Monitoring wild pig populations: a review of methods.
Wild pigs (Sus scrofa) are widespread across many landscapes throughout the world and are considered to be an invasive pest to agriculture and the environment, or conversely a native or desired game species and resource for hunting. Wild pig population monitoring is often required for a variety of management or research objectives, and many methods and analyses for monitoring abundance are available. Here, we describe monitoring methods that have proven or potential applications to wild pig management. We describe the advantages and disadvantages of methods so that potential users can efficiently consider and identify the option(s) best suited to their combination of objectives, circumstances, and resources. This paper offers guidance to wildlife managers, researchers, and stakeholders considering population monitoring of wild pigs and will help ensure that they can fulfill their monitoring objectives while optimizing their use of resources.


Transfer of class 1 integron-mediated antibiotic resistance genes from shiga toxin-producing Escherichia coli to a susceptible E. coli K-12 strain in storm water and bovine feces.
Transfer of class 1 integron-mediated antibiotic resistance genes has been demonstrated under laboratory conditions. However, there is no information concerning the transfer of these genes in an agricultural environment. The present study sought to determine if integron-mediated streptomycin and sulfisoxazole resistance genes could be transferred from Shiga toxin-producing Escherichia coli (STEC) strains 6-20 (O157:H7) and 7-63 (O111:H8) to the susceptible strain E. coli K-12 MG1655 in bovine feces (pH 5.5, 6.0, or 6.5) and storm water (pH 5, 6, 7, or 8) at 4, 15, and 28 degrees C, which are average seasonal temperatures for winter, spring-fall, and summer, respectively, in the Griffin, GA, area. The results indicated that at 28 degrees C, the integron-mediated antibiotic resistance genes were transferred from both of the STEC donors in bovine feces. Higher conjugation efficiencies were, however, observed in the conjugation experiments involving STEC strain 6-20. In storm water, the resistance genes were transferred only from STEC strain 6-20. Greater numbers of transconjugants were recovered in the conjugation experiments performed with pH 6.5 bovine feces and with pH 7 storm water. Antibiotic susceptibility tests confirmed the transfer of integron-mediated streptomycin resistance and sulfisoxazole resistance, as well as the transfer of non-integron-mediated oxytetracycline resistance and tetracycline resistance in the transconjugant cells. These results suggest that the antibiotic resistance genes in STEC could serve as a source of antibiotic resistance genes disseminated via conjugation to susceptible cells of other E. coli strains in an agricultural environment.


Pornography Addiction in Adults: A Systematic Review of Definitions and Reported Impact.
Self-perceived pornography addiction (SPPA) has increasingly emerged as a concept in research and popular culture, and commentators warn of the reported negative impact that it has. Despite this, "pornography or porn addiction" is not a formally recognized disorder and there is disagreement among researchers regarding its definition or even its existence. Therefore, how SPPA is operationalized often varies, and this is likely to influence the conclusions made about the impact of SPPA. This review aimed to examine what the supposed impact of SPPA is, and how the concept is operationalized. A systematic review of quantitative and qualitative peer-reviewed journal articles was conducted. The following databases were searched up to November 2015: CINAHL (2001-2015), Embase (1974-2015), Medline (1946-2015), PsychARTICLES (1980), and PsychInfo (1806-2015). Terms used were porn*, sexually explicit material, SEM, erotic*, nonparaphilic, cyberpornography, addict*, problematic, excess*, compul*, impul*, impact, effec*, behav*, and cause. An asterisk after a term means that all terms that begin with that root were included in the search. A review of the the current literature pertaining to SPPA and its reported impact. We found that SPPA is most frequently operationalized as excessive pornography use and negative consequences. As a result, researchers tended to focus on the frequency of pornography use and related impact as determinants of SPPA. SPPA is reported to affect users and their partners in similar ways, such as increased feelings of isolation and relationship breakdowns. However, we found some methodologic limitations of the primary studies, which limit the strength of the conclusions that can be drawn. Limitations include the lack of representative samples and inadequate measurements of SPPA and its impact. There still exist a debate regarding the definition and etiology of SPPA as distinct from self-perceived sex addiction. As such, the research landscape is shaped by different theoretical perspectives. Without evidence to suggest one theoretical position as superior to another, clinicians might be at risk of recommending treatment that is in line with their theoretical perspective (or personal biases) but at odds with the motivations driving an individual to engage in particular sexual behaviors. In light of these findings, the review concludes with recommendations for future research.


Decreased survival of glioma patients with astrocytoma grade IV (glioblastoma multiforme) associated with long-term use of mobile and cordless phones.
On 31 May 2011 the WHO International Agency for Research on Cancer (IARC) categorised radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, and from other devices that emit similar non-ionising electromagnetic fields, as a Group 2B, i.e., a "possible", human carcinogen. A causal association would be strengthened if it could be shown that the use of wireless phones has an impact on the survival of glioma patients. We analysed survival of 1678 glioma patients in our 1997-2003 and 2007-2009 case-control studies. Use of wireless phones in the >20 years latency group (time since first use) yielded an increased hazard ratio (HR) = 1.7, 95% confidence interval (CI) = 1.2-2.3 for glioma. For astrocytoma grade IV (glioblastoma multiforme; n = 926) mobile phone use yielded HR = 2.0, 95% CI = 1.4-2.9 and cordless phone use HR = 3.4, 95% CI = 1.04-11 in the same latency category. The hazard ratio for astrocytoma grade IV increased statistically significant per year of latency for wireless phones, HR = 1.020, 95% CI = 1.007-1.033, but not per 100 h cumulative use, HR = 1.002, 95% CI = 0.999-1.005. HR was not statistically significant increased for other types of glioma. Due to the relationship with survival the classification of IARC is strengthened and RF-EMF should be regarded as human carcinogen requiring urgent revision of current exposure guidelines.


Complications of liver resection in geriatric patients.
Introduction and aims. Liver resection is the treatment of choice for many primary and secondary liver diseases. Most studies in the elderly have reported resection of primary and secondary liver tumors, especially hepatocellular carcinoma and colorectal metastatic cancer. However, over the last two decades, hepatectomy has become safe and is now performed in the older population, implying a paradigm shift in the approach to these patients. We retrospectively evaluated the risk factors for postoperative complications in patients over 65 years of age in comparison with those under 65 years of age after liver resection (n = 360). The set comprised 127 patients older than 65 years (35%) and 233 patients younger than 65 years (65%). In patients younger than 65 years, there was a significantly higher incidence of benign liver tumors (P = 0.0073); in those older than 65 years, there was a significantly higher incidence of metastasis of colorectal carcinoma to the liver (0.0058). In patients older than 65 years, there were significantly more postoperative cardiovascular complications (P = 0.0028). Applying multivariate analysis, we did not identify any independent risk factors for postoperative complications. The 12-month survival was not significantly different (younger versus older patients), and the 5-year survival was significantly worse in older patients (P = 0.0454). In the case of liver resection, age should not be a contraindication. An individualized approach to the patient and multidisciplinary postoperative care are the important issues.


The pattern of localization of the putative oocyte activation factor, phospholipase Czeta, in uncapacitated, capacitated, and ionophore-treated human spermatozoa.
Recent studies suggest that in mammals, oocyte activation at fertilization is triggered by a sperm-specific phospholipase C, PLCzeta. We investigated PLCzeta localization in human spermatozoa. A polyclonal antibody was generated against human PLCzeta and used in immunoblotting and immunofluorescence studies of ejaculated human sperm in uncapacitated and capacitated states. An ionophore was also used to induce the acrosome reaction in vitro. After verifying specificity of the anti-PLCzeta antibody by immunoblotting, immunofluorescence studies showed that the predominant localization of PLCzeta in uncapacitated sperm was in the equatorial region, a pattern maintained following capacitation and ionophore treatment. The analysis of pooled samples showed approximately 88% of uncapacitated sperm expressed PLCzeta in the equatorial region, whereas approximately 35% and approximately 21% of sperm expressed additional populations of PLCzeta in the acrosomal or post-acrosomal region, respectively. One population of PLCzeta was observed in the post-acrosomal region of approximately 12% of sperm. The proportion of cells with post-acrosomal PLCzeta increased following capacitation and ionophore treatment (P < 0.05). The same tendency was found in individual samples. There was a strong correlation (r = 0.716, P < 0.0001) between presence of an intact acrosome and proportion of sperm immunoreactive to PLCzeta in the acrosomal region. PLCzeta was variably detectable in three localities within the sperm head: the equatorial segment and acrosomal/post-acrosomal region. Variability in PLCzeta localization in sperm from fertile males may reflect differences in oocyte activation capabilities between individuals or within an ejaculate. This approach may help in investigating the possible links between PLCzeta and certain types of male infertility.


Description and evaluation of a bench porcine model for teaching surgical residents vascular anastomosis skills.
Numerous models, of variable quality, exist to impart the complex skills required to perform vascular anastomosis. These models differ with regard to the kinds of materials used, as well as their sizes, the time needed for their preparation, their availability, and the associated costs. The present study describes a bench model that uses formalin-fixed porcine aorta, and its evaluation by young surgical residents during a recent skills course. The aortic segments used were a by-product of slaughtering. They were fixed and stored after harvesting for eventual use. Ten young surgical residents participated, and each performed one end-to-side vascular anastomosis. The evaluation was a questionnaire maintaining anonymity of the participant containing questions addressing particular aspects of the model and the experiences of the trainee, along with their ratings concerning the need for a training course to learn vascular anastomosis techniques. The scoring on the survey was done using a global 6-point rating scale (Likert Scale). In addition, we ranked the present model by reviewing the current literature for models that address vascular anastomosis skills.The trainees who participated were within their first two years of training (1.25 +/- 0.46). A strong agreement in terms of the necessity of training for vascular anastomosis techniques was evident among the participating trainees (5.90 +/- 0.32), who had only few prior manual experiences (total number 1.50 +/- 0.53). The query revealed a strong agreement that porcine aorta is a suitable model that fits the needs for training vascular anastomosis skills (5.70 +/- 0.48). Only a few bench models designed to teach surgical residents vascular anastomosis techniques were available in the literature. The preparatory and financial resources needed to perform anastomosis skills training using porcine aorta are few. The presented bench model appears to be appropriate for learning vascular anastomosis skills, as rated by the surgical trainees themselves.


Correlates of reward-predictive value in learning-related hippocampal neural activity.
Temporal difference learning (TD) is a popular algorithm in machine learning. Two learning signals that are derived from this algorithm, the predictive value and the prediction error, have been shown to explain changes in neural activity and behavior during learning across species. Here, the predictive value signal is used to explain the time course of learning-related changes in the activity of hippocampal neurons in monkeys performing an associative learning task. The TD algorithm serves as the centerpiece of a joint probability model for the learning-related neural activity and the behavioral responses recorded during the task. The neural component of the model consists of spiking neurons that compete and learn the reward-predictive value of task-relevant input signals. The predictive-value signaled by these neurons influences the behavioral response generated by a stochastic decision stage, which constitutes the behavioral component of the model. It is shown that the time course of the changes in neural activity and behavioral performance generated by the model exhibits key features of the experimental data. The results suggest that information about correct associations may be expressed in the hippocampus before it is detected in the behavior of a subject. In this way, the hippocampus may be among the earliest brain areas to express learning and drive the behavioral changes associated with learning. Correlates of reward-predictive value may be expressed in the hippocampus through rate remapping within spatial memory representations, they may represent reward-related aspects of a declarative or explicit relational memory representation of task contingencies, or they may correspond to reward-related components of episodic memory representations. These potential functions are discussed in connection with hippocampal cell assembly sequences and their reverse reactivation during the awake state. The results provide further support for the proposal that neural processes underlying learning may be implementing a temporal difference-like algorithm.


Clinical features of patients with morphea and the pansclerotic subtype: a cross-sectional study from the morphea in adults and children cohort.
Pansclerotic morphea is a poorly described form of morphea with little information on prevalence, demographics, and clinical features. Classification criteria for this subtype varies and the distinction from other forms of morphea, such as extensive generalized morphea and pansclerotic morphea, is not always clear. The purpose of our study was to clarify classification criteria for pansclerotic morphea by identifying its prevalence in the morphea in adults and children (MAC) cohort and describing its demographic and clinical features as compared with generalized morphea. Patients who met predefined criteria for generalized and pansclerotic morphea were identified using a modified Laxer and Zulian classification system. Baseline demographic and clinical features of the patients were compiled and then analyzed for traits characteristic of pansclerotic morphea versus those of generalized morphea. One hundred and thirteen patients met the criteria for inclusion: pansclerotic (n = 13) and generalized morphea type (n = 100). Patients with pansclerotic morphea were more frequently male (46.2% vs 6%; p < 0.0001); had a shorter time to diagnosis (mean difference of 10.4 mos; 95% CI: 0.8-19.9 mos; p = 0.0332); higher rates of functional impairment (61.5% vs 16%; p = 0.0046); higher rates of deep involvement (61.5% vs 17%; p = 0.004); and higher average Rodnan Skin Score (mean difference of 10.8 points; 95% CI: 5-16.6; p = 0.0017), Localized Scleroderma Skin Damage Index (mean difference 28.3; 95% CI: 9-47.6; p = 0.009), and Physician Global Assessment of Disease Damage scores (mean difference 25.1; 95% CI: 0.3-50; p = 0.048). Our results suggest demographic and clinical features are sufficient to define the pansclerotic subtype as they represent a distinct clinical phenotype with a more rapidly progressive and severe course commonly accompanied by disability. Presence of features of the pansclerotic phenotype should alert practitioners to the possibility of significant morbidity and the need for early aggressive treatment.


Influence of drug class and healthcare setting on systemic antifungal expenditures in the United States, 2005-15.
Overall and specific class trends in systemic antifungal expenditures in various U.S. healthcare settings from 2005 through 2015 were evaluated. Systemic antifungal expenditures from January 1, 2005, through December 31, 2015, were obtained from the QuintilesIMS National Sales Perspective database, which provides a statistically valid projection of medication purchases from multiple markets throughout the United States. Summary data for total antifungal expenditures over the entire period are reported, as are growth and the percentage change in expenditures from one year to the next. Expenditures were also assessed specifically by year, class, and healthcare setting. Expenditure trends over the study period were assessed using simple linear trend regression models. Overall expenditures for the 11-year period were $9.37 billion. The greatest proportion of expenditures occurred in nonfederal hospitals (47.2%) and for triazoles (57.6%). From 2005 through 2015, total expenditures decreased from $1.1 billion to $894 million (-18.8%, p = 0.09); however, expenditures in clinics and retail pharmacies increased (202%, p < 0.01, and 13.8%, p = 0.04, respectively), a trend most pronounced after 2012. Expenditures for flucytosine also increased (968.1%, p < 0.01), particularly in clinics where there was a dramatic 6,640.9% increase (p < 0.01). From 2005 through 2015, an increase in systemic antifungal expenditures was observed in community settings, despite an overall decrease in total antifungal expenditures in the United States. Large increases in flucytosine expenditures were observed, particularly in the community.


Anesthesia differentially modulates spontaneous network dynamics by cortical area and layer.
Anesthesia is widely used in medicine and research to achieve altered states of consciousness and cognition. Whereas changes to macroscopic cortical activity patterns by anesthesia measured at the spatial resolution of electroencephalography have been widely studied, modulation of mesoscopic and microscopic network dynamics by anesthesia remain poorly understood. To address this gap in knowledge, we recorded spontaneous mesoscopic (local field potential) and microscopic (multiunit activity) network dynamics in primary visual cortex (V1) and prefrontal cortex (PFC) of awake and isoflurane anesthetized ferrets (Mustela putoris furo). This approach allowed for examination of activity as a function of cortical area, cortical layer, and anesthetic depth with much higher spatial and temporal resolution than in previous studies. We hypothesized that a primary sensory area and an association cortical area would exhibit different patterns of network modulation by anesthesia due to their different functional roles. Indeed, we found effects specific to cortical area and cortical layer. V1 exhibited minimal changes in rhythmic structure with anesthesia but differential modulation of input layer IV. In contrast, anesthesia profoundly altered spectral power in PFC, with more uniform modulation across cortical layers. Our results demonstrate that anesthesia modulates spontaneous cortical activity in an area- and layer-specific manner. These finding provide the basis for 1) refining anesthesia monitoring algorithms, 2) reevaluating the large number of systems neuroscience studies performed in anesthetized animals, and 3) increasing our understanding of differential dynamics across cortical layers and areas.


Complementary Metal Oxide Semiconductor-Compatible, High-Mobility, ⟨111⟩-Oriented GaSb Nanowires Enabled by Vapor-Solid-Solid Chemical Vapor Deposition.
Using CMOS-compatible Pd catalysts, we demonstrated the formation of high-mobility ⟨111⟩-oriented GaSb nanowires (NWs) via vapor-solid-solid (VSS) growth by surfactant-assisted chemical vapor deposition through a complementary experimental and theoretical approach. In contrast to NWs formed by the conventional vapor-liquid-solid (VLS) mechanism, cylindrical-shaped Pd5Ga4 catalytic seeds were present in our Pd-catalyzed VSS-NWs. As solid catalysts, stoichiometric Pd5Ga4 was found to have the lowest crystal surface energy and thus giving rise to a minimal surface diffusion as well as an optimal in-plane interface orientation at the seed/NW interface for efficient epitaxial NW nucleation. These VSS characteristics led to the growth of slender NWs with diameters down to 26.9 ± 3.5 nm. Over 95% high crystalline quality NWs were grown in ⟨111⟩ orientation for a wide diameter range of between 10 and 70 nm. Back-gated field-effect transistors (FETs) fabricated using the Pd-catalyzed GaSb NWs exhibit a superior peak hole mobility of ∼330 cm2 V-1 s-1, close to the mobility limit for a NW channel diameter of ∼30 nm with a free carrier concentration of ∼1018 cm-3. This suggests that the NWs have excellent homogeneity in phase purity, growth orientation, surface morphology and electrical characteristics. Contact printing process was also used to fabricate large-scale assembly of Pd-catalyzed GaSb NW parallel arrays, confirming the potential constructions and applications of these high-performance electronic devices.


ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.
Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.


Self-regulation in tip-growth: the role of cell wall ageing.
We develop a model to describe the effect of cell wall ageing on the local expansion rate of tip-growing cells. Starting from an exact equation for the stationary age-distribution of the wall material, we propose a generic measure for the local expansion propensity of the wall if the ageing process is described by a constant rate Poissonian decay process. This ageing process may be either interpreted as biochemical in nature describing the finite lifetime of regulatory proteins, or as mechanical in nature describing the gradual "hardening" of the wall through cross-linking or gelation of the wall polymers. In this way we can construct models for tip-growth in which material deposition, evolving wall properties and surface expansion are self-consistently intertwined. As a proof of principle, we implement our ageing approach in two different idealised models of tip-growth, obtaining the stationary tip shapes as a function of the ageing parameter. In the first, the spatial distribution of delivery of growth material is determined by the local curvature of the cell and the growth mode is orthogonal. In the second, the growth material originates from a Vesicle Supply Center, a point-like representation of the Spitzenkörper as found in fungal hyphae, and the growth mode is isometric.


Immature murine hippocampal neurones do not develop long-term structural changes after a single isoflurane exposure.
Studies in developing animals show that a clinically relevant anaesthesia exposure increases neuronal death and alters brain structure. In the hippocampal dentate gyrus, the anaesthetic isoflurane induces selective apoptosis among roughly 10% of 2-week-old hippocampal granule cells in 21-day-old mice. In this work, we queried whether the 90% of granule cells surviving the exposure might be 'injured' and integrate abnormally into the brain. The long-term impact of isoflurane exposure on granule cell structure was studied using a transgenic mouse model fate-mapping approach to identify and label immature granule cells. Male and female mice were exposed to isoflurane for 6 h when the fate-mapped granule cells were 2 weeks old. The morphology of the fate-mapped granule cells was quantified 2 months later. The gross structure of the dentate gyrus was not affected by isoflurane treatment, with granule cells present in the correct subregions. Individual isoflurane-exposed granule cells were structurally normal, exhibiting no changes in spine density, spine type, dendrite length, or presynaptic axon terminal structure (P>0.05). Granule cell axon terminals were 13% larger in female mice relative to males; however, this difference was evident regardless of treatment (difference of means=0.955; 95% confidence interval, 0.37-1.5; P=0.010). A single, prolonged isoflurane exposure did not impair integration of this age-specific cohort of granule cells, regardless of the animal's sex. Nonetheless, although 2-week-old cells were not affected, the results should not be extrapolated to other age cohorts, which may respond differently.


The role of the fatosphere in fat adults' responses to obesity stigma: a model of empowerment without a focus on weight loss.
Obese adults face pervasive and repeated weight-based stigma. Few researchers have explored how obese individuals proactively respond to stigma outside of a dominant weight-loss framework. Using a grounded theory approach, we explored the experiences of 44 bloggers within the Fatosphere--an online fat-acceptance community. We investigated participants' pathways into the Fatosphere, how they responded to and interacted with stigma, and how they described the impact of fat acceptance on their health and well-being. The concepts and support associated with the fat-acceptance movement helped participants shift from reactive strategies in responding to stigma (conforming to dominant discourses through weight loss) to proactive responses to resist stigma (reframing "fat" and self-acceptance). Participants perceived that blogging within the Fatosphere led them to feel more empowered. Participants also described the benefits of belonging to a supportive community, and improvements in their health and well-being. The Fatosphere provides an alternative pathway for obese individuals to counter and cope with weight-based stigma.


Violence against metropolitan bus drivers and fare collectors in Brazil.
OBJECTIVE To analyze the correlation between sociodemographic factors and working conditions of bus workers in a metropolitan area and violence against them. METHODS This cross-sectional study used a nonprobabilistic sample estimated according to the number of workers employed in bus companies located in three cities in the Belo Horizonte metropolitan region in 2012 (N = 17,470). Face-to-face interviews were conducted using a digital questionnaire. The factors associated with violence were analyzed in two stages using Poisson regression, according to each level. The magnitude of the association was evaluated using prevalence ratios with robust variance and a statistical significance of 5%, and 95% confidence intervals were obtained. RESULTS The study sample comprised 782 drivers and 691 fare collectors; 45.0% participants reported at least one act of violence in the workplace in the last 12 months, with passengers being predominantly responsible. The age of the bus workers was inversely associated with violence. Chronic diseases, sickness absenteeism, and working conditions were also associated with violence. CONCLUSIONS The findings on the correlation between violence and working conditions are essential for implementing prevention strategies by transportation service managers.


Association of maternal nutrition with transient neonatal hyperinsulinism.
The objective was to determine whether maternal nutritional factors are associated with transient neonatal hyperinsulinism (HI). Case control study in 4 French tertiary Obstetrics and Neonatology Departments between 2008 and 2015. Sixty-seven mothers of neonates diagnosed with transient hyperinsulinism and 113 mothers of controls were included. The screening for hyperinsulinemic hypoglycemia in neonates was performed because of clinical symptoms suggestive of hypoglycemia or in the presence of conventional risk factors (small-for-gestational-age, prematurity, anoxo-ischemia, hypothermia, macrosomia, gestational diabetes). Hyperinsulinemic hypoglycemia was confirmed in the HI neonates and ruled out in the controls. This allowed for comparing maternal nutrition in cases and controls in a context of similar risk factors. One to 2 mothers of control neonates were included per case, and a food frequency questionnaire was addressed to the mothers between day 5 and day 10 after the birth of their newborn. Crude odds ratio showed that maternal weight gain, abnormal fetal rate, C-section, gender, consumption of fresh cooked vegetables, fresh fruits and fruit juices, low fat diary products, light fat products, and daily bread were significantly associated with hyperinsulinism. Maternal body mass index, hypertension, gestational diabetes, birth weight percentile, gestational age and 5-minute Apgar score were not related to HI. In a multiple backward logistic regression model, consumption of fresh cooked vegetable ≥1/day (OR = 0.33 [0.14-0.77]) and light-fat products ≥1/week (OR = 0.24 [0.08-0.71]) was protective against hyperinsulinism, whereas gestational weight gain >20 kg (OR = 9.5 [2.0-45.5]) and between 15-20 kg (OR = 4.0 [1.2-14.0]), abnormal fetal heart rate (OR = 4.4 [1.6-12.0]), and C-section (OR = 3.4 [1.3-8.9]) were risk factors. A diet rich in fresh cooked vegetable and reduced in fat, together with the avoidance of a high gestational weight gain may be protective against transient neonatal hyperinsulinism.


Land application of sewage sludge (biosolids) in Australia: risks to the environment and food crops.
Australia is a large exporter of agricultural products, with producers responsible for a range of quality assurance programs to ensure that food crops are free from various contaminants of detriment to human health. Large volumes of treated sewage sludge (biosolids), although low by world standards, are increasingly being recycled to land, primarily to replace plant nutrients and to improve soil properties; they are used in agriculture, forestry, and composted. The Australian National Biosolids Research Program (NBRP) has linked researchers to a collective goal to investigate nutrients and benchmark safe concentrations of metals nationally using a common methodology, with various other research programs conducted in a number of states specific to regional problems and priorities. The use of biosolids in Australia is strictly regulated by state guidelines, some of which are under review following recent research outcomes. Communication and research between the water industry, regulators and researchers specific to the regulation of biosolids is further enhanced by the Australian and New Zealand Biosolids Partnership (ANZBP). This paper summarises the major issues and constraints related to biosolids use in Australia using specific case examples from Western Australia, a member of the Australian NBRP, and highlights several research projects conducted over the last decade to ensure that biosolids are used beneficially and safely in the environment. Attention is given to research relating to plant nutrient uptake, particularly nitrogen and phosphorus (including that of reduced phosphorus uptake in alum sludge-amended soil); the risk of heavy metal uptake by plants, specifically cadmium, copper and zinc; the risk of pathogen contamination in soil and grain products; change to soil pH (particularly following lime-amended biosolids); and the monitoring of faecal contamination by biosolids in waterbodies using DNA techniques. Examples of products that are currently produced in Western Australia from sewage sludge include mesophilic anaerobically digested and dewatered biosolids cake, lime-amended biosolids, alum sludge and compost.


Interleukin-18 and cytotoxic impairment are independent and synergistic causes of murine virus-induced hyperinflammation.
Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory syndromes typically associated with underlying hematologic and rheumatic diseases, respectively. Familial HLH is associated with genetic cytotoxic impairment and thereby to excessive antigen presentation. Extreme elevation of serum interleukin-18 (IL-18) has been observed specifically in patients with MAS, making it a promising therapeutic target, but how IL-18 promotes hyperinflammation remains unknown. In an adjuvant-induced MAS model, excess IL-18 promoted immunopathology, whereas perforin deficiency had no effect. To determine the effects of excess IL-18 on virus-induced immunopathology, we infected Il18-transgenic (Il18tg) mice with lymphocytic choriomeningitis virus (LCMV; strain Armstrong). LCMV infection is self-limited in wild-type mice, but Prf1-/- mice develop prolonged viremia and fatal HLH. LCMV-infected Il18-transgenic (Il18tg) mice developed cachexia and hyperinflammation comparable to Prf1-/- mice, albeit with minimal mortality. Like Prf1-/- mice, immunopathology was largely rescued by CD8 depletion or interferon-γ (IFNg) blockade. Unlike Prf1-/- mice, they showed normal target cell killing and normal clearance of viral RNA and antigens. Rather than impairing cytotoxicity, excess IL-18 acted on T lymphocytes to amplify their inflammatory responses. Surprisingly, combined perforin deficiency and transgenic IL-18 production caused spontaneous hyperinflammation specifically characterized by CD8 T-cell expansion and improved by IFNg blockade. Even Il18tg;Prf1-haplosufficient mice demonstrated hyperinflammatory features. Thus, excess IL-18 promotes hyperinflammation via an autoinflammatory mechanism distinct from, and synergistic with, cytotoxic impairment. These data establish IL-18 as a potent, independent, and modifiable driver of life-threatening innate and adaptive hyperinflammation and support the rationale for an IL-18-driven subclass of hyperinflammation.


Efficacy of condensed tannins against larval Hymenolepis diminuta (Cestoda) in vitro and in the intermediate host Tenebrio molitor (Coleoptera) in vivo.
Natural anti-parasitic compounds in plants such as condensed tannins (CT) have anthelmintic properties against a range of gastrointestinal nematodes, but for other helminths such effects are unexplored. The aim of this study was to assess the effects of CT from three different plant extracts in a model system employing the rat tapeworm, Hymenolepis diminuta, in its intermediate host, Tenebrio molitor. An in vitro study examined infectivity of H. diminuta cysticercoids (excystation success) isolated from infected beetles exposed to different concentrations of CT extracts from pine bark (PB) (Pinus sps), hazelnut pericarp (HN) (Corylus avellana) or white clover flowers (WC) (Trifolium repens), in comparison with the anthelmintic drug praziquantel (positive control). In the in vitro study, praziquantel and CT from all three plant extracts had dose-dependent inhibitory effects on cysticercoid excystation. The HN extract was most effective at inhibiting excystation, followed by PB and WC. An in vivo study was carried out on infected beetles (measured as cysticercoid establishment) fed different doses of PB, HN and praziquantel. There was a highly significant inhibitory effect of HN on cysticercoid development (p=0.0002). Overall, CT showed a promising anti-cestodal effect against the metacestode stage of H. diminuta.


Once Upon A Time In Visualization: Understanding the Use of Textual Narratives for Causality.
Causality visualization can help people understand temporal chains of events, such as messages sent in a distributed system, cause and effect in a historical conflict, or the interplay between political actors over time. However, as the scale and complexity of these event sequences grows, even these visualizations can become overwhelming to use. In this paper, we propose the use of textual narratives as a data-driven storytelling method to augment causality visualization. We first propose a design space for how textual narratives can be used to describe causal data. We then present results from a crowdsourced user study where participants were asked to recover causality information from two causality visualizations-causal graphs and Hasse diagrams-with and without an associated textual narrative. Finally, we describe Causeworks, a causality visualization system for understanding how specific interventions influence a causal model. The system incorporates an automatic textual narrative mechanism based on our design space. We validate Causeworks through interviews with experts who used the system for understanding complex events.


Infliximab induces downregulation of the IL-12/IL-23 axis in 6-sulfo-LacNac (slan)+ dendritic cells and macrophages.
The spectrum of TNF-α-producing cells in patients with psoriasis, as well as their fate during treatment with TNF-α antagonists, is not clearly defined. We sought to analyze the effects of anti-TNF-α treatment on TNF-α(+) cells in the skin and blood of patients with psoriasis. Lesional psoriatic skin was analyzed by means of immunohistologic staining and quantitative RT-PCR, and peripheral blood cells were phenotypically characterized by means of multicolor immunofluorescence labeling. By using a tyramide-based signal amplification system, TNF-α was detected in dermal CD45(+)HLA-DR(+) leukocytes consisting of CD11c(+) dendritic cells and CD163(+) macrophages. In peripheral blood we observed an increase in the TNF-α-producing myeloid subsets of CD14(-) 6-sulfo-LacNac(+) dendritic cells and CD14(+)CD16(+) "intermediate" monocytes compared with healthy control subjects. Strikingly, we did not find detectable levels of TNF-α in other cells, including keratinocytes or T cells, making these cell types unlikely targets of TNF-α blockers. Up to 48 hours after the intravenous administration of the TNF-α antagonist infliximab, we encountered no overt changes in numbers of TNF-α(+) cells or signs of apoptosis in lesional psoriatic skin. Yet we observed a rapid decrease in IL-12p40, IL-1β, CCL20, and IL12RB1 mRNA levels. Consistently, TNF-α blockade during in vitro stimulation of 6-sulfo-LacNac DCs resulted in decreased production of IL-12 and IL-23 but not IL-6. In a mixed leukocyte reaction infliximab led to significantly decreased proliferation rates of T cells independent of the Fc antibody fragment. The decrease in tissue inflammation during anti-TNF-α therapy is not due to immediate killing of TNF-α-producing cells but rather results from a rapid downregulation of the pathogenic IL-12/IL-23-driven immune response.


Guidewire biliary cannulation does not reduce post-ERCP pancreatitis compared with the contrast injection technique in low-risk and high-risk patients.
Guidewire (GW) cannulation can reduce the risk of post-ERCP pancreatitis (PEP) by avoiding the opacification of the main pancreatic duct. To compare the effects of conventional contrast ERCP and GW cannulation of the common bile duct on the rate of PEP in low- and high-risk patients. Prospective, comparative-intervention single-center study. Tertiary referral center. Patients with biliary disease with an intact papilla were prospectively examined by ERCP. Biliary cannulation using a sphincterotome with contrast injection (ConI) or a hydrophilic GW without contrast injection. Pancreatitis rate in the GW group and the contrast injection (ConI) group. PEP occurred in 60 of 1249 patients (4.8%), 35 of 678 (5.2%) in the GW group and 25 of 571 (4.4%) in the ConI group (not significant). The overall rate of PEP was significantly higher in high-risk patients (12.2%) than in low-risk patients (3.5%) (P < .001), but was similar for the 2 techniques within each of these 2 groups. In patients with unintended main pancreatic duct (MPD) cannulation or opacification, the rate of PEP was not significantly different with the GW (15.2%) and ConI (8.4%) techniques but was associated with a significantly higher rate of pancreatitis (11.9%) than in patients in whom the contrast medium or GW did not enter the MPD (3.5%) (P < .001). Multivariate analysis indicated that more than 10 papillary cannulation attempts, MPD cannulation or opacification, suspected sphincter of Oddi dysfunction, and precut methods were significant risk factors independently associated with PEP. Lack of randomization. For selective cannulation of the CBD, the risk of inducing PEP is similar with the ConI and GW techniques in high-risk and low-risk patients. Any manipulation of the MPD must be considered a high-risk factor for PEP, such as multiple attempts on the papilla or use of the precut method.


A randomized controlled multimodal behavioral intervention trial for improving antiepileptic drug adherence.
Medication nonadherence is one of the most important reasons for treatment failure in patients with epilepsy. The present study investigated the effectiveness of a multicomponent intervention to improve adherence to antiepileptic drug (AED) medication in patients with epilepsy. In a prospective, randomized multicenter trial, three sessions of face-to-face motivational interviewing (MI) in combination with complementary behavior change techniques were compared with standard care. Motivational interviewing prompted change talk and self-motivated statements from the patients, planning their own medication intake regimen and also identifying and overcoming barriers that may prevent adherence. Participants were provided with calendars to self-monitor their medication taking behavior. A family member and the health-care team were invited to attend the last session of MI in order to improve the collaboration and communication between patients, their caregiver or family member, and their health-care provider. At baseline and 6-month follow-up, psychosocial variables and medical adherence were assessed. In total, 275 participants were included in the study. Compared with the active control group, patients in the intervention group reported significantly higher medication adherence, as well as stronger intention and perceptions of control for taking medication regularly. The intervention group also reported higher levels of action planning, coping planning, self-monitoring, and lower medication concerns. This study shows that MI can be effective in clinical practice to improve medication adherence in patients with epilepsy. It also provides evidence that combining volitional interventions, including action planning, coping planning, and self-monitoring with motivational interviewing can promote the effectiveness of the medical treatments for epilepsy by improving adherence.


Anti-N-methyl-D-aspartate receptor encephalitis associated with an ovarian teratoma: two cases report and anesthesia considerations.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated syndrome caused by the production of anti-NMDAR receptor antibodies. The syndrome characterised by psychosis, seizures, sleep disorders, hallucinations and short-term memory loss. Ovarian teratoma is the confirmed tumour associated with anti-NMDAR antibodies. The patients with anti-NMDAR encephalitis complicated by ovarian teratoma require surgical treatment under general anesthesia. NMDARs are important targets of many anesthetic drugs. The perioperative management and complications of anti-NMDAR encephalitis, including hypoventilation, paroxysmal sympathetic hyperactivity (PSH) and epilepsy, are challenging for ansthesiologists. This report described two female patients who presented for resection of the ovarian teratoma, they had confirmed anti-NMDAR encephalitis accompanied by ovarian teratoma. Two patients received gamma globulin treatments and the resection of the ovarian teratoma under total intravenous anesthesia. They were recovered and discharged on the 20(th) and 46(th) postoperative day respectively. There is insufficient evidence about the perioperative management, monitoring and anesthesia management of anti-NMDAR encephalitis. This report was based on the consideration that controversial anesthetics that likely act on NMDARs should be avoided. Additionally, BIS monitoring should to be prudently applied in anti-NMDAR encephalitis because of abnormal electric encephalography (EEG). Anesthesiologists must be careful with regard to central ventilation dysfunctions and PSH due to anti-NMDAR encephalitis.


Statistical short-term earthquake prediction.
A statistical procedure, derived from a theoretical model of fracture growth, is used to identify a foreshock sequence while it is in progress. As a predictor, the procedure reduces the average uncertainty in the rate of occurrence for a future strong earthquake by a factor of more than 1000 when compared with the Poisson rate of occurrence. About one-third of all main shocks with local magnitude greater than or equal to 4.0 in central California can be predicted in this way, starting from a 7-year database that has a lower magnitude cut off of 1.5. The time scale of such predictions is of the order of a few hours to a few days for foreshocks in the magnitude range from 2.0 to 5.0.


Using response time distributions and race models to characterize primacy and recency effects in free recall initiation.
Primacy and recency effects are common benchmarks for models of free recall and episodic memory. In this work, we show that RT distributions carry diagnostic information about how items enter into competition for recall, and how that competition impacts on the dynamics of recall and leads to novel conclusions about the forms of primacy and recency effects. We jointly fit RT distributions and serial position functions for free recall initiation with both a racing diffusion model and the linear ballistic accumulator (LBA: Brown & Heathcote, 2008). The models were fit in a hierarchical Bayesian framework, factorially varying different assumptions of how primacy and recency are generated. Recency functions were either exponential or power law in shape. Primacy was treated either as a strength boost to the early list items so that both primacy and recency items jointly compete to be retrieved; a mixture of primacy and recency gradients reflecting the usage of different retrieval cues; or a primacy-as-recency account in which primacy items are functionally recent due to the contribution of rehearsal. Although serial position curves do not distinguish between these accounts, they make distinct predictions about how RT distributions vary across serial positions. Results from a number of data sets strongly favor an exponential recency function along with a mixture model of primacy and recency gradients. These results suggest that complete RT distributions can provide informative constraints on models of free recall. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


The effect of ego depletion on challenge and threat evaluations during a potentially stressful public speaking task.
It has been well established that challenge and threat evaluations affect the performance of potentially stressful tasks. However, the factors that influence these evaluations have rarely been examined. Objective: This study examined the effects of ego depletion on challenge and threat evaluations during a public speaking task. Method: 262 participants (150 males, 112 females; Mage = 20.5, SD = 4.3) were randomly assigned to either an ego depletion or control group. Participants then completed self-report measures of trait self-control. The ego depletion group performed a written transcription task requiring self-control, while the control group transcribed the text normally. Before the public speaking task, participant's challenge and threat evaluations and subjective ratings of performance were assessed via self-report items. Results: The results of independent t-tests supported the effectiveness of the self-control manipulation. There were no significant differences between the ego depletion and control groups in terms of challenge and threat evaluations or subjective performance. Additional correlation analyses revealed that trait measures of self-control were significantly and negatively related to challenge and threat evaluations and subjective performance. Conclusion: Findings suggest that ego depletion might not influence appraisals of potentially stressful tasks, and thus add to recent evidence questioning the ego-depletion phenomenon.


Association of six-minute walk distance with subsequent lower extremity events in peripheral artery disease.
The prognostic significance of the six-minute walk distance for lower extremity events in people with peripheral artery disease (PAD) is unknown. This longitudinal study assessed whether a poorer six-minute walk distance at baseline was associated with higher rates of subsequent lower extremity atherosclerotic disease events in PAD. A total of 369 patients (mean age 69.4 ± 10.0 years; mean ankle-brachial index (ABI) 0.67 ± 0.17; 31% women; 30% black individuals) from Chicago-area medical centers with PAD were enrolled. Participants underwent baseline six-minute walk testing and returned for annual study visits. Lower extremity events consisted of one or more of the following: ABI decline greater than 15% or medical record adjudicated lower extremity revascularization, critical limb ischemia, or amputation. At a mean follow-up of 33.3 months, lower extremity events occurred in 66/123 (53.7%) people in the first (worst) tertile of six-minute walk performance, 55/124 (44.4%) in the second tertile, and 56/122 (45.9%) in the third (best) tertile. After adjusting for age, sex, race, ABI, comorbidities, and other confounders, participants in the first (worst) tertile of six-minute walk distance at baseline had higher rates of lower extremity events during follow-up, compared to those in the best tertile at baseline (HR = 1.74, 95% CI 1.17-2.60, p = 0.0067). Among people with PAD, a poorer six-minute walk distance was associated with higher rates of subsequent lower extremity PAD-related events after adjusting for confounders. Further study is needed to determine whether interventions that improve six-minute walk distance can reduce lower extremity adverse events in people with PAD.


Balanced mineralization in the arterial system: possible role of osteoclastogenesis/osteoblastogenesis in abdominal aortic aneurysm and stenotic disease.
Arterial calcification is the result of the same highly organized processes as seen in bone, which rely on a delicate balance between osteoblasts and osteoclasts. Although previously understood as passive precipitation, evidence has accumulated to suggest that arterial calcification is the result of organized, regulated processes bearing many similarities to osteogenesis in bone, including the presence of subpopulations of arterial wall cells that retain osteoblastic lineage potential. These cells have the potential to form mineralized nodules and express osteoblast markers, including bone morphogenetic protein-2, osteocalcin, osteopontin, and alkaline phosphatase. By contrast, osteoclast-like cells mediate the catabolic process of mineral resorption. Recent data shows that cells positive for tartrate-resistant acid phosphatase, a major marker for osteoclasts, have been histologically identified in atherosclerotic lesions and are referred to as osteoclast-like cells. Evidence has accumulated to suggest that initial arterial calcification through passive precipitation of calcium phosphate initiates balanced mineralization regulated by osteoclast-like and osteoblast-like cells. Subsequently, various pathogenic conditions may trigger an imbalance between osteoblastogenesis and osteoclastogenesis, leading to either calcification in stenotic/occlusive disease or destruction of the extracellular matrix in aneurysmal disease. Further elucidation of these newly emerging concepts could lead to a novel therapeutic approach to arterial stenotic/occlusive disease and/or abdominal aortic aneurysm.


Appendix-Sparing Transabdominal Preperitoneal Laparoscopic Hernioplasty for a De Garengeot's Hernia: Video Demonstration.
Background and Objectives: Less than 300 cases of a De Garengeot's hernia have been published. This rare femoral hernia with the vermiform appendix included appears almost exclusively on the right side, mainly in females, and it generally debuts as an incarcerated femoral hernia. Although most of the times there is a concomitant appendicitis, clinical signs of peritonitis are absent. The wide use of radiologic exams has not favored its preoperative diagnosis, but been usually found incidentally during a surgical emergency. The best surgical approach to a De Garengeot's hernia is not totally defined and many critical questions still remain unanswered. Open surgery is considered the standard treatment procedure, but since the emergence of laparoscopy for incarcerated hernias, this is certainly an option. Methods: We report the successful laparoscopic management of an 83-year-old woman who had been operated on her right inguinal hernia, with a Rutkow-Robbins' technique, 4 months earlier. She had noticed the protrusion of a lump in her right inguinal region for 2 months. Radiological studies were not conclusive. With a miss diagnosis of a recurrent incarcerated inguinal hernia, a minimal invasive endoscopic approach was performed. A representative case of this fully laparoscopic TAPP procedure is presented. Results: The patient made an uninterrupted recovery. She left the hospital the day after in a stable condition and has enjoyed good health since. Conclusion: A fully laparoscopic TAPP approach seems perfectly safe and feasible to treat this entity, and could be considered the first line alternative when enough expertise is available.


Abdominal Obesity and Lung Cancer Risk: Systematic Review and Meta-Analysis of Prospective Studies.
Several meta-analyses of observational studies have been performed to examine the association between general obesity, as measured by body mass index (BMI), and lung cancer. These meta-analyses suggest an inverse relation between high BMI and this cancer. In contrast to general obesity, abdominal obesity appears to play a role in the development of lung cancer. However, the association between abdominal obesity (as measured by waist circumference (WC) (BMI adjusted) and waist to hip ratio (WHR)) and lung cancer is not fully understood due to sparse available evidence regarding this association. PubMed and Web of Science databases were searched for studies assessing the association between abdominal obesity and lung cancer up to October 2016. The summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with a random-effects model. Six prospective cohort studies with 5827 lung cancer cases among 831,535 participants were included in our meta-analysis. Each 10 cm increase in WC and 0.1 unit increase in WHR were associated with 10% (RR 1.10; 95% CI 1.04, 1.17; I² = 27.7%, p-heterogeneity = 0.198) and 5% (RR 1.05; 95% CI 1.00, 1.11; I² = 25.2%, p-heterogeneity = 0.211) greater risks of lung cancer, respectively. According to smoking status, greater WHR was only positively associated with lung cancer among former smokers (RR 1.11; 95% CI 1.00, 1.23). In contrast, greater WC was associated with increased lung cancer risk among never smokers (RR 1.11; 95% CI 1.00, 1.23), former smokers (RR 1.12; 95% CI 1.03, 1.22) and current smokers (RR 1.16; 95% CI 1.08, 1.25). The summary RRs for highest versus lowest categories of WC and WHR were 1.32 (95% CI 1.13, 1.54; I² = 18.2%, p-heterogeneity = 0.281) and 1.10 (95% CI 1.00, 1.23; I² = 24.2%, p-heterogeneity = 0.211), respectively. In summary, abdominal obesity may play an important role in the development of lung cancer.


Changes in Caribbean coral disease prevalence after the 2005 bleaching event.
Bleaching events and disease epizootics have increased during the past decades, suggesting a positive link between these 2 causes in producing coral mortality. However, studies to test this hypothesis, integrating a broad range of hierarchical spatial scales from habitats to distant localities, have not been conducted in the Caribbean. In this study, we examined links between bleaching intensity and disease prevalence collected from 6 countries, 2 reef sites for each country, and 3 habitats within each reef site (N = 6 x 2 x 3 = 36 site-habitat combinations) during the peak of bleaching in 2005 and a year after, in 2006. Patterns of disease prevalence and bleaching were significantly correlated (Rho = 0.58, p = 0.04). Higher variability in disease prevalence after bleaching occurred among habitats at each particular reef site, with a significant increase in prevalence recorded in 4 of the 10 site-habitats where bleaching was intense and a non-significant increase in disease prevalence in 18 out of the 26 site-habitats where bleaching was low to moderate. A significant linear correlation was found (r = 0.89, p = 0.008) between bleaching and the prevalence of 2 virulent diseases (yellow band disease and white plague) affecting the Montastraea species complex. Results of this study suggest that if bleaching events become more intense and frequent, disease-related mortality of Caribbean coral reef builders could increase, with uncertain effects on coral reef resilience.


Clonal emergence of extended-spectrum beta-lactamase (CTX-M-2)-producing Salmonella enterica serovar Virchow isolates with reduced susceptibilities to ciprofloxacin among poultry and humans in Belgium and France (2000 to 2003).
Antibiotic treatment is not required in cases of Salmonella enterica gastroenteritis but is essential in cases of enteric fever or invasive salmonellosis or in immunocompromised patients. Although fluoroquinolones and extended-spectrum cephalosporins are the drugs of choice to treat invasive Salmonella, resistance to these antibiotics is increasing worldwide. During the period 2000 to 2003, 90 Salmonella enterica serovar Virchow poultry and poultry product isolates and 11 serovar Virchow human isolates were found to produce an extended-spectrum beta-lactamase, CTX-M-2, concomitantly with a TEM-1 beta-lactamase. The bla(CTX-M-2) gene was located on a large conjugative plasmid (>100 kb). Pulsed-field gel electrophoresis indicated a clonal relationship between the poultry and human isolates. All these isolates displayed additional resistance to trimethoprim-sulfamethoxazole and tetracycline as well as a reduced susceptibility to ciprofloxacin (MICs of between 0.5 and 1 mug/ml). CTX-M-2-producing Salmonella with a reduced susceptibility to fluoroquinolones constitutes a major concern, since such strains could disseminate on a large scale and jeopardize classical antibiotic therapy in immunocompromised patients.


Dyspepsia in England and Scotland.
A validated postal questionnaire has been used to establish the prevalence of dyspeptic symptoms in five geographical locations from the south coast of England to the north of Scotland. The six month period prevalence of dyspepsia in the 7428 respondents to the questionnaire is 41% and equal between the sexes, with similar prevalence rates in the centres studied. There is considerable overlap between upper abdominal symptoms and symptoms of heartburn; 56% of patients with dyspepsia experience both groups of symptoms. Symptom frequency falls progressively with age in men and women, but the proportion of people seeking medical advice for dyspepsia rises with age. One quarter of the dyspeptic patients studied have consulted a general practitioner about their symptoms. This study suggests that the prevalence of dyspepsia in the community has changed little over the last 30 years, despite evidence that the frequency of peptic ulcer disease is falling. Symptom prevalence is unrelated to social class, but this factor is associated with consultation behaviour, the consultation rate rising from 17% in social class 1 to 29% in social class 4. The use of investigations--barium meal and endoscopy--is similarly related to social class; the lowest rate for ulcer diagnosis (4.7%) is found in social class 1 and the highest (17.1%) in social class 5.


Suicidality in the prospective Zurich study: prevalence, risk factors and gender.
Our prospective Zurich study (1978-2008) found that suicidal ideation had occurred in 40.5% and suicide attempts in 6.6% of the population by age 50. Important gender differences were found in both suicidality and its risk factors. Suicide attempts were earlier and more frequent among women than among men: 70 versus 44% reported their first suicide attempt before 20. For women, the relative risk of suicide attempts was 1.6, but the relative risk of suicidal ideation was about equal (1.1 for women). The main risk factors for suicidal ideation in women were low social support (OR 4.0) and frequent punishment in childhood (OR 3.7), and in men, a depressive (OR 6.5) and an anxious personality (OR 4.6). The main risk factors for suicide attempts in women were a broken home (OR 10.2) and sexual abuse/violence (OR 7.9) in childhood; in men, no multivariate analyses of suicide attempt were conducted because of insufficient statistical power.


Caribbean contributions to contemporary psychiatric psychopathology.
The intellectual exploration of phenomenological and psychiatric discovery that has flowered in the Caribbean in the period of political independence from British colonization is a reflection of the scholarship that has emerged from the academic nurturance by The University of the West Indies. Burgeoning migration of Caribbean people to England in the twentieth century has resulted in high reported rates of psychosis for this migrant population. Caribbean research into this condition has revealed that there exist hostile racial and environmental challenges in Britain that have had a profound pathological effect on the mental health of African Caribbean migrants. These findings have significantly shifted the pendulum of understanding of the aetiology of this condition from a genetic to a biopsychosocial position. Research has also revealed longstanding psychopathological effects of slavery and colonialism in the Caribbean that have had significantly negative long term effects on the mental health of many within the Caribbean population. Current research suggests that there is a need to nurture protective strategies to enhance resilience and social capital, which would ensure the wellness and continued survival of Caribbean people in spite of the many challenges they face.


Vitamins C and E: acute interactive effects on biomarkers of antioxidant defence and oxidative stress.
Oxidative stress is implicated in the aetiology of many diseases; however, most supplementation trials with antioxidant micronutrients have not shown expected beneficial effects. This randomized, double-blinded, placebo-controlled study evaluated acute effects (at 90, 180min and 24h [fasting] post-ingestion) of single doses of Vitamins C (500mg) and E (400IU), alone and in combination, on biomarkers of plasma antioxidant status, lipid peroxidation and lymphocyte DNA damage in 12 healthy, consenting volunteers. Plasma ascorbic acid increased significantly (P < 0.01) within 2h of ingestion of Vitamin C, and alpha-tocopherol was significantly (P < 0.01) higher at 24h post-ingestion Vitamin E. The pattern of response was not significantly different whether Vitamin C (or Vitamin E) was taken alone or in combination, indicating no augmentation of response to one by co-ingestion of the other vitamin. No significant changes were seen in plasma FRAP in the group overall (although increases (P < 0.05) were seen at 90 and 180min post-ingestion in women after Vitamin C ingestion) or in MDA across treatments, and no evidence of increased DNA damage, or of DNA protection, was seen at any time point after Vitamin C and/or E ingestion. In conclusion, the data from this first controlled study of acute effects of single doses of Vitamin C and/or E show no evidence of either a protective or deleterious effect on DNA damage, resistance of DNA to oxidant challenge, or lipid peroxidation. No evidence of a synergistic or cooperative interaction between Vitamins C and E was seen, but further study is needed to determine possible interactive effects in a staggered supplementation cycle, and study of subjects under increased oxidative stress or with marginal antioxidant status would be useful. It would be of interest also to study the effects of these vitamins ingested with, or in, whole food, to determine if they are directly protective at doses above the minimum required to prevent deficiency, if combinations with other food components are needed for effective protection, or if Vitamins C and E are largely surrogate biomarkers of a 'healthy' diet, but are not the key protective agents.


Global monitoring of water supply and sanitation: history, methods and future challenges.
International monitoring of drinking water and sanitation shapes awareness of countries' needs and informs policy, implementation and research efforts to extend and improve services. The Millennium Development Goals established global targets for drinking water and sanitation access; progress towards these targets, facilitated by international monitoring, has contributed to reducing the global disease burden and increasing quality of life. The experiences of the MDG period generated important lessons about the strengths and limitations of current approaches to defining and monitoring access to drinking water and sanitation. The methods by which the Joint Monitoring Programme (JMP) of WHO and UNICEF tracks access and progress are based on analysis of data from household surveys and linear regression modelling of these results over time. These methods provide nationally representative and internationally comparable insights into the drinking water and sanitation facilities used by populations worldwide, but also have substantial limitations: current methods do not address water quality, equity of access, or extra-household services. Improved statistical methods are needed to better model temporal trends. This article describes and critically reviews JMP methods in detail for the first time. It also explores the impact of, and future directions for, international monitoring of drinking water and sanitation.


The transient receptor potential channel TRPV6 is dynamically expressed in bone cells but is not crucial for bone mineralization in mice.
Bone is the major store for Ca(2+) in the body and plays an important role in Ca(2+) homeostasis. During bone formation and resorption Ca(2+) must be transported to and from bone by osteoblasts and osteoclasts, respectively. However, little is known about the Ca(2+) transport machinery in these bone cells. In this study, we examined the epithelial Ca(2+) channel TRPV6 in bone. TRPV6 mRNA is expressed in human and mouse osteoblast-like cells as well as in peripheral blood mononuclear cell-derived human osteoclasts and murine tibial bone marrow-derived osteoclasts. Also other transcellular Ca(2+) transport genes, calbindin-D(9k) and/or -D(28K), Na(+)/Ca(2+) exchanger 1, and plasma membrane Ca(2+) ATPase (PMCA1b) were expressed in these bone cell types. Immunofluorescence and confocal microscopy on human osteoblasts and osteoclasts and mouse osteoclasts revealed TRPV6 protein at the apical domain and PMCA1b at the osteoidal domain of osteoblasts, whereas in osteoclasts TRPV6 was predominantly found at the bone-facing site. TRPV6 was dynamically expressed in human osteoblasts, showing maximal expression during mineralization of the extracellular matrix. 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) did not change TRPV6 expression in both mineralizing and non-mineralizing SV-HFO cultures. Lentiviral transduction-mediated overexpression of TRPV6 in these cells did not alter mineralization. Bone microarchitecture and mineralization were unaffected in Trpv6(D541A/D541A) mice in which aspartate 541 in the pore region was replaced with alanine to render TRPV6 channels non-functional. In summary, TRPV6 and other proteins involved in transcellular Ca(2+) transport are dynamically expressed in bone cells, while TRPV6 appears not crucial for bone metabolism and matrix mineralization in mice.


Wasp, the Drosophila Wiskott-Aldrich syndrome gene homologue, is required for cell fate decisions mediated by Notch signaling.
Wiskott-Aldrich syndrome proteins, encoded by the Wiskott-Aldrich syndrome gene family, bridge signal transduction pathways and the microfilament-based cytoskeleton. Mutations in the Drosophila homologue, Wasp (Wsp), reveal an essential requirement for this gene in implementation of cell fate decisions during adult and embryonic sensory organ development. Phenotypic analysis of Wsp mutant animals demonstrates a bias towards neuronal differentiation, at the expense of other cell types, resulting from improper execution of the program of asymmetric cell divisions which underlie sensory organ development. Generation of two similar daughter cells after division of the sensory organ precursor cell constitutes a prominent defect in the Wsp sensory organ lineage. The asymmetric segregation of key elements such as Numb is unaffected during this division, despite the misassignment of cell fates. The requirement for Wsp extends to additional cell fate decisions in lineages of the embryonic central nervous system and mesoderm. The nature of the Wsp mutant phenotypes, coupled with genetic interaction studies, identifies an essential role for Wsp in lineage decisions mediated by the Notch signaling pathway.


The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").
The amphetamine derivative (+/-)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.


Respiratory syncytial virus prophylaxis: a survey of pediatric solid organ transplant centers.
RSV can cause respiratory illness after SOT, yet preventive recommendations are lacking for this population. To ascertain current preventive practices against RSV disease in pediatric SOT candidates and recipients, a survey was developed. The survey was mailed to 108 SOT programs in the United States (liver, 42; heart, 28; lung, 11; intestinal, 25; and heart-lung, 2). Results were tabulated and analyzed using standard methods. Sixty-two percent (67/108) of surveys were completed. Forty-nine percent (33/67) of programs reported using RSV prophylaxis; palivizumab was used at 97% (32/33) of centers with 26 giving palivizumab to candidates and 27 to recipients. Prophylaxis was provided to infants aged 0-12 months by 27/29 (93%) of responding centers; 23/29 of centers extended its use to infants aged 0-24 months. Three centers gave prophylaxis to children between ages two and four yr and two centers for those over four yr. RSV prophylactic strategies, and in particular the use of palivizumab, are employed by almost 50% of responding pediatric SOT centers. Strategies varied at centers based on age and organ type. Data on RSV hospitalization and outcome are needed to refine approaches to RSV immunoprophylaxis in these high-risk patients.


Break-up of droplets in a concentrated emulsion flowing through a narrow constriction.
This paper describes the break-up of droplets in a concentrated emulsion during its flow as a 2D monolayer in a microchannel consisting of a narrow constriction. Analysis of the behavior of a large number of drops (N > 4000) shows that the number of break-ups increases with increasing flow rate, entrance angle to the constriction, and size of the drops relative to the width of the constriction. As single drops do not break at the highest flow rate used in the system, break-ups arise primarily from droplet-droplet interactions. Analysis of droplet properties at a high temporal resolution of 10 microseconds makes it possible to relate droplet deformation with droplet break-up probability. Similar to previous studies on single drops, no break-up is observed below a set of critical flow rates and droplet deformations. Unlike previous studies, however, not all drops undergo break-up above the critical values. Instead, the probability of droplet break-up increases with flow rate and the deformation of the drops. The probabilistic nature of the break-up process arises from the stochastic variations in the packing configuration of the drops as they enter the constriction. Local break-up dynamics involves two primary drops. A close look at the interactions between the pair of drops reveals that the competing time scales of droplet rearrangement relative to the relaxation of the opposing drop govern whether break-up occurs or not. Practically, these results can be used to calculate the maximum throughput of the serial interrogation process often employed in droplet microfluidics. For 40 pL-drops, the highest throughput with less than 1% droplet break-up was measured to be approximately 7000 drops per second. In addition, the results presented are useful for understanding the behavior of concentrated emulsions in applications such as mobility control in enhanced oil recovery, and for extrapolating critical parameters such as injection rates to ensure the stability of the fluids going through small pore throats.


Local temperature fine-tunes the timing of spring migration in birds.
Evidence for climate-driven phenological changes is rapidly increasing at all trophic levels. Our current poor knowledge of the detailed control of bird migration from the level of genes and hormonal control to direct physiological and behavioral responses hampers our ability to understand and predict consequences of climatic change for migratory birds. In order to better understand migration phenology and adaptation in environmental changes, we here assess the scale at which weather affects timing of spring migration in passerine birds. We use three commonly used proxies of spring-time climatic conditions: (1) vegetation "greenness" (NDVI) in Europe, (2) local spring temperatures in northern Europe, and (3) the North Atlantic Oscillation Index (NAO) as predictors of the phenology of avian migration as well as the strength of their effect on different subsets of populations and the dependence of correlations on species-specific migratory strategy. We analyze phenological patterns of the entire spring migration period in 12 Palaearctic passerine species, drawing on long-term data collected at three locations along a longitudinal gradient situated close to their northern European breeding area. Local temperature was the best single predictor of phenology with the highest explanatory power achieved in combination with NAO. Furthermore, early individuals are more affected by climatic variation compared to individuals on later passage, indicating that climatic change affects subsets of migratory populations differentially. Species wintering closer to the breeding areas were affected more than were those travelling longer distances and this pattern was strongest for the earliest subsets of the population. Overall, our results suggest that at least early subsets of the population are affected by local conditions and early birds use local conditions to fine-tune the date of their spring arrival while individuals arriving later are driven by other factors than local conditions e.g. endogenous control. Understanding what cues migratory organisms use to arrive at an optimum time is important for increasing our knowledge of fundamental issues like decision making in organisms during migration and is crucial for future protection of migratory organisms.


Ancient DNA reveals the chronology of walrus ivory trade from Norse Greenland.
The importance of the Atlantic walrus ivory trade for the colonization, peak, and collapse of the medieval Norse colonies on Greenland has been extensively debated. Nevertheless, no studies have directly traced medieval European ivory back to distinct Arctic populations of walrus. Analysing the entire mitogenomes of 37 archaeological specimens from Europe, Svalbard, and Greenland, we here discover that Atlantic walrus comprises two monophyletic mitochondrial (MT) clades, which diverged between 23 400 and 251 120 years ago. Our improved genomic resolution allows us to reinterpret the geographical distribution of partial MT data from 306 modern and nineteenth-century specimens, finding that one of these clades was exclusively accessible to Greenlanders. With this discovery, we ascertain the biological origin of 23 archaeological specimens from Europe (most dated between 900 and 1400 CE). These results reveal a significant shift in trade from an early, predominantly eastern source towards a near exclusive representation of Greenland ivory. Our study provides empirical evidence for how this remote Arctic resource was progressively integrated into a medieval pan-European trade network, contributing to both the resilience and vulnerability of Norse Greenland society.


Exosomes as Mediators of the Systemic Adaptations to Endurance Exercise.
Habitual endurance exercise training is associated with multisystemic metabolic adaptations that lower the risk of inactivity-associated disorders such as obesity and type 2 diabetes mellitus (T2DM). Identification of complex systemic signaling networks responsible for these benefits are of great interest because of their therapeutic potential in metabolic diseases; however, specific signals that modulate the multisystemic benefits of exercise in multiple tissues and organs are only recently being discovered. Accumulated evidence suggests that muscle and other tissues have an endocrine function and release peptides and nucleic acids into the circulation in response to acute endurance exercise to mediate the multisystemic adaptations. Factors released from skeletal muscle have been termed myokines and we propose that the total of all factors released in response to endurance exercise (including peptides, nucleic acids, and metabolites) be termed, "exerkines." We propose that many of the exerkines are released within extracellular vesicles called exosomes, which regulate peripheral organ cross talk. Exosomes (30-140 nm) and larger microvesicles [MVs] (100-1000 nm) are subcategories of extracellular vesicles that are released into the circulation. Exosomes contain peptides and several nucleic acids (microRNA [miRNA], messenger RNA [mRNA], mitochondrial DNA [mtDNA]) and are involved in intercellular/tissue exchange of their contents. An acute bout of endurance exercise increases circulating exosomes that are hypothesized to mediate organ cross talk to promote systemic adaptation to endurance exercise. Further support for the role of exosomes (and possibly MVs) in mediating the systemic benefits of exercise comes from the fact that the majority of the previously reported myokines/exerkines are found in extracellular vesicles databases (Vesiclepedia and ExoCarta). We propose that exosomes isolated from athletes following exercise or exosomes bioengineered to incorporate one or many of known exerkines will be therapeutically useful in the treatment of obesity, T2DM, and other aging-associated metabolic disorders.


Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.
Cannabinoids have been shown to promote the expression of the intercellular adhesion molecule 1 (ICAM-1) on lung cancer cells as part of their anti-invasive and antimetastatic action. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study addressed the impact of cannabinoid-induced ICAM-1 on cancer cell adhesion to lymphokine-activated killer (LAK) cells and LAK cell-mediated cytotoxicity. Cannabidiol (CBD), a non-psychoactive cannabinoid, enhanced the susceptibility of cancer cells to adhere to and subsequently be lysed by LAK cells, with both effects being reversed by a neutralizing ICAM-1 antibody. Increased cancer cell lysis by CBD was likewise abrogated when CBD-induced ICAM-1 expression was blocked by specific siRNA or by antagonists to cannabinoid receptors (CB1, CB2) and to transient receptor potential vanilloid 1. In addition, enhanced killing of CBD-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen-1 (LFA-1) suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. ICAM-1-dependent pro-killing effects were further confirmed for the phytocannabinoid Δ(9)-tetrahydrocannabinol (THC) and R(+)-methanandamide (MA), a hydrolysis-stable endocannabinoid analogue. Finally, each cannabinoid elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less pronounced (CBD, THC) or absent (MA) ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate cannabinoid-induced upregulation of ICAM-1 on lung cancer cells to be responsible for increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of cannabinoids.


Ras-independent oncogenic transformation by an EGF-receptor mutant.
Mutations in the ligand-binding domain of the epidermal growth factor receptor have been identified in several types of human cancers, including malignant gliomas. These mutations render signaling by this receptor to be constitutively ligand-independent. In fibroblasts transformed with ligand-independent epidermal growth factor receptor mutants, there is a correlation between the formation of a unique phosphotyrosine protein complex and oncogenic transformation. This phosphoprotein complex includes Grb2, Shc, Sos, tyrosine-phosphorylated form of caldesmon, and two, as yet, unidentified proteins. The presence of Grb2, Shc, and Sos in this complex implicates Ras in ligand-independent signaling by these oncogenic epidermal growth factor receptor mutants. We, therefore, have used retroviral co-infections of cultured primary fibroblasts to determine if Ras activation is required for phosphoprotein complex formation, stress fiber loss, or transformation. As predicted, expression of a dominant-negative Ras mutant (N17Ras) completely abrogates ligand-stimulated soft agar colony growth of primary fibroblasts. In contrast, N17Ras expression has no effect on v-ErbB mediated stress fiber disassembly, soft agar colony growth, or phosphoprotein complex assembly. In addition, our data suggest that ligand-dependent Ras activation may be suppressed by oncogenic v-ErbB expression. Together these observations suggest that oncogenic signaling by v-ErbB does not require Ras activation, and implicate an alternative signal transduction pathway in ligand-independent epidermal growth factor receptor oncogenic signaling.


A characterization of cis- and trans-heritability of RNA-Seq-based gene expression.
Insights into individual differences in gene expression and its heritability (h2) can help in understanding pathways from DNA to phenotype. We estimated the heritability of gene expression of 52,844 genes measured in whole blood in the largest twin RNA-Seq sample to date (1497 individuals including 459 monozygotic twin pairs and 150 dizygotic twin pairs) from classical twin modeling and identity-by-state-based approaches. We estimated for each gene h2total, composed of cis-heritability (h2cis, the variance explained by single nucleotide polymorphisms in the cis-window of the gene), and trans-heritability (h2res, the residual variance explained by all other genome-wide variants). Mean h2total was 0.26, which was significantly higher than heritability estimates earlier found in a microarray-based study using largely overlapping (>60%) RNA samples (mean h2 = 0.14, p = 6.15 × 10-258). Mean h2cis was 0.06 and strongly correlated with beta of the top cis expression quantitative loci (eQTL, ρ = 0.76, p < 10-308) and with estimates from earlier RNA-Seq-based studies. Mean h2res was 0.20 and correlated with the beta of the corresponding trans-eQTL (ρ = 0.04, p < 1.89 × 10-3) and was significantly higher for genes involved in cytokine-cytokine interactions (p = 4.22 × 10-15), many other immune system pathways, and genes identified in genome-wide association studies for various traits including behavioral disorders and cancer. This study provides a thorough characterization of cis- and trans-h2 estimates of gene expression, which is of value for interpretation of GWAS and gene expression studies.


Voltage-gated calcium channels mediate intracellular calcium increase in weaver dopaminergic neurons during stimulation of D2 and GABAB receptors.
The weaver (wv) mutation affects the pore-forming region of the inwardly rectifying potassium channel (GIRK) leading to degeneration of cerebellar granule and midbrain dopaminergic neurons. The mutated channel (wvGIRK) loses its potassium selectivity, allowing sodium (Na+) and possibly calcium ions (Ca2+) to enter the cell. Here we performed whole cell patch-clamp recordings combined with microfluorometry to investigate possible differences in calcium ([Ca2+]i) dynamics in native dopaminergic neurons (expressing the wvGIRK2 subunits) in the midbrain slice preparation from homozygous weaver (wv/wv) and control (+/+) mice. Under resting conditions, [Ca2+]i was similar in wv/wv compared with +/+ neurons. Activation of wvGIRK2 channels by D2 and GABAB receptors increased [Ca2+]i in wv/wv neurons, whereas activation of wild-type channels decreased [Ca2+]i in +/+ neurons. The calcium rise in wv/wv neurons was abolished by antagonists of the voltage-gated calcium channels (VGCC); voltage clamp of the neuron at -60 mV; and hyperpolarization of the neuron to -80 mV or more, in current clamp, and was unaffected by TTX. Therefore we propose that wvGIRK2 channels in native dopamine neurons are not permeable to Ca2+, and when activated by D2 and GABAB receptors they mediate membrane depolarization and an indirect Ca2+ influx through VGCC rather than via wvGIRK2 channels. Such calcium influx may be the trigger for calcium-mediated excitotoxicity, responsible for selective neuronal death in weaver mice.


Prognosis and value of adjuvant chemotherapy in stage III mucinous colorectal carcinoma.
Colorectal mucinous adenocarcinoma (MC) has been associated with impaired prognosis compared with nonmucinous adenocarcinoma (NMC). Response to palliative chemotherapy is poor in metastatic disease, but the benefit of adjuvant chemotherapeutic treatment has never been assessed in large patient groups. This study analyses overall survival and efficacy of adjuvant chemotherapy in terms of survival in patients following radical resection for MC. This population-based study involved 27 251 unselected patients diagnosed with colorectal carcinoma between 1990 and 2010 and recorded in a prospective pathology-based registry. Kaplan-Meier analysis and log-rank testing were used to estimate survival. Cox proportional hazard model was used to calculate multivariate hazard ratios for death. MC was found in 12.3% (N = 3052) of colorectal tumors with a different distribution compared with NMC, with 24.4% located in the rectum and 54.3% in the proximal colon (versus 38.0% and 30.6%), P < 0.0001. NMC was more often classified as stage I disease than MC (20.5% versus 10.9%), P < 0.0001. After adjustments for covariates, MC was associated with a higher risk of death only when located in the rectum [hazard ratio 1.22; 95% confidence interval (CI) 1.11-1.34]. Multivariate regression analysis showed a similar survival after adjuvant chemotherapy for stage III MC and NMC patients. The poor prognosis for MC is only present in rectal cancer. In the adjuvant setting, there is no difference in the efficacy of chemotherapy between MC and NMC; therefore, current adjuvant treatment recommendations should not take histology into account.


Mental health nurses' experience of physical health care and health promotion initiatives for people with severe mental illness.
Health care for people with severe mental illness is often divided into physical health care and mental health care despite the importance of a holistic approach to caring for the whole person. Mental health nurses have an important role not only in preventing ill health, but also in promoting health, to improve the overall health among people with severe mental illness and to develop a more person-centred, integrated physical and mental health care. Thus, the aim of this study was to describe mental health nurses' experiences of facilitating aspects that promote physical health and support a healthy lifestyle for people with severe mental illness. Interviews were conducted with mental health nurses (n = 15), and a qualitative content analysis was used to capture the nurse's experiences. Analysis of the interviews generated three categories: (i) to have a health promotion focus in every encounter, (ii) to support with each person's unique prerequisites in mind and (iii) to take responsibility for health promotion in every level of the organization. The results show the importance of a health promotion focus that permeates the entire organization of mental health care. Shared responsibility for health and health promotion activities should exist at all levels: in the person-centred care in the relation with the patient, embedded in a joint vision within the working unit, and in decisions at management level.


[A case of anti-Hu antibody- and anti-GluR epsilon2 antibody-positive paraneoplastic neurological syndrome presenting with limbic encephalitis and peripheral neuropathy].
We report a case of paraneoplastic neurological syndrome with anti-neuronal antibodies, namely anti-Hu and anti-GluR epsilon 2 antibodies in sera. A 72-year-old male had a transient history of eye movement disorder and sensory neuropathy, which improved spontaneously. Two years later, he was admitted to another hospital because of gait disturbance, numbness of the hands and an attack of unconsciousness with generalized convulsion. He was admitted to our hospital with prolonged consciousness disturbance and muscular weakness of all extremities. On admission his consciousness deteriorated slightly without neck stiffness. His cranial nervous system was normal except for incomplete abduction and elevation of both eyes. The patient had severe distal dominant weakness and atrophy in the muscles of all four limbs. Muscle tonus was decreased and hyporeflexia was noted in the four extremities. Plantar response was extensor. Neither sensory disturbance nor ataxia was observed. Cranial MRI showed T2-weighted high intensity lesions in the bilateral mesial temporal lobes, including the hippocampi. A nerve conduction study revealed motor-dominant peripheral neuropathy with prolonged latency; the amplitudes of compound muscle action potentials were severely reduced in all four limbs and those of sensory nerve action potentials were moderately reduced in the right upper and lower extremities. We also found a left hilar lymphadenopathy showing accumulation of FDG on PET, suggesting a possibility of malignancy. Anti-Hu and anti-GluR epsilon 2 antibodies were detected in sera but not in CSF. We diagnosed him with limbic encephalitis and peripheral neuropathy due to paraneoplastic neurological syndrome and treated him with two courses of intravenous immunoglobulin (IVIg) (400 mg/kg, 5 days). The consciousness disturbance, and prolonged distal latency revealed by motor nerve conduction studies improved slightly. Although the roles of anti-neuronal antibodies in paraneoplastic conditions remain unknown, we consider that IVIg may be worth using to treat cases with anti-Hu and anti-GluR epsilon 2 antibodies.


Excitability tests using high-density surface-EMG: A novel approach to studying single motor units.
To study excitability of single motor units (MUs) using high-density surface-EMG. Motor unit action potentials (MUAPs) were evoked by submaximal stimulation of the median nerve at the wrist and recorded with a 9 × 14 electrode grid on the skin overlying the thenar muscles. For excitability tests of single MUs, the most optimal specific single-channel surface-EMG signal was selected based on the spatiotemporal profile of single MUs. Axonal excitability measures were successfully obtained from 14 single MUs derived from ten healthy subjects. Selecting the optimal single-channel surface-EMG signals minimized interference from other single MUs and improved signal-to-noise ratio. The muscle fiber conduction velocity (MFCV) could also be derived from the unique spatiotemporal profile of single MUs. High-density surface-EMG helps to isolate single MUAP responses, making it a suitable technique for assessing excitability in multiple single motor axons per nerve. Our method enables the reliable study of ion-channel dysfunction in single motor axons of nerves without any requirement for specific conditions, such as prominent MU loss or enlarged MUAPs due to collateral sprouting.


Two-mode division multiplexing in a silicon-on-insulator ring resonator.
Mode-division multiplexing (MDM) is an emerging multiple-input multiple-output method, utilizing multimode waveguides to increase channel numbers. In the past, silicon-on-insulator (SOI) devices have been primarily focused on single-mode waveguides. We present the design and fabrication of a two-mode SOI ring resonator for MDM systems. By optimizing the device parameters, we have ensured that each mode is treated equally within the ring. Using adiabatic Bezier curves in the ring bends, our ring demonstrated a signal-to-crosstalk ratio above 18 dB for both modes at the through and drop ports. We conclude that the ring resonator has the potential for filtering and switching for MDM systems on SOI.


Doing-being-becoming: occupational experiences of persons with life-threatening illnesses.
Life-threatening illness profoundly affects people's occupational functioning, yet continuing occupational engagement seems vital to their well-being. This qualitative study used a doing-being-becoming framework to explore the place of occupation in human lives threatened by illness. The experiences of 13 male and 10 female day hospice participants were investigated through a combination of focus groups, individual interviews, and participant observation. These data were interpreted by a process of constant comparison, coding, and theme building. Experiences of doing were evident in accounts of losing and maintaining valued occupations and striving to preserve physical and mental functioning. A sense of being through occupational engagement arose in social relationships and self-exploration that enhanced feelings of self-worth. Occupation promoted the experience of becoming by providing fresh learning opportunities and a sense of contributing to others' welfare. The data offer new insights into the potential benefits of occupational engagement for persons dealing with life-threatening illnesses. Use of the doing-being-becoming framework enriched analysis of these data, which, in turn, have contributed to the understanding of the framework's theoretical concepts.