentation task. We asked 16 participants to explore a data set on European values and to prepare a short presentation of their insights using a physical display. We analyze: (1) users' body movements to understand how they approach and react to the physicalization, (2) their hand-gestures to understand how they interact with physical data, (3) system interactions to understand which subsets of the data they explored and which features they used in the process, and (4) strategies used to explore the data and present observations. We discuss the implications of our findings for the use of dynamic data physicalizations and avenues for future work.


Self-reported musculoskeletal pain predicts long-term increase in general health care use: a population-based cohort study with 20-year follow-up.
Musculoskeletal pain and disability is a modern epidemic and a major reason for seeking health care. The aim of this study is to determine absolute and relative rates of care seeking over 20 years for adults reporting musculoskeletal complaints. Interview data on musculoskeletal pain reported during the past two weeks from the Danish National Cohort Study were merged with data from the Danish National Health Insurance Registry and the National Patient Registry containing information on consultations in the Danish primary and secondary care sector. Absolute and relative rates for all seeking of care with general practitioners, physiotherapists, chiropractors, outpatient hospital contacts and hospital admissions are reported for persons reporting no musculoskeletal pain and for persons reporting pain in the neck, shoulder, wrist/hands, mid back, low back, hips, knees and ankles/feet. Regardless of site, persons experiencing a musculoskeletal complaint had a statistically increased risk of consulting a general practitioner when compared with persons reporting no musculoskeletal complaint. For physiotherapists and chiropractors, only persons complaining of neck pain and back pain had an increased risk of seeking care. Regardless of pain site, except for shoulder pain, persons reporting musculoskeletal pain had a statistically significant increased risk of outpatient hospital consultations and hospital admissions. Few differences were found between pain sites in relation to any of the outcomes. Self-report of musculoskeletal pain reported within the past two weeks predicts a statistically significant long-term increase in general use of health care services in both the primary and the secondary health care sector.


In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells.
Multipotent stem cells have been successfully isolated from various tissues and are currently utilized for tissue-engineering and cell-based therapies. Among the many sources, skin has recently emerged as an attractive source for multipotent cells because of its abundance. Recent literature showed that skin stromal cells (SSCs) possess mesoderm lineage differentiation potential; however, the endothelial differentiation and angiogenic potential of SSC remains elusive. In our study, SSCs were isolated from human neonatal foreskin (hNFSSCs) and adult dermal skin (hADSSCs) using explants cultures and were compared with bone marrow (hMSC-TERT) and adipose tissue-derived mesenchymal stem cells (hADMSCs) for their potential differentiation into osteoblasts, adipocytes, and endothelial cells. Concordant with previous studies, both MSCs and SSCs showed similar morphology, surface protein expression, and were able to differentiate into osteoblasts and adipocytes. Using an endothelial induction culture system combined with an in vitro matrigel angiogenesis assay, hNFSSCs and hADSSCs exhibited the highest tube-forming capability, which was similar to those formed by human umbilical vein endothelial cells (HUVEC), with hNFSSCs forming the most tightly packed, longest, and largest diameter tubules among the three cell types. CD146 was highly expressed on hNFSSCs and HUVEC followed by hADSSCs, and hMSC-TERT, while its expression was almost absent on hADMSCs. Similarly, higher vascular density (based on the expression of CD31, CD34, vWF, CD146 and SMA) was observed in neonatal skin, followed by adult dermal skin and adipose tissue. Thus, our preliminary data indicated a plausible relationship between vascular densities, and the expression of CD146 on multipotent cells derived from those tissues. Our data is the first to demonstrate that human dermal skin stromal cells can be differentiated into endothelial lineage. Hence, SSCs represents a novel source of stem/stromal cells for tissue regeneration and the vascularization of engineered tissues. Moreover, the CD146 investigations suggested that the microenvironmental niche might contribute to direct stromal cells multipotency toward certain lineages, which warrants further investigation.


Monte Carlo vs. pencil beam based optimization of stereotactic lung IMRT.
The purpose of the present study is to compare finite size pencil beam (fsPB) and Monte Carlo (MC) based optimization of lung intensity-modulated stereotactic radiotherapy (lung IMSRT). A fsPB and a MC algorithm as implemented in a biological IMRT planning system were validated by film measurements in a static lung phantom. Then, they were applied for static lung IMSRT planning based on three different geometrical patient models (one phase static CT, density overwrite one phase static CT, average CT) of the same patient. Both 6 and 15 MV beam energies were used. The resulting treatment plans were compared by how well they fulfilled the prescribed optimization constraints both for the dose distributions calculated on the static patient models and for the accumulated dose, recalculated with MC on each of 8 CTs of a 4DCT set. In the phantom measurements, the MC dose engine showed discrepancies < 2%, while the fsPB dose engine showed discrepancies of up to 8% in the presence of lateral electron disequilibrium in the target. In the patient plan optimization, this translates into violations of organ at risk constraints and unpredictable target doses for the fsPB optimized plans. For the 4D MC recalculated dose distribution, MC optimized plans always underestimate the target doses, but the organ at risk doses were comparable. The results depend on the static patient model, and the smallest discrepancy was found for the MC optimized plan on the density overwrite one phase static CT model. It is feasible to employ the MC dose engine for optimization of lung IMSRT and the plans are superior to fsPB. Use of static patient models introduces a bias in the MC dose distribution compared to the 4D MC recalculated dose, but this bias is predictable and therefore MC based optimization on static patient models is considered safe.


Hybrid terahertz plasmonic waveguide for sensing applications.
The suitability of a terahertz plasmonic sensor for sensing applications is successfully demonstrated using a hybrid planar waveguide composed of a subwavelength plastic ribbon waveguide and a diffraction metal grating. The subwavelength-confined terahertz plasmons on the hybrid waveguide resonantly reflect from the periodic metal structure under phase-matched conditions and perform resonant transmission dips. The resonant plasmonic frequencies are found to be strongly dependent on the refractive indices and thicknesses of analytes laid on the hybrid planar waveguide. Both plastic films with varying thicknesses and granular analytes in different quantities are successfully identified according to the spectral shifts of resonant dips. An optimal refractive index sensitivity of 261 GHz per refractive index unit is achieved. Within localized and enhanced terahertz plasmonic fields, the minimum detectable optical path difference can be reduced to 2.7 μm corresponding to λ/289, and the minimum detectable amount of analytes in powdered form reaches 17.3 nano-mole/mm(2). The sensing technique can be used to detect particles in a chemical reaction or monitor pollutants.


For3D: Full organ reconstruction in 3D, an automatized tool for deciphering the complexity of lymphoid organs.
To decipher the complex topology of lymphoid structures, we developed an automated process called Full Organ Reconstruction in 3D (For3D). A dedicated image-processing pipeline is applied to entire collections of immunolabeled serial sections, acquired with a slide-scanning microscope. This method is automated, flexible and readily applicable in two days to frozen or paraffin-embedded organs stained by fluorescence or brightfield immunohistochemistry. 3D-reconstructed organs can be visualized, rotated and analyzed to quantify substructures of interest. Usefulness of For3D is exemplified here through topological analysis of several mouse lymphoid organs exhibiting a complex organization: (i) the thymus, composed of two compartments, a medulla intricately imbricated into a surrounding cortex, (ii) lymph nodes, also highly compartmentalized into cortex, paracortex and medulla and (iii) the vascularization of an EG7 primary thymoma. This open-source algorithm, based on ImageJ and Matlab scripts, offers a user-friendly interface and is widely applicable to any organ or tissue, hence readily adaptable to a broad range of biomedical samples.


Human V2A: A map of the peripheral visual hemifield with functional connections to scene-selective cortex.
Humans can recognize a scene in the blink of an eye. This gist-based visual scene perception is thought to be underpinned by specialized visual processing emphasizing the visual periphery at a cortical locus relatively low in the visual processing hierarchy. Using wide-field retinotopic mapping and population receptive field (pRF) modeling, we identified a new visual hemifield map anterior of area V2d and inferior to area V6, which we propose to call area V2A. Based on its location relative to other visual areas, V2A may correspond to area 23V described in nonhuman primates. The pRF analysis revealed unique receptive field properties for V2A: a large (FWHM ∼23°) and constant receptive field size across the central ∼70° of the visual field. Resting-state fMRI connectivity analysis further suggests that V2A is ideally suited to quickly feed the scene-processing network with information that is not biased towards the center of the visual field. Our findings not only indicate a likely cortical locus for the initial stages of gist-based visual scene perception, but also suggest a reappraisal of the organization of human dorsomedial occipital cortex with a strip of separate hemifield representations anterior to the early visual areas (V1, V2d, and V3d).


A new method for distinguishing colony social forms of the fire ant, Solenopsis invicta.
Two distinct forms of colony social organization occur in the fire ant Solenopsis invicta Buren (Hymenoptera: Formicidae): colonies of the monogyne social form are headed by a single egg-laying queen, whereas those of the polygyne social form contain multiple egg-laying queens. This major difference in social organization is associated with genetic variation at a single gene (Gp-9) whereby all polygyne queens possess at least one b-like allele, while monogyne queens lack such b-like alleles and instead harbor B-like alleles only. Further, a recent study of native populations revealed that all b-like alleles in polygyne queens consistently contain three diagnostic amino acid residues: possession of only one or two of these critical residues is not sufficient for polygyny. TaqMan allelic discrimination assays were developed to survey the variable nucleotide sites associated with these three critical amino acid residues. The assays were validated by surveying nests of known social form from the species' introduced in the USA and from native South American ranges, as well as by comparing the results to Gp-9 sequence data from a subset of samples. The results demonstrate these new molecular assays consistently and accurately identify the variable nucleotides at all three sites characteristic of the B-like and b-like Gp-9 allele classes, allowing for accurate determination of colony social form.


The importance of phase equilibrium for doping efficiency: iodine doped PbTe.
Semiconductor engineering relies heavily on doping efficiency and dopability. Low doping efficiency may cause low mobility and failure to reach target carrier concentrations or even the desired carrier type. Semiconducting thermoelectric materials perform best with degenerate carrier concentrations, meaning high performance in new materials might not be realized experimentally without a route to optimal doping. Doping in the classic PbTe thermoelectric system has been largely successful but reported doping efficiencies can vary, raising concerns about reproducibility. Here, we stress the importance of phase equilibria considerations during synthesis to avoid undesired intrinsic defects leading to sub-optimal doping. By saturation annealing at 973 K, we decidedly fix the composition in single crystal iodine-doped PbTe samples to be Pb-rich or Te-rich without introducing impurity phases. We show that, regardless of iodine concentration, degenerate n-type carrier concentrations with ideal doping efficiency require Pb-rich compositions. Electrons in Te-rich samples are heavily compensated by charged intrinsic Pb vacancy defects. From Hall effect measurements and a simple defect model supported by modern defect calculations, we map out the 973 K ternary Pb-Te-I phase diagram to explicitly link carrier concentration and composition. Furthermore, we discuss unintentional composition changes due to loss of volatile Te during synthesis and measurements. The methods and concepts applied here may guide doping studies on other lead chalcogenide systems as well as any doped, complex semiconductor.


Development of a teledermatopathology consultation system using virtual slides.
An online consultation system using virtual slides (whole slide images; WSI) has been developed for pathological diagnosis, and could help compensate for the shortage of pathologists, especially in the field of dermatopathology and in other fields dealing with difficult cases. This study focused on the performance and future potential of the system. In our system, histological specimens on slide glasses are digitalized by a virtual slide instrument, converted into web data, and up-loaded to an open server. Using our own purpose-built online system, we then input patient details such as age, gender, affected region, clinical data, past history and other related items. We next select up to ten consultants. Finally we send an e-mail to all consultants simultaneously through a single command. The consultant receives an e-mail containing an ID and password which is used to access the open server and inspect the images and other data associated with the case. The consultant makes a diagnosis, which is sent to us along with comments. Because this was a pilot study, we also conducted several questionnaires with consultants concerning the quality of images, operability, usability, and other issues. We solicited consultations for 36 cases, including cases of tumor, and involving one to eight consultants in the field of dermatopathology. No problems were noted concerning the images or the functioning of the system on the sender or receiver sides. The quickest diagnosis was received only 18 minutes after sending our data. This is much faster than in conventional consultation using glass slides. There were no major problems relating to the diagnosis, although there were some minor differences of opinion between consultants. The results of questionnaires answered by many consultants confirmed the usability of this system for pathological consultation. (16 out of 23 consultants.) We have developed a novel teledermatopathological consultation system using virtual slides, and investigated the usefulness of the system. The results demonstrate that our system can be a useful tool for international medical work, and we anticipate its wider application in the future. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1902376044831574.


The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL.
Cytotoxic T lymphocytes (CTL) appear to play an important role in the control of human cytomegalovirus (HCMV) in the normal virus carrier: previous studies have identified peripheral blood CD8+ CTL specific for the HCMV major immediate-early gene product (IE1) and more recently, by bulk culture and cloning techniques, have identified CTL specific for a structural gene product, the lower matrix protein pp65. In order to determine the relative contributions of CTL which recognize the HCMV proteins IE1, pp65, and glycoprotein B (gB) to the total HCMV-specific CTL response, we have used a limiting-dilution analysis system to quantify HCMV-specific CTL precursors with different specificities, allowing the antigenic specificity of multiple short-term CTL clones to be assessed, in a group of six healthy seropositive donors. All donors showed high frequencies of HCMV-specific major histocompatibility complex-restricted CTL precursors. There was a very high frequency of CTL specific for pp65 (lower matrix protein); IE1-specific CTL were also detectable at lower frequencies in three of five donors, while CTL directed to gB were undetectable. A pp65 gene deletion mutant of HCMV was then used to estimate the contribution of pp65-specific CTL to the total HCMV-specific CTL response; this showed that between 70 and 90% of all CTL recognizing HCMV-infected cells were pp65 specific. Analysis of the peptide specificity of pp65-specific CTL showed that some donors have a highly focused response recognizing a single peptide; the T-cell receptor Vbeta gene usage in these two donors was shown to be remarkably restricted, with over half of the responding CD8+ T cells utilizing a single Vbeta gene rearrangement. Other subjects recognized multiple pp65 peptides: nine new pp65 CTL peptide epitopes were defined, and for five of these the HLA-presenting allele has been identified. All four of the HLA A2 donors tested in this study recognized the same peptide. This apparent domination of the CTL response to HCMV during persistent infection by a single structural protein, irrespective of major histocompatibility complex haplotype, is not clearly described for other persistent virus infections, and the mechanism requires further investigation.


Amerindian (but not African or European) ancestry is significantly associated with diurnal preference within an admixed Brazilian population.
Significant questions remain unanswered regarding the genetic versus environmental contributions to racial/ethnic differences in sleep and circadian rhythms. We addressed this question by investigating the association between diurnal preference, using the morningness-eveningness questionnaire (MEQ), and genetic ancestry within the Baependi Heart Study cohort, a highly admixed Brazilian population based in a rural town. Analysis was performed using measures of ancestry, using the Admixture program, and MEQ from 1,453 individuals. We found an association between the degree of Amerindian (but not European of African) ancestry and morningness, equating to 0.16 units for each additional percent of Amerindian ancestry, after adjustment for age, sex, education, and residential zone. To our knowledge, this is the first published report identifying an association between genetic ancestry and MEQ, and above all, the first one based on ancestral contributions within individuals living in the same community. This previously unknown ancestral dimension of diurnal preference suggests a stratification between racial/ethnic groups in an as yet unknown number of genetic polymorphisms.


The detection of both global motion and global form is disrupted in glaucoma.
It is well known that glaucoma results in performance impairments on tasks processed early in the visual pathways. Glaucoma should also impair cortical visual processing because of reduced input from retinal ganglion cells and also possibly because of abnormal cortical function. This study was undertaken to assess whether cortically processed global percepts are disrupted in glaucoma in areas of visual field classified as normal by standard automated perimetry (SAP). Performance on global tasks (motion and form) was compared to measures of presumed precortical magnocellular and parvocellular function in the same individuals. Fifteen control subjects and 12 patients with primary open-angle glaucoma participated. Testing was performed foveally and midperipherally (12.5 degrees). Contrast-discrimination thresholds were measured by using the steady-pedestal (magnocellular) and pulsed-pedestal (parvocellular) contrast-discrimination tasks of Pokorny and Smith. Global motion coherence and global form coherence thresholds were measured at high and low contrast. Patients with glaucoma demonstrated higher global motion and form-coherence thresholds than did control subjects for targets presented in the midperiphery (P < 0.05), but not foveally. Different individuals performed poorly on the motion and form tasks. The subjects with the greatest presumed magnocellular and parvocellular loss were those with the largest deficits on the global motion and form tasks, respectively. Some subjects with glaucoma demonstrate profound impairments of global motion or global form integration in areas of visual field classified as normal by SAP. This finding implies that some people with glaucoma may have far greater difficulty with complex visual tasks (for example, navigation through the environment or face recognition) than is predicted by their visual field loss.


Job satisfaction, occupational stress, and personality characteristics of Air Force military training instructors.
The authors present findings from the preliminary stage of a research program intended to improve the selection and retention of U.S. Air Force military training instructors (MTIs). Data derived from an initial sample of 100 incumbent instructors are discussed. Global job satisfaction and occupational stress levels, along with normal personality traits measured by the Revised NEO Personality Inventory, are presented. Results indicate a wide range of reported job satisfaction and stress among MTIs, with a sizable proportion indicating that they would not volunteer for this duty again. Several personality characteristics appear to be salient in distinguishing satisfied and adaptive MTIs from those who are unsatisfied and coping poorly. The authors outline plans for the long-term continuation and expansion of the project to develop an empirically based selection system for the MTI career field.


Role of tobacco smoking in hangover symptoms among university students.
Although hangover results from excessive alcohol consumption, the specific pathways through which hangover symptoms arise have not been elucidated. Research on predictors of hangover sensitivity may provide clues about such mechanisms. The present study investigated whether tobacco smoking on days of heavy drinking affects next-day hangover incidence and severity. The study drew on diary data from a study on smoking and drinking among 113 students at a midwestern university in the United States. Participants completed a daily, web-based, 26-item survey for 8 weeks to assess prior-day alcohol and tobacco use as well as current-day hangover symptoms. Hierarchical linear modeling was used to test the hypothesis that amount of smoking is related to hangover, controlling for amount of alcohol consumed, sex, and other individual characteristics. Analyses were conducted after selecting only days with alcohol consumption levels that typically elicit hangover, then repeated on lighter drinking days for comparison. Validity of the hangover items was checked by comparing reports after such heavy drinking days with days of lighter drinking. Across all possible person-days, 92% of daily reports were obtained. When selecting only events where an estimated blood alcohol concentration of 110 mg/dl was attained, smoking significantly increased the odds of hangover incidence and hangover severity while controlling for number of drinks consumed and sex. Additional analyses controlling for age first smoked regularly, frequency of drug use, type of drug involvement, or smoking status resulted in findings that were unchanged. Smoking more on heavy drinking days affects hangover sensitivity and severity, possibly because of acute pharmacological effects.


Development and characterization of a potent immunoconjugate targeting the Fn14 receptor on solid tumor cells.
TNF-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor (FGF)-inducible 14 (Fn14) are a TNF superfamily ligand-receptor pair involved in many cellular processes including proliferation, migration, differentiation, inflammation, and angiogenesis. The Fn14 receptor is expressed at relatively low levels in normal tissues, but it is known to be dramatically elevated in a number of tumor types, including brain and breast tumors. Thus, it seems to be an excellent candidate for therapeutic intervention. We first analyzed Fn14 expression in human tumor cell lines. Fn14 was expressed in a variety of lines including breast, brain, bladder, skin, lung, ovarian, pancreatic, colon, prostate, and cervical cancer cell lines. We then developed an immunoconjugate containing a high-affinity anti-Fn14 monoclonal antibody (ITEM-4) conjugated to recombinant gelonin (rGel), a highly cytotoxic ribosome-inactivating N-glycosidase. Both ITEM-4 and the conjugate were found to bind to cells to an equivalent extent. Confocal microscopic analysis showed that ITEM4-rGel specifically and rapidly (within 2 hours) internalized into Fn14-positive T-24 bladder cancer cells but not into Fn14-deficient mouse embryonic fibroblasts. Cytotoxicity studies against 22 different tumor cell lines showed that ITEM4-rGel was highly cytotoxic to Fn14-expressing cells and was 8- to 8 × 10(4)-fold more potent than free rGel. ITEM4-rGel was found to kill cells by inducing apoptosis with high-mobility group box 1 protein release. Finally, ITEM4-rGel immunoconjugate administration promoted long-term tumor growth suppression in nude mice bearing T-24 human bladder cancer cell xenografts. Our data support the use of an antibody-drug conjugate approach to selectively target and inhibit the growth of Fn14-expressing tumors.


Familial L723P Mutation Can Shift the Distribution between the Alternative APP Transmembrane Domain Cleavage Cascades by Local Unfolding of the Ε-Cleavage Site Suggesting a Straightforward Mechanism of Alzheimer's Disease Pathogenesis.
Alzheimer's disease is an age-related pathology associated with accumulation of amyloid-β peptides, products of enzymatic cleavage of amyloid-β precursor protein (APP) by secretases. Several familial mutations causing early onset of the disease have been identified in the APP transmembrane (TM) domain. The mutations influence production of amyloid-β, but the molecular mechanisms of this effect are unclear. The "Australian" (L723P) mutation located in the C-termini of APP TM domain is associated with autosomal-dominant, early onset Alzheimer's disease. Herein, we describe the impact of familial L723P mutation on the structural-dynamic behavior of APP TM domain studied by high-resolution NMR in membrane-mimicking micelles and augmented by molecular dynamics simulations in explicit lipid bilayer. We found L723P mutation to cause local unfolding of the C-terminal turn of the APP TM domain helix and increase its accessibility to water required for cleavage of the protein backbone by γ-secretase in the ε-site, thus switching between alternative ("pathogenic" and "non-pathogenic") cleavage cascades. These findings suggest a straightforward mechanism of the pathogenesis associated with this mutation, and are of generic import for understanding the molecular-level events associated with APP sequential proteolysis resulting in accumulation of the pathogenic forms of amyloid-β. Moreover, age-related onset of Alzheimer's disease can be explained by a similar mechanism, where the effect of mutation is emulated by the impact of local environmental factors, such as oxidative stress and/or membrane lipid composition. Knowledge of the mechanisms regulating generation of amyloidogenic peptides of different lengths is essential for development of novel treatment strategies of the Alzheimer's disease.


Mode conversion using optical analogy of shortcut to adiabatic passage in engineered multimode waveguides.
A shortcut to adiabatic mode conversion in multimode waveguides using optical analogy of stimulated Raman adiabatic passage is investigated. The design of mode converters using the shortcut scheme is discussed. Computer-generated planar holograms are used to mimic the shaped pulses used to speed up adiabatic passage in quantum systems based on the transitionless quantum driving algorithm. The mode coupling properties are analyzed using the coupled mode theory and beam propagation simulations. We show reduced device length using the shortcut scheme as compared to the common adiabatic scheme. Modal evolution in the shortened device indeed follows the adiabatic eigenmode exactly amid the violation of adiabatic criterion.


Fossil birds from the hawaiian islands: evidence for wholesale extinction by man before Western contact.
Thousands of fossil bird bones from the Hawaiian Islands collected since 1971 include remains of at least 39 species of land birds that are not known to have survived into the historic period; this more than doubles the number of endemic species of land birds previously known from the main islands. Bones were found in deposits of late Quaternary age; most are Holocene and many are contemporaneous with Polynesian culture. The loss of species of birds appears to be due to predation and destruction of lowland habitats by humans before the arrival of Europeans. Because the historically known fauna and flora of the Hawaiian Islands represent only afraction of natural species diversity, biogeographical inferences about natural processes based only on historically known taxa may be misleading or incorrect.


Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and coronary artery disease in 19 case-control studies.
We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.


The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer.
Neutrophil gelatinase associated lipocalin (NGAL), also known as oncogene 24p3, uterocalin, siderocalin or lipocalin 2, is a 24kDa secreted glycoprotein originally purified from a culture of mouse kidney cells infected with simian virus 40 (SV-40). Subsequent investigations have revealed that it is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. Since then, NGAL expression has been reported in several normal tissues where it serves to provide protection against bacterial infection and modulate oxidative stress. Its expression is also dysregulated in several benign and malignant diseases. Its small size, secreted nature and relative stability have led to it being investigated as a diagnostic and prognostic biomarker in numerous diseases including inflammation and cancer. Functional studies, conducted primarily on lipocalin 2 (Lcn2), the mouse homologue of human NGAL have revealed that Lcn2 has a strong affinity for iron complexed to both bacterial siderophores (iron-binding proteins) and certain human proteins like norepinephrine. By sequestering iron-laden siderophores, Lcn2 deprives bacteria of a vital nutrient and thus inhibits their growth (bacteriostatic effect). In malignant cells, its proposed functions range from inhibiting apoptosis (in thyroid cancer cells), invasion and angiogenesis (in pancreatic cancer) to increasing proliferation and metastasis (in breast and colon cancer). Ectopic expression of Lcn2 also promotes BCR-ABL induced chronic myelogenous leukemia in murine models. By transporting iron into and out of the cell, NGAL also regulates iron responsive genes. Further, it stabilizes the proteolytic enzyme matrix metalloprotease-9 (MMP-9) by forming a complex with it, and thereby prevents its autodegradation. The factors regulating NGAL expression are numerous and range from pro-inflammatory cytokines like interleukins, tumor necrosis factor-α and interferons to vitamins like retinoic acid. The purpose of this review article is to examine the expression, structure, regulation and biological role of NGAL and critically assess its potential as a novel diagnostic and prognostic marker in both benign and malignant human diseases.


Rad52-independent mitotic gene conversion in Saccharomyces cerevisiae frequently results in chromosomal loss.
We have examined spontaneous, interchromosomal mitotic recombination events between his4 alleles in both Rad+ and rad52 strains of Saccharomyces cerevisiae. In Rad+ strains, 74% of the His+ prototrophs resulted from gene conversion events without exchange of flanking markers. In diploids homozygous for the rad52-1 mutation, the frequency of His+ prototroph formation was less than 5% of the wild-type value, and more than 80% of the gene conversion events were accompanied by an exchange of flanking markers. Most of the rad52 intragenic recombination events arose by gene conversion accompanied by an exchange of flanking markers and not by a simple reciprocal exchange between the his4A and his4C alleles. There were also profound effects on the kinds of recombinant products that were recovered. The most striking effect was that RAD52-independent mitotic recombination frequently results in the loss of one of the two chromosomes participating in the gene conversion event.


Ultralight Dark Matter Resonates with Binary Pulsars.
We consider the scenario where dark matter (DM) is represented by an ultralight classical scalar field performing coherent periodic oscillations. We point out that such DM perturbs the dynamics of binary systems either through its gravitational field or via direct coupling to ordinary matter. This perturbation gets resonantly amplified if the frequency of DM oscillations is close to a (half-)integer multiple of the orbital frequency of the system and leads to a secular variation of the orbital period. We suggest using binary pulsars as probes of this scenario and estimate their sensitivity. While the current accuracy of observations is not yet sufficient to probe the purely gravitational effect of DM, it already yields constraints on direct coupling that are competitive with other bounds. The sensitivity will increase with the upcoming radio observatories such as the Square Kilometer Array.


Biobanking residual tissues.
Health-care research relies largely on human materials stored in highly specialised biorepositories. Medical translational research on tissues can be performed using a variety of resources in distinct situations. The best known is the secondary use of pathology archives where paraffin-embedded tissues are stored for diagnostic reasons. Another is collecting and storing frozen material obtained from leftover surgical diagnosis. Such residual tissues can either be used directly in research projects or used in the context of a clinical trial with new interventional medicinal products. The latter can make the regulations governing the use of these materials for medical research much more complicated. The use of residual materials is very distinct from biobanking projects for which tissue is specifically collected. This article describes the consequences of using residual human material from different sources in distinct situations and why signed informed consent is not always the preferred choice of individual countries regarding the use of residual material. In addition, signed informed consent is overdone when using residual tissues in medical research. We maintain that the opt-out system is a balanced choice if certain requirements are met, relating to sufficient transparency about using residual tissue for research, the purpose of such research and to the confidentiality of the data used in that research. Finally, the international exchange of samples can be based on the laws and regulations of the countries of origin. Respecting these form the basis of what can and cannot be done in the country where the research on the samples is being performed.


A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization.
The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization. Because sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle cells, we compared a sirolimus-eluting stent with a standard uncoated stent in patients with angina pectoris. We performed a randomized, double-blind trial to compare the two types of stents for revascularization of single, primary lesions in native coronary arteries. The trial included 238 patients at 19 medical centers. The primary end point was in-stent late luminal loss (the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months). Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis (luminal narrowing of 50 percent or more). We also analyzed a composite clinical end point consisting of death, myocardial infarction, and percutaneous or surgical revascularization at 1, 6, and 12 months. At six months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the sirolimus-stent group, as compared with 26.6 percent of those in the standard-stent group, had restenosis of 50 percent or more of the luminal diameter (P<0.001). There were no episodes of stent thrombosis. During a follow-up period of up to one year, the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001). The difference was due entirely to a higher rate of revascularization of the target vessel in the standard-stent group. As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events.


A low surgical Apgar score is a predictor of anastomotic leakage after transthoracic esophagectomy, but not a prognostic factor.
The surgical Apgar score (SAS) has been a useful predictor of postoperative complications in several types of cancer. However, there are few reports about the correlation of SAS and esophageal cancer. This study aimed to examine the utility of SAS as a predictor of major complications, particularly anastomotic leakage, in patients who underwent transthoracic esophagectomy, and investigate the correlation between SAS and patient prognosis. This is a single-center, retrospective observational study. A total of 190 patients who underwent esophagectomy for esophageal cancer in 2012-2016 were reviewed to find the correlation between SAS and postoperative complications (Clavien-Dindo classification III or higher). SAS was calculated based on intraoperative estimated blood loss, lowest mean arterial pressure, and lowest heart rate. Major complications included anastomotic leakage, respiratory, cardiac, recurrent nerve palsy, chylothorax, and other complications. We also reviewed how SAS was correlated with 3 year overall survival (OS) and recurrence-free survival (RFS). A high SAS was defined as ≥ 6, and a low SAS as < 6. On univariate analysis, SAS showed a statistical significance in all major complications and anastomotic leakage. On multiple logistic regression analysis, a low SAS was detected as a risk factor of the major complications and anastomotic leakage, with a significant difference. Moreover, we conducted survival analysis with SAS; however, we could not detect that a low SAS had a negative impact on OS and RFS. A low SAS can be a predictor of postoperative complications, especially anastomotic leakage. However, SAS was not correlated with OS or RFS.


Antibodies to peptides corresponding to a conserved sequence of gonococcal pilins block bacterial adhesion.
Antisera generated against each of seven synthetic peptides corresponding to constant and variable sequences of the pilin from gonococcal strain MS11 were assayed for their ability to crossreact with intact pili from both homologous and heterologous strains. The peptides elicited roughly equal antipeptide responses but varied substantially in their ability to elicit antisera that crossreacted with intact pili. Of the antisera to peptides corresponding to regions of conserved sequence, antisera directed against residues 69-84 were the most efficient in binding pili from all strains tested in both solid-phase assays and immunoblots. Anti-69-84 also efficiently precipitated a tryptic fragment of pilin known to bind human endocervical cells. Sera against the two peptides (121-134 and 135-151) previously shown to contain strain-specific epitopes crossreacted with MS11 pili equally well, but differed in their ability to bind pili from heterologous strains. Anti-121-134 was strain-specific whereas anti-135-151 bound all pilin tested. Each of the sera was examined for its ability to inhibit bacterial adhesion to a human endometrial carcinoma cell line. Sera generated against residues 41-50 and 69-84 successfully inhibited a heterologous gonococcal strain from binding. These peptides could be important components of an effective vaccine for the prevention of gonorrhea.


Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter-observational study.
Comorbidities between psychiatric diseases and use of traditional substances of abuse are common. Nevertheless, there are few data regarding the use of novel psychoactive substances (NPS) among psychiatric patients. Aim of this multicentre survey is to investigate the consumption of a number of psychoactive substances in a young psychiatric sample. Between December 2013 and September 2015, a questionnaire was administered in 10 Italian psychiatric care facilities to a sample of 671 patients, aged 18-26 (mean age 22.24; SD 2.87). About 8.2% of the sample declared to have used NPS at least once, and 2.2% had consumed NPS in the previous 3 months. The three psychiatric diagnoses most frequently associated with NPS use were bipolar disorder (23.1%), personality disorders (11.8%), and schizophrenia and related disorders (11.6%). In univariate regression analysis, bipolar disorder was positively associated with NPS consumption, an association that did not reach statistical significance in the multivariate analysis. The use of NPS in a young psychiatric population appears to be frequent, and probably still underestimated. Bipolar disorder shows an association with NPS use. Careful and constant monitoring and an accurate evaluation of possible clinical effects related to NPS use are necessary.


Codoping in SnTe: Enhancement of Thermoelectric Performance through Synergy of Resonance Levels and Band Convergence.
We report a significant enhancement of the thermoelectric performance of p-type SnTe over a broad temperature plateau with a peak ZT value of ∼1.4 at 923 K through In/Cd codoping and a CdS nanostructuring approach. Indium and cadmium play different but complementary roles in modifying the valence band structure of SnTe. Specifically, In-doping introduces resonant levels inside the valence bands, leading to a considerably improved Seebeck coefficient at low temperature. Cd-doping, however, increases the Seebeck coefficient of SnTe remarkably in the mid- to high-temperature region via a convergence of the light and heavy hole bands and an enlargement of the band gap. Combining the two dopants in SnTe yields enhanced Seebeck coefficient and power factor over a wide temperature range due to the synergy of resonance levels and valence band convergence, as demonstrated by the Pisarenko plot and supported by first-principles band structure calculations. Moreover, these codoped samples can be hierarchically structured on all scales (atomic point defects by doping, nanoscale precipitations by CdS nanostructuring, and mesoscale grains by SPS treatment) to achieve highly effective phonon scattering leading to strongly reduced thermal conductivities. In addition to the high maximum ZT the resultant large average ZT of ∼0.8 between 300 and 923 K makes SnTe an attractive p-type material for high-temperature thermoelectric power generation.


Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.
Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.


Design and performance optimization of fiber optic adaptive filters.
There is a great need for easy-to-fabricate and versatile fiber optic signal processing systems in which optical fibers are used for the delay and storage of wideband guided lightwave signals. We describe the design of the least-mean-square algorithm-based fiber optic adaptive filters for processing guided lightwave signals in real time. Fiber optic adaptive filters can learn to change their parameters or to process a set of characteristics of the input signal. In our realization we employ as few electronic devices as possible and use optical computation to utilize the advantages of optics in the processing speed, parallelism, and interconnection. Many schemes for optical adaptive filtering of electronic signals are available in the literature. The new optical adaptive filters described in this paper are for optical processing of guided lightwave signals, not electronic signals. We analyzed the convergence or learning characteristics of the adaptive filtering process as a function of the filter parameters and the fiber optic hardware errors. From this analysis we found that the effects of the optical round-off errors and noise can be reduced, and the learning speed can be comparatively increased in our design through an optimal selection of the filter parameters. A general knowledge of the fiber optic hardware, the statistics of the lightwave signal, and the desired goal of the adaptive processing are enough for this optimum selection of the parameters. Detailed computer simulations validate the theoretical results of performance optimization.


Alignment of "phrase accent" lows in dutch falling rising questions: theoretical and methodological implications.
In the first part of this study, we measured the alignment (relative to segmental landmarks) of the low F0 turning points between the accentual fall and the final boundary rise in short Dutch falling-rising questions of the form Do you live in [place name]? produced as read speech in a laboratory setting. We found that the alignment of these turning points is affected by the location of a postaccentual secondary stressed syllable if one is present. This is consistent with the findings and analyses of Grice, Ladd, & Arvaniti, 2000 (Phonology 17, 143-185), suggesting that the low turning points are the phonetic reflex of a "phrase accent." In the second part of this study, we measured the low turning points in falling-rising questions produced in a task-oriented dialog setting and found that their alignment is affected in the same way as in the read speech data. This suggests that read speech experiments are a valid means of investigating the phonetic details of intonation contours.


Peptide-Dependent Recognition of HLA-B*57:01 by KIR3DS1.
Killer cell immunoglobulin-like receptors (KIRs) play an important role in the activation of natural killer (NK) cells, which in turn contribute to the effective immune control of many viral infections. In the context of HIV infection, the closely related KIR3DL1 and KIR3DS1 molecules, in particular, have been associated with disease outcome. Inhibitory signals via KIR3DL1 are disrupted by downregulation of HLA class I ligands on the infected cell surface and can also be impacted by changes in the presented peptide repertoire. In contrast, the activatory ligands for KIR3DS1 remain obscure. We used a structure-driven approach to define the characteristics of HLA class I-restricted peptides that interact with KIR3DL1 and KIR3DS1. In the case of HLA-B*57:01, we used this knowledge to identify bona fide HIV-derived peptide epitopes with similar properties. Two such peptides facilitated productive interactions between HLA-B*57:01 and KIR3DS1. These data reveal the presence of KIR3DS1 ligands within the HIV-specific peptide repertoire presented by a protective HLA class I allotype, thereby enhancing our mechanistic understanding of the processes that enable NK cells to impact disease outcome. Natural killer (NK) cells are implicated as determinants of immune control in many viral infections, but the precise molecular mechanisms that initiate and control these responses are unclear. The activating receptor KIR3DS1 in combination with HLA-Bw4 has been associated with better outcomes in HIV infection. However, evidence of a direct interaction between these molecules is lacking. In this study, we demonstrate that KIR3DS1 recognition of HLA-Bw4 is peptide dependent. We also identify HIV-derived peptide epitopes presented by the protective HLA-B*57:01 allotype that facilitate productive interactions with KIR3DS1. Collectively, these findings suggest a mechanism whereby changes in the peptide repertoire associated with viral infection provide a trigger for KIR3DS1 engagement and NK cell activation.


High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).
Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism.


Clinical long-term survival of two-retainer and single-retainer all-ceramic resin-bonded fixed partial dentures.
All-ceramic resin-bonded fixed partial dentures (RBFPDs) were introduced as a conservative treatment approach 15 years ago. The purpose of this prospective study was to evaluate the long-term clinical survival of RBFPDs made with a conventional two-retainer design or a cantilever single-retainer design. A total of 37 anterior RBFPDs were made from the glass-infiltrated alumina ceramic In-Ceram. Sixteen RBFPDs with a conventional two-retainer design were inserted in 14 patients, and 21 RBFPDs with a cantilever single-retainer design were inserted in 16 patients. Panavia or Panavia 21 were used as luting agents either after silica-coating and silanation or after air-abrasion only. Patients were recalled every year for a clinical examination to evaluate the restorations with regard to function and possible failures. The mean observation time in the two-retainer group was 75.8 months, and in the single-retainer group it was 51.7 months. No restoration debonded. In the two-retainer group, one restoration was lost because it fractured after 3 months at both connectors and one restoration was removed alio loco accidentally. Also in this group, four RBFPDs fractured within 15 months after insertion at one connector, but the pontic remained in situ as a cantilever RBFPD for several years. In the single-retainer group, only one FPD fractured and was lost 48 months after insertion. The 5-year survival rate was 73.9% in the two-retainer group and 92.3% in the single-retainer group. When unilateral fracture of a FPD was taken as criterion for failure, the five-year survival rate decreased to 67.3% in the two-retainer group. Cantilever all-ceramic resin-bonded fixed partial dentures made from high-strength oxide ceramics present a promising treatment alternative to two-retainer RBFPDs in the anterior region.


Do all psychological treatments really work the same in posttraumatic stress disorder?
A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology Review, 28, 746-758) concluded that all bona fide treatments are equally effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta-analyses or systematic reviews concluded that there is good evidence that trauma-focused psychological treatments (trauma-focused cognitive behavior therapy and eye movement desensitization and reprocessing) are effective in PTSD; but that treatments that do not focus on the patients' trauma memories or their meanings are either less effective or not yet sufficiently studied. International treatment guidelines therefore recommend trauma-focused psychological treatments as first-line treatments for PTSD. We examine possible reasons for the discrepant conclusions and argue that (1) the selection procedure of the available evidence used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis and conclusions fail to take into account the need to demonstrate that treatments for PTSD are more effective than natural recovery. Furthermore, significant increases in effect sizes of trauma-focused cognitive behavior therapies over the past two decades contradict the conclusion that content of treatment does not matter. To advance understanding of the optimal treatment for PTSD, we recommend further research into the active mechanisms of therapeutic change, including treatment elements commonly considered to be non-specific. We also recommend transparency in reporting exclusions in meta-analyses and suggest that bona fide treatments should be defined on empirical and theoretical grounds rather than by judgments of the investigators' intent.


Discourses with potential to disrupt traditional nursing education: Nursing teachers' talk about norm-critical competence.
This paper describes the discourses underlying nursing teachers' talk about their own norm-critical competence. Norm criticism is an approach that promotes awareness and criticism of the norms and power structures that exert an excluding effect in society in general and in the healthcare encounter in particular. Given the unequal relationships that can exist in healthcare, for example relationships shaped by racism, sexism and classism, a norm-critical approach to nursing education would help illuminate these matters. The studied empirical material consisted of focus group interviews. Nursing teachers discussed their norm-critical competence based on the university course "Norm-Aware Caring" in which they had recently participated. Through a critical discourse analysis, three discourses were identified in their talk, all of which had the potential to disrupt traditional, normative nursing education. However, in all three discourses there was an underlying discourse of normality, clearly positioning the teachers as exemplifying the "normal." The binary constructed between normality and otherness contradicts a basic tenet of the norm-critical approach and may hamper the development of genuine norm-critical competence in nursing education.


Post-treatment of real municipal wastewater effluents by means of granular activated carbon (GAC) based catalytic processes: A focus on abatement of pharmaceutically active compounds.
Pharmaceutically active compounds (PhACs) widely present in urban wastewater effluents pose a threat to ecosystems in the receiving aquatic environment. In this work, efficiency of granular activated carbon (GAC) - based catalytic processes, namely catalytic wet peroxide oxidation (CWPO), peroxymonosulfate oxidation (PMS/GAC) and peroxydisulfate oxidation (PDS/GAC) at ambient temperature and pressure were studied for removal of 22 PhACs (ng L-1 level) that were present in secondary effluents of real urban wastewater. Concentrations of PhACs were measured using Ultra Performance Liquid Chromatography - Triple Quadrupole Mass Spectrometry (UPLC-QqQ-MS/MS). Catalytic experiments were conducted in discontinuous mode using up-flow fixed bed reactors with granular activated carbon (GAC) as a catalyst. The catalyst was characterized by means of N2 adsorption-desorption isotherm, mercury intrusion porosimetry (MIP), elemental analysis, X-ray fluorescence spectroscopy (WDXRF), X-ray diffraction (XRD), thermal gravimetry and differential temperature analyses coupled mass spectrometry (TGA-DTA-MS). Results indicate that the highest efficiency in terms of TOC removal was achieved during CWPO performed at optimal operational conditions (stoichiometric dose of H2O2; TOC removal ~ 82%) followed by PMS/GAC (initial PMS concentration 100 mg L-1; TOC removal ~73.7%) and PDS/GAC (initial PDS concentration 100 mg L-1; TOC removal ~ 67.9%) after 5 min of contact time. Full consumption of oxidants was observed in all cases for CWPO and PDS/GAC at contact times of 2.5 min, while for PMS/GAC it was 1.5 min. In general, for 18 out of 22 target PhACs, very high removal efficiencies (> 92%) were achieved in all tested processes (including adsorption) performed at optimal operational conditions during 5 min of contact time. However, moderate (40 - 70%) and poor (< 40%) removal efficiencies were achieved for salicylic acid, ofloxacin, norfloxacin and ciprofloxacin, which can be possibly attributed to insufficient contact time. Despite high efficiency of all studied processes for PhACs elimination from urban wastewater effluent, CWPO seems to be more promising for continuous operation.


Electrically induced liquid-liquid phase transition in water at room temperature.
In this work we expand on findings previously reported [Wexler et al., Phys. Chem. Chem. Phys., 2016, 18, 16281] on the experimental observation of a phase transition in a hydrogen bonded liquid manifesting in long range dipole-dipole interactions. The studied system, liquid water stressed by an electric field, exhibits collective oscillations brought about through spontaneous breakdown of symmetry. Raman spectroscopy identifies the primary excitation of the emergent phase as transverse optically active phonon-like sidebands that appear on the hydrogen bonded asymmetric stretch mode. The phase transition is observed throughout the entire volume of liquid. The system also exhibits a self-similarity relation between the scattered Raman intensity and the electric field strength which further supports the conclusion that collective behavior persists against thermal disruption. The experimental findings are discussed in terms of a quantum field theory for macroscopic quantum systems.


Gamma knife surgery for cavernous hemangiomas: an analysis of 125 patients.
The authors sought to determine the value of gamma knife surgery (GKS) in the treatment of cavernous hemangiomas (CHs). Between 1993 and 2002, a total of 125 patients with symptomatic CHs were treated with GKS. Ninety-seven patients presented with bleeding and 45 of these had at least two bleeding episodes. Thirteen patients presented with seizures combined with hemorrhage, and 15 patients presented with seizures alone. The mean margin dose of radiation was 12.1 Gy and the mean follow-up time was 5.4 years. In the 112 patients who had bled the number of rebleeds after GKS was 32. These rebleeds were defined both clinically and based on magnetic resonance imaging for an annual rebleeding rate of 32 episodes/492 patient-years or 6.5%. Twenty-three of the 32 rebleeding episodes occurred within 2 years after GKS. Nine episodes occurred after 2 years; thus, the annual rebleeding rate after GKS was 10.3% for the first 2 years and 3.3% thereafter (p = 0.0038). In the 45 patients with at least two bleeding episodes before GKS, the rebleeding rate dropped from 29.2% (55 episodes/188 patient-years) before treatment to 5% (10 episodes/197 patient-years) after treatment (p < 0.0001). Among the 28 patients who presented with seizures, 15 (53%) had good outcomes (Engel Grades I and II). In this study of 125 patients, symptomatic radiation-induced complications developed in only three patients. Gamma knife surgery can effectively reduce the rebleeding rate after the first symptomatic hemorrhage in patients with CH. In addition, GKS may be useful in reducing the severity of seizures in patients with CH.


Domain-wall induced phase shifts in spin waves.
We study the interaction between two important features of ferromagnetic nanoparticles: magnetic domain walls and spin waves. Micromagnetic simulations reveal that magnetostatic spin waves change their phase as they pass through domain walls. Similar to an Aharonov-Bohm experiment, we suggest to probe this effect by splitting the waves on different branches of a ring. The interference of merging waves depends on the domain walls in the branches. A controlled manipulation of spin-wave phases could be the first step towards nanoscaled ferromagnetic devices performing logical operations based on spin-wave propagation.