Alternative dry separation of PM10 from soils for characterization by kinetic extraction: example of new Caledonian mining soils.
A simple new device for dry separation of fine particulate matter from bulk soil samples is presented here. It consists of a stainless steel tube along which a nitrogen flow is imposed, resulting in the displacement of particles. Taking into account particle transport, fluid mechanics, and soil sample composition, a tube 6-m long, with a 0.04-m diameter, was found best adapted for PM10 separation. The device rapidly produced several milligrams of particulate matter, on which chemical extractions with EDTA were subsequently performed to study the kinetic parameters of extractable metals. New Caledonian mining soils were chosen here, as a case-study. Although the easily extracted metal pool represents only 0.5-6.4 % of the total metal content for the elements studied (Ni, Co, Mn), the total concentrations are extremely high. This pool is therefore far from negligible, and can be troublesome in the environment. This dry technique for fine particle separation from bulk parent soil eliminates the metal-leaching risks inherent in wet filtration and should therefore ensure safe assessment of environmental quality in fine-textured, metal-contaminated soils.


Correlation of methane production and functional gene transcriptional activity in a peat soil.
The transcription dynamics of subunit A of the key gene in methanogenesis (methyl coenzyme M reductase; mcrA) was studied to evaluate the relationship between process rate (methanogenesis) and gene transcription dynamics in a peat soil ecosystem. Soil methanogen process rates were determined during incubation of peat slurries at temperatures from 4 to 37 degrees C, and real-time quantitative PCR was applied to quantify the abundances of mcrA genes and transcripts; corresponding transcriptional dynamics were calculated from mcrA transcript/gene ratios. Internal standards suggested unbiased recovery of mRNA abundances in comparison to DNA levels. In comparison to those in pure-culture studies, mcrA transcript/gene ratios indicated underestimation by 1 order of magnitude, possibly due to high proportions of inactive or dead methanogens. Methane production rates were temperature dependent, with maxima at 25 degrees C, but changes in abundance and transcription of the mcrA gene showed no correlation with temperature. However, mcrA transcript/gene ratios correlated weakly (regression coefficient = 0.76) with rates of methanogenesis. Methanogen process rates increased over 3 orders of magnitude, while the corresponding maximum transcript/gene ratio increase was only 18-fold. mcrA transcript dynamics suggested steady-state expression in peat soil after incubation for 24 and 48 h, similar to that in stationary-phase cultures. mcrA transcript/gene ratios are therefore potential in situ indicators of methanogen process rate changes in complex soil systems.


Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events.
We aimed to analyze the diagnostic value of total tau (T-tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8±50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. T-tau was higher in patients with stroke [1.0 pg/ml (IQR=0.3-2.2)] than with TIA [0.5 pg/ml (IQR=0.2-1.0), p=0.02]. The levels of S100B were also increased in stroke [0.082 μg/l (IQR=0.049-0.157)] patients compared to TIA patients [0.045 μg/l (IQR=0.03-0.073), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 μg/l (IQR=9.30-16.14)] compared to those with TIA [10.96 μg/l (IQR=7.98-15.33), p=0.30] were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months.


Changes in Physician Decision Making after CT: A Prospective Multicenter Study in Primary Care Settings.
Purpose To determine the effect of computed tomography (CT) results on physician decision making in three common clinical scenarios in primary care. Materials and Methods This research was approved by the institutional review board (IRB) and was HIPAA compliant. All physicians consented to participate with an opt-in or opt-out mechanism; patient consent was waived with IRB approval. In this prospective multicenter observational study, outpatients referred by primary care providers (PCPs) for CT evaluation of abdominal pain, hematuria, or weight loss were identified. Prior to CT, PCPs were surveyed to elicit their leading diagnosis, confidence in that diagnosis (confidence range, 0%-100%), a rule-out diagnosis, and a management plan if CT were not available. Surveys were repeated after CT. Study measures were the proportion of patients in whom leading diagnoses and management changed (PCP management vs specialist referral vs emergency department transfer), median changes in diagnostic confidence, and the proportion of patients in whom CT addressed rule-out diagnoses. Regression analyses were used to identify associations between study measures and site and participant characteristics. Specifically, logistic regression analysis was used for binary study measures (change in leading diagnosis, change in management), and linear regression analysis was used for the continuous study measure (change in diagnostic confidence). Accrual began on September 5, 2012, and ended on June 28, 2014. Results In total, 91 PCPs completed pre- and post-CT surveys in 373 patients. In patients with abdominal pain, hematuria, or weight loss, leading diagnoses changed after CT in 53% (131 of 246), 49% (36 of 73), and 57% (27 of 47) of patients, respectively. Management changed in 35% (86 of 248), 27% (20 of 74), and 54% (26 of 48) of patients, respectively. Median absolute changes in diagnostic confidence were substantial and significant (+20%, +20%, and +19%, respectively; P ≤ .001 for all); median confidence after CT was high (90%, 88%, and 80%, respectively). PCPs reported CT was helpful in confirming or excluding rule-out diagnoses in 98% (184 of 187), 97% (59 of 61), and 97% (33 of 34) of patients, respectively. Significant associations between primary measures and site and participant characteristics were not identified. Conclusion Changes in PCP leading diagnoses and management after CT were common, and diagnostic confidence increased substantially. © RSNA, 2016 Online supplemental material is available for this article.


The Effect of Taper Angle and Spline Geometry on the Initial Stability of Tapered, Splined Modular Titanium Stems.
Design parameters affecting initial mechanical stability of tapered, splined modular titanium stems (TSMTSs) are not well understood. Furthermore, there is considerable variability in contemporary designs. We asked if spline geometry and stem taper angle could be optimized in TSMTS to improve mechanical stability to resist axial subsidence and increase torsional stability. Initial stability was quantified with stems of varied taper angle and spline geometry implanted in a foam model replicating 2cm diaphyseal engagement. Increased taper angle and a broad spline geometry exhibited significantly greater axial stability (+21%-269%) than other design combinations. Neither taper angle nor spline geometry significantly altered initial torsional stability.


Antiseptic efficacies of waterless hand rub, chlorhexidine scrub, and povidone-iodine scrub in surgical settings: a meta-analysis of randomized controlled trials.
Presurgical hand washing is crucial for preventing surgical site infections (SSIs). Chlorhexidine gluconate (CHG) and povidone-iodine (PI) products have been conventionally used as hand scrubs for presurgical hand preparation. However, waterless hand rub (WHR) products have been developed for operating room staff. The aim of this study was to conduct a systematic review and meta-analysis to compare the antiseptic efficacies of WHR, CHG, and PI in surgical settings. PubMed, Embase, and Cochrane Library databases as well as the ClinicalTrials.gov registry were searched for studies published before October 2018. Randomized controlled trials (RCTs) comparing the clinical outcomes of the use of WHRs, CHG, or PI for presurgical hand washing were included. A random effects model was used for meta-analysis. Colony-forming unit (cfu) counts, SSI rates, and preference and compliance were determined to measure efficacies. Eleven RCTs involving 5135 participants were included. Residual cfu counts were significantly lower in the WHR and CHG groups than in the PI group. The differences in cfu counts between the WHR and CHG groups were non-significant. No significant differences were observed in the SSI rates between the WHR and traditional hand scrub groups. Moreover, WHRs were considered most favourable and were associated with higher compliance rates than the other products. WHRs and CHG exhibited higher antiseptic efficacies than PI. However, additional studies with consistent outcome measurements and accurate grouping are required to obtain comprehensive results. Moreover, preference, compliance, and the cost determine the selection of hand wash products.


Estimation of dynamic time activity curves from dynamic cardiac SPECT imaging.
Whole-heart coronary flow reserve (CFR) may be useful as an early predictor of cardiovascular disease or heart failure. Here we propose a simple method to extract the time-activity curve, an essential component needed for estimating the CFR, for a small number of compartments in the body, such as normal myocardium, blood pool, and ischemic myocardial regions, from SPECT data acquired with conventional cameras using slow rotation. We evaluated the method using a realistic simulation of (99m)Tc-teboroxime imaging. Uptake of (99m)Tc-teboroxime based on data from the literature were modeled. Data were simulated using the anatomically-realistic 3D NCAT phantom and an analytic projection code that realistically models attenuation, scatter, and the collimator-detector response. The proposed method was then applied to estimate time activity curves (TACs) for a set of 3D volumes of interest (VOIs) directly from the projections. We evaluated the accuracy and precision of estimated TACs and studied the effects of the presence of perfusion defects that were and were not modeled in the estimation procedure.The method produced good estimates of the myocardial and blood-pool TACS organ VOIs, with average weighted absolute biases of less than 5% for the myocardium and 10% for the blood pool when the true organ boundaries were known and the activity distributions in the organs were uniform. In the presence of unknown perfusion defects, the myocardial TAC was still estimated well (average weighted absolute bias <10%) when the total reduction in myocardial uptake (product of defect extent and severity) was ≤ 5%. This indicates that the method was robust to modest model mismatch such as the presence of moderate perfusion defects and uptake nonuniformities. With larger defects where the defect VOI was included in the estimation procedure, the estimated normal myocardial and defect TACs were accurate (average weighted absolute bias ≈ 5% for a defect with 25% extent and 100% severity).


Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase.
We report the results of a binding free energy-based virtual screening campaign of a library of 77 α-hydroxytropolone derivatives against the challenging RNase H active site of the reverse transcriptase (RT) enzyme of human immunodeficiency virus-1. Multiple protonation states, rotamer states, and binding modalities of each compound were individually evaluated. The work involved more than 300 individual absolute alchemical binding free energy parallel molecular dynamics calculations and over 1 million CPU hours on national computing clusters and a local campus computational grid. The thermodynamic and structural measures obtained in this work rationalize a series of characteristics of this system useful for guiding future synthetic and biochemical efforts. The free energy model identified key ligand-dependent entropic and conformational reorganization processes difficult to capture using standard docking and scoring approaches. Binding free energy-based optimization of the lead compounds emerging from the virtual screen has yielded four compounds with very favorable binding properties, which will be the subject of further experimental investigations. This work is one of the few reported applications of advanced-binding free energy models to large-scale virtual screening and optimization projects. It further demonstrates that, with suitable algorithms and automation, advanced-binding free energy models can have a useful role in early-stage drug-discovery programs.


Complement C5a Functions as a Master Switch for the pH Balance in Neutrophils Exerting Fundamental Immunometabolic Effects.
During sepsis, excessive activation of the complement system with generation of the anaphylatoxin C5a results in profound disturbances in crucial neutrophil functions. Moreover, because neutrophil activity is highly dependent on intracellular pH (pHi), we propose a direct mechanistic link between complement activation and neutrophil pHi In this article, we demonstrate that in vitro exposure of human neutrophils to C5a significantly increased pHi by selective activation of the sodium/hydrogen exchanger. Upstream signaling of C5a-mediated intracellular alkalinization was dependent on C5aR1, intracellular calcium, protein kinase C, and calmodulin, and downstream signaling regulated the release of antibacterial myeloperoxidase and lactoferrin. Notably, the pH shift caused by C5a increased the glucose uptake and activated glycolytic flux in neutrophils, resulting in a significant release of lactate. Furthermore, C5a induced acidification of the extracellular micromilieu. In experimental murine sepsis, pHi of blood neutrophils was analogously alkalinized, which could be normalized by C5aR1 inhibition. In the clinical setting of sepsis, neutrophils from patients with septic shock likewise exhibited a significantly increased pHi These data suggest a novel role for the anaphylatoxin C5a as a master switch of the delicate pHi balance in neutrophils resulting in profound inflammatory and metabolic changes that contribute to hyperlactatemia during sepsis.


Screening tests for syphilis. A comparison of the Treponema pallidum haemagglutination assay with two automated serological tests.
Two Treponema pallidum haemagglutination assay (TPHA) tests (Wellcome and Fuzizoki) were compared with the automated reagin test and the automated Reiter protein complement-fixation test in a routine screening system. The Wellcome TPHA was shown to lack sensitivity, and it is recommended that it should be used at a lower screening dilution. The Fuzizoki TPHA recorded a significant number of false positive and false negative results, and was therefore inferior to the fluorescent treponemal antibody absorption (FTA-ABS) test as a definitive test for syphilis. It is suggested that the TPHA be used in conjunction with a reagin test to replace some of the more inadequate screening tests currently in use. The automated screening tests were shown to have a similar sensitivity to the TPHA as well as several other advantages; they are recommended for testing large numbers of specimens.


A trait-based trade-off between growth and mortality: evidence from 15 tropical tree species using size-specific relative growth rates.
A life-history trade-off between low mortality in the dark and rapid growth in the light is one of the most widely accepted mechanisms underlying plant ecological strategies in tropical forests. Differences in plant functional traits are thought to underlie these distinct ecological strategies; however, very few studies have shown relationships between functional traits and demographic rates within a functional group. We present 8 years of growth and mortality data from saplings of 15 species of Dipterocarpaceae planted into logged-over forest in Malaysian Borneo, and the relationships between these demographic rates and four key functional traits: wood density, specific leaf area (SLA), seed mass, and leaf C:N ratio. Species-specific differences in growth rates were separated from seedling size effects by fitting nonlinear mixed-effects models, to repeated measurements taken on individuals at multiple time points. Mortality data were analyzed using binary logistic regressions in a mixed-effects models framework. Growth increased and mortality decreased with increasing light availability. Species differed in both their growth and mortality rates, yet there was little evidence for a statistical interaction between species and light for either response. There was a positive relationship between growth rate and the predicted probability of mortality regardless of light environment, suggesting that this relationship may be driven by a general trade-off between traits that maximize growth and traits that minimize mortality, rather than through differential species responses to light. Our results indicate that wood density is an important trait that indicates both the ability of species to grow and resistance to mortality, but no other trait was correlated with either growth or mortality. Therefore, the growth mortality trade-off among species of dipterocarp appears to be general in being independent of species crossovers in performance in different light environments.


Endosymbiont-dependent host reproduction maintains bacterial-fungal mutualism.
Bacterial endosymbionts play essential roles for many organisms, and thus specialized mechanisms have evolved during evolution that guarantee the persistence of the symbiosis during or after host reproduction. The rice seedling blight fungus Rhizopus microsporus represents a unique example of a mutualistic life form in which a fungus harbors endobacteria (Burkholderia sp.) for the production of a phytotoxin. Here we report the unexpected observation that in the absence of endosymbionts, the host is not capable of vegetative reproduction. Formation of sporangia and spores is restored only upon reintroduction of endobacteria. To monitor this process, we succeeded in GFP labeling cultured endosymbionts. We also established a laserbeam transformation technique for the first controlled introduction of bacteria into fungi to observe their migration to the tips of the aseptate hyphae. The persistence of this fungal-bacterial mutualism through symbiont-dependent sporulation is intriguing from an evolutionary point of view and implies that the symbiont produces factors that are essential for the fungal life cycle. Reproduction of the host has become totally dependent on endofungal bacteria, which in return provide a highly potent toxin for defending the habitat and accessing nutrients from decaying plants. This scenario clearly highlights the significance for a controlled maintenance of this fungal-bacterial symbiotic relationship.


All-cause and cause-specific mortality in people with mental disorders and intellectual disabilities, before and during the COVID-19 pandemic: cohort study.
People with mental disorders and intellectual disabilities experience excess mortality compared with the general population. The impact of COVID-19 on exacerbating this, and in widening ethnic inequalities, is unclear. Prospective data (N=167,122) from a large mental healthcare provider in London, UK, with deaths from 2019 to 2020, used to assess age- and gender-standardised mortality ratios (SMRs) across nine psychiatric conditions (schizophrenia-spectrum disorders, affective disorders, somatoform/ neurotic disorders, personality disorders, learning disabilities, eating disorders, substance use disorders, pervasive developmental disorders, dementia) and by ethnicity. Prior to the World Health Organization (WHO) declaring COVID-19 a public health emergency on 30th January 2020, all-cause SMRs across all psychiatric cohorts were more than double the general population. By the second quarter of 2020, when the UK experienced substantial peaks in COVID-19 deaths, all-cause SMRs increased further, with COVID-19 SMRs elevated across all conditions (notably: learning disabilities: SMR: 9.24 (95% CI: 5.98-13.64), pervasive developmental disorders: 5.01 (95% CI: 2.40-9.20), eating disorders: 4.81 (95% CI: 1.56-11.22), schizophrenia-spectrum disorders: 3.26 (95% CI: 2.55-4.10), dementia: 3.82 (95% CI: 3.42, 4.25) personality disorders 4.58 (95% CI: 3.09-6.53)). Deaths from other causes remained at least double the population average over the whole year. Increased SMRs were similar across ethnic groups. People with mental disorders and intellectual disabilities were at a greater risk of deaths relative to the general population before, during and after the first peak of COVID-19 deaths, with similar risks by ethnicity. Mortality from non-COVID-19/ other causes was elevated before/ during the pandemic, with higher COVID-19 mortality during the pandemic. ESRC (JD, CM), NIHR (JD, RS, MH), Health Foundation (JD), GSK, Janssen, Takeda (RS).


Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure.
An increase in myocardial collagen content may contribute to the development of heart failure; this might be inhibited or reversed by mineralocorticoid receptor antagonists (MRAs). We investigated changes in serum concentrations of the collagen synthesis biomarkers N-terminal propeptide of procollagen type III (PIIINP) (primary outcome) and C-terminal propeptide of procollagen type I (PICP) (secondary outcome) after non-randomised initiation of spironolactone as add-on therapy among patients with resistant hypertension enrolled in the 'Anglo-Scandinavian Cardiac Outcomes' trial (ASCOT). An age/sex matching plus propensity-scored logistic regression model incorporating variables related to the outcome and spironolactone treatment was created to compare patients treated with spironolactone for a 9-month period versus matched controls. A within-person analysis comparing changes in serum biomarker concentrations in the 9 months before versus after spironolactone treatment was also performed. Patients included in the between-person analysis (n=146) were well matched: the mean age was 63±7 years and 11% were woman. Serum concentrations of PIIINP and PICP rose in 'controls' and fell during spironolactone treatment (adjusted means +0.52 (-0.05 to 1.09) vs -0.41 (-0.97 to 0.16) ng/mL, p=0.031 for PIIINP and +4.54(-1.77 to 10.9) vs -6.36 (-12.5 to -0.21) ng/mL, p=0.023 for PICP). For the within-person analysis (n=173), spironolactone treatment was also associated with a reduction in PICP (beta estimate=-11.82(-17.53 to -6.10) ng/mL, p<0.001) but not in PIIINP levels. Treatment with spironolactone was associated with a reduction in serum biomarkers of collagen synthesis independently of blood pressure in patients with hypertension, suggesting that spironolactone might exert favourable effects on myocardial collagen synthesis and fibrosis. Whether this effect might contribute to slowing the progression to heart failure is worth investigating.


Chicken Egg Yolk Antibodies (IgY) for Prophylaxis and Treatment of Rotavirus Diarrhea in Human and Animal Neonates: A Concise Review.
The rotavirus-induced diarrhea of human and animal neonates is a major public health concern worldwide. Until recently, no effective therapy is available to specifically inactivate the rotavirion particles within the gut. Passive immunotherapy by oral administration of chicken egg yolk antibody (IgY) has emerged of late as a fresh alternative strategy to control infectious diseases of the alimentary tract and has been applied in the treatment of diarrhea due to rotavirus infection. The purpose of this concise review is to evaluate evidence on the properties and performance of anti-rotavirus immunoglobulin Y (IgY) for prevention and treatment of rotavirus diarrhea in human and animal neonates. A survey of relevant anti-rotavirus IgY basic studies and clinical trials among neonatal animals (since 1994-2015) and humans (since 1982-2015) have been reviewed and briefly summarized. Our analysis of a number of rotavirus investigations involving animal and human clinical trials revealed that anti-rotavirus IgY significantly reduced the severity of clinical manifestation of diarrhea among IgY-treated subjects relative to a corresponding control or placebo group. The accumulated information as a whole depicts oral IgY to be a safe and efficacious option for treatment of rotavirus diarrhea in neonates. There is however a clear need for more randomized, placebo controlled and double-blind trials with bigger sample size to further solidify and confirm claims of efficacy and safety in controlling diarrhea caused by rotavirus infection especially among human infants with health issues such as low birth weights or compromised immunity in whom it is most needed.


Detection of asphyxia using heart rate variability.
The long-term aims of this study are to find a parameter derived from the ECG that has a high sensitivity and specificity to asphyxia and, once we know or suspect that asphyxia occurred, to estimate how severe it was. We carried out a pilot study in which 24 adult Wistar rats were anaesthetised and subjected to controlled asphyxia for specified durations. We measured the pH, 'neurological score' and the ECG, extracting from this heart rate and heart rate variability (HRV). We have developed a technique capable of detecting asphyxia in less than 1 min, based on monitoring the ECG and estimating HRV by measuring the standard deviation of normal RR intervals (the RR interval is the time interval between two consecutive R-points of the QRS complex). In all cases the heart rate decreased and HRV increased, by an average of 46 +/- 33 ms in relation to the baseline, at the onset of asphyxia. The comparison of the base level of HRV after and before asphyxia shows promise for the estimation of the severity of the episode; however, the limitations of this study should be noted as they include the small size of the cohort and the methods of analysis.


The therapeutic dimension of research about spirituality: Particularities of cancer, mental health and infertility.
Healthcare is moving from a biomedical paradigm into a holistic paradigm, which includes all dimensions and needs of patients and families. Health conditions may trigger a spiritual journey for believers or non-believers bringing to light the nature of the human being and its vulnerable condition. Healthcare professionals are full participants in this life and health scenario and have an unquestionable duty related to the provision of spiritual care, on the basis of legislation, ethical codes, and on research evidence. Researchers are seizing better and broader knowledge about spirituality in healthcare, and research about this phenomenon is growing internationally. But, spirituality is considered complex, an area of intimacy and deep subjective meaning. These factors may raise some ethical concerns when submitting research projects to the ethics committees. In this paper, the authors share their experience in research about spirituality in the beginning of life issues/infertility and with adults with severe health conditions, and describe participants' perspectives on research engagement.


Disproportionate Sterilization of Latinos Under California's Eugenic Sterilization Program, 1920-1945.
To compare population-based sterilization rates between Latinas/os and non-Latinas/os sterilized under California's eugenics law. We used data from 17 362 forms recommending institutionalized patients for sterilization between 1920 and 1945. We abstracted patient gender, age, and institution of residence into a data set. We extracted data on institution populations from US Census microdata from 1920, 1930, and 1940 and interpolated between census years. We used Spanish surnames to identify Latinas/os in the absence of data on race/ethnicity. We used Poisson regression with a random effect for each patient's institution of residence to estimate incidence rate ratios (IRRs) and compare sterilization rates between Latinas/os and non-Latinas/os, stratifying on gender and adjusting for differences in age and year of sterilization. Latino men were more likely to be sterilized than were non-Latino men (IRR = 1.23; 95% confidence interval [CI] = 1.15, 1.31), and Latina women experienced an even more disproportionate risk of sterilization relative to non-Latinas (IRR = 1.59; 95% CI = 1.48, 1.70). Eugenic sterilization laws were disproportionately applied to Latina/o patients, particularly Latina women and girls. Understanding historical injustices in public health can inform contemporary public health practice.


Public support in England for a total ban on the sale of tobacco products.
This study aimed to determine the level of support for a sales ban on tobacco in England to provide a benchmark against which any changes over time can be assessed. 8735 people from England who participated in one of five monthly cross-sectional household surveys in 2008 were asked to indicate whether they would support the statement that 'the government should work towards banning the sale of tobacco completely within the next 10 years'. In addition, sociodemographic and smoking characteristics were assessed. A substantial proportion of the total sample (44.5%; 95% CI 43.5% to 45.6%) would support a move towards a complete ban. While never smokers (OR 2.02; 95% CI 1.82 to 2.25) and ex-smokers (OR 1.41; 95% CI 1.21 to 1.65) were more likely to support this idea, even among current smokers, a third would favour moving towards a sales ban of tobacco products. Adjusting for other background characteristics, younger, female participants, those living in London and those from lower socioeconomic groups were most likely to support a ban. Among smokers, a higher cigarette consumption, smoking enjoyment and contentment with being a smoker were associated with opposition to a ban, while feeling uncomfortable being a smoker, wanting to be a non-smoker and being worried about future health consequences of smoking were associated with support for a ban. Support for movement towards a ban on the sale of tobacco is higher than might be imagined. It is conceivable that as smoking prevalence falls further and smoking becomes more socially unacceptable, support might grow to a point where such a policy could become feasible.


Expression and prognostic impact of matrix metalloproteinase-2 (MMP-2) in astrocytomas.
Astrocytomas are the most frequent primary brain tumors in adults, and despite aggressive treatment patients often experience recurrence. Survival decreases with increasing tumor grade, and especially patients with grade IV glioblastoma have poor prognosis due to the aggressive character of this tumor. Matrix metalloproteinase-2 (MMP-2) is an extracellular matrix degrading enzyme which has been shown to play important roles in different cancers. The aim of this study was to investigate the expression and prognostic potential of MMP-2 in astrocytomas. Tissue samples from 89 patients diagnosed with diffuse astrocytoma, anaplastic astrocytoma and glioblastoma were stained immunohistochemically using a monoclonal MMP-2 antibody. The MMP-2 intensity in cytoplasm/membrane was quantified by a trained software-based classifier using systematic random sampling in 10% of the tumor area. We found MMP-2 expression in tumor cells and blood vessels. Measurements of MMP-2 intensity increased with tumor grade, and MMP-2 expression was found to be significantly higher in glioblastomas compared to normal brain tissue (p<0.001), diffuse astrocytomas (p<0.001) and anaplastic astrocytomas (p<0.05). MMP-2 expression was associated with shorter overall survival in patients with grade II-IV astrocytic tumors (HR 1.60; 95% CI 1.03-2.48; p = 0.036). In glioblastoma, high MMP-2 was associated with poorer prognosis in patients who survived longer than 8.5 months independent of age and gender (HR 2.27; 95% CI 1.07-4.81; p = 0.033). We found a positive correlation between MMP-2 and tissue inhibitor of metalloproteinases-1 (TIMP-1), and combined MMP-2 and TIMP-1 had stronger prognostic value than MMP-2 alone also when adjusting for age and gender (HR 2.78; 95% CI 1.30-5.92; p = 0.008). These findings were validated in bioinformatics databases. In conclusion, this study indicates that MMP-2 is associated with aggressiveness in astrocytomas and may hold an unfavorable prognostic value in patients with glioblastoma.


Nonsuicidal self-injury, suicidal thoughts and suicide attempts among sexual minority youth in Ireland during their emerging adult years.
This study aimed to examine whether or not sexual minority youth constitute an at-risk group for nonsuicidal self-injury, suicidal ideation or suicide attempts during their emerging adult years. Using data from the Challenging Times Study, a population-based study of psychopathology and suicide in Ireland, analyses were conducted to test the associations between sexual minority status and the odds of any lifetime experience of nonsuicidal self-injury, suicidal thoughts or suicide attempts among Irish youth aged 19-24 years. Sexual minority youth had 6.6-fold (95% CI 1.7-24.7) increased risk of nonsuicidal self-injury, a 5.0-fold (95% CI 1.3-18.3) increased risk of suicidal ideation, a 7.7-fold (95% CI 1.8-32.0) increased risk of suicide intent and a 6.8-fold (95% CI 1.6-27.6) increased risk of a suicide attempt during their lifetime compared to their heterosexual peers. This study shows that emerging adulthood is a period of risk for suicide and nonsuicidal self-injurious behaviour among sexual minority youth.


Endurant stent graft demonstrates promising outcomes in challenging abdominal aortic aneurysm anatomy.
We aimed to assess the 5-year safety and effectiveness outcomes of patients enrolled in the Endurant Stent Graft Natural Selection Global Post Market Registry (ENGAGE) who were treated outside the approved indications for use (IFU) of the Endurant stent graft. Our primary outcome measure was 12-month treatment success, defined as successful endograft delivery and deployment and the absence of type I or III endoleak, stent migration or limb occlusion, late conversion, and abdominal aortic aneurysm diameter increase or rupture. Secondary outcome measures included 30-day all-cause mortality, major adverse events, secondary procedures, technical observations, aneurysm-related mortality, and all-cause mortality within 12 months. Demographic characteristics of ENGAGE patients treated outside (225 [17.8%]) and within (1038 [82.2%]) the IFUs were similar, except that female patients comprised a much higher percentage of the outside IFU group (19.1% vs 8.7%; P < .001). The outside IFU group presented with lower rates of coronary artery disease and cardiac revascularization and a greater number of symptomatic patients compared with the within IFU group (21.3% vs 15.0%; P = .020). Technical success was achieved in more than 99% of all patients. The outside and within IFU groups showed a comparable and low occurrence of uncorrected type I (0.9% vs 1.2%; P = 1.00) and type III endoleak (0.4% vs 0.3%; P = .54) immediately after device implantation. The 5-year freedom from type IA endoleaks was 89.4% vs 96.7% (P < .0001) for those patients outside and within the IFUs, respectively, although both groups had similar type III endoleaks through 5 years (P = .61). Stent graft limb occlusion estimated overall survival, and freedom from aneurysm-related mortality and endovascular interventions were comparable in both patient groups through the 5-year follow-up. The Kaplan-Meier estimates at 5 years showed a trend for low but increased need for type I or III endoleak correction procedures in the outside IFU group compared with the within IFU group (7.2% vs 5.2%; P = .099). Differences were not observed in all-cause mortality, aneurysm-related mortality, and secondary procedures between within and outside IFU patients through a 5-year follow-up in the ENGAGE registry. Proximal necks with angulation or diameters outside the IFUs were the most common reasons for patients identified as being outside IFU, and the cohort had increased incidence of type IA endoleaks. Despite the challenges presented from the broad range of aortic and abdominal aortic aneurysm morphologies, the Endurant stent graft showed promising 5-year outcomes.


Maternal prenatal felt security and infant health at birth interact to predict infant fussing and crying at 12 months postpartum.
Infants born with medical problems are at risk for less optimal developmental outcomes. This may be, in part, because neonatal medical problems are associated with maternal distress, which may adversely impact infants. However, the reserve capacity model suggests that an individual's bank of psychosocial resources buffers the adverse effects of later-encountered stressors. This prospective longitudinal study examined whether preexisting maternal psychosocial resources, conceptualized as felt security in close relationships, moderate the association between neonatal medical problems and infant fussing and crying 12 months postpartum. Maternal felt security was measured by assessing its indicators in 5,092 pregnant women. At birth, infants were classified as healthy or having a medical problem. At 12 months, experience sampling was used to assess daily maternal reports of fussing and crying in 135 mothers of infants who were healthy or had medical problems at birth. Confirmatory factor analyses revealed that attachment, relationship quality, self-esteem, and social support can be conceptualized as indicators of a single felt security factor. Multiple regression analyses revealed that prenatal maternal felt security interacts with infant health at birth to predict fussing and crying at 12 months. Among infants born with medical problems, higher felt security predicted decreased fussing and crying. Maternal felt security assessed before birth dampens the association between neonatal medical problems and subsequent infant behavior. This supports the hypothesis that psychosocial resources in reserve can be called upon in the face of a stressor to reduce its adverse effects on the self or others.


Prioritising the role of community health workers in the COVID-19 response.
COVID-19 disproportionately affects the poor and vulnerable. Community health workers are poised to play a pivotal role in fighting the pandemic, especially in countries with less resilient health systems. Drawing from practitioner expertise across four WHO regions, this article outlines the targeted actions needed at different stages of the pandemic to achieve the following goals: (1) PROTECT healthcare workers, (2) INTERRUPT the virus, (3) MAINTAIN existing healthcare services while surging their capacity, and (4) SHIELD the most vulnerable from socioeconomic shocks. While decisive action must be taken now to blunt the impact of the pandemic in countries likely to be hit the hardest, many of the investments in the supply chain, compensation, dedicated supervision, continuous training and performance management necessary for rapid community response in a pandemic are the same as those required to achieve universal healthcare and prevent the next epidemic.


Hydroethanolic extract of Carthamus tinctorius induces antidepressant-like effects: modulation by dopaminergic and serotonergic systems in tail suspension test in mice.
Studies indicate that major deficiency in the levels of monoaminergic transmitters is a reason for severe depression. On the other hand, it is shown that Carthamus tinctorius L. (CT) may improve neuropsychological injuries by regulation of the monoamine transporter action. Hence, the present study was undertaken to evaluate the involvement of monoaminergic systems in antidepressant-like effect of CT extract in the tail suspension test (TST) in mice. The mice were intraperitoneally (IP) treated with CT extract (100-400 mg/kg) 1 hr before the TST. To investigate the involvement of monoaminergic systems in antidepressant-like effect, the mice were treated with receptor antagonists 15 min before CT extract treatment (400 mg/kg, IP) and 1 hr before the TST. Findings showed that CT extract (100-400 mg/kg, IP), dose-dependently induced antidepressant-like effect (P<0.001), but it was not accompanied by alterations in spontaneous locomotor activity in the open-field test. Pretreatment of mice with SCH23390, sulpiride, haloperidol, WAY100135, cyproheptadine, ketanserin and p-chlorophenylalanine (PCPA) inhibited the antidepressant-like effect of CT extract (400 mg/kg, IP), but not with prazosin and yohimbine. Co-administration of CT extract (100 mg/kg, IP) with sub-effective doses of fluoxetine (5 mg/kg, IP) or imipramine (5 mg/kg, IP) increased their antidepressant-like response. Our findings firstly showed that components (especially N-Hexadecanoic acid) of CT extract induce antidepressant-like effects by interaction with dopaminergic (D1 and D2) and serotonergic (5HT1A, 5-HT2A receptors) systems. These findings validate the folk use of CT extract for the management of depression.


Real-World Adherence to Oral Methotrexate Measured Electronically in Patients With Established Rheumatoid Arthritis.
To assess methotrexate (MTX) adherence using the Medication Event Monitoring System (MEMS) and characterize associations with adherence in patients with rheumatoid arthritis (RA). Eligible patients participated in Forward, the National Databank for Rheumatic Diseases, and recently (12 months or sooner) initiated oral MTX. MEMS was used to compile MTX weekly dosing over 24 weeks. The Beliefs about Medicines Questionnaire (BMQ) was completed, and baseline demographics and disease characteristics obtained. MTX adherence (percentage of weeks dose taken correctly), implementation (percentage of weeks dose taken correctly from initiation until last dose), and persistence (duration from initiation to last dose) were calculated. Analyses measured associations between patient characteristics and adherence, modeled using logistic generalized estimating equations and censored Poisson regression, and persistence modeled using Cox regression. Overall, 60 of 119 eligible patients were included in the analysis. MTX adherence, implementation, and persistence were 75%, 80%, and 83%, respectively, at 24 weeks. Demographics and disease characteristics were generally similar between patients with 1 week or less and 2 weeks or more of missed MTX. Unemployment, less disability, higher Patient Global scores, and no prior disease-modifying antirheumatic drug (DMARD) use were associated with correct dosing. No significant differences in adherence were observed between patients receiving concomitant MTX versus MTX monotherapy, and biologic DMARD-experienced versus biologic DMARD-naïve patients. Higher scores in BMQ Specific Necessity (indicating a greater belief in the necessity of the medication) was associated with a decreased likelihood of dosing at an interval shorter than prescribed (odds ratio 0.89). Even in a participatory group over a short period, MTX adherence was suboptimal and associated with certain demographics, medication experience, and beliefs about medicines. This suggests a need for screening and alternative treatment opportunities in nonadherent MTX patients with RA.


Characterizing active and inactive brown adipose tissue in adult humans using PET-CT and MR imaging.
Activated brown adipose tissue (BAT) plays an important role in thermogenesis and whole body metabolism in mammals. Positron emission tomography (PET)-computed tomography (CT) imaging has identified depots of BAT in adult humans, igniting scientific interest. The purpose of this study is to characterize both active and inactive supraclavicular BAT in adults and compare the values to those of subcutaneous white adipose tissue (WAT). We obtained [(18)F]fluorodeoxyglucose ([(18)F]FDG) PET-CT and magnetic resonance imaging (MRI) scans of 25 healthy adults. Unlike [(18)F]FDG PET, which can detect only active BAT, MRI is capable of detecting both active and inactive BAT. The MRI-derived fat signal fraction (FSF) of active BAT was significantly lower than that of inactive BAT (means ± SD; 60.2 ± 7.6 vs. 62.4 ± 6.8%, respectively). This change in tissue morphology was also reflected as a significant increase in Hounsfield units (HU; -69.4 ± 11.5 vs. -74.5 ± 9.7 HU, respectively). Additionally, the CT HU, MRI FSF, and MRI R2* values are significantly different between BAT and WAT, regardless of the activation status of BAT. To the best of our knowledge, this is the first study to quantify PET-CT and MRI FSF measurements and utilize a semiautomated algorithm to identify inactive and active BAT in the same adult subjects. Our findings support the use of these metrics to characterize and distinguish between BAT and WAT and lay the foundation for future MRI analysis with the hope that some day MRI-based delineation of BAT can stand on its own.


Color modeling of stratified pictorial layers using the radiative transfer equation solved by the auxiliary function method.
The diffuse reflectance spectra and the trichromatic coordinates of diffusing stratified paints are modeled. Each layer contains its own pigments, and their optical properties are first determined from experiments. The radiative transfer equation is then solved by the auxiliary function method for modeling the total light scattered by the stratified systems. The results are in good agreement with experimental spectra and validate the modeling. The calculations are then applied on the same stratified systems to study the influence of the observation angle in a bidirectional configuration and to study the influence of the thickness of the layers in a given configuration. In both cases, the reflectance spectra and the trichromatic coordinates are calculated and compared.


Mutations within the conserved NS1 nuclear export signal lead to inhibition of influenza A virus replication.
The influenza A virus NS1 protein is a virulence factor and an antagonist of host cell innate immune responses. During virus infection NS1 protein has several functions both in the nucleus and in the cytoplasm and its intracellular localization is regulated by one or two nuclear localization signals (NLS) and a nuclear export signal (NES). In order to investigate the role of NS1 NES in intracellular localization, virus life cycle and host interferon responses, we generated recombinant A/Udorn/72 viruses harboring point mutations in the NES sequence. NS1 NES was found to be inactivated by several of the mutations resulting in nuclear retention of NS1 at late stages of infection confirming that this sequence is a bona fide functional NES. Some of the mutant viruses showed reduced growth properties in cell culture, inability to antagonize host cell interferon production and increased p-IRF3 levels, but no clear correlation between these phenotypes and NS1 localization could be made. Impaired activation of Akt phosphorylation by the replication-deficient viruses indicates possible disruption of NS1-p85β interaction by mutations in the NES region. We conclude that mutations within the NS1 NES result in impairment of several NS1 functions which extends further from the NES site being only involved in regulating the nuclear-cytoplasmic trafficking of NS1.


p53 is active in murine stem cells and alters the transcriptome in a manner that is reminiscent of mutant p53.
Since it was found that p53 is highly expressed in murine embryonic stem cells, it remained a mystery whether p53 is active in this cell type. We show that a significant part of p53 is localised in the nucleus of murine embryonic stem cells and that the majority of this nuclear p53 is bound to DNA. According to its nuclear localisation, we show that p53 alters the transcriptional program of stem cells. Nevertheless, the anti-proliferative activity of p53 is compromised in stem cells, and this control is due, at least in part, to the high amount of MdmX that is present in embryonic stem cells and bound to p53. Instead of the anti-proliferative activity that p53 has in differentiated cells, p53 controls transcription of pro-proliferative genes in embryonic stem cells including c-myc and c-jun. The impeded anti-proliferative activity of p53 and the induction of certain proto-oncogenes by p53 in murine embryonic stem cells can explain why stem cells proliferate efficiently despite having high levels of p53.


Can general practitioners do the follow-ups after surgery with ventilation tubes in the tympanic membrane? Two years audiological data.
A university hospital in Mid-Norway has modified their guidelines for follow-up after insertion of ventilation tubes (VTs) in the tympanic membrane, transferring the controls of the healthiest children to general practitioners (GPs). The aim of this study was to evaluate the implementation of these guidelines by exploring audiological outcome and subjective hearing complaints two years after surgery, assessing if follow-ups in general practice resulted in poorer outcome. A retrospective observational study was performed at the university hospital and in general practice in Mid-Norway. Children below 18 years who underwent surgery with VTs between Nov 1st 2007 and Dec 31st 2008 (n = 136) were invited to participate. Pure tone audiometry, speech audiometry and tympanometry were measured. A self-report questionnaire assessed subjective hearing, ear complaints and the location of follow-ups. This study includes enough patients to observe group differences in mean threshold (0.5-1-2-4 kHz) of 9 dB or more. There were no preoperative differences in audiometry or tympanometry between the children scheduled for follow-ups by GPs (n = 23) or otolaryngologists (n = 50). Two years after surgery there were no differences between the GP and otolaryngologist groups in improvement of mean hearing thresholds (12.8 vs 12.6 dB, p = 0.9) or reduction of middle ears with effusion (78.0 vs 75.0%, p = 0.9). We found no differences between the groups in terms of parental reports of child hearing or ear complaints. Implementation of new clinical guidelines for follow-ups after insertion of VTs did not negatively affect audiological outcomes or subjective hearing complaints two years after surgery.


Hemagglutination and graft-versus-host disease in the severe combined immunodeficiency mouse lymphoproliferative disease model.
In the course of evaluating the severe combined immunodeficiency mouse-human peripheral blood lymphocyte (SCID-PBL) model of lymphoproliferative disease, we noted hemagglutination occurring in peripheral blood smears of mice with serum human immunoglobulin levels greater than 1.0 mg/ml. The hemagglutinating process was mediated by human anti-mouse red cell antibodies of the IgM class, peaked at five to seven weeks post-transfer of 5 to 7 x 10(7) human PBL and was generally self limiting. However, death resulted in some mice when serum immunoglobulin levels were greater than 3.0 mg/ml. The most severely affected mice had hemagglutination induced congestion of liver, lungs and spleen. Several mice also had lesions consistent with graft-versus-host disease (GVHD) including focal hepatic necrosis and destruction of mouse splenic hematopoietic elements. The lesions associated with hemagglutination and GVHD in SCID-PBL mice are distinct from those associated with EBV-induced lymphoproliferation. Recognition of these pathologic processes are required for a thorough understanding of the SCID-PBL model.


Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.


[Not Available].
Despite ranking third as a cause of hospital-acquired acute kidney injury (AKI), iatrogenic contrast-induced nephropathy (CIN) impacts significantly on morbidity and mortality and is associated with high hospital costs. In sub-Saharan Africa, the rates and risk factors for CIN and patient outcomes remain unexplored. We conducted a prospective observational study at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa, from 1 July 2014 to 30 July 2015. Hospitalised patients undergoing computed tomography scan contrast media administration and angiography were consecutively recruited to the study and followed up for development of AKI. CIN was defined as an increase in serum creatinine >25% or an absolute increase of >44 μmol/L from baseline at 48 - 72 hours post exposure to contrast media. Outcome variables were the occurrence of CIN, length of hospitalisation and in-hospital mortality. We recruited 371 hospitalised patients with a mean (standard deviation) age of 49.3 (15.9). The rates of CIN, assessed using an absolute or relative increase in serum creatinine from baseline, were 4.6% and 16.4%, respectively. Anaemia was an independent predictor for the development of CIN (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.01 - 2.87; p=0.04). The median serum albumin was 34 g/L (interquartile range (IQR) 29 - 39.5) and 38 g/L (IQR 31 - 42) in the CIN and control groups, respectively (p=0.01), and showed a significant trend for CIN development (RR 1.68, 95% CI 0.96 - 2.92; p=0.06). Mortality was significantly increased in the CIN group (22.4% v. 6.8%; p<0.001), and CIN together with anaemia increased mortality twofold (RR 2.39, 95% CI 1.20 - 4.75; p=0.01) and threefold (RR 3.32, 95% CI 1.48 - 7.43; p=0.003), respectively. CIN has a relatively high incidence in sub-Saharan Africa and predicts poorer clinical outcomes. The presence of CIN and anaemia positively predicted mortality. Caution should be exercised in patients with hypoalbuminaemia and anaemia undergoing contrast media administration.


Stimulating Anopheles gambiae swarms in the laboratory: application for behavioural and fitness studies.
Male Anopheles mosquitoes that swarm rely in part on features of the environment including visual stimuli to locate swarms. Swarming is believed to be the primary behaviour during which mating occurs in the field, but is not a common behaviour in the laboratory. Features that stimulate male Anopheles gambiae G3 strain swarming were created in novel large indoor cages. The following visual features were tested in all combinations to determine which were important for swarm formation. Large cages and fading ceiling lights at dusk alone did not stimulate swarming while a dark foreground and contrasting illuminated background with a contrasting landmark stimulated and localized swarm formation during artificial twilight. Given the need to test transgenic strains in as natural a setting as possible, in this study it was investigated whether induced swarm behaviour and cage size would affect relative mating performance of wild-type and transgenic β2Ppo1 and β2Ppo2 A. gambiae sexually sterile males. Even using a mosquito colony that has been in laboratory culture for 39 years, swarming behaviour was induced by this novel arrangement. The presence of swarming stimuli was associated with an increase in insemination frequency from 74.3 to 97.7% in large cages. Transgenic males showed a lower competitiveness in large cages compared to small cages regardless of the presence of swarming stimuli. The results of the present study are discussed in view of the progressive evaluation of genetically modified A. gambiae strains and the potential applications of reproducing swarms in controlled conditions to dissect the mating behaviour of this species and the mechanisms controlling it.


An investigation into the level of empowerment of rural women in the Zululand district of KwaZulu-Natal province of South Africa.
The aim of the study was to evaluate the outcome of the empowerment of rural women in relation to gender issues, power, and communication within the Zululand District of KwaZulu-Natal in SouthAfrica after implementation of a four-year Primary Health Care project in partnership with the Provincial Department of Health, and two Schools of Nursing at the University of KwaZulu-Natal and McMaster University in Canada. This project is based on substantial evidence which reveals that rural women are being neglected to the extent that these women have missed out on opportunities for development. The reasons for this disempowerment of women, particularly rural women, are thought to be due to the feminisation of poverty, as well as female submission, educational deprivation, privacy of domestic violence, exploitation, domination by men and cultural oppression (patriarchy). A qualitative research approach was used. Focus group discussion was utilised as the data collection technique, and this was also applied during the collection of baseline data. An interview guide covered issues of concern in the communities and households, including what the women would, or had done about these, how they engaged in decision-making in their families, how they handled situations when there was a difference of opinion, and their awareness of, and ability to claim their rights, including control of their lives. The data was collected from six clinics, from groups of six to ten women in the predominantly rural Zululand District of KwaZulu-Natal. The project has revealed improvement in the women's realisation of their rights, albeit limited, in communication, self-confidence, and reliance, including partnerships between Primary Health Care Nurses and women's groups. The formation of women's groups facilitated community development and participation in their own health, socio-economic and emotional development. The project suggests that such groups be encouraged and allowed to network for support as they understand their own problems better, they merely require facilitation.


Outcomes of Patients With Syncope and Suspected Dementia.
Syncope and near-syncope are common in patients with dementia and a leading cause of emergency department (ED) evaluation and subsequent hospitalization. The objective of this study was to describe the clinical trajectory and short-term outcomes of patients who presented to the ED with syncope or near-syncope and were assessed by their ED provider to have dementia. This multisite prospective cohort study included patients 60 years of age or older who presented to the ED with syncope or near-syncope between 2013 and 2016. We analyzed a subcohort of 279 patients who were identified by the treating ED provider to have baseline dementia. We collected comprehensive patient-level, utilization, and outcomes data through interviews, provider surveys, and chart abstraction. Outcome measures included serious conditions related to syncope and death. Overall, 221 patients (79%) were hospitalized with a median length of stay of 2.1 days. A total of 46 patients (16%) were diagnosed with a serious condition in the ED. Of the 179 hospitalized patients who did not have a serious condition identified in the ED, 14 (7.8%) were subsequently diagnosed with a serious condition during the hospitalization, and an additional 12 patients (6.7%) were diagnosed postdischarge within 30 days of the index ED visit. There were seven deaths (2.5%) overall, none of which were cardiac-related. No patients who were discharged from the ED died or had a serious condition in the subsequent 30 days. Patients with perceived dementia who presented to the ED with syncope or near-syncope were frequently hospitalized. The diagnosis of a serious condition was uncommon if not identified during the initial ED assessment. Given the known iatrogenic risks of hospitalization for patients with dementia, future investigation of the impact of goals of care discussions on reducing potentially preventable, futile, or unwanted hospitalizations while improving goal-concordant care is warranted.


A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development.
Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.


Neutralization of adrenomedullin inhibits the growth of human glioblastoma cell lines in vitro and suppresses tumor xenograft growth in vivo.
Presently, there is no effective treatment for glioblastoma, the most malignant and common brain tumor. Growth factors are potential targets for therapeutic strategies because they are essential for tumor growth and progression. Peptidylglycine alpha-amidating monooxygenase is the enzyme producing alpha-amidated bioactive peptides from their inactive glycine-extended precursors. The high expression of peptidylglycine alpha-amidating monooxygenase mRNA in glioblastoma and glioma cell lines points to the involvement of alpha-amidated peptides in tumorigenic growth processes in the brain. After screening of amidated peptides, it was found that human glioblastoma cell lines express high levels of adrenomedullin (AM) mRNA, and that immunoreactive AM is released into the culture medium. AM is a multifunctional regulatory peptide with mitogenic and angiogenic capabilities among others. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis showed that AM mRNA was correlated to the tumor type and grade, with high expression in all glioblastomas analyzed, whereas a low expression was found in anaplastic astrocytomas and barely detectable levels in low-grade astrocytomas and oligodendrogliomas. In the present study we also demonstrate the presence of mRNA encoding the putative AM receptors, calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CRLR/RAMP2; CRLR/RAMP3) in both glioma tissues and glioblastoma cell lines and further show that exogenously added AM can stimulate the growth of these glioblastoma cells in vitro. These findings suggest that AM may function as an autocrine growth factor for glioblastoma cells. One way to test the autocrine hypothesis is to interrupt the function of the endogenously produced AM. Herein, we demonstrate that a polyclonal antibody specific to AM, blocks the binding of the hormone to its cellular receptors and decreases by 33% (P < 0.001) the growth of U87 glioblastoma cells in vitro. Intratumoral administration of the anti-AM antibody resulted in a 70% (P < 0.001) reduction in subcutaneous U87 xenograft weight 21 days after treatment. Furthermore, the density of vessels was decreased in the antibody-treated tumors. These findings support that AM may function as a potent autocrine/paracrine growth factor for human glioblastomas and demonstrate that inhibition of the action of AM (produced by tumor cells) may suppress tumor growth in vivo.


Smoking and smoking cessation effects on oncological outcomes in nonmuscle invasive bladder cancer.
Cigarette smoking is the best established risk factor for the development of bladder cancer. Nevertheless, the impact of smoking and smoking cessation on the outcomes of patients with nonmuscle invasive bladder cancer (NMIBC) remains poorly investigated. Currently, there are no prospective studies analyzing the impact of smoking on NMIBC outcomes. The majority of retrospective studies found an association between smoking status as well as cumulative lifetime exposure and disease recurrence. A recently published study demonstrated a significant impact of smoking on disease progression; however, the evidence regarding this end point is weak. There are insufficient data investigating the impact on cancer-specific and overall survival in patients with NMIBC. Assessment of the impact of smoking on particular subsets of patients with NMIBC including T1 or high-risk disease, patients receiving intravesical therapies, or sex-specific differences is limited because of a lack of data and controversial findings. Smoking cessation seems to mitigate the detrimental effects on outcomes. Although there are limited data, the growing body of evidence indicates that smoking increases the risk of disease recurrence and potentially disease progression in patients with NMIBC. Current and heavy long-term smokers seem to be at the greatest risk for both end points. Smoking cessation may limit these effects thereby improving prognosis. To improve our understanding of the associations of this important, modifiable risk factor with outcomes in patients with NMIBC, smoking should be incorporated into clinical trial design and analysis. It is the duty of each urologist to raise awareness regarding the greatest preventable cause of the development of bladder cancer, morbidity, and mortality.


Continuity of care: why it matters and what we can do.
Continuity of care matters; however, expansion and specialisation of the health system tends to fragment care. Continuity of care is accompanied by a range of patient benefits, including reduced all-cause mortality; lower rates of hospital presentation and preventable admission; and improved patient satisfaction. Potential concerns have been raised about some aspects of continuity of care, but these are outweighed by the perceived benefits. There are many barriers to achieving continuity, especially in rural and remote settings. Some practical solutions have been proposed that include adapting clinic procedures, utilising a small team approach, improving staff retention and ongoing advocacy.


Effects of β-lapachone on the production of Th1 and Th2 cytokines in C57BL/6 mice.
In this study, we investigated the effects of β-lapachone (β-lap) on the production of cytokines in C57BL/6 mice. The culture supernatants of splenocytes exposed to β-lap plus lipopolysaccharide or concanavalin A (Con A) were harvested to determine Th1 (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1β, IL-2, IL-17A, and IL-12) and Th2 (IL-4, IL-5, IL-6, and IL-10) cytokines. IL-2, a Th1 cytokine, was expressed at higher levels in splenocytes treated with β-lap and with lipopolysaccharide plus β-lap. Expression of Th2 cytokines, including IL-4, IL-5, IL-6, and IL-10, was lower in the culture supernatants of mouse splenocytes exposed to Con A plus β-lap than in supernatants from cells that were exposed to Con A alone. These findings demonstrate that β-lap downregulates the immediate hypersensitivity reaction induced by Con A. Therefore, Th2 responses involve the downregulation of IL-4, IL-5, IL-6, and IL-10, preventing the occurrence of allergies and various manifestations of allergic inflammation. These results suggest that β-lap may have potential preventive or adjunct anti-inflammatory therapy applications because of its function in modulating the production of cytokines. However, further in vivo investigations of this process are necessary to elucidate the mechanisms involved.


Implementation Lessons Learned From the Benefits of Enhanced Terminal Room (BETR) Disinfection Study: Process and Perceptions of Enhanced Disinfection with Ultraviolet Disinfection Devices.
OBJECTIVE To summarize and discuss logistic and administrative challenges we encountered during the Benefits of Enhanced Terminal Room (BETR) Disinfection Study and lessons learned that are pertinent to future utilization of ultraviolet (UV) disinfection devices in other hospitals DESIGN Multicenter cluster randomized trial SETTING AND PARTICIPANTS Nine hospitals in the southeastern United States METHODS All participating hospitals developed systems to implement 4 different strategies for terminal room disinfection. We measured compliance with disinfection strategy, barriers to implementation, and perceptions from nurse managers and environmental services (EVS) supervisors throughout the 28-month trial. RESULTS Implementation of enhanced terminal disinfection with UV disinfection devices provides unique challenges, including time pressures from bed control personnel, efficient room identification, negative perceptions from nurse managers, and discharge volume. In the course of the BETR Disinfection Study, we utilized several strategies to overcome these barriers: (1) establishing safety as the priority; (2) improving communication between EVS, bed control, and hospital administration; (3) ensuring availability of necessary resources; and (4) tracking and providing feedback on compliance. Using these strategies, we deployed ultraviolet (UV) disinfection devices in 16,220 (88%) of 18,411 eligible rooms during our trial (median per hospital, 89%; IQR, 86%-92%). CONCLUSIONS Implementation of enhanced terminal room disinfection strategies using UV devices requires recognition and mitigation of 2 key barriers: (1) timely and accurate identification of rooms that would benefit from enhanced terminal disinfection and (2) overcoming time constraints to allow EVS cleaning staff sufficient time to properly employ enhanced terminal disinfection methods. TRIAL REGISTRATION Clinical trials identifier: NCT01579370 Infect Control Hosp Epidemiol 2018;39:157-163.


Paradoxical antiproliferative effect by a murine mammary tumor-derived epithelial cell line.
Despite significant advancement in breast cancer therapy, there is a great need for a better understanding of the mechanisms involved in breast carcinogenesis and progression, as well as of the role of epigenetic contributions from stromal cells in mammary tumorigenesis. In this study, we isolated and characterized murine mammary tumor-derived epithelial and myofibroblast cell lines, and investigated the in vitro and in vivo effect of cellular soluble factors produced by the epithelial cell line on tumor cells. Morphology, immunophenotype, cytogenetics, invasiveness, and tumorigenicity of epithelial (LM-234ep) and myofibroblast (LM-234mf) cell lines isolated from two murine mammary adenocarcinomas with common ancestor were studied. The in vitro effects of LM-234ep conditioned medium on proliferation, cell cycle distribution, and expression of cell cycle proteins, were investigated in LM-234mf cells, mouse melanoma cells (B16-F10), and human cervical adenocarcinoma cells (HeLa). The in vivo anti-tumor activity of LM-234ep conditioned media was evaluated in subcutaneous tumors formed in nude mice by B16-F10 and HeLa cells. LM-234ep cells were found to be cytokeratin positive and hipertriploid, whereas LM-234mf cells were alpha-smooth muscle actin positive and hypohexaploid. Chromosome aberrations were found in both cases. Only LM-234mf revealed to be invasive in vitro and to secrete active MMP-2, though neither of the cell types were able to produce progressing tumors. LM-234ep-derived factors were able to inhibit the in vitro growth of LM-234mf, B16-F10, and HeLa cells, inducing cell cycle arrest in G0/G1 phase. The administration of LM-234ep conditioned medium inhibited the growth of B16-F10 and HeLa tumors in nude mice. Our data suggest the existence of epithelial cell variants with tumor suppressive properties within mammary tumors. To our knowledge, this is the first report showing antiproliferative and antineoplastic activities induced by tumor-derived epithelial cells.


Associations of bullying, victimization, and daytime sleepiness with academic problems in adolescents attending an alternative high school.
Adolescents attending alternative high schools often present with high rates of academic and behavior problems. They are also at increased risk of poor health behaviors and engaging in physical violence compared with students in traditional high school settings. To address the needs of students in these educational settings, examining factors that influence academic problems in this population is essential. Research has established that both bullying/victimization and sleep problems increase adolescents' risk for academic problems. Little is known about how these 2 factors together may exacerbate risk for academic problems among students attending an alternative high school. The current study investigated the interaction between teacher-reported bullying, victimization and daytime sleepiness on academic concerns (attention and learning problems) among a sample of 172 students (56% female; age M = 18.07 years, SD = 1.42) attending an alternative high school in a large, Southeastern U.S. city. Findings from path models indicated that daytime sleepiness, bullying, and victimization were uniquely associated with attention and learning problems. Further, significant interactions indicated that the association between victimization/bullying and attention/learning problems weakened as levels of daytime sleepiness increased. Results suggest the importance of assessing and addressing multiple contextual risk factors in adolescents attending alternative high schools to provide comprehensive intervention for students in these settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Sarcopenia and its association with falls and fractures in older adults: A systematic review and meta-analysis.
Sarcopenia is a potentially modifiable risk factor for falls and fractures in older adults, but the strength of the association between sarcopenia, falls, and fractures is unclear. This study aims to systematically assess the literature and perform a meta-analysis of the association between sarcopenia with falls and fractures among older adults. A literature search was performed using MEDLINE, EMBASE, Cochrane, and CINAHL from inception to May 2018. Inclusion criteria were the following: published in English, mean/median age ≥ 65 years, sarcopenia diagnosis (based on definitions used by the original studies' authors), falls and/or fractures outcomes, and any study population. Pooled analyses were conducted of the associations of sarcopenia with falls and fractures, expressed in odds ratios (OR) and 95% confidence intervals (CIs). Subgroup analyses were performed by study design, population, sex, sarcopenia definition, continent, and study quality. Heterogeneity was assessed using the I2 statistics. The search identified 2771 studies. Thirty-six studies (52 838 individuals, 48.8% females, and mean age of the study populations ranging from 65.0 to 86.7 years) were included in the systematic review. Four studies reported on both falls and fractures. Ten out of 22 studies reported a significantly higher risk of falls in sarcopenic compared with non-sarcopenic individuals; 11 out of 19 studies showed a significant positive association with fractures. Thirty-three studies (45 926 individuals) were included in the meta-analysis. Sarcopenic individuals had a significant higher risk of falls (cross-sectional studies: OR 1.60; 95% CI 1.37-1.86, P < 0.001, I2 = 34%; prospective studies: OR 1.89; 95% CI 1.33-2.68, P < 0.001, I2 = 37%) and fractures (cross-sectional studies: OR 1.84; 95% CI 1.30-2.62, P = 0.001, I2 = 91%; prospective studies: OR 1.71; 95% CI 1.44-2.03, P = 0.011, I2 = 0%) compared with non-sarcopenic individuals. This was independent of study design, population, sex, sarcopenia definition, continent, and study quality. The positive association between sarcopenia with falls and fractures in older adults strengthens the need to invest in sarcopenia prevention and interventions to evaluate its effect on falls and fractures.


Pregnancy-associated cancers: frequency and temporal trends in Italy.
Limited data are available on the frequency and time trends of pregnancy-associated cancers, particularly from Southern European countries. The aim of this study was to analyze the frequency and time trends of pregnancy-associated cancer in Italy. This was a population-based linkage study using the regional hospital discharge forms database of four Italian regions with more than 17 million inhabitants. All resident women with a hospital discharge form reporting a birth or abortion in the time period under consideration were identified. The time period of the study was 2003-2015 for the Piemonte and Puglia region, 2006-2015 for the Tuscany region, and 2005-2015 for the Veneto region. Risk of developing a pregnancy-associated cancer was calculated as the ratio of the number of pregnancy-related cancers to the total number of pregnancies. A total of 2 297 648 pregnancies were identified. Overall, the pregnancy-associated cancer frequency was 134.8 per 100 000 pregnancies: the frequency ranged from 127.1 in Puglia to 157.3 in Tuscany. The frequency for 100 000 pregnancies was 66.4 in women aged <30 years; the risk increased with age, with a frequency of 275.6 among women aged 40+ years. Approximately two-thirds of cancers were associated with pregnancies resulting in a delivery and one-third with pregnancies resulting in a termination of pregnancy or spontaneous pregnancy loss. No clear trend emerged in the risk of pregnancy-associated cancer per 100 000 pregnancies and calendar year. No clear time trend was observed in the frequency of pregnancy-associated cancers in Italy during the last 10 years, the rates being 104, 164, and 130 per 100 000 pregnancies, respectively, in 2003, 2010, and 2015.


Estimating the global clinical burden of Plasmodium falciparum malaria in 2007.
The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches. In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales. Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349-552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk. Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques. Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated.


Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA.
In higher eukaryotes, a multiprotein exon junction complex is deposited on spliced messenger RNAs. The complex is organized around a stable core, which serves as a binding platform for numerous factors that influence messenger RNA function. Here, we present the crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I.


Advantages of myocardial revascularization after admission for critical limb ischemia in diabetic patients with coronary artery disease: data of a cohort of 564 consecutive patients.
To evaluate the survival benefit from myocardial revascularization in diabetic patients with critical limb ischemia and coronary artery disease (CAD) in a consecutive series of 564 diabetic patients hospitalized from 1999 to 2003 and followed up until December 2005. Three hundred and thirteen patients had a history of CAD, 60 of them (19.2%) with previous myocardial revascularization. Sixty-one patients with an ejection fraction of 40% or less underwent subsequent myocardial revascularization. Five hundred and fifty-seven patients (98.8%) were followed up until December 2005, including 310 of the 313 patients with a history of CAD. One hundred and ten patients died because of CAD, 25 of the 251 patients without a history of CAD and 85 of the 313 patients with a history of CAD. Specifically, 74 (86.9%) of these 85 deaths occurred in the 192 patients without previous myocardial revascularization, nine (10.7%) in the 60 patients with previous myocardial revascularization, and two (2.4%) in the 61 patients in whom myocardial revascularization was performed after hospital admission for critical limb ischemia. The Cox model showed significant hazard ratio for mortality associated with age [hazard ratio 1.06 for 1 year, P = 0.003, confidence interval (CI) 1.02-1.09], history of CAD (hazard ratio 2.16, P < 0.001, CI 1.53-3.06), dialysis (hazard ratio 3.52, P < 0.001, CI 2.08-5.97), and impaired ejection fraction (hazard ratio 1.08 for one point percentage, P < 0.001, CI 1.05-1.09). Myocardial revascularization appeared to have a protective role: hazard ratio 0.29, P < 0.001, CI 0.33-0.93. Paying attention to CAD in diabetic patients during their hospitalization for critical limb ischemia is useful for a subsequent myocardial revascularization, and it may increase survival in these patients.


Enactment of compassionate leadership by nursing and midwifery managers: results from an international online survey.
To explore the views of an international sample of nursing and midwifery managers concerning attributes that they associate with compassionate management. A cross-sectional online survey. Using a snowballing sampling method, 1217 responses were collected from nursing and midwifery managers in 17 countries. A total of complete 933 responses to a question related to which actions and behaviours indicated that a manager was exercising compassionate leadership were analysed for this paper. First, content analysis of the responses was conducted, and second, a relative distribution of the identified themes for the overall sample and for each participating country was calculated. Six main themes were identified describing the attributes of a compassionate leader: (1) Virtuous support, (2) Communication, (3) Personal virtues of the manager, (4) Participatory communication, (5) Growth/flourishing/ nurturing and (6) Team cohesion. The first three themes mentioned above collectively accounted for 63% of the responses, and can therefore be considered to be the most important characteristics of compassionate management behaviour. The key indicators of compassionate management in nursing and midwifery which were identified emphasise approachability, active and sensitive listening, sympathetic responses to staff members' difficulties (especially concerning child and other caring responsibilities), active support of and advocacy for the staff team and active problem solving and conflict resolution. While there were differences between the countries' views on compassionate healthcare management, some themes were widely represented among different countries' responses, which suggest key indicators of compassionate management that apply across cultures.


Guidelines for calibration of stimulus and recording parameters used in clinical electrophysiology of vision. Calibration Standard Committee of the International Society for Clinical Electrophysiology of Vision (ISCEV).
In order to perform a technically adequate clinical electrophysiological procedure it is necessary to calibrate the stimulating and recording equipment. Published standards for the electroretinogram (ERG), electro-oculogram (EOG), visual evoked potential (VEP), and guidelines for the Pattern ERG (PERG) specify stimulus and recording parameters. Yet, most commercial instruments do not provide the means for calibration of these parameters. The goal of this document is to provide guidelines for proper calibration of stimulus and recording equipment. The need for such guidelines is clear on both clinical and scientific grounds. Stimulus and amplifier characteristics have substantial effects on the peak latency and amplitude measurements that are commonly used in clinical electrophysiology. Many review articles on clinical electrophysiology emphasize the need for establishing norms for each laboratory as a function of age and gender rather than relying on published norms. However, if stimulus and recording parameters are not calibrated periodically, then these norms may actually be misleading due to changes in stimulus or recording conditions induced by aging of equipment or inadvertent change in settings. This document is divided into two major sections. The first is concerned with calibration of the visual stimulus. It begins with background technical information on the physics of light and its measurement. This is followed by protocols for measurement of the luminous intensity of flash stimuli and the mean luminance, contrast, and visual angle of pattern stimuli. The second section is concerned with calibration of electrophysiologic recording systems. It begins with a description of the characteristics of bioelectrical signals and their measurement. This is followed by protocols for measurement of electrode impedance and amplifier calibration. Although this document was prepared as guidelines for clinical electrophysiological testing, it should be noted that the techniques described are more generally applicable to studies which are dependent upon accurate measurement of luminance or electrophysiological signals.


Ultrastable and polyamorphic states of vapor-deposited 2-methyltetrahydrofuran.
This work reports results gained from dielectric spectroscopy on the organic molecular glass-former 2-methyltetrahydrofuran (MTHF), which was deposited onto an interdigitated electrode device by physical vapor deposition. By a suitable selection of preparation parameters (deposition temperature, deposition rate, and annealing conditions), various states of MTHF could be created: ultrastable glass, a liquid state with unusual dielectric properties, or the ordinary liquid state as obtained by supercooling. Observations on kinetic stability as well as on the suppression of dielectric loss in the ultrastable state resemble previous findings for other molecular glass-formers. Remarkably, after annealing just above Tg, all vapor-deposited films of MTHF display a static dielectric constant in the liquid state (εs) that is up to a factor of two below that of the ordinary bulk liquid. A structural transition to the ordinary liquid-cooled state of MTHF occurs at temperatures far above its conventional Tg, indicative of polyamorphism: the formation of an unusual structure that is achieved by physical vapor deposition and that differs from the ordinary liquid state obtained by supercooling. The present results also reveal that the dielectric constant of the as deposited glass (ε∞) is reduced to practically the value of the squared refractive index, n2.


Bullies and victims at school: are they the same pupils?
The reported prevalence of bully-victims and aggressive/provocative victims varies quite considerably in previous research, and only a few studies have reported prevalence rates across grades. There is also a lack of detailed analyses of the extent to which victims are also bullies, and bullies are also victims. To study the prevalence of male and female bully-victims across grade/age and to establish the degree of overlap or relative size of the bully-victim group by relating them to all victims, all bullies and all involved students. Participants in Study 1 were 5,171 pupils in grades 5-9 from 37 schools. Study 2 comprised 12,983 pupils in grades 4-10 from 66 schools. The Olweus Bully/Victim Questionnaire was administered to the pupils in their ordinary classrooms. The prevalence of bully-victims was low and mainly declined across grades. There were far more boys than girls in the bully-victim group. Bully-victims resembled victims only (pure victims) in terms of age-trends and bullies only (pure bullies) in terms of sex composition. The overlap of bully-victims with the total victim group was fairly small (10-20%) in all grades. In primary grades, bully-victims constituted about 30-50% of the total bully group, whereas in higher grades these proportions were considerably lower. Our analyses and overview of previous research suggest that the bully-victim group is small, and that the large variations across studies are mainly due to differences in choice of cutoff point. Bully-victims should generally be seen and treated statistically as a distinct subgroup. The relatively larger proportion of bully-victims in lower grades should be explored further.


Contribution of epigenetic variation to adaptation in Arabidopsis.
In plants, transgenerational inheritance of some epialleles has been demonstrated but it remains controversial whether epigenetic variation is subject to selection and contributes to adaptation. Simulating selection in a rapidly changing environment, we compare phenotypic traits and epigenetic variation between Arabidopsis thaliana populations grown for five generations under selection and their genetically nearly identical ancestors. Selected populations of two distinct genotypes show significant differences in flowering time and plant architecture, which are maintained for at least 2-3 generations in the absence of selection. While we cannot detect consistent genetic changes, we observe a reduction of epigenetic diversity and changes in the methylation state of about 50,000 cytosines, some of which are associated with phenotypic changes. Thus, we propose that epigenetic variation is subject to selection and can contribute to rapid adaptive responses, although the extent to which epigenetics plays a role in adaptation is still unclear.


Four-dimensional CT as a valid approach to detect and quantify kinematic changes after selective ankle ligament sectioning.
The objective of the current study was to explore the potential of dynamic computed tomography to detect kinematic changes, induced by sequential sectioning of the lateral collateral ligaments of the ankle, during full motion sequence of the talocrural joint. A custom-made device was used to induce cyclic controlled ankle inversion movement in one fresh frozen cadaver leg. A 256-slice CT scanner was used to investigate four different scenarios. Scenario 1 with all ligaments intact was first investigated followed by sequential section of the anterior talo-fibular ligament (Scenario 2), the calcaneo-fibular ligament (Scenario 3) and posterior talo-fibular ligament (Scenario 4). Off-line image processing based on semi-automatic segmentation and bone rigid registration was performed. Motion parameters such as translation, rotational angles and orientation and position of the axis of rotation were calculated. Differences between scenarios were calculated. Progressive increase of cranio-caudal displacement up to 3.9 mm and flexion up to 10° compared to Scenario 1 were reported. Progressive changes in orientation (up to 20.6°) and position (up to 4.1 mm) of the axis of rotation were also shown. Estimated effective dose of 0.005 mSv (1.9 mGy CTDIvol) was reported. This study demonstrated that kinematic changes due to the absence of ligament integrity can be detected with 4DCT with minimal radiation exposure. Identifying abnormal kinematic patterns could have future application in helping clinicians to choose patients' optimal treatment. Therefore, further studies with bigger in vitro sample sizes and consequent investigations in vivo are recommended to confirm the current findings.


Evaluation by nurses and students of a new assessment form for clinical nursing education.
An assessment form was developed, based on Swedish higher education regulations and international guidelines for nursing education, to be used during clinical education regardless of the level of the programme or clinical specialty. Nurses who acted as supervisors for students used the form for continuous and formal assessment, and students used it for self-assessment. Once developed, the assessment form covered 18 professional and academic areas. After one semester nurses (n = 323) and students (n = 154) from two university colleges evaluated their experiences of using the form by answering a questionnaire. In addition, the completed assessment forms filled in by the nurses were reviewed and analysed. The evaluation showed that the nurses and the students considered the assessment form highly valuable. Both groups believed that the form highlighted the requirements for clinical education and was useful in assessing the students' development. Almost all 18 factors were found to be important to assess. Least important and most difficult to assess were 'the use of research and developmental work' and 'the ability to inform and teach co-workers and students'. Some areas that were regarded as difficult to assess were also marked by the nurses in the assessment form as 'not possible or relevant to assess'. The form was found to be useful in assessing students' development towards the goals of nursing education. The study also revealed that essential areas in nursing education have unclear educational demands for those involved.