British American Tobacco's tactics during China's accession to the World Trade Organization.
China entered the World Trade Organization (WTO) in 2001 after years of negotiations. As a WTO member, China had to reduce tariffs on imported cigarettes and remove non-tariff barriers to allow foreign cigarettes to be more competitive in the Chinese market. Among foreign tobacco companies, British American Tobacco (BAT) was the most active lobbyist during China's WTO negotiations. To review and analyse BAT's tactics and activities relating to China's entry into the WTO. Internal tobacco industry documents were reviewed and are featured here. Industry documents were searched mainly on the website of BAT's Guildford Depository and other documents' websites. 528 documents were evaluated and 142 were determined to be relevant to China's entry into the WTO. BAT was extremely active during the progress of China's entry into the WTO. The company focused its lobbying efforts on two main players in the negotiations: the European Union (EU) and the US. Because of the negative moral and health issues related to tobacco, BAT did not seek public support from officials associated with the WTO negotiations. Instead, BAT lobbyists suggested that officials protect the interests of BAT by presenting the company's needs as similar to those of all European companies. During the negotiation process, BAT officials repeatedly spoke favourably of China's accession into the WTO, with the aim of presenting BAT as a facilitator in this process and of gaining preferential treatment from their Chinese competitor. BAT's activities clearly suggest that tobacco companies place their own interests above public health interests. Today, China struggles with issues of tobacco control that are aggravated by the aggressive practices of transnational tobacco companies, tobacco-tariff reductions and the huge number of smokers. For the tobacco-control movement to progress in China, health advocates must understand how foreign tobacco companies have undermined anti-tobacco activities by taking advantage of trade liberalisation policies. China should attach importance to public health and comprehensive tobacco-control policies and guarantee strong protection measures from national and international tobacco interests supported by international trade agreements.


The disposition of diammonium glycyrrhizinate and glycyrrhetinic acid in the isolated perfused rat intestine and liver.
The major component of liquorice root extract, glycyrrhizinate (GZ), has been formulated as an injection for the treatment of hepatitis. If given orally, GZ has poor bioavailability and is catalysed to glycyrrhetinic acid (GA) by intestinal bacteria. GA is subsequently responsible for significant side effects. This study was conducted to clarify the relationship between GZ and GA absorption and bioavailability. GZ and GA absorption were investigated using the in situ single pass isolated perfused intestine (IPI). Hepatic disposition was investigated using isolated perfused liver (IPL) and in vivo biliary excretion models. The apparent permeability and absorption rate constants in the IPI for GZ were 0.36 +/- 0.31 cm/min and 0.35 +/- 0.33 min (-1), while those for GA were 5.73 +/- 0.11 cm/min and 1.53 +/- 0.05 min (-1), respectively. The hepatic extraction ratios of unbound GZ and GA in the IPL were 0.22 +/- 0.01 and 0.44 +/- 0.15, respectively. Seven hours after intra-portal venous injection in vivo, the cumulative biliary excretion ratio for GZ was 96 %. There was negligible biliary excretion of unchanged GA during the same period. It was apparent in all models used that in the absence of intestinal bacteria GZ was not metabolised to GA, or vice versa. Hence, GZ can be absorbed unchanged from the intestine provided it has sufficient time and is protected from intestinal bacteria. This opens up the possibility that the use of pharmaceutical carrier systems or similar formulation approaches may allow effective oral administration of therapeutic levels of GZ without the side effects associated with GA.


Genetics of life history in Drosophila melanogaster. I. Sib analysis of adult females.
A sib analysis of adult life-history characters was performed on about twelve hundred females from a laboratory Drosophila melanogaster population that had been sampled from nature and cultured so as to preserve its genetic variability. The following results were found. There was no detectable trend with age in additive or dominance genetic variances for age-specific fecundity. Environmental variance for age-specific fecundity increased with age. The genetic variance for fecundity characters was primarily additive. The genetic variance for longevity was primarily dominance variance. There were negative genetic correlations between early fecundity and lifespan, as well as between mean egg-laying rate and longevity.


A deep hierarchy of predictions enables online meaning extraction in a computational model of human speech comprehension.
Understanding speech requires mapping fleeting and often ambiguous soundwaves to meaning. While humans are known to exploit their capacity to contextualize to facilitate this process, how internal knowledge is deployed online remains an open question. Here, we present a model that extracts multiple levels of information from continuous speech online. The model applies linguistic and nonlinguistic knowledge to speech processing, by periodically generating top-down predictions and incorporating bottom-up incoming evidence in a nested temporal hierarchy. We show that a nonlinguistic context level provides semantic predictions informed by sensory inputs, which are crucial for disambiguating among multiple meanings of the same word. The explicit knowledge hierarchy of the model enables a more holistic account of the neurophysiological responses to speech compared to using lexical predictions generated by a neural network language model (GPT-2). We also show that hierarchical predictions reduce peripheral processing via minimizing uncertainty and prediction error. With this proof-of-concept model, we demonstrate that the deployment of hierarchical predictions is a possible strategy for the brain to dynamically utilize structured knowledge and make sense of the speech input.


Slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow.
Three-dimensional cellular imaging techniques have become indispensable tools in biological research and medical diagnostics. Conventional 3D imaging approaches employ focal stack collection to image different planes of the cell. In this work, we present the design and fabrication of a slanted channel microfluidic chip for 3D fluorescence imaging of cells in flow. The approach employs slanted microfluidic channels fabricated in glass using ultrafast laser inscription. The slanted nature of the microfluidic channels ensures that samples come into and go out of focus, as they pass through the microscope imaging field of view. This novel approach enables the collection of focal stacks in a straight-forward and automated manner, even with off-the-shelf microscopes that are not equipped with any motorized translation/rotation sample stages. The presented approach not only simplifies conventional focal stack collection, but also enhances the capabilities of a regular widefield fluorescence microscope to match the features of a sophisticated confocal microscope. We demonstrate the retrieval of sectioned slices of microspheres and cells, with the use of computational algorithms to enhance the signal-to-noise ratio (SNR) in the collected raw images. The retrieved sectioned images have been used to visualize fluorescent microspheres and bovine sperm cell nucleus in 3D while using a regular widefield fluorescence microscope. We have been able to achieve sectioning of approximately 200 slices per cell, which corresponds to a spatial translation of ∼ 15 nm per slice along the optical axis of the microscope.


Occupational Therapy Wellness Program: Youth and Parent Perspectives.
In this study, we explored the impact of an occupational therapy wellness program on daily habits and routines through the perspectives of youth and their parents. Data were collected through semistructured interviews with children and their parents, the Pizzi Healthy Weight Management Assessment(©), and program activities. Three themes emerged from the interviews: Program Impact, Lessons Learned, and Time as a Barrier to Health. The most common areas that both youth and parents wanted to change were time spent watching television and play, fun, and leisure time. Analysis of activity pie charts indicated that the youth considerably increased active time in their daily routines from Week 1 to Week 6 of the program. An occupational therapy program focused on health and wellness may help youth and their parents be more mindful of their daily activities and make health behavior changes.


Growth and remodeling play opposing roles during postnatal human heart valve development.
Tissue growth and remodeling are known to govern mechanical homeostasis in biological tissue, but their relative contributions to homeostasis remain unclear. Here, we use mechanical models, fueled by experimental findings, to demonstrate that growth and remodeling have different effects on heart valve stretch homeostasis during physiological postnatal development. Two developmental stages were considered: early-stage (from infant to adolescent) and late-stage (from adolescent to adult) development. Our models indicated that growth and remodeling play opposing roles in preserving tissue stretch and with time. During early-stage development, excessive tissue stretch was decreased by tissue growth and increased by remodeling. In contrast, during late-stage development tissue stretch was decreased by remodeling and increased by growth. Our findings contribute to an improved understanding of native heart valve adaptation throughout life, and are highly relevant for the development of tissue-engineered heart valves.


A modified hyperplane clustering algorithm allows for efficient and accurate clustering of extremely large datasets.
As the number of publically available microarray experiments increases, the ability to analyze extremely large datasets across multiple experiments becomes critical. There is a requirement to develop algorithms which are fast and can cluster extremely large datasets without affecting the cluster quality. Clustering is an unsupervised exploratory technique applied to microarray data to find similar data structures or expression patterns. Because of the high input/output costs involved and large distance matrices calculated, most of the algomerative clustering algorithms fail on large datasets (30,000 + genes/200 + arrays). In this article, we propose a new two-stage algorithm which partitions the high-dimensional space associated with microarray data using hyperplanes. The first stage is based on the Balanced Iterative Reducing and Clustering using Hierarchies algorithm with the second stage being a conventional k-means clustering technique. This algorithm has been implemented in a software tool (HPCluster) designed to cluster gene expression data. We compared the clustering results using the two-stage hyperplane algorithm with the conventional k-means algorithm from other available programs. Because, the first stage traverses the data in a single scan, the performance and speed increases substantially. The data reduction accomplished in the first stage of the algorithm reduces the memory requirements allowing us to cluster 44,460 genes without failure and significantly decreases the time to complete when compared with popular k-means programs. The software was written in C# (.NET 1.1). The program is freely available and can be downloaded from http://www.amdcc.org/bioinformatics/bioinformatics.aspx. Supplementary data are available at Bioinformatics online.


Characterisation and antibiotic susceptibilities of Streptobacillus moniliformis.
The characteristics of seven strains of Streptobacillus moniliformis, including four isolates from a recent outbreak of Haverhill fever, are reported. Acid production from carbohydrates was uniform apart from variable reactions with mannose and salicin. Enzymatic reactions determined by the API ZYM system and fatty-acid profiles were generally consistent and may be of value in the rapid identification of S. moniliformis. Penicillin was the most active of the antibiotics tested in vitro, which supports its use as the drug of choice in the treatment of Haverhill fever.


Sympathetic Nerve Injury in Thyroid Cancer.
The double innervation of the thyroid comes from the sympathetic and parasympathetic nervous system. Injury rates during surgery are at 30% but can be minimized by upwardly preparing the thyroid vessels at the level of thyroid capsule. Several factors have been accused of increasing the risk of injury including age and tumor size. Our aim was to investigate of there is indeed any possible correlations between these factors and a possible increase in injury rates following thyroidectomy. Seven studies were included in the meta-analysis. Statistical correlation was observed for a positive relationship between injury of the sympathetic nerve and thyroid malignancy surgery (p 2 = 74%) No statistical correlations were observed for a negative or positive relationship between injury of the sympathetic nerve and tumor size. There was also no statistically significant value observed for the correlation of the patients' age with the risk of sympathetic nerve injury (p = 0.388). Lack of significant correlation reported could be due to the small number of studies and great heterogeneity between them.


A probit- log- skew-normal mixture model for repeated measures data with excess zeros, with application to a cohort study of paediatric respiratory symptoms.
A zero-inflated continuous outcome is characterized by occurrence of "excess" zeros that more than a single distribution can explain, with the positive observations forming a skewed distribution. Mixture models are employed for regression analysis of zero-inflated data. Moreover, for repeated measures zero-inflated data the clustering structure should also be modeled for an adequate analysis. Diary of Asthma and Viral Infections Study (DAVIS) was a one year (2004) cohort study conducted at McMaster University to monitor viral infection and respiratory symptoms in children aged 5-11 years with and without asthma. Respiratory symptoms were recorded daily using either an Internet or paper-based diary. Changes in symptoms were assessed by study staff and led to collection of nasal fluid specimens for virological testing. The study objectives included investigating the response of respiratory symptoms to respiratory viral infection in children with and without asthma over a one year period. Due to sparse data daily respiratory symptom scores were aggregated into weekly average scores. More than 70% of the weekly average scores were zero, with the positive scores forming a skewed distribution. We propose a random effects probit/log-skew-normal mixture model to analyze the DAVIS data. The model parameters were estimated using a maximum marginal likelihood approach. A simulation study was conducted to assess the performance of the proposed mixture model if the underlying distribution of the positive response is different from log-skew normal. Viral infection status was highly significant in both probit and log-skew normal model components respectively. The probability of being symptom free was much lower for the week a child was viral positive relative to the week she/he was viral negative. The severity of the symptoms was also greater for the week a child was viral positive. The probability of being symptom free was smaller for asthmatics relative to non-asthmatics throughout the year, whereas there was no difference in the severity of the symptoms between the two groups. A positive association was observed between viral infection status and both the probability of experiencing any respiratory symptoms, and their severity during the year. For DAVIS data the random effects probit -log skew normal model fits significantly better than the random effects probit -log normal model, endorsing our parametric choice for the model. The simulation study indicates that our proposed model seems to be robust to misspecification of the distribution of the positive skewed response.


The neurobiology of psychedelic drugs: implications for the treatment of mood disorders.
After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders. These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity.


Multiple channel types contribute to the low-voltage-activated calcium current in hippocampal CA3 pyramidal neurons.
Hippocampal neurons exhibit low-voltage-activated (LVA) and high-voltage-activated (HVA) calcium currents. We characterized the LVA current by recording whole-cell Ca2+ currents from acutely isolated rat hippocampal CA3 pyramidal neurons in 2 mM Ca2+. Long depolarizing steps to -50 mV revealed two components to the LVA current: transient and sustained. The transient phase had a fast decay time constant of 59 msec. The sustained phase persisted throughout the depolarization, even for steps lasting several seconds. The transient current was inhibited by the classic T-type channel antagonists Ni2+ and amiloride. The anticonvulsant phenytoin preferentially blocked the sustained phase, but ethosuximide had no effect. Steady-state inactivation of the transient component was half-maximal at -80 mV. Nimodipine, an L-type channel antagonist, partly inhibited the sustained current. BayK-8644, an L-type channel agonist, potentiated the sustained current. Calciseptine, another L-type channel antagonist, inhibited the sustained component. omega-Conotoxin-MVIIC, a nonselective toxin for HVA channels, had no effect on either of the LVA current components. omega-Grammotoxin-SIA, another nonselective toxin, partially inhibited the sustained component. The voltage dependence of activation of the nimodipine-sensitive current could be fit with a single Boltzmann, consistent with a homogenous population of L-type channels in CA3 neurons. Half-maximal activation of the nimodipine-sensitive current occurred at -30 mV, considerably more negative than the remaining HVA current. These results suggest that in physiologic Ca2+ more than one type of Ca2+ channel contributes to the LVA current in CA3 neurons. The transient current is carried by T-type channels. The sustained current is carried, at least in part, by dihydropyridine-sensitive channels. Thus, the designation "low-voltage-activated" should not be limited to T-type channels. These findings challenge the traditional designation of L-type channels as exclusively HVA and reveal a possible role in subthreshold Ca2+ signaling.


Pheromones exert top-down effects on visual recognition in the jumping spider Lyssomanes viridis.
In diverse and productive habitats, predaceous arthropods are expected to frequently encounter dangerous conspecifics and heterospecifics. This should make quick and accurate discriminations between species and sexes adaptive. By simultaneously sampling both visual cues and pheromones, and by utilizing stringent species- and sex-specific visual recognition templates, an individual should be able to increase both its speed and accuracy in making such discriminations. We tested for the use and stringency of visual recognition templates in the jumping spider Lyssomanes viridis by presenting males with animated images of conspecifics, heterospecifics and composite images that combined the facial coloration and morphology of one sex or species with the leg coloration of another. Males' courtship versus threat displays indicated whether a stimulus was perceived as a potential mate or a threat. By comparing males' visual inspection times of, and display types towards, the various images in the presence versus absence of female pheromones, we were able to deduce whether males tend to inspect a subset of the color pattern and morphological features that make up their conspecific recognition templates (i.e. those on just the face or just the legs), or all features, and whether this changes in the presence of pheromones. We found that the male recognition template for conspecific female was surprisingly coarse, whereas the recognition template for conspecific male, and especially the male face, was more specific. Pheromones hastened the recognition of images with coloration and morphology closely matching those of conspecifics, presumably by activating conspecific visual recognition templates. When males were presented with an image that was, overall, a poor match to a conspecific female, but that contained a subset of female or female-like features, female pheromones usually did not hasten recognition, but did increase the likelihood that the image would be identified as a female. Taken together, our data suggest that males examined features on both the face and the legs in both the presence and absence of pheromones, and that female pheromones tipped the balance in favor of a female identification when a male was unsure how to categorize an incongruous set of visual features.


Genomic studies of adaptive evolution in outcrossing Arabidopsis species.
Large-scale population genomic approaches have very recently been fruitfully applied to the Arabidopsis relatives Arabidopsis halleri, A. lyrata and especially A. arenosa. In contrast to A. thaliana, these species are obligately outcrossing and thus the footprints of natural selection are more straightforward to detect. Furthermore, both theoretical and empirical studies indicate that outcrossers are better able to evolve in response to selection pressure. As a result, recent work in these species serves as a paradigm of population genomic studies of adaptation both to environmental as well as intracellular challenges.


Implications of adopting new WHO guidelines for antiretroviral therapy initiation in Ethiopia.
To assess the implications of implementing the World Health Organization (WHO) 2010 guidelines for antiretroviral therapy (ART) initiation in adults and adolescents with human immunodeficiency virus (HIV) infection, which recommend initiating ART at a CD4+ T lymphocyte (CD4+) threshold of ≤ 350 cells/mm(3) instead of ≤ 200 cells/mm(3), which was the earlier threshold. Between April and May 2010, CD4+ test results were collected for all HIV-infected patients recorded in the pre-ART and ART registers of 19 high-patient-load health centres in Addis Ababa, Ethiopia, and the regions of Amhara, Oromia, SNNPR (Southern Nations, Nationalities and People's Region) and Tigray. At 12 centres patient records were independently reviewed to assess data accuracy. To estimate the total number of patients who would need ART at health centres if Ethiopia adopted the new WHO guidelines, the number of patients needing ART based on current guidelines were added to the number of asymptomatic patients enrolled in pre-ART with a CD4+ count > 200 but ≤ 350 cells/mm(3) Adoption of the new WHO guidelines would increase the total number of patients on ART in the 19 health centres in Ethiopia by about 30%: from 3583 to 4640. The shift in the CD4+ threshold for ART initiation will substantially increase the demand for ART in Ethiopia. Since under the current systems only 60% of Ethiopia's patients in need of ART are receiving the medications, scaling up ART programmes to accommodate the increased demand for drugs will not be possible unless government funding and support increase concurrently.


Characterizing herbivore resistance mechanisms: spittlebugs on Brachiaria spp. as an example.
Plants can resist herbivore damage through three broad mechanisms: antixenosis, antibiosis and tolerance(1). Antixenosis is the degree to which the plant is avoided when the herbivore is able to select other plants(2). Antibiosis is the degree to which the plant affects the fitness of the herbivore feeding on it(1).Tolerance is the degree to which the plant can withstand or repair damage caused by the herbivore, without compromising the herbivore's growth and reproduction(1). The durability of herbivore resistance in an agricultural setting depends to a great extent on the resistance mechanism favored during crop breeding efforts(3). We demonstrate a no-choice experiment designed to estimate the relative contributions of antibiosis and tolerance to spittlebug resistance in Brachiaria spp. Several species of African grasses of the genus Brachiaria are valuable forage and pasture plants in the Neotropics, but they can be severely challenged by several native species of spittlebugs (Hemiptera: Cercopidae)(4).To assess their resistance to spittlebugs, plants are vegetatively-propagated by stem cuttings and allowed to grow for approximately one month, allowing the growth of superficial roots on which spittlebugs can feed. At that point, each test plant is individually challenged with six spittlebug eggs near hatching. Infestations are allowed to progress for one month before evaluating plant damage and insect survival. Scoring plant damage provides an estimate of tolerance while scoring insect survival provides an estimate of antibiosis. This protocol has facilitated our plant breeding objective to enhance spittlebug resistance in commercial brachiariagrases(5).


The impact of compulsory cycle helmet legislation on cyclist head injuries in New South Wales, Australia.
The study aimed to assess the effect of compulsory cycle helmet legislation on cyclist head injuries given the ongoing debate in Australia as to the efficacy of this measure at a population level. We used hospital admissions data from New South Wales, Australia, from a 36 month period centred at the time legislation came into effect. Negative binomial regression of hospital admission counts of head and limb injuries to cyclists were performed to identify differential changes in head and limb injury rates at the time of legislation. Interaction terms were included to allow different trends between injury types and pre- and post-law time periods. To avoid the issue of lack of cyclist exposure data, we assumed equal exposures between head and limb injuries which allowed an arbitrary proxy exposure to be used in the model. As a comparison, analyses were also performed for pedestrian data to identify which of the observed effects were specific to cyclists. In general, the models identified a decreasing trend in injury rates prior to legislation, an increasing trend thereafter and a drop in rates at the time legislation was enacted, all of which were thought to represent background effects in transport safety. Head injury rates decreased significantly more than limb injury rates at the time of legislation among cyclists but not among pedestrians. This additional benefit was attributed to compulsory helmet legislation. Despite numerous data limitations, we identified evidence of a positive effect of compulsory cycle helmet legislation on cyclist head injuries at a population level such that repealing the law cannot be justified.


Predictive computational phenotyping and biomarker discovery using reference-free genome comparisons.
The identification of genomic biomarkers is a key step towards improving diagnostic tests and therapies. We present a reference-free method for this task that relies on a k-mer representation of genomes and a machine learning algorithm that produces intelligible models. The method is computationally scalable and well-suited for whole genome sequencing studies. The method was validated by generating models that predict the antibiotic resistance of C. difficile, M. tuberculosis, P. aeruginosa, and S. pneumoniae for 17 antibiotics. The obtained models are accurate, faithful to the biological pathways targeted by the antibiotics, and they provide insight into the process of resistance acquisition. Moreover, a theoretical analysis of the method revealed tight statistical guarantees on the accuracy of the obtained models, supporting its relevance for genomic biomarker discovery. Our method allows the generation of accurate and interpretable predictive models of phenotypes, which rely on a small set of genomic variations. The method is not limited to predicting antibiotic resistance in bacteria and is applicable to a variety of organisms and phenotypes. Kover, an efficient implementation of our method, is open-source and should guide biological efforts to understand a plethora of phenotypes ( http://github.com/aldro61/kover/ ).


Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.
The purpose of this study was to estimate which strategy is the most cost-effective for the prevention of preterm birth and associated morbidity. We used decision-analytic and cost-effectiveness analyses to estimate which of 4 strategies was superior based on quality-adjusted life-years, cost in US dollars, and number of preterm births prevented. Universal sonographic screening for cervical length and treatment with vaginal progesterone was the most cost-effective strategy and was the dominant choice over the 3 alternatives: cervical length screening for women at increased risk for preterm birth and treatment with vaginal progesterone; risk-based treatment with 17 alpha-hydroxyprogesterone caproate (17-OHP-C) without screening; no screening or treatment. Universal screening represented savings of $1339 ($8325 vs $9664), when compared with treatment with 17-OHP-C, and led to a reduction of 95,920 preterm births annually in the United States. Universal sonographic screening for short cervical length and treatment with vaginal progesterone appears to be cost-effective and yields the greatest reduction in preterm birth at <34 weeks' gestation.


Managing the post-resuscitation patient in the field.
The principal goal after successful resuscitation of a cardiac arrest patient is to maintain the patient's pulse and avoid a pulseless state. Of equal importance in the post-resuscitation patient are efforts to prevent myocardial dysfunction and increase the likelihood of a good neurologic outcome. To optimize cardiac and hemodynamic resuscitation, paramedics should obtain good background information, which could provide clues to factors contributing to the cardiac arrest, such as the use of certain drugs or being overdue for dialysis, and could aid in customizing therapy for rhythm disturbances and hemodynamic aberrations. Treatment of rhythm disturbances depends on the type of arrhythmia identified, the history of present illness, and the resuscitation efforts provided. Common post-resuscitation dysrhythmias are wide-complex tachycardia, narrow-complex tachycardia, and bradycardia. Optimizing neurologic resuscitation is difficult, but evidence suggests that hypertensive reperfusion, hemodilution, and mild hypothermia may be of benefit in improving neurologic outcome after resuscitation. Unfortunately, to date, no proven therapies are available to improve neurologic outcome after resuscitation from cardiac arrest.


A Dynamic Three-Dimensional Covalent Organic Framework.
A guest-induced reversible crystal-structure transformation is identified in a new 3D covalent organic framework (COF) by comprehensive analyses using powder X-ray diffraction, organic vapor sorption isotherm, and 129Xe NMR spectroscopy. The revolving imine bond in interpenetrating 3D networks is uncovered as the key to the dynamic behavior, the potential applications of which are illustrated by gas separation and heterogeneous catalysis, thus paving the way to the design of stimuli-responsive and multifunctional COF materials.


Influenza virus polymerase confers independence of the cellular cap-binding factor eIF4E for viral mRNA translation.
The influenza virus mRNAs are structurally similar to cellular mRNAs nevertheless; the virus promotes selective translation of viral mRNAs despite the inhibition of host cell protein synthesis. The infection proceeds normally upon functional impairment of eIF4E cap-binding protein, but requires functional eIF4A helicase and eIF4G factor. Here, we have studied whether the presence of cis elements in viral mRNAs or the action of viral proteins is responsible for this eIF4E-independence. The eIF4E protein is required for viral mRNA translation in vitro, indicating that cis-acting RNA sequences are not involved in this process. We also show that PB2 viral polymerase subunit interacts with the eIF4G protein. In addition, a chimeric mRNA containing viral UTR sequences transcribed by the viral polymerase out of the infection is successfully translated independently of an impaired eIF4E factor. These data support that the viral polymerase is responsible for the eIF4E independence of influenza virus mRNA translation.


The influence of health systems on hypertension awareness, treatment, and control: a systematic literature review.
Hypertension (HT) affects an estimated one billion people worldwide, nearly three-quarters of whom live in low- or middle-income countries (LMICs). In both developed and developing countries, only a minority of individuals with HT are adequately treated. The reasons are many but, as with other chronic diseases, they include weaknesses in health systems. We conducted a systematic review of the influence of national or regional health systems on HT awareness, treatment, and control. Eligible studies were those that analyzed the impact of health systems arrangements at the regional or national level on HT awareness, treatment, control, or antihypertensive medication adherence. The following databases were searched on 13th May 2013: Medline, Embase, Global Health, LILACS, Africa-Wide Information, IMSEAR, IMEMR, and WPRIM. There were no date or language restrictions. Two authors independently assessed papers for inclusion, extracted data, and assessed risk of bias. A narrative synthesis of the findings was conducted. Meta-analysis was not conducted due to substantial methodological heterogeneity in included studies. 53 studies were included, 11 of which were carried out in LMICs. Most studies evaluated health system financing and only four evaluated the effect of either human, physical, social, or intellectual resources on HT outcomes. Reduced medication co-payments were associated with improved HT control and treatment adherence, mainly evaluated in US settings. On balance, health insurance coverage was associated with improved outcomes of HT care in US settings. Having a routine place of care or physician was associated with improved HT care. This review supports the minimization of medication co-payments in health insurance plans, and although studies were largely conducted in the US, the principle is likely to apply more generally. Studies that identify and analyze complexities and links between health systems arrangements and their effects on HT management are required, particularly in LMICs. Please see later in the article for the Editors' Summary.


An assay for galactosyltransferase-I activity in articular cartilage.
UDP-D-Galactose:D-xylose galactosyltransferase (Galactosyltransferase-I) is an enzyme involved in the synthesis of the linkage region of chondroitin sulfate. Measurement of galactosyltransferase-I in mature articular cartilage has depended on milling such tissue in liquid nitrogen to break open the cells and enable interaction of exogenous substrates with galactosyltransferase-I. This process requires large amounts (approximately 1 g wet wt) of cartilage. This paper reports the development of an assay for galactosyltransferase-I in articular cartilage where 10-25 mg (wet wt) of the tissue was extracted with a buffer containing the detergent Thesit. This assay was more time efficient, required less tissue, and was linear for up to 6 h. It was effective on both mature bovine articular cartilage and embryonic chick epiphyseal cartilage, detecting 100 and 68% of total galactosyltransferase-I activity, respectively. The higher number of measurements available allowed kinetic studies to be conducted on bovine articular cartilage explant cultures under conditions of up- and down-regulation. Incubation with fetal calf serum resulted in an increase in galactosyltransferase-I activity. Galactosyltransferase-I activity, however, did not change markedly in cartilage cultured in the absence of fetal calf serum or in the presence of cycloheximide. A soluble preparation of galactosyltransferase-I, extracted from bovine articular cartilage using Thesit, eluted from a Superose-6 column, with a molecular mass of about 55 kDa.


Pathogens, density dependence and the coexistence of tropical trees.
There is increasing interest in the role played by density-dependent mortality from natural enemies, particularly plant pathogens, in promoting the coexistence and diversity of tropical trees. Here, we review four issues in the analysis of pathogen-induced density dependence that have been overlooked or inadequately addressed. First, the methodology for detecting density dependence must be robust to potential biases. Observational studies, in particular, require a careful analysis to avoid biases generated by measurement error, and existing studies could be criticized on these grounds. Experimental studies manipulating plant density and pathogen incidence will often be preferable, or should be run in parallel. Second, the form of density dependence is not well understood and, in particular, there are no data indicating whether pathogens cause compensating or overcompensating density responses. Owing to this, we argue that the potential for pathogen-induced density dependence to generate diversity-enhancing outcomes, such as the Janzen-Connell effect, remains uncertain, as coexistence is far more probable if density dependence is overcompensating. Third, there have been few studies examining the relative importance of intra- or interspecific density dependence resulting from pathogens (or, more widely, natural enemies). This is essentially equivalent to asking to what extent pathogens are host-specific. If pathogens are generalists, then mortality rates will respond to overall plant density, irrespective of plant species identity. This will weaken the intraspecific density dependence and reduce the diversity-promoting effects of pathogens. Finally, we highlight the need for studies that integrate observations and experiments on pathogens and density dependence into the whole life cycle of trees, because as yet it is not possible to be certain of the degree to which pathogens contribute to observed dynamics.


Development of a 'communication disability model' and its implication on service delivery in low-income countries.
This paper argues that higher priority should be given to the development of services which support people with communication disabilities in low income countries and that these services should be different from those in other countries. Present services for this population group have poor coverage levels, tend to be centrally located and are orientated to specialist services. WHO (Health Programme Evaluation, Geneva, WHO, 1981) argue that health services should be based on meeting people's needs. This paper describes an analysis of 'needs related' qualitative data concerning people with communication disabilities and their families in two low income countries and examines the results in relation to service development. The data was collected as part of five different studies concerning people with communication disabilities carried out in Uganda and Nigeria. Using the principles of established theory, these data helped develop, a theoretical model. This model is compared with WHO's classification of Impairment Disability and Handicap ICIDH-2 WHO (International Classification of Impairments Disabilities and Handicaps (ICIDH-2), A manual of classification relating to the consequences of diseases, Geneva, WHO. 1997a; 1999). Suggestions are made as to how this model might inform planning and practice from the perspective of the five major stakeholder groups; government and non-government organizations, people with communication disabilities, their families and professionals. Consideration is also given as to how this theory can be used to strengthen existing services, or encourage a complete paradigm shift, with the creation of different services in new and innovative ways.


Applying the Theoretical Domains Framework to understand knowledge broker decisions in selecting evidence for knowledge translation in low- and middle-income countries.
Health-related organisations disseminate an abundance of clinical and implementation evidence that has potential to improve health outcomes in low- and middle-income countries (LMICs), but little is known about what influences a user decision to select particular evidence for action. Knowledge brokers (KBs) play a part as intermediaries supporting evidence-informed health policy and practice by selecting and synthesising evidence for research users, and therefore understanding the basis for KB decisions, can help inform knowledge translation strategies. The Theoretical Domains Framework (TDF), a synthesis of psychological theories, was selected as a promising analysis approach because of its widespread use in identifying influences on decisions to act on evidence-based healthcare guidelines. This study explored its application in the context of KB decisions regarding evidence for use in LMICs. The study analysed data collected from participants of a 2015 global maternal and newborn health conference in Mexico. A total of 324 conference participants from 56 countries completed an online survey and 20 from 15 countries were interviewed about evidence use and sharing after the conference. TDF domains and constructs were retrospectively applied and adapted during coding of qualitative data to enhance understanding of the KB decision process in selecting evidence for action. Application of the TDF involved challenges related to overlapping constructs, retrospective use, and complexities of global health settings and relevant knowledge. Codes needed to be added or adapted to account for how KBs' internal reflections on external factors influenced their actions in selecting evidence to share and use, and the decisions they made during the process. Four themes of the rationale for changing the TDF were identified during analysis, namely Influences from Beyond the Organisation, Knowledge Selection as a Process, Access and Packaging of Knowledge, and Fit for Use. Theories of individual behaviour, such as those in the TDF, can enhance understanding of the decisions made by actors such as KBs along dissemination and knowledge translation pathways. Understanding how KBs reflect on evidence and interact with their environment has the potential for improving global dissemination efforts and LMIC-to-LMIC exchange of implementation evidence.


Maternal infection and white matter toxicity.
Studies examining maternal infection as a risk factor for neurological disorders in the offspring have suggested that altered maternal immune status during pregnancy can be considered as an adverse event in prenatal development. Infection occurring in the mother during the gestational period has been implicated in multiple neurological effects. The current manuscript will consider the issue of immune/inflammatory conditions during prenatal development where adverse outcomes have been linked to maternal systemic infection. The discussions will focus primary on white matter and oligodendrocytes as they have been identified as target processes. This white matter damage occurs in very early preterm infants and in various other human diseases currently being examined for a linkage to maternal or early developmental immune status. The intent is to draw attention to the impact of altered immune status during pregnancy on the offspring for the consideration of such contributing factors to the general assessment of developmental neurotoxicology.


Genomic mapping with I-Ceu I, an intron-encoded endonuclease specific for genes for ribosomal RNA, in Salmonella spp., Escherichia coli, and other bacteria.
Construction of physical maps of genomes by pulsed-field gel electrophoresis requires enzymes which cut the genome into an analyzable number of fragments; most produce too many fragments. The enzyme I-Ceu I, encoded by a mobile intron in the chloroplast 23S ribosomal RNA (rrl) gene of Chlamydomonas eugametos, cuts a 26-bp site in the rrl gene. This enzyme digests DNA of Salmonella typhimurium at seven sites, each corresponding to one of the rrl genes of the rrn operons, but at no other site. These seven fragments were located on the previously determined Xba I physical map, and the I-Ceu I sites, and thus the rrn genes of S. typhimurium, were mapped on the 4800-kb chromosome. Escherichia coli K-12 also yields seven fragments of sizes similar to those of S. typhimurium, indicating conservation of rrn genes and their location, and a chromosome size of 4600 kb. The sizes of the E. coli fragments are close to the size predicted from restriction maps and nucleotide sequence. The I-Ceu I maps of Salmonella enteritidis, Salmonella paratyphi A, B, C, and Salmonella typhi were deduced after digesting genomic DNA and I-Ceu I and probing with DNA of S. typhimurium; the data indicated strong conservation of rrn gene number and position and genome sizes up to 4950 kb. Digestion of DNA of other bacteria (species of Haemophilus, Neisseria, Proteus, and Pasteurella) suggested that only rrn genes are cut in all these species. I-Ceu I digestion followed by pulsed-field gel electrophoresis is a powerful tool for determining genome structure and evolution.


Controlling signal transduction with synthetic ligands.
Dimerization and oligomerization are general biological control mechanisms contributing to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. Cell permeable, synthetic ligands were devised that can be used to control the intracellular oligomerization of specific proteins. To demonstrate their utility, these ligands were used to induce intracellular oligomerization of cell surface receptors that lacked their transmembrane and extracellular regions but contained intracellular signaling domains. Addition of these ligands to cells in culture resulted in signal transmission and specific target gene activation. Monomeric forms of the ligands blocked the pathway. This method of ligand-regulated activation and termination of signaling pathways has the potential to be applied wherever precise control of a signal transduction pathway is desired.


Breast ultrasound scans - surgeons' expectations.
Recent years have witnessed a dynamic development of mammary gland imaging techniques, particularly ultrasonography and magnetic resonance imaging. A challenge related to these studies is the increase in the precision of the anatomical assessment of breast, particularly for early detection of subclinical lesions, performance of ultrasound- guided biopsy procedures, and accurate preoperative location of pathological lesions so as to optimize the surgical treatment. Ultrasound imaging is a primary and baseline diagnostic procedure the patient with suspected pathological lesions within breast is referred to by the surgeon. Lesions visualized in ultrasound scans are classified according to the BI-RADS US assessment categories. The successive categories (2 through 6) encompass individual pathological lesions, estimating the risk of malignancy and provide guidelines for further diagnostic and therapeutic management. This article described the important aspects of ultrasonographic imaging of focal lesions within the breasts as significant from the standpoint of surgical treatment of patients falling within BI-RADS US categories 3, 4, 5, and 6. Attention is drawn to the importance of ultrasound scans in the assessment of axillary fossa lymph nodes before the decision regarding the surgical treatment.


Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.


Mechanical and energetic scaling relationships of running gait through ontogeny in the ostrich (Struthio camelus).
It is unclear whether small animals, with their high stride frequency and crouched posture, or large animals, with more tendinous limbs, are more reliant on storage and return of elastic energy during locomotion. The ostrich has a limb structure that appears to be adapted for high-speed running with long tendons and short muscle fibres. Here we investigate biomechanics of ostrich gait through growth and, with consideration of anatomical data, identify scaling relationships with increasing body size, relating to forces acting on the musculoskeletal structures, effective mechanical advantage (EMA) and mechanical work. Kinematic and kinetic data were collected through growth from running ostriches. Joint moments scaled in a similar way to the pelvic limb segments as a result of consistent posture through growth, such that EMA was independent of body mass. Because no postural change was observed, relative loads applied to musculoskeletal tissues would be predicted to increase during growth, with greater muscle, and hence tendon, load allowing increased potential for elastic energy storage with increasing size. Mass-specific mechanical work per unit distance was independent of body mass, resulting in a small but significant increase in the contribution of elastic energy storage to locomotor economy in larger ostriches.


Pneumonia during therapy for childhood acute lymphoblastic leukemia.
The incidence of pneumonia was evaluated in 844 children undergoing initial treatment for acute lymphoblastic leukemia (ALL). A total of 310 episodes occurred in 239 patients followed up for five to 36 months after diagnosis. The peak incidences occurred in the periods 0 to 20 days and 40 to 80 days after the start of antileukemic therapy. Bacterial pneumonias occurred primarily during the first 20 days after diagnosis of ALL. No episode of Pneumocystis carinii pneumonia was noted before 40 days, and the majority of instances occurred 50 to 120 days after diagnosis. In 80% of all episodes, a specific causative organism was not detected. The incidence of P carinii pneumonia was greater in patients receiving intrathecal methotrexate as part of CNS prophylaxis than in those receiving only CNS irradiation. Pneumonia is a frequent event during the therapy of ALL in childhood.


HLA class I polymorphisms are associated with development of infectious mononucleosis upon primary EBV infection.
Infectious mononucleosis (IM) is an immunopathological disease caused by EBV that occurs in young adults and is a risk factor for Hodgkin lymphoma (HL). An association between EBV-positive HL and genetic markers in the HLA class I locus has been identified, indicating that genetic differences in the HLA class I locus may alter disease phenotypes associated with EBV infection. To further determine whether HLA class I alleles may affect development of EBV-associated diseases, we analyzed 2 microsatellite markers and 2 SNPs located near the HLA class I locus in patients with acute IM and in asymptomatic EBV-seropositive and -seronegative individuals. Alleles of both microsatellite markers were significantly associated with development of IM. Specific alleles of the 2 SNPs were also significantly more frequent in patients with IM than in EBV-seronegative individuals. IM patients possessing the associated microsatellite allele had fewer lymphocytes and increased neutrophils relative to IM patients lacking the allele. These patients also displayed higher EBV titers and milder IM symptoms. The results of this study indicate that HLA class I polymorphisms may predispose patients to development of IM upon primary EBV infection, suggesting that genetic variation in T cell responses can influence the nature of primary EBV infection and the level of viral persistence.


The Remarkable Change in Euro-American Cranial Shape and Size.
Secular changes in stature, weight, or other components of the body that can be obtained from historical records have been extensively studied. Cranial change has been central to anthropology for more than a century, but the focus has normally been on change measured in centuries or millennia. Cranial change measured in decades, normally considered to result from plastic response to the environment, has been less studied. This article reports on change in cranial vault dimensions in white Americans. Variables were glabello-occipital length (GOL), basion-bregma height (BBH), basion-nasion length (BNL), maximum cranial breadth (XCB), and biauricular breadth (AUB). Cranial size was calculated as the geometric mean of these variables, and shape dimensions were calculated as described by Darroch and Mosimann ( 1985 ). Cranial module and cranial capacity were also calculated. Samples consisted of 1,112 males and 668 females complete for those variables. Samples were organized into 10-year birth cohorts, with birth years ranging from 1820 to 1990. One-way ANOVA was used to test for variation among cohorts. The pattern of secular change was examined graphically and was compared with quality-of-life and environmental indicators, including stature, infant mortality, calories per person, and relative number of immigrants. All variables showed significant secular change, but BBH, XCB, and BNL responded most strongly. Over the past 170 years, crania became relatively higher, narrower, and larger with longer cranial bases. Both sexes changed, but female change was less pronounced than male change. The cranial variables tracked secular changes in stature, most prominently BNL. The highest correlation between a cranial variable and quality-of-life indicator was BBH and infant mortality. We are not able to identify specific causes of secular changes in cranial morphology. However, given that modern Americans have introduced themselves into a novel environment never before experienced by human populations, we consider it unlikely that it is pure plasticity. In addition to possible plastic responses, it is likely that selection, acting through the dramatic changes in infant mortality, is also involved.


Prevalence of antibodies to Trypanosoma cruzi in raccoons (Procyon lotor) from an urban area of northern Virginia.
Raccoons (Procyon lotor) are reservoir hosts for Trypanosoma cruzi. A 3-yr-long serological survey was conducted to determine the prevalence of antibodies to this zoonotic parasite in raccoons collected from Fairfax County, Virginia, a suburban/urban area outside Washington, D.C. Serum samples from 464 raccoons were examined for T. cruzi antibodies at a 1:40 dilution with an indirect fluorescent antibody test (IFAT) and Brazil strain T. cruzi amastigotes and trypomastigotes as antigen. A positive IFAT test was found in 154 (33%) of the 464 samples. The yearly prevalence was 49 of 132 (37%) in 2000; 19 of 120 (16%) in 2001; and 86 of 212 (41%) in 2002. Our study indicates that raccoons in this area of Virginia are frequently exposed to T. cruzi.


Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity.
The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach.


An unusual foreign body aspiration requiring an unusual retrieval technique.
Foreign body aspiration during medical procedures has been reported in the literature. These iatrogenic incidents could be related to instruments malfunction or to accidental occurrences during medical treatment. In this paper, we present a report of a woman coming for a laparoscopic abdominal hysterectomy who developed intraoperative bronchospasm. In an attempt to administer aerosolized albuterol, the resident anesthesia provider fractured the Luer-lock tip of the 60-cc syringe, which he was using to hold the albuterol nebulizer. The plastic tip was dislodged into the endotracheal tube (ETT). On further inspection with a fiberoptic instrument the plastic tip was located loosely adherent to the distal part of the ETT and was held in place by the moisture, which had precipitated in the distal tube. An intraoperative consult with interventional pulmonary medicine was obtained after unsuccessfully attempting to retrieve the foreign body with a grasper. The syringe tip was then removed using a Fogarty balloon catheter that was threaded through the hole of the plastic tip.


Phenotypic Variation of Cell Wall Composition and Stem Morphology in Hemp (Cannabis sativa L.): Optimization of Methods.
The growing demands for sustainable fibers have stimulated the study of genetic diversity in the quality of hemp fiber (Cannabis sativa L.). Nevertheless, the lack of high-throughput phenotyping methods that are suited for the analysis of hemp fiber, hampers the analysis of many accessions, and consequently the breeding for this complex trait. In the present report, we developed and optimized the throughput of five methods to study the diversity in hemp fiber quality including cell wall extraction, biochemical composition of cell wall polysaccharides, quantification of lignin, quantification of crystalline polysaccharides and morphology of the stems. Six hemp accessions contrasting for cell wall properties were used to assess the throughput and suitability of these methods for genetic studies. The methods presented revealed to be highly repeatable, with low coefficients of variation between technical replicates. With these methods we were able to detect significant phenotypic variation in cell wall composition and stem morphology between the six accessions. In addition, the throughput of the methods has been upgraded to a level that enables their use for phenotyping cell wall traits in breeding programs. The cell wall extraction was optimized to extract enough material for the complete characterization of the cell wall of hemp while reducing the time for the entire analysis. The throughput of the stem morphological analysis was improved by decreasing the timing of fixation, infiltration, and embedding of mature and dry hemp stems. Notwithstanding, our methods already have the potential to phenotype large number of accessions in a relatively short period of time. Our methods will enable exploration of genetic diversity of fiber quality and will contribute to the development of new hemp varieties with advanced quality of fibers.


[Exploration of the Association Between Workplace Bullying and Attitudes Toward Patient Safety in Female Nurses].
Workplace bullying is known to have a significant and detrimental effect on the physical and psychological outcomes of its victims. The reactions of victims to bullying may decrease clinical care outcomes and patient safety. To explore the relationship between workplace bullying and the attitudes of female nurses toward the safety of their patients. This cross-sectional survey study used convenience sampling. Participants included female nurses from a regional teaching hospital. The research tool was a three-part, structured questionnaire that included a basic personal information datasheet, negative behavior scale, and patient safety attitude scale. The researcher distributed 420 questionnaires and collected 329 valid samples (valid return rate: 78.3%). Data were analyzed using SPSS software version 22.0. The analysis found that 29.8% of the participants had suffered from various degrees of workplace bullying. The mean score for patient safety attitudes was 3.58 (standard deviation = 0.55). Workplace bullying and patient safety attitudes were negatively correlated (p < .1), and being a recipient of workplace bullying was identified as a significant predictor of attitudes toward patient safety. Based on the results, we suggest that supervisors should take the initiative to care for their nursing staffs and to provide them with training in conflict-oriented skills. Organization managers should set up relevant committee-notification mechanisms that construct the safe working environment necessary to reduce workplace bullying and to enhance the patient safety attitudes of nurses, which will indirectly improve the quality of patient care.


Porphysome nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model: a pilot study.
Local disease control is a major challenge in pancreatic cancer treatment, because surgical resection of the primary tumor is only possible in a minority of patients and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for focal ablation of pancreatic tumors, this approach remains underinvestigated. Using photothermal sensitizers in combination with laser light irradiation for PTT can result in more efficient conversion of light energy to heat and improved spatial confinement of thermal destruction to the tumor. Porphysomes are self-assembled nanoparticles composed mainly of pyropheophorbide-conjugated phospholipids, enabling the packing of ∼80,000 porphyrin photosensitizers per particle. The high-density porphyrin loading imparts enhanced photonic properties and enables high-payload tumor delivery. A patient-derived orthotopic pancreas xenograft model was used to evaluate the feasibility of porphysome-enhanced PTT for pancreatic cancer. Biodistribution and tumor accumulation were evaluated using fluorescence intensity measurements from homogenized tissues and imaging of excised organs. Tumor surface temperature was recorded using IR optical imaging during light irradiation to monitor treatment progress. Histological analyses were conducted to determine the extent of PTT thermal damage. These studies may provide insight into the influence of heat-sink effect on thermal therapy dosimetry for well-perfused pancreatic tumors.


Energy and macronutrient intake and risk of differentiated thyroid carcinoma in the European Prospective Investigation into Cancer and Nutrition study.
Incidence rates of differentiated thyroid carcinoma (TC) have increased in many countries. Adiposity and dietary risk factors may play a role, but little is known on the influence of energy intake and macronutrient composition. The aim of this study was to investigate the associations between TC and the intake of energy, macronutrients, glycemic index (GI) and glycemic load in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The study included 477,274 middle-age participants (70.2% women) from ten European countries. Dietary data were collected using country-specific validated dietary questionnaires. Total carbohydrates, proteins, fats, saturated, monounsaturated and polyunsaturated fats (PUFA), starch, sugar, and fiber were computed as g/1,000 kcal. Multivariable Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence interval (CI) by intake quartile (Q). After a mean follow-up time of 11 years, differentiated TC was diagnosed in 556 participants (90% women). Overall, we found significant associations only with total energy (HRQ4 vs .Q1 , 1.29; 95% CI, 1.00-1.68) and PUFA intakes (HRQ4 vs .Q1 , 0.74; 95% CI, 0.57-0.95). However, the associations with starch and sugar intake and GI were significantly heterogeneous across body mass index (BMI) groups, i.e., positive associations with starch and GI were found in participants with a BMI ≥ 25 and with sugar intake in those with BMI < 25. Moreover, inverse associations with starch and GI were observed in subjects with BMI < 25. In conclusion, our results suggest that high total energy and low PUFA intakes may increase the risk of differentiated TC. Positive associations with starch intake and GI in participants with BMI ≥ 25 suggest that those persons may have a greater insulin response to high starch intake and GI than lean people.


Immune persistence after pertussis vaccination.
Pertussis is one of the most prevalent vaccine-preventable diseases worldwide. The true infection rate is significantly higher than the reported incidence rate. An increased prevalence of pertussis in older populations has been found, mainly caused by waning immunity after vaccination. Vaccine-induced immunity differs due to variation in vaccine content, schedule and coverage. Protection following acellular pertussis vaccines has been suggested to wane faster than whole cell pertussis vaccines. However, long-term immune persistence of whole cell pertussis vaccines may be confounded by a progressive acquisition of natural immunity. The World Health Organization has recommended that a switch from whole cell to acellular pertussis vaccines for primary immunization in infants should only be considered if additional periodic boosters or maternal immunization can be ensured and sustained in the national immunization schedules. In this review, we present data on immune persistence after different pertussis vaccinations and compare the findings from countries with different vaccination strategies. Future aspects in serological studies are briefly discussed.


Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program.
We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL.min(-1).1.73 m(-2) compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both P<0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin. Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.


Controllability of complex networks.
The ultimate proof of our understanding of natural or technological systems is reflected in our ability to control them. Although control theory offers mathematical tools for steering engineered and natural systems towards a desired state, a framework to control complex self-organized systems is lacking. Here we develop analytical tools to study the controllability of an arbitrary complex directed network, identifying the set of driver nodes with time-dependent control that can guide the system's entire dynamics. We apply these tools to several real networks, finding that the number of driver nodes is determined mainly by the network's degree distribution. We show that sparse inhomogeneous networks, which emerge in many real complex systems, are the most difficult to control, but that dense and homogeneous networks can be controlled using a few driver nodes. Counterintuitively, we find that in both model and real systems the driver nodes tend to avoid the high-degree nodes.


Troxerutin protects against DHT-induced polycystic ovary syndrome in rats.
The exact pathogenesis of polycystic ovary syndrome (PCOS), the most common neuroendocrine disorder in women of reproductive age, has not been fully elucidated. Recent studies suggested that chronic inflammation and neurotransmitter disorder involved in the progress of PCOS. Troxerutin, a natural flavonoid, was reported to possess neuroprotective effect in several disease models by inhibiting inflammation or enhancing neurotrophic factor. In this study, we investigated the possible protective effect and mechanism of troxerutin in a dihydrotestosterone (DHT)-induced rat model of PCOS. The PCOS rat models were treated with troxerutin at a dose of 150 mg/kg or 300 mg/kg for up to 4 weeks. Results showed that 300 mg/kg troxerutin significantly decreased the body weight gain and improved the pathological changes of ovary induced by DHT. Meanwhile, the elevated gonadotrophin-releasing hormone (GnRH), gonadotrophin and testosterone in the serum of PCOS rats were reduced with the treatment of troxerutin. The expression of kisspeptin and NKB in arcuate nucleus and their receptors kiss1r and NK3r in GnRH positive neurons of median eminence were markedly decreased in troxerutin-treated rats. Of note, the GnRH inhibitory regulator GABA and stimulatory regulator glutamate were also restored to the normal level by troxerutin. The present study indicated that troxerutin may exhibit a protective effect in PCOS rat model via regulating neurotransmitter release.


Binding of a cytosolic protein to the iron-responsive element of human ferritin messenger RNA.
The human ferritin H chain messenger RNA contains a specific iron-responsive element (IRE) in its 5' untranslated region, which mediates regulation by iron of ferritin translation. An RNA gel retardation assay was used to demonstrate the affinity of a specific cytosolic binding protein for the IRE. A single-base deletion in the IRE eliminated both the interaction of the cytoplasmic protein with the IRE and translational regulation. Thus, the regulatory potential of the IRE correlates with its capacity to specifically interact with proteins. Titration curves of binding activity after treatment of cells with an iron chelator suggest that the factor acts as a repressor of ferritin translation.


Research highlights: increasing paper possibilities.
In this issue we highlight three recent papers that demonstrate new strategies to extend the capabilities of paper microfluidics. Paper (a mesh of porous fibers) has a long history as a substrate to perform biomolecular assays. Traditional lateral flow immunoassays (LFAs) are widely used for rapid diagnostic tests, and perform well when a yes or no answer is required and the analyte of interest is at relatively high concentrations. High concentrations are required because usually only a small volume of analyte-containing fluid flows past the detection region, leading to a limited signal. Further, the small pores within paper matrices prevent the use of paper to control the flow of larger particles and cells, limiting the use of paper microfluidics for cell-based diagnostics. The work we highlight addresses these important unmet challenges in paper microfluidics: enriching low concentration analytes to a higher concentration in a smaller volume that can be processed effectively, and using paper to pump flows in larger channels amenable to cells. Applying these new approaches may allow diagnosis of disease states currently technically unachievable using current LFA systems, while maintaining many of the "un-instrumented" advantages of an assay on self-wicking paper.


Stage-specific effects of X-irradiation on yeast meiosis.
Previous work has shown that cdc13 causes meiotic arrest of Saccharomyces cerevisiae following DNA replication by a RAD9-dependent mechanism. In the present work, we have further investigated the implicit effects of chromosomal lesions on progression through meiosis by exposing yeast cells to X-irradiation at various times during sporulation. We find that exposure of RAD9 cells to X-irradiation early in meiosis prevents sporulation, arresting the cells at a stage prior to premeiotic DNA replication. rad9 meiotic cells are much less responsive to X-irradiation damage, completing sporulation after treatment with doses sufficient to cause arrest of RAD9 strains. These findings thereby reveal a RAD9-dependent checkpoint function in meiosis that is distinct from the G2 arrest previously shown to result from cdc13 dysfunction. Analysis of the spores that continued to be produced by either RAD9 or rad9 cultures that were X-irradiated in later stages of sporulation revealed most spores to be viable, even after exposure to radiation doses sufficient to kill most vegetative cells. This finding demonstrates that the lesions induced by X-irradiation at later times fail to trigger the checkpoint function revealed by cdc13 arrest and suggests that the lesions may be subject to repair by serving as intermediates in the recombination process. Strains mutant for chromosomal synapsis and recombination, and therefore defective in meiotic disjunction, were tested for evidence that X-ray-induced lesions might alleviate inviability by promoting recombination. Enhancement of spore viability when spo11 (but not hop 1) diploids were X-irradiated during meiosis indicates that induced lesions may partially substitute for SPO11-dependent functions that are required for the initiation of recombination.


Are Nutrition-Related Knowledge and Attitudes Reflected in Lifestyle and Health Among Elderly People? A Study Across Five European Countries.
Background: Nutrition-related knowledge (NRK) and nutrition-related attitudes (NRAs) are necessary for dietary changes toward healthier dietary patterns. In turn, healthier dietary patterns can be beneficial in maintaining health of older adults. Therefore, the aim of this cross-sectional study was to investigate whether NRK and NRAs were associated with lifestyle and health features among older adults (65+ years) from five European countries (France, Italy, Poland, the Netherlands and United Kingdom). Methods: Within the European project NU-AGE, 1,144 healthy elderly volunteers (65-79 years) were randomly assigned to two groups: intervention (NU-AGE diet) or control. After 1-year of follow-up, both NRK and NRAs were assessed during exit interviews, in combination with a number of lifestyle and health variables (e.g., physical activity, smoking, alcohol use, BMI, self-assessed health status). Multivariable linear regression models were used in data analysis. Results: In the NU-AGE study sample, good NRK was associated with lower BMI and higher physical activity. More positive NRAs were related to lower BMI and self-reported very good or good appetite. Moreover, both NRK and NRAs were associated with some socio-economic determinants, like financial situation, age, education, living area (for NRK), and country (for NRAs). Participants in the intervention group showed a better NRK (β = 0.367 [95% CI: 0.117; 0.617], p = 0.004) and more positive NRAs (β = 0.838 [95% CI: 0.318; 1.358], p = 0.002) than those in the control group. Higher self-evaluated knowledge was also significantly related to more positive NRAs (p < 0.001). The most popular sources of nutrition information were food labels, books and magazines on health, the dietitian and the doctor's office, although their importance varied significantly among countries, and, to a lesser extent, between women and men and between intervention and control group. Conclusion: Higher NRK and NRA scores were associated with lower BMI and higher physical activity level. Therefore, a good nutrition-related knowledge and positive nutrition-related attitudes can strongly and positively influence the health status and quality of life among the older population. These results offer a great opportunity for policy makers to implement educational programs in order to counteract the epidemic of obesity and to improve the health span of European population.


LEM domain-containing protein 3 antagonizes TGFβ-SMAD2/3 signaling in a stiffness-dependent manner in both the nucleus and cytosol.
Transforming growth factor-β (TGFβ) signaling through SMAD2/3 is an important driver of pathological fibrosis in multiple organ systems. TGFβ signaling and extracellular matrix (ECM) stiffness form an unvirtuous pathological circuit in which matrix stiffness drives activation of latent TGFβ, and TGFβ signaling then drives cellular stress and ECM synthesis. Moreover, ECM stiffness also appears to sensitize cells to exogenously activated TGFβ through unknown mechanisms. Here, using human fibroblasts, we explored the effect of ECM stiffness on a putative inner nuclear membrane protein, LEM domain-containing protein 3 (LEMD3), which is physically connected to the cell's actin cytoskeleton and inhibits TGFβ signaling. We showed that LEMD3-SMAD2/3 interactions are inversely correlated with ECM stiffness and TGFβ-driven luciferase activity and that LEMD3 expression is correlated with the mechanical response of the TGFβ-driven luciferase reporter. We found that actin polymerization but not cellular stress or LEMD3-nuclear-cytoplasmic couplings were necessary for LEMD3-SMAD2/3 interactions. Intriguingly, LEMD3 and SMAD2/3 frequently interacted in the cytosol, and we discovered LEMD3 was proteolytically cleaved into protein fragments. We confirmed that a consensus C-terminal LEMD3 fragment binds SMAD2/3 in a stiffness-dependent manner throughout the cell and is sufficient for antagonizing SMAD2/3 signaling. Using human lung biopsies, we observed that these nuclear and cytosolic interactions are also present in tissue and found that fibrotic tissues exhibit locally diminished and cytoplasmically shifted LEMD3-SMAD2/3 interactions, as noted in vitro Our work reveals novel LEMD3 biology and stiffness-dependent regulation of TGFβ by LEMD3, providing a novel target to antagonize pathological TGFβ signaling.


Tackling child health inequalities due to deprivation: using health equity audit to improve and monitor access to a community paediatric service.
Deprived children constitute a large population with high levels of ill health, and difficulty with access to healthcare contributes to their poor health outcomes. There is debate on how best to engage deprived families and the literature on differential access to paediatric care based on deprivation is limited. To demonstrate that community paediatrics can contribute to reduction of health inequalities by providing services that are accessible to and preferentially used by children whose health is likely to be affected by deprivation. To provide a template for others to improve and monitor equity in their services. Long-term service reconfiguration and health equity audit. We used routinely collected activity data and the Indices of Multiple Deprivation to construct equity profiles of the children using our service, and compared these with the profile of the population aged 0-16 years in the geographical area covered by the service. The new patient contact rate for the most deprived children in the population was more than three times that of the least deprived [odds ratio (OR) 3.29, 95% confidence interval (CI) 2.76-3.93]. Deprived children were more than twice as likely to require multi-agency meetings as part of their medical care (OR 2.28, 95% CI 1.94-2.69). Seventy per cent (3693/5312) of our total contacts were with children in the two most deprived quintiles. There was a marked socio-economic gradient in all types of contact. The model of care used by our community paediatric service successfully engages deprived families, thereby reducing health inequalities due to poor access. Key features are multi-agency working, removing barriers to access, raising staff awareness and use of health equity audit. Our findings provide support for tackling health inequalities via health services that are available to all, but capable of responding proportionately according to level of need, a model recently described as proportionate universalism.


Radiologic study of marginal bone loss around 108 dental implants and its relationship to smoking, implant location, and morphology.
To investigate peri-implant bone resorption around 108 ITI dental implants 1 year after prosthetic loading using extraoral panoramic, conventional intraoral periapical, and digital radiologic techniques. A total of 108 implants were placed (59 in the maxilla and 49 in the mandible) in 42 patients (16 men and 26 women) with a mean age of 44.2 years (range 14 to 68 years). Orthopantomographic, conventional periapical, and digital radiographs were obtained at loading and again 1 year later. Bone loss was calculated from the difference between the initial and final measurements. Mean loss in alveolar bone height was determined to be 1.36 mm by extraoral panoramic radiography, 0.76 mm by intraoral periapical radiography, and 0.95 mm by digital radiography. The implants located in the maxilla and those placed in patients who smoked 11 to 20 cigarettes per day were associated with significantly greater bone loss. The results in relation to peri-implant bone loss in the first year after loading were similar to those published by other authors. Conventional periapical films and digital radiographs were more accurate than orthopantomography in the assessment of peri-implant bone loss. Smoking and implant location in the maxilla were associated with increased peri-implant marginal bone resorption.


Behavioral health services following implementation of screening in Massachusetts Medicaid children.
To determine the relationship of child behavioral health (BH) screening results to receipt of BH services in Massachusetts Medicaid (MassHealth) children. After a court decision, Massachusetts primary care providers were mandated to conduct BH screening at well-child visits and use a Current Procedural Terminology code along with a modifier indicating whether a BH need was identified. Using MassHealth claims data, a cohort of continuously enrolled (July 2007-June 2010) children was constructed. The salient visit (first use of the modifier, screening code, or claim in fiscal year 2009) was considered a reference point to examine BH history and postscreening BH services. Bivariate and multivariate logistic regression analyses were performed to determine predictors of postscreening BH services. Of 261,160 children in the cohort, 45% (118,464) were screened and 37% had modifiers. Fifty-seven percent of children screening positive received postscreening BH services compared with 22% of children screening negative. However, only 30% of newly identified children received BH services. The strongest predictors of postscreening BH services for children without a BH history were being in foster care (odds ratio, 10.38; 95% confidence interval, 9.22-11.68) and having a positive modifier (odds ratio, 3.79; 95% confidence interval, 3.53-4.06). Previous BH history, a positive modifier, and foster care predicted postscreening BH services. Only one-third of newly identified children received services. Thus although screening is associated with an increase in BH recognition, it may be insufficient to improve care. Additional strategies may be needed to enhance engagement in BH services.


Registered or unregistered? Levels and differentials in registration and certification of births in Ghana.
The birth of a child is a vital event that needs to be registered but this is not always the case as an estimated 40 million births go unregistered annually. Birth registration safeguards the basic rights of children and gives them an identity, citizenship/nationality and legal protection against violence, abuse and human rights violations. It is therefore necessary that all births are registered and even more critical that the registration of a birth is followed by the issuance of a birth certificate. But sadly, birth registration in many African countries continues to remain below acceptable international standards and not all registered births are certified. This paper examined birth registration and certification in Ghana. Differentials in the characteristics of children and mothers of children whose births are registered and certified, children whose births are registered but not certified and children whose births are not registered were examined. This paper analysed data from the 2014 Ghana Demographic and Health Survey drawing on variables from the household and children's data files. Descriptive analytical tools (frequencies, percentage and cross tabulations) and multinomial logistic regression analysis were used to examine differentials in birth registration status among an analytical sample of 3880 (weighted) children aged 0-4 years. The birth of about every 1 in 4 (28.89%) children in Ghana have never been registered. Birth registration and certification was lowest among children born to young mothers (15-19 years), children whose mothers have no formal education, mothers who reside in rural areas and mothers in the poorest wealth quintile. Additionally, home births and births that were not assisted by a medical professional were observed to have the lowest proportion of registered and certified births. Furthermore, the birth of children who are less than a year old was significantly more likely not to be registered or issued with a birth certificate. Efforts aimed at improving birth registration and certification in Ghana need to target groups of children and mothers with low levels of registration and certification particularly children who are born at home, children born to young mothers and children whose mothers are poor and or reside in rural areas.


Risk factors for early recurrence after ischemic stroke: the role of stroke syndrome and subtype.
Information regarding risk factors for early recurrence is limited. Our aim was to identify the clinical predictors of early recurrence after ischemic stroke. We prospectively examined 297 patients (mean age, 72.0+/-8.4 years) hospitalized with ischemic stroke to identify recurrent strokes occurring within 90 days of the index stroke. Survival free of recurrence was estimated using Kaplan-Meier analysis stratified by demographic variables; vascular risk factors; stroke syndrome, subtype, vascular territory, and severity; scores on the Barthel Index and Mini-Mental State Examination during hospitalization; blood pressure on admission; and selected laboratory data. We estimated the relative risk (RR) of early recurrence associated with those variables using proportional hazards analysis. We identified 22 recurrent events in the first 90 days after the index stroke, resulting in an early stroke recurrence rate of 7.4%, and death occurred immediately after recurrence in 6 of the 22 patients. A major hemispheric stroke syndrome (RR=2.9; 95% confidence interval [CI]=1.2 to 7.1), atherothrombotic stroke mechanism (RR=3.3; CI=1.3 to 8.3), and atrial fibrillation (RR=2.2; CI=0.8 to 6.1) were independent predictors of early recurrence, after adjustment for demographic variables. Conclusions-Early recurrence was frequent and resulted in increased mortality. Attention to the clinical features of the index stroke, including the presenting syndrome and the ischemic mechanism, and the recognition of atrial fibrillation may help in the selection of patients for the initiation of targeted interventions to prevent early recurrence and subsequent mortality.


The EUROCARE-5 study on cancer survival in Europe 1999-2007: Database, quality checks and statistical analysis methods.
Since 25years the EUROCARE study monitors the survival of cancer patients in Europe through centralised collection, quality check and statistical analysis of population-based cancer registries (CRs) data. The European population covered by the study increased remarkably in the latest round. The study design and statistical methods were also changed to improve timeliness and comparability of survival estimates. To interpret the EUROCARE-5 results on adult cancer patients better here we assess the impact of these changes on data quality and on survival comparisons. In EUROCARE-5 the survival differences by area were studied applying the complete cohort approach to data on nearly nine million cancer patients diagnosed in 2000-2007 and followed up to 2008. Survival time trends were analysed applying the period approach to data on about 10 million cancer cases diagnosed from 1995 to 2007 and followed up to 2008. Differently from EUROCARE-4, multiple primary cancers were included and relative survival was estimated with the Ederer II method. EUROCARE-5 covered a population of 232 million resident persons, corresponding to 50% of the 29 participating countries. The population coverage increased particularly in Eastern Europe. Cases identified from death certificate only (DCO) were on average 2.9%, range 0-12%. Microscopically confirmed cases amounted to over 85% in most CRs. Compared to previous methods, including multiple cancers and using the Ederer II estimator reduced survival estimates by 0.4 and 0.3 absolute percentage points, on average. The increased population size and registration coverage of the EUROCARE-5 study ensures more robust and comparable estimates across European countries. This enlargement did not impact on data quality, which was generally satisfactory. Estimates may be slightly inflated in countries with high or null DCO proportions, especially for poor prognosis cancers. The updated methods improved the comparability of survival estimates between recently and long-term established registries and reduced biases due to informative censoring.


Knowledge and Attitudes Regarding Non-Invasive Prenatal Testing (NIPT) and Preferences for Risk Information among High School Students in Sweden.
Non-invasive prenatal testing (NIPT) was recently introduced for prenatal testing of genetic disorders. Cell-free fetal DNA is present in maternal blood during pregnancy and enables detection of fetal chromosome aberrations in a maternal blood sample. The public perspective to this new, simple method has not been illuminated. The views of young people (i.e. future parents) are important to develop suitable counseling strategies regarding prenatal testing. The aim was to explore Swedish high school students' attitudes, knowledge and preferences regarding NIPT. A questionnaire was completed by 305 students recruited from one high school in Stockholm, November and December 2014. Most students (80 %) considered prenatal testing as good. The majority (65 %) was positive or very positive towards NIPT and 62 % stated that they potentially would like to undergo the test if they or their partner was pregnant. The vast majority (94 %) requested further information about NIPT. Most students (61 %) preferred verbal information, whereas 20 % preferred information via the Internet. The majority of the high school students was positive towards prenatal testing and most was positive towards NIPT. Further, information was requested by the vast majority before making a decision about NIPT. Most of the students preferred verbal information and to a lesser extent information via the Internet. The attitudes, knowledge and preferences for risk information concerning NIPT in young adults are important, in order to increase knowledge on how to educate and inform future parents.


Prevalence of sleep problems and pain among the elderly in Sweden.
Sleep problems and pain are common among the elderly and have been shown to affect quality of life. The objectives were to determine the prevalence of sleep problems and pain among the elderly and to compare the two factors in relation to age and gender. A cross-sectional study based on baseline material collected by the Swedish National Study on Aging and Care in Blekinge (SNAC-Blekinge). The data were gathered from questionnaires distributed between the years 2001 and 2003 in the municipality of Karlskrona, Sweden. The participants comprised 1402 Swedish men and women aged 60-96. Of all the participants 70 percent met the criteria for sleep problems and 62 percent indicated some experience of pain during the preceding 4 weeks. Both sleep problems and pain were more frequent among women than men and sleep problems tended to be more common with increasing age. Among the participants who experienced pain during the preciding 4 weeks 77 percent suffered from sleep problems. Sleep problems and pain are common among older people. Furthermore it is common to suffer from sleep problems when pain has been experienced during the preciding 4 weeks.


The Number Of Health Information Exchange Efforts Is Declining, Leaving The Viability Of Broad Clinical Data Exchange Uncertain.
The diffusion of health information exchange (HIE), in which clinical data are electronically linked to patients in many different care settings, is a top priority for policy makers. To drive HIE, community and state efforts were federally funded to broadly engage providers in exchanging data in ways that improved patient care. To assess the current landscape, we conducted a national survey of community and state HIE efforts soon after federal funding ended. We found 106 operational HIE efforts that, as a group, engaged more than one-third of all US providers in 2014. However, the number of operational HIE efforts is down from 119 in 2012, representing the first decline observed since the tracking of these efforts began in 2006. Only half of operational efforts reported being financially viable, and all efforts reported a variety of barriers to continuation. These findings raise important questions about whether the current vision for HIE efforts will allow for the broad exchange of clinical data, or whether alternative approaches would be more successful.