Cancer patient and staff ratings of caring behaviors: relationship to level of pain intensity.
This study explored differences in the perceived importance of nursing caring behaviors between patients with cancer pain and oncology nurses and to explore the relationship between level of pain intensity and the importance of various nursing caring behaviors. The study included 50 matched cancer patient-staff pairs from oncology inpatient units of 3 hospitals in northern Taiwan. The Brief Pain Inventory-Chinese version (BPI-C) and the Caring Assessment Report Evaluation Q-sort (CARE-Q) were used for data collection. Results revealed that cancer pain patients ranked "being accessible," "monitors and follows through," and "anticipates" as being the most important nursing caring behaviors; the nursing staff ranked "being accessible," "explains and facilitates," and "monitors and follows through" as being the most important behaviors. No correlations were found between cancer pain patients and staff rankings of the perceived importance of various caring behaviors. The self-reported level of pain intensity by patients was significantly positively correlated with the patient rating of the "anticipates" behavior. Patient self-reported level of pain interference was significantly positively correlated with the "monitors and follows through" behavior and significantly negatively correlated with the "explains and facilitates" behavior. Staff perception of both a patient's level of pain intensity and pain interference was significantly positively correlated with staff rating of the "being accessible" behavior. Results demonstrated that greater patient-staff communication is needed for staff to more accurately provide caring interventions to make patients with cancer pain feel cared for.


Quantifying phosphorus levels in soils, plants, surface water, and shallow groundwater associated with bahiagrass-based pastures.
Recent assessments of water quality status have identified eutrophication as one of the major causes of water quality 'impairment' not only in the USA but also around the world. In most cases, eutrophication has accelerated by increased inputs of phosphorus due to intensification of crop and animal production systems since the early 1990 s. Despite substantial measurements using both laboratory and field techniques, little is known about the spatial and temporal variability of phosphorus dynamics across landscapes, especially in agricultural landscapes with cow-calf operations. Critical to determining environmental balance and accountability is an understanding of phosphorus excreted by animals, phosphorus removal by plants, acceptable losses of phosphorus within the manure management and crop production systems into soil and waters, and export of phosphorus off-farm. Further research effort on optimizing forage-based cow-calf operations to improve pasture sustainability and protect water quality is therefore warranted. We hypothesized that properly managed cow-calf operations in subtropical agroecosystem would not be major contributors to excess loads of phosphorus in surface and ground water. To verify our hypothesis, we examined the comparative concentrations of total phosphorus among soils, forage, surface water, and groundwater beneath bahiagrass-based pastures with cow-calf operations in central Florida, USA. Soil samples were collected at 0-20; 20-40, 40-60, and 60-100 cm across the landscape (top slope, middle slope, and bottom slope) of 8 ha pasture in the fall and spring of 2004 to 2006. Forage availability and phosphorus uptake of bahiagrass were also measured from the top slope, middle slope, and bottom slope. Bi-weekly (2004-2006) groundwater and surface water samples were taken from wells located at top slope, middle slope, and bottom slope, and from the runoff/seepage area. Concentrations of phosphorus in soils, forage, surface water, and shallow groundwater beneath a bahiagrass-based pasture and forage availability at four different landscape positions and soil depth (for soil samples only) in 2004, 2005, and 2006 were analyzed statistically following a two-way analysis of variance using the SAS PROC general linear models model. Where the F-test indicated a significant (p <or= 0.05) effect, means were separated following the method of Duncan multiple range test using the appropriate error mean squares. Concentrations of soil total phosphorus and degree of phosphorus saturation varied significantly (p <or= 0.001) with landscape position and sampling depth, but there was no interaction effect of landscape position and sampling depth. Overall, there was slight buildup of soil total phosphorus. There was no movement of total phosphorus into the soil pedon since average degree of phosphorus saturation in the upper 20 cm was 21% while degree of phosphorus saturation at 60-100 cm was about 3%. Our livestock operations contributed negligible concentrations of phosphorus to groundwater (0.67 mg L(-1)) and surface water (0.55 mg L(-1)). The greatest forage mass of 6,842 kg ha(-1) and the greatest phosphorus uptake of 20.4 kg P ha(-1) were observed at the top slope in 2005. Both forage availability and phosphorus uptake of bahiagrass at the bottom slope were consistently the lowest when averaged across landscape position and years. These results can be attributed to the grazing patterns as animals tend to graze more and leave more excretions at the bottom slope. This behavior may lead to an increase in the concentration of soil phosphorus. Effective use and cycling of phosphorus is critical for pasture productivity and environmental stability. Phosphorus cycling in pastures is complex and interrelated, and pasture management practices can influence the interactions and transformations occurring within the phosphorus cycle. Our results indicate that current pasture management systems which include cattle rotation in terms of grazing days and current fertilizer application (inorganic + manures + urine) for bahiagrass pastures in subtropical climates on loamy sand soils offer little potential for negatively impacting the environment. Properly managed livestock operations contribute negligible loads of phosphorus to shallow groundwater and surface water. Overall, there was no buildup of soil total phosphorus in bahiagrass-based pasture. Therefore, results of this study may help to renew the focus on improving inorganic fertilizer efficiency in subtropical beef cattle systems and maintaining a balance of phosphorus removed to phosphorus added to ensure healthy forage growth and minimize phosphorus runoff. Research on the pathways and rates of movement of phosphorus deposited in urine and dung through various pools and back to the plants will be the focal point of our future investigations. Further studies are needed to determine whether the environmental and ecological implications of grazing and haying in forage-based pastures are satisfied over the longer term. New knowledge based on the whole-farm approach is desirable to identify pastureland at risk of degradation and to prescribe treatments or management practices needed to protect the natural resources while maintaining an economically and environmentally viable operation.


Positive expiratory pressure in patients with chronic obstructive pulmonary disease--a systematic review.
Breathing exercises against a resistance during expiration are often used as treatment for patients with chronic obstructive pulmonary disease (COPD). Controversy still exists regarding the clinical application and efficacy. The aim of this systematic review was to determine the effects of chest physiotherapy techniques with positive expiratory pressure (PEP) for the prevention and treatment of pulmonary impairment in adults with COPD. The review was conducted on randomised, controlled clinical trials in which breathing exercises with positive expiratory pressure were compared with other chest physical therapy techniques or with no treatment, in adult patients with COPD. A computer-assisted literature search of available databases from 1970 to January 2008 was performed. Two reviewers extracted data independently and assessed the trials systematically with an instrument for measuring methodological quality. In total, 11 trials met the inclusion criteria, of which 5 reached an adequate level of internal validity. Several kinds of PEP techniques with a diversity of intensities and durations of treatment have been evaluated with different outcome measures and follow-up periods. Benefits of PEP were found in isolated outcome measures in separate studies with a follow-up period <1 month. Concerning long-term effects, the results are contradictory. Prior to widespread prescription of long-term PEP treatment, more research is required to establish the benefit of the technique in patients with COPD.


ZNF804A Gene Variants Have a Cross-diagnostic Influence on Psychosis and Treatment Improvement in Mood Disorders.
Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with major depression and bipolar disorder. In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments. We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with major depression and 132 patients diagnosed with bipolar disorder and 326 healthy controls; an Italian sample composed 151 major depression subjects, 189 bipolar disorder subjects and 38 outpatients diagnosed for a primary anxiety disorder. Our analyses reported an association of rs1344706 with psychotic phenotype in the cross-diagnostic pooled sample (geno p = 4.15 × 10-4, allelic p = 1.06 × 10-4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p = 0.025, allelic p = 0.007). The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance; however, further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.


Locomotor sensitization and decrease in [3H]mazindol binding to the dopamine transporter in the nucleus accumbens are delayed after chronic treatments by GBR12783 or cocaine.
Rats were treated once daily for 15 consecutive days with either cocaine or the specific dopamine uptake inhibitor 1-[2- (diphenylmethoxy)ethyl]-4-(3-phenyl-2-(propenyl)-piperazine (GBR12783) at a dose (10 mg/kg) that given acutely increases locomotor activity. Two or 14 days after the last administration, the motor stimulant responses of rats to a challenge dose (5 mg/kg) of the drug administered previously were compared with the motor stimulant responses of rats daily injected with solvent. A sensitization to the acute stimulant locomotor effect of these drugs was only observed 14 days after cessation of chronic treatments. After this withdrawal period, autoradiographic analysis revealed a significant decrease in the desipramine-insensitive [3H]mazindol binding to the dopamine transporter in the shell of the nucleus accumbens. No change was noticed in other regions with high dopamine content: core of nucleus accumbens, striatum, olfactory tubercle, substantia nigra and ventral tegmental area. Absence of concomitant decrease in [3H]dihydrotetrabenazine labeling, which indicates lack of effect on vesicular monoamine transporters, suggests that the decrease in accumbal [3H]mazindol binding did not result from a cytotoxic effect on corresponding dopamine neurons. In addition, 14 days after the last administration of GBR12783, the levels of dopamine and metabolites (dihydroxy-phenylacetic acid, homovanillic acid) and the ability of acute GBR12783 to synergize with haloperidol-induced increase in these metabolites were not modified either in the whole nucleus accumbens or in the striatum.


Driving ability after acute and sub-chronic administration of levocetirizine and diphenhydramine: a randomized, double-blind, placebo-controlled trial.
Sedation following antihistamine use poses a danger to ambulant patients involved in daily activities such as driving. To investigate effects of levocetirizine (5 mg), diphenhydramine (50 mg), and placebo on driving ability during normal traffic. Forty-eight healthy volunteers participated in a double-blind, placebo-controlled, randomized clinical trial. Treatments were administrated on days 1, 2, 3 and 4, exactly 1.5 h before the start of the standardized driving test (performed on day 1 and day 4). In the standardized driving test, subjects were instructed to drive with a steady lateral position, while maintaining a constant speed (95 km/h). Primary parameter was the standard deviation of lateral position (SDLP; cm). Statistical analyses were performed separately for day 1 and day 4, using analysis of variance and an equivalence test. Equivalence to placebo was evidenced if the 95% confidence interval lay between -2.6 cm and +2.6 cm. SDLP after levocetirizine was equivalent to placebo on both day 1 (-0.66 cm; +1.12 cm) and day 4 (-0.37 cm; +1.28 cm). In contrast, SDLP after diphenhydramine differed significantly from placebo on both day 1 ( P<0.0001) and day 4 ( P<0.0003). On day 1, the 95% confidence interval of diphenhydramine (+1.85 cm; +3.63 cm) was partially above the upper equivalence limit (+2.6 cm), indicating clinically relevant driving impairment. On day 4, however, the 95% confidence interval of diphenhydramine (+0.74 cm; +2.38 cm) was contained within the acceptance range. In contrast to diphenhydramine, driving performance was not significantly affected while using 5 mg levocetirizine once daily.


Critical librarianship in health sciences libraries: an introduction.
The Medical Library Association recently announced its commitment to diversity and inclusion. While this is a positive start, critical librarianship takes the crucial concepts of diversity and inclusion one step further by advocating for social justice action and the dismantling of oppressive institutional structures, including white supremacy, patriarchy, and capitalism. Critical librarianship takes many forms, but, at its root, is focused on interrogating and disrupting inequitable systems, including changing racist cataloging rules, creating student-driven information literacy instruction, supporting inclusive and ethical publishing models, and rejecting the notion of libraries as neutral spaces. This article presents examples of the application of critical practice in libraries as well as ideas for applying critical librarianship to the health sciences.


Lifespan Dispersion in Times of Life Expectancy Fluctuation: The Case of Central and Eastern Europe.
Central and Eastern Europe (CEE) have experienced considerable instability in mortality since the 1960s. Long periods of stagnating life expectancy were followed by rapid increases in life expectancy and, in some cases, even more rapid declines, before more recent periods of improvement. These trends have been well documented, but to date, no study has comprehensively explored trends in lifespan variation. We improved such analyses by incorporating life disparity as a health indicator alongside life expectancy, examining trends since the 1960s for 12 countries from the region. Generally, life disparity was high and fluctuated strongly over the period. For nearly 30 of these years, life expectancy and life disparity varied independently of each other, largely because mortality trends ran in opposite directions over different ages. Furthermore, we quantified the impact of large classes of diseases on life disparity trends since 1994 using a newly harmonized cause-of-death time series for eight countries in the region. Mortality patterns in CEE countries were heterogeneous and ran counter to the common patterns observed in most developed countries. They contribute to the discussion about life expectancy disparity by showing that expansion/compression levels do not necessarily mean lower/higher life expectancy or mortality deterioration/improvements.


Lexical and nonlexical processing in developmental dyslexia: a case for different resources and different impairments.
In a group of adult dyslexics word reading and, especially, word spelling are predicted more by what we have called lexical learning (tapped by a paired-associate task with pictures and written nonwords) than by phonological skills. Nonword reading and spelling, instead, are not associated with this task but they are predicted by phonological tasks. Consistently, surface and phonological dyslexics show opposite profiles on lexical learning and phonological tasks. The phonological dyslexics are more impaired on the phonological tasks, while the surface dyslexics are equally or more impaired on the lexical learning tasks. Finally, orthographic lexical learning explains more variation in spelling than in reading, and subtyping based on spelling returns more interpretable results than that based on reading. These results suggest that the quality of lexical representations is crucial to adult literacy skills. This is best measured by spelling and best predicted by a task of lexical learning. We hypothesize that lexical learning taps a uniquely human capacity to form new representations by recombining the units of a restricted set.


Strehl ratio and amplitude-weighted generalized orthonormal Zernike-based polynomials.
The concept of orthonormal polynomials is revisited by developing a Zernike-based orthonormal set for a non-circular pupil that is transmitting an aberrated, non-uniform field. We refer to this pupil as a general pupil. The process is achieved by using the matrix form of the Gram-Schmidt procedure on Zernike circle polynomials and is interpreted as a process of balancing each Zernike circle polynomial by adding those of lower order in the general pupil, a procedure which was previously performed using classical aberrations. We numerically demonstrate this concept by comparing the representation of phase in a square-Gaussian pupil using the Zernike-Gauss square and Zernike circle polynomials. As expected, using the Strehl ratio, we show that only specific lower-order aberrations can be used to balance specific aberrations, for example, tilt cannot be used to balance spherical aberration. In the process, we present a possible definition of the Maréchal criterion for the analysis of the tolerance of systems with apodized pupils.


Drinking pattern in persons with alcohol dependence with and without cirrhosis: A hospital-based comparative study.
Worldwide, alcohol is the most frequently used and socially accepted hepatotoxin. However, not everyone who has alcohol dependence develops alcoholic cirrhosis, and does quantity/type or pattern of alcohol intake determine the development of cirrhosis? A study of this nature would help in delineating similarities/differences in the drinking pattern between alcohol dependence and alcohol-induced cirrhosis groups. The aim was to study the drinking pattern of persons with alcohol dependence syndrome (ADS) and alcohol-induced cirrhosis. Alcohol Intake database and Severity of Alcohol Dependence Questionnaire (SADQ) were administered to eighty male inpatients with a reliable family member of which forty were in ADS group and forty were in alcohol dependence with cirrhosis group. Persons in the cirrhosis group were older with longer duration of drinking. There is no statistically significant difference in the educational status, religion, occupation, socioeconomic class, mean age of onset of drinking, mean age of development of dependence, type of beverage preferred, and initiating/maintaining factors between the two groups. The amount of alcohol consumed was significantly high in the cirrhosis group, with 33.5% in the high severity of dependence. They usually were drinking alone, outside meal times with regular and intermittent binge pattern. Alcohol dependence and alcohol-induced cirrhosis may be on a continuum but form a different group of heavy drinkers who may require different approaches to management.


FREALIGN: high-resolution refinement of single particle structures.
The refinement of three-dimensional reconstructions and correction for the contrast transfer function of the microscope are important steps in the determination of macromolecular structures by single particle electron microscopy. The algorithms implemented in the computer program FREALIGN are optimized to perform these tasks efficiently. A general overview and details on how to use FREALIGN are provided. The program is free and available for download on the author's web page.


Beyond Urinary Tract Infections (UTIs) and Delirium: A Systematic Review of UTIs and Neuropsychiatric Disorders.
Urinary tract infections (UTIs) are among the most common bacterial infections. Although comorbid UTI in geriatric patients with delirium or dementia is well known, the prevalence and scope of the association with other neuropsychiatric disorders is unclear. We performed a systematic review of the association between UTIs and delirium, dementia, psychotic disorders, and mood disorders in hospitalized patients. We identified studies by searching PubMed, PsycInfo, and Web of Knowledge, and the reference lists of identified studies and review papers. Seventeen publications met the inclusion criteria. The primary findings were: (1) 88% of publications reported a positive association between UTIs and neuropsychiatric disorders; (2) 47% reported that the clinical course of a neuropsychiatric disorder may be precipitated or exacerbated by a UTI; (3) the mean weighted prevalence of UTIs in subjects was 19.4% for delirium, 11.2% for dementia, 21.7% for nonaffective psychotic disorders, and 17.8% for mood disorders. Our findings, which must be interpreted carefully given the heterogeneity among the studies, suggest that UTIs are highly comorbid in hospitalized patients and may precipitate or exacerbate some neuropsychiatric disorders. The association extends beyond geriatric patients with delirium, affects males and females, and includes adults with psychotic and mood disorders. These findings underscore the important interface between physical and mental health. Potential underlying mechanisms are also reviewed, including complex interactions between the immune system and the brain.


Efficacy of Self-guided Internet-Based Cognitive Behavioral Therapy in the Treatment of Depressive Symptoms: A Meta-analysis of Individual Participant Data.
Self-guided internet-based cognitive behavioral therapy (iCBT) has the potential to increase access and availability of evidence-based therapy and reduce the cost of depression treatment. To estimate the effect of self-guided iCBT in treating adults with depressive symptoms compared with controls and evaluate the moderating effects of treatment outcome and response. A total of 13 384 abstracts were retrieved through a systematic literature search in PubMed, Embase, PsycINFO, and Cochrane Library from database inception to January 1, 2016. Randomized clinical trials in which self-guided iCBT was compared with a control (usual care, waiting list, or attention control) in individuals with symptoms of depression. Primary authors provided individual participant data from 3876 participants from 13 of 16 eligible studies. Missing data were handled using multiple imputations. Mixed-effects models with participants nested within studies were used to examine treatment outcomes and moderators. Outcomes included the Beck Depression Inventory, Center for Epidemiological Studies-Depression Scale, and 9-item Patient Health Questionnaire scores. Scales were standardized across the pool of the included studies. Of the 3876 study participants, the mean (SD) age was 42.0 (11.7) years, 2531 (66.0%) of 3832 were female, 1368 (53.1%) of 2574 completed secondary education, and 2262 (71.9%) of 3146 were employed. Self-guided iCBT was significantly more effective than controls on depressive symptoms severity (β = -0.21; Hedges g = 0.27) and treatment response (β = 0.53; odds ratio, 1.95; 95% CI, 1.52-2.50; number needed to treat, 8). Adherence to treatment was associated with lower depressive symptoms (β = -0.19; P = .001) and greater response to treatment (β = 0.90; P < .001). None of the examined participant and study-level variables moderated treatment outcomes. Self-guided iCBT is effective in treating depressive symptoms. The use of meta-analyses of individual participant data provides substantial evidence for clinical and policy decision making because self-guided iCBT can be considered as an evidence-based first-step approach in treating symptoms of depression. Several limitations of the iCBT should be addressed before it can be disseminated into routine care.


Enantiomeric Profiling of Chiral Pharmacologically Active Compounds in the Environment with the Usage of Chiral Liquid Chromatography Coupled with Tandem Mass Spectrometry.
The issue of drug chirality is attracting increasing attention among the scientific community. The phenomenon of chirality has been overlooked in environmental research (environmental occurrence, fate and toxicity) despite the great impact that chiral pharmacologically active compounds (cPACs) can provoke on ecosystems. The aim of this paper is to introduce the topic of chirality and its implications in environmental contamination. Special attention has been paid to the most recent advances in chiral analysis based on liquid chromatography coupled with mass spectrometry and the most popular protein based chiral stationary phases. Several groups of cPACs of environmental relevance, such as illicit drugs, human and veterinary medicines were discussed. The increase in the number of papers published in the area of chiral environmental analysis indicates that researchers are actively pursuing new opportunities to provide better understanding of environmental impacts resulting from the enantiomerism of cPACs.


A review and methodologic critique of the literature supporting 'chronic whiplash injury': part I - research articles.
The existence of a 'chronic whiplash injury' has been a source of debate in the medical literature for many years. Some authors have published articles suggesting that chronic whiplash syndrome is the result of chronic pathology (injury), and that this injury may occur at any collision speed; others have stated that any psychological factors are secondary rather than primary (etiologic) to the problem of chronic pain, or that secondary gain is a rare or uncommon phenomenon. These articles contradict scientific measures and efforts which show that for Quebec Task Force Grade 1 and 2 whiplash-associated disorders, the highly prevalent problem of chronic pain may be a culturally and psychosocially determined phenomenon, in which confounding psychosocial variables determine the behaviour and outcome following an otherwise benign acute injury. The authors of the current literature critique reviewed the biomedical and engineering literature relating to whiplash syndrome, searching for articles that supported the construct of 'chronic whiplash injuries'. Thirty seven articles containing fourteen distinct statements supporting the construct of 'chronic whiplash injuries' were found that fit the inclusion criteria. The methodology described in these articles was evaluated critically to determine if the authors' conclusions regarding 'chronic whiplash injuries' were scientifically sound. The authors of the current critique found that all of the articles contained significant methodologic errors relative to their respective authors' statements regarding chronic whiplash. The most frequent concerns reside with sampling, experimental design and interpretation of data.


A tool for predicting the outcome of reperfusion in ST-elevation myocardial infarction using age, thrombotic burden and index of microcirculatory resistance (ATI score).
Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction is difficult to predict. A method to assess the likelihood of a suboptimal response to conventional pharmacomechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI. A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) >40 was initially derived in a cohort of 85 STEMI patients (derivation cohort). This score was then tested and validated in three further cohorts of patients (retrospective [30 patients], prospective [42 patients] and external [29 patients]). The ATI score (age [>50=1]; pre-stenting IMR [>40 and <100=1; ≥100=2]; thrombus score [4=1; 5=3]) was highly predictive of a post-stenting IMR >40 in all four cohorts (AUC: 0.87; p<0.001-derivation cohort, 0.84; p=0.002-retrospective cohort, 0.92; p<0.001-prospective cohort and 0.81; p=0.006-external cohort). In the whole population, an ATI score ≥4 presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred in the presence of an ATI score <2. The ATI score appears to be a promising tool capable of identifying patients during PPCI who are at the highest risk of coronary microvascular impairment following revascularisation. This procedural risk stratification has a number of potential research and clinical applications and warrants further investigation.


Evaluation of the psychometric properties of the brief Internalized Stigma of Mental Illness Scale (ISMI-10).
A significant number of psychiatric patients stigmatize themselves because of their mental struggles. Such self-stigmatization has an adverse impact on patients' well-being and effectiveness of the treatment of mental disorders. The goal of this study was to standardize the brief Internalized Stigma of Mental Illness Scale (ISMI-10), which could be used in studies targeting the self-stigma among the psychiatric patients. 354 psychiatric patients participated in the study between the years 2012 and 2014. All individuals were undergoing treatment in the outpatient care or the psychotherapeutic ward of the Department of Psychiatry, University Hospital Olomouc. The mean age of the participants was 41.5±13.3 years. The majority of them were women (n=195). The patients suffered from various mental disorders - neurotic disorders (n=166), mood disorders (n=65), substance use disorders (n=47), psychoses (n=40), personality disorders (n=32), and organic mental illness (n=4). Each patient completed a demographic questionnaire and the ISMI-10. The ordinal alpha of the scale was 0.86, indicating its good internal consistency. The overall scores of the full and abbreviated version of the scale were almost perfectly correlated (r=0.95, p<0.001). The factor analysis confirmed a good internal structure of the scale. The created norms for the scale score were based on stens. The ISMI-10 may be a useful method for measuring the self-stigma among adults with a mental disorder. The area of its use lies mainly in research.


HIV-1 can escape from RNA interference by evolving an alternative structure in its RNA genome.
HIV-1 replication can be efficiently inhibited by intracellular expression of an siRNA targeting the viral RNA. However, HIV-1 escape variants emerged after prolonged culturing. These RNAi-resistant viruses contain nucleotide substitutions or deletions in or near the targeted sequence. We observed an inverse correlation between the level of resistance and the stability of the siRNA/target-RNA duplex. However, two escape variants showed a higher level of resistance than expected based on the duplex stability. We demonstrate that these mutations induce alternative folding of the RNA such that the target sequence is occluded from binding to the siRNA, resulting in reduced RNAi efficiency. HIV-1 can thus escape from RNAi-mediated inhibition not only through nucleotide substitutions or deletions in the siRNA target sequence, but also through mutations that alter the local RNA secondary structure. The results highlight the enormous genetic flexibility of HIV-1 and provide detailed molecular insight into the sequence specificity of RNAi and the impact of target RNA secondary structure.


The complex dynamics of products and its asymptotic properties.
We analyse global export data within the Economic Complexity framework. We couple the new economic dimension Complexity, which captures how sophisticated products are, with an index called logPRODY, a measure of the income of the respective exporters. Products' aggregate motion is treated as a 2-dimensional dynamical system in the Complexity-logPRODY plane. We find that this motion can be explained by a quantitative model involving the competition on the markets, that can be mapped as a scalar field on the Complexity-logPRODY plane and acts in a way akin to a potential. This explains the movement of products towards areas of the plane in which the competition is higher. We analyse market composition in more detail, finding that for most products it tends, over time, to a characteristic configuration, which depends on the Complexity of the products. This market configuration, which we called asymptotic, is characterized by higher levels of competition.


Swine genome science comes of age.
Pigs were among the first animals to be domesticated and pork is one of the most widely eaten meats in the world today. The pig has also been an excellent biomedical model for understanding a variety of human health issues such as obesity, diabetes, cancer, female reproductive health, cardiovascular disease, and infectious diseases. Genome sequencing, mapping, expression and functional analyses have significantly advanced our ability to unravel the secrets of the pig. Therefore, this edition, with six reviews from leading scientists, offers the opportunity for all interested researchers and readers to see the big picture of porcine genomics.


Context, cultural bias, and health risk perception: the "everyday" nature of pesticide policy preferences in London, Calgary, and Halifax.
Risk perception and the cultural theory of risk have often been contrasted in relation to risk-related policy making; however, the local context in which risks are experienced, an important component of everyday decision making, remains understudied. What is unclear is the extent to which localized community beliefs and behaviors depend on larger belief systems about risk (i.e., worldviews). This article reports on a study designed to understand the relative importance of health risk perceptions (threat of harm); risk-related worldviews (cultural biases); and the experiences of local context (situated risk) for predicting risk-related policy preferences regarding cosmetic pesticides. Responses to a random telephone questionnaire are used to compare residents' risk perceptions, cultural biases, and pesticide bylaw preferences in Calgary (Alberta), Halifax (Nova Scotia), and London (Ontario), Canada. Logistic regression shows that the most important determinants of pesticide bylaw preference are risk perception, lack of benefit, and pesticide "abstinence." Though perception of health risk is the best single predictor of differences in bylaw preferences, social factors such as gender and situated risk factors like conflict over chemical pesticides, are also important. Though cultural biases are not important predictors of pesticide bylaw preference, as in other studies, they are significant predictors of health risk perception. Pesticide bylaw preference is therefore more than just a health risk perception or worldview issue; it is also about how health risk becomes situated-contextually-in the experiences of residents' everyday lives.


Borna disease virus infection in animals and humans.
The geographic distribution and host range of Borna disease (BD), a fatal neurologic disease of horses and sheep, are larger than previously thought. The etiologic agent, Borna disease virus (BDV), has been identified as an enveloped nonsegmented negative-strand RNA virus with unique properties of replication. Data indicate a high degree of genetic stability of BDV in its natural host, the horse. Studies in the Lewis rat have shown that BDV replication does not directly influence vital functions; rather, the disease is caused by a virus-induced T-cell mediated immune reaction. Because antibodies reactive with BDV have been found in the sera of patients with neuropsychiatric disorders, this review examines the possible link between BDV and such disorders. Seroepidemiologic and cerebrospinal fluid investigations of psychiatric patients suggest a causal role of BDV infection in human psychiatric disorders. In diagnostically unselected psychiatric patients, the distribution of psychiatric disorders was found to be similar in BDV seropositive and seronegative patients. In addition, BDV-seropositive neurologic patients became ill with lymphocytic meningoencephalitis. In contrast to others, we found no evidence is reported for BDV RNA, BDV antigens, or infectious B DV in peripheral blood cells of psychiatric patients.


Worse in-hospital outcomes in patients with transient ischemic attack in association with acute kidney injury: analysis of nationwide in-patient sample.
The effect of acute kidney injury (AKI) on outcomes of transient ischemic attack (TIA) is largely unknown. We wanted to determine the impact of AKI on the outcomes of patients admitted with TIA. Data from all adult patients admitted to the U.S. hospitals between 2005 and 2011 with a primary discharge diagnosis of TIA and secondary diagnosis of AKI were included, using the nationwide in-patient dataset. The association of AKI with TIA-related mortality and discharge outcomes was analyzed after adjusting for potential confounders using logistic regression analysis. Of the 1,173,340 patients admitted with TIA, 45,974 (3.8%) had AKI. Dialysis was required in 29 (0.06%) patients. TIA patients with AKI had higher rates of moderate-to-severe disability (21.2 vs. 13.7%, p ≤ 0.0001), and in-hospital mortality (0.6 vs. 0.1%, p ≤ 0.0001) compared with those without AKI. After adjusting for age, sex, and potential confounders; TIA patients with AKI had higher odds of moderate-to-severe disability [OR 1.3, 95% CI 1.2-1.4, p < 0.0001] and death (OR 4.2, 95% CI 3.0-6.1, p < 0.0001). AKI in patients with TIA is associated with significantly higher rates of moderate-to-severe disability at discharge and in-hospital mortality compared with those without AKI.


Diagnosis, management, histology and genetics of sporadic primary hyperparathyroidism: old knowledge with new tricks.
Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from inappropriately high PTH secretion. It usually results from the presence of a single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma. All these conditions require different management, and it is important to be able to differentiate the underlined pathology, in order for the clinicians to provide the best therapeutic approach. Elucidation of the genetic background of each of these clinical entities would be of great interest. However, the molecular factors that control parathyroid tumorigenesis are poorly understood. There are data implicating the existence of specific genetic pathways involved in the emergence of parathyroid tumorigenesis. The main focus of the present study is to present the current optimal diagnostic and management protocols for pHPT as well as to review the literature regarding all molecular and genetic pathways that are to be involved in the pathophysiology of sporadic pHPT.


Retrograde behavior revisited: implications for confined fluid phase equilibria in nanopores.
Many fluid mixtures exhibit retrograde behavior, including those that define natural gases. While the behavior is well understood for mixtures in bulk, it is not so in nanosize porous space that dominates shale formations in unconventional reservoirs. The lack of experimental data creates the need for modeling works to make estimates as good as possible due to immediate needs in gas recovery. However, such efforts have been straying without firm guidance from systematic studies over what we have known so far. This article is intended to present the results of such a study that would incite further investigations in this area of research. Revisiting the retrograde behavior in the bulk is appropriate to start with, followed by a short review of what we know about fluids confined in nanosize pores. Based on this information, implications for the behavior of confined mixtures in the retrograde region can be inferred. The implied features that have been supported by experimental evidence are the locations of the confined dew point and bubble point at low temperatures, which are both at pressures lower than their bulk counterparts. Another feature found in this study is completely new, and therefore still open for further investigation. We reveal that the dew-point and bubble-point curves of confined mixtures end at moderate pressures on a multiphase curve, beyond which equilibrium occurs among the bulk and confined phases. The well-known points in the bulk retrograde region, i.e. the critical point and cricondenbar, are consequently absent in confined mixtures.


Perception of burden experienced during diagnostic tests by melanoma patients with lymph node metastases.
Melanoma patients with lymph node metastases have to deal with diagnostic tests to exclude the presence of distant metastases; results of the tests could have major implications for their prognosis and treatment. There are, however, few studies concerning the patients' psychological issues and perception of diagnostic tests. The aim of this study was to describe the burden of diagnostic tests [radiograph, computed tomography (CT) and positron emission tomography (PET)] experienced by melanoma patients with lymph node metastases. Patients were asked to complete a questionnaire concerning satisfaction and burden experienced during the diagnostic tests. The levels of embarrassment, discomfort and anxiety for the different tests, as well as total scores for each burden were calculated. Logistic regression was used to examine factors associated with the degree of experienced burden. Fifty-nine of the 68 patients completed the questionnaire and the response rate was 87%. The overall mean scores on satisfaction and quality of life were high. More than half of the patients experienced no burden during PET, 65% no burden during computed tomography and 80% no burden during chest radiograph. Patients experienced significantly more discomfort during the PET scan than during the CT (P=0.003). Less burden was experienced (in univariate analysis) by patients who were more satisfied. The overall experienced burden by patients is low and should therefore not interfere with primary choice for a diagnostic test based on accuracy, costs and percentage of patients upstaged. Attention should be paid in explaining the procedure and answering questions of the patients to reduce burden.


Rapid detection of peste des petits ruminants virus by a reverse transcription loop-mediated isothermal amplification assay.
Peste des petits ruminants virus (PPRV) is the causative agent of peste des petits ruminants (PPR), an economically important viral disease of small ruminants. In this report, a one-step, single-tube, reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for the detection of PPRV. A set of six LAMP primers were designed based on the matrix gene sequence of PPRV to amplify the target RNA by incubation at 63°C for 60min with Bst DNA polymerase and reverse transcriptase. The amplified products could be observed by the naked eye. The specificity of the RT-LAMP assay was validated by amplifying eight strains of PPRV isolated in different geographical areas. No cross-reactivity with other related viruses, including rinderpest virus, canine distemper virus and measles virus, was detected. The sensitivity of the assay was similar to that of real-time reverse transcription polymerase chain reaction (RT-PCR) and 10-fold higher than that of conventional RT-PCR. Twenty clinical samples were evaluated by the RT-LAMP assay, and the results were consistent with those of real-time RT-PCR. As a simple, rapid and accurate detection method, this RT-LAMP assay has important potential applications in the clinical diagnosis of PPR and the surveillance of PPRV.


Real-world treatment patterns and adverse events in metastatic renal cell carcinoma from a large US claims database.
Vascular endothelial growth factor (VEGF), tyrosine kinase (TK) and mechanistic target of rapamycin kinase (mTOR) inhibitors are common first-line (1 L) treatments for metastatic renal cell carcinoma (mRCC). Despite treatment availability, the 5-year survival rate in patients diagnosed at the metastatic stage is only ≈ 10%. To gain contemporary insights into RCC treatment trends that may inform clinical, scientific and payer considerations, treatment patterns and adverse events (AEs) associated with 1 L therapy were examined in a retrospective, longitudinal, population-based, observational study of patients with mRCC. US administrative claims data (Truven Health MarketScan Commercial Databases) were used to assess trends in 1 L treatment initiation in mRCC (2006-2015) and characterize patterns of individual 1 L treatments, baseline characteristics, comorbidities and treatment-related AEs from 2011 through 2015. Outcomes were evaluated by drug class and route of administration. Ten-year trend analysis (n = 4270) showed that TK/VEGF-directed therapy rapidly became more common than mTOR-directed therapy, and oral treatments were favored over intravenous (IV) treatments. Overall, 1992 eligible patients initiated 1 L treatment for mRCC from 2011 through 2015: 1752 (88%) received TK/VEGF-directed agents and 233 (12%) received mTOR-directed agents; 1674 (84%) received oral treatments, and 318 (16%) received IV treatments. The most common 1 L treatment was sunitinib (n = 849), followed by pazopanib (n = 631), temsirolimus (n = 157) and bevacizumab (n = 154). Patient characteristics and comorbidities, including age, diabetes and congestive heart failure, were independent predictors of 1 L mRCC treatment choice. The three most common potentially 1 L treatment-related AEs were nausea/vomiting (128.2 per 100 patient-years [PY]), hypertension (69 per 100 PY) and renal insufficiency (44.6 per 100 PY). A wide variety of agents were used as second-line (2 L) therapy. Substantial latency of onset was observed for several potentially treatment-related toxicities in patients treated with TK/VEGF- or mTOR-directed agents. In the US, 1 L TK/VEGF inhibitor uptake in recent years appears largely in line with national approvals and guidelines, with varied 2 L agent use. Although retrospective evaluation of claims data cannot assess underlying causality, insights from these real-world RCC treatment and AE patterns will be useful in informing medical and payer decisions.


Recurrence Patterns and Timing Courses Following Curative-Intent Resection for Intrahepatic Cholangiocarcinoma.
Recurrence of intrahepatic cholangiocarcinoma (ICC) after curative resection is common. The aim of this study was to investigate the patterns, timing and risk factors of disease recurrence after curative-intent resection for ICC. Patients undergoing curative resection for ICC were identified from a multi-institutional database. Data on clinicopathological and initial operation information, timing and first sites of recurrence, recurrence management, and long-term outcomes were analyzed. A total of 920 patients were included. With a median follow-up of 38 months, 607 patients (66.0%) experienced ICC recurrence. In the cohort, 145 patients (23.9%) recurred at the surgical margin, 178 (29.3%) recurred within the liver away from the surgical margin, 90 (14.8%) recurred at extraheptatic sites, and 194 (32.0%) developed both intrahepatic and extrahepatic recurrence. Intrahepatic margin recurrence (median 6.0 m) and extrahepatic-only recurrence (median 8.0 m) tended to occur early, while intrahepatic recurrence at non-margin sites occurred later (median 14.0 m; p < 0.05). On multivariate analysis, surgical margin < 10 mm was associated with increased margin recurrence (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.11-2.60; p = 0.014), whereas female sex (HR 2.12, 95% CI 1.40-3.22; p < 0.001) and liver cirrhosis (HR 2.36, 95% CI 1.31-4.25; p = 0.004) were both associated with an increased risk of intrahepatic recurrence at other sites. Median survival after recurrence was better among patients who underwent repeat curative-intent surgery (48.7 months) versus other treatments (9.7 months) [p < 0.001]. Different recurrence patterns and timing of recurrence suggest biological heterogeneity of ICC tumor recurrence. Understanding timing and risk factors associated with different types of recurrence can hopefully inform discussions around adjuvant therapy, surveillance, and treatment of recurrent disease.


Actionable gene expression-based patient stratification for molecular targeted therapy in hepatocellular carcinoma.
The effectiveness of molecular targeted agents is modest in hepatocellular carcinoma (HCC). Efficacy of molecular targeted therapies has been better in cancer patients with high expression of actionable molecules defined as cognate target molecules. However, patient stratification based on the actionable molecules dictating the effectiveness of targeted drugs has remained understudied in HCC. EXPERIMENTAL DESIGN & RESULTS: Paired tumor and non-tumoral tissues derived from a total of 130 HCC patients were studied. Real-time RT-PCR was used to analyze the mRNA expression of actionable molecules in the tissues. mRNA levels of EGFR, VEGFR2, PDGFRβ, FGFR1, and mTOR were up-regulated in tumors compared to non-tumors in 35.4, 42.3, 61.5, 24.6, and 50.0% of patients, respectively. Up-regulation of EGFR was observed at early stage and tended to gradually decrease toward late stages (BCLC stage A: 41.9%; B: 30.8%; C: 17.6%). Frequency of VEGFR2 expression in tumors at stage C was lower than that in the other stages (BCLC stage A: 45.9%; B: 41.0%; C: 29.4%). PDGFRβ and mTOR were observed to be up-regulated in more than 50% of tumors in all the stages whereas FGFR1 was up-regulated in only about 20% of HCC irrespective of stages. A cluster analysis of actionable gene expression revealed that HCC can be categorized into different subtypes that predict the effectiveness of molecular targeted agents and combination therapies in clinical trials. Analysis of in vitro sensitivity to sorafenib demonstrated that HCC cells with up-regulation of PDGFRβ and c-Raf mRNA are more susceptible to sorafenib treatment in a dose and time-dependent manner than cells with low expression of the genes. mRNA expression analysis of actionable molecules could provide the rationale for new companion diagnostics-based therapeutic strategies in the treatment of HCC.


Treatment of CIDP.
Chronic inflammatory demyelinating polyneuropathy is a disabling but treatable disorder. However, misdiagnosis is common, and it can be difficult to optimise its treatment. Various agents are used both for first and second line. First-line options are intravenous immunoglobulin, corticosteroids and plasma exchange. Second-line therapies may be introduced as steroid-sparing agents or as more potent escalation therapy. It is also important to consider symptomatic treatment of neuropathic pain and non-pharmacological interventions. We discuss the evidence for the various treatments and explain the practicalities of the different approaches. We also outline strategies for monitoring response and assessing the ongoing need for therapy.


High-Intensity Interval Training for Overweight Adolescents: Program Acceptance of a Media Supported Intervention and Changes in Body Composition.
High-intensity interval training (HIIT) consists of short intervals of exercise at high intensity intermitted by intervals of lower intensity and is associated with improvement of body composition and metabolic health in adults. Studies in overweight adolescents are scarce. We conducted a randomized controlled trial in overweight adolescents to compare acceptance and attendance of HIIT with or without weekly motivational encouragement through text messages and access to a study website. HIIT was offered for six months (including summer vacation) twice a week (60 min/session). Participation rates were continuously assessed and acceptance was measured. Clinical parameters were assessed at baseline and after six months. Twenty-eight adolescents participated in this study (age 15.5 ± 1.4; 54% female). The standard deviation score for body mass index over all participants was 2.33 at baseline and decreased by 0.026 (95% CI -0.048 to 0.10) units, p = 0.49. Waist to height ratio was 0.596 at baseline and decreased by 0.013 (95% CI 0.0025 to 0.024), p = 0.023. Participation within the first two months ranged from 65% to 75%, but fell to 15% within the last three months. Attendance in the intervention group was 14% (95% CI -8 to 37), p = 0.18, higher than the control group. Overall program content was rated as "good" by participants, although high drop-out rates were observed. Summer months constitute a serious problem regarding attendance. The use of media support has to be assessed further in appropriately powered trials.


Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.
Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) - associated systemic vasculitis (AAV) with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA. Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D. We show that SLE is associated with rs11594656 (P = 3.87 x 10-7) and there is some evidence of association of rs41295061 with AAV (P = 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D - associated SNP in the IL2RA locus, is not associated with either SLE or AAV. We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease.


Nonlinear Rashba spin splitting in transition metal dichalcogenide monolayers.
Single-layer transition-metal dichalcogenides (TMDs) such as MoS2 and MoSe2 exhibit unique electronic band structures ideal for hosting many exotic spin-orbital orderings. It has been widely accepted that Rashba spin splitting (RSS) is linearly proportional to the external field in heterostructure interfaces or to the potential gradient in polar materials. Surprisingly, an extraordinary nonlinear dependence of RSS is found in semiconducting TMD monolayers under a gate field. In contrast to small and constant RSS in polar materials, the potential gradient in non-polar TMDs gradually increases with the gate bias, resulting in nonlinear RSS with a Rashba coefficient an order-of-magnitude larger than the linear one. Most strikingly, under a large gate field MoSe2 demonstrates the largest anisotropic spin splitting among all known semiconductors to our knowledge. Based on the k·p model via symmetry analysis, we identify that the third-order contributions are responsible for the large nonlinear Rashba splitting. The gate tunable spin splitting found in semiconducting pristine TMD monolayers promises future spintronics applications in that spin polarized electrons can be generated by external gating in an experimentally accessible way.


Type 2 diabetes in octogenarians is associated with decreased low molecular weight adiponectin.
Adiponectin circulates in the blood in three different multimer isoforms, of which the high molecular weight form (HMW) is presumed to mediate insulin sensitivity. We examined whether adiponectin oligomer distribution is associated with aging and type 2 diabetes (T2D) in octogenarians without characteristic features of metabolic syndrome. The study included 154 octogenarians (58 men, 96 women), 24 normoglycemic middle-aged controls (11 men, 13 women; mean age 44 years), and 33 middle-aged individuals (14 men, 19 women; mean age 55 years) with T2D. Based on oral glucose tolerance test 62 octogenarians had normal, 63 impaired glucose tolerance, and 29 octogenarians had newly detected T2D. Serum adiponectin multimer isoforms were measured after overnight fast by enzyme-linked immunosorbent assays. Compared to the normoglycemic middle-aged control group, male normoglycemic octogenarians revealed significantly higher total adiponectin and all adiponectin isoforms. The same was true for females with the exception of low molecular weight (LMW) adiponectin, which was not statistically higher in octogenarians. Male and female octogenarians with T2D had significantly higher levels of total, HMW, and middle molecular weight (MMW) adiponectin, but not LMW adiponectin, than middle-aged individuals with T2D. Female, but not male, octogenarians revealed significantly lower total adiponectin than normoglycemic octogenarians. Compared with normoglycemic octogenarians, male and female octogenarians with T2D were characterized by significantly lower LMW adiponectin. In male and female octogenarians, total adiponectin and all multimer isoforms were directly correlated with HDL cholesterol. LMW adiponectin in octogenarians of both sexes was inversely correlated with glucose level at 2-hour oral glucose tolerance test. Serum levels of total adiponectin as well as its HMW and MMW isoforms were significantly higher in octogenarians with normoglycemia or T2D than in corresponding middle-aged control groups. In male and female octogenarians without metabolic syndrome, T2D was associated with lower LMW adiponectin, while the HMW and MMW isoforms were not statistically different.


Effect of crosslinking in cartilage-like collagen microstructures.
The mechanical performance of biological tissues is underpinned by a complex and finely balanced structure. Central to this is collagen, the most abundant protein in our bodies, which plays a dominant role in the functioning of tissues, and also in disease. Based on the collagen meshwork of articular cartilage, we have developed a bottom-up spring-node model of collagen and examined the effect of fibril connectivity, implemented by crosslinking, on mechanical behaviour. Although changing individual crosslink stiffness within an order of magnitude had no significant effect on modelling predictions, the density of crosslinks in a meshwork had a substantial impact on its behaviour. Highly crosslinked meshworks maintained a 'normal' configuration under loading, with stronger resistance to deformation and improved recovery relative to sparsely crosslinked meshwork. Stress on individual fibrils, however, was higher in highly crosslinked meshworks. Meshworks with low numbers of crosslinks reconfigured to disease-like states upon deformation and recovery. The importance of collagen interconnectivity may provide insight into the role of ultrastructure and its mechanics in the initiation, and early stages, of diseases such as osteoarthritis.


Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection.
OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection.


Signatures of seaway closures and founder dispersal in the phylogeny of a circumglobally distributed seahorse lineage.
The importance of vicariance events on the establishment of phylogeographic patterns in the marine environment is well documented, and generally accepted as an important cause of cladogenesis. Founder dispersal (i.e. long-distance dispersal followed by founder effect speciation) is also frequently invoked as a cause of genetic divergence among lineages, but its role has long been challenged by vicariance biogeographers. Founder dispersal is likely to be common in species that colonize remote habitats by means of rafting (e.g. seahorses), as long-distance dispersal events are likely to be rare and subsequent additional recruitment from the source habitat is unlikely. In the present study, the relative importance of vicariance and founder dispersal as causes of cladogenesis in a circumglobally distributed seahorse lineage was investigated using molecular dating. A phylogeny was reconstructed using sequence data from mitochondrial and nuclear markers, and the well-documented closure of the Central American seaway was used as a primary calibration point to test whether other bifurcations in the phylogeny could also have been the result of vicariance events. The feasibility of three other vicariance events was explored: a) the closure of the Indonesian Seaway, resulting in sister lineages associated with the Indian Ocean and West Pacific, respectively; b) the closure of the Tethyan Seaway, resulting in sister lineages associated with the Indo-Pacific and Atlantic Ocean, respectively, and c) continental break-up during the Mesozoic followed by spreading of the Atlantic Ocean, resulting in pairs of lineages with amphi-Atlantic distribution patterns. Comparisons of pairwise genetic distances among the seahorse species hypothesized to have diverged as a result of the closure of the Central American Seaway with those of published teleost sequences having the same distribution patterns show that the seahorses were among the last to diverge. This suggests that their cladogenesis was associated with the final closure of this seaway. Although two other divergence events in the phylogeny could potentially have arisen as a result of the closures of the Indonesian and Tethyan seaways, respectively, the timing of the majority of bifurcations in the phylogeny differed significantly from the dates of vicariance events suggested in the literature. Moreover, several divergence events that resulted in the same distribution patterns of lineages at different positions in the phylogeny did not occur contemporaneously. For that reason, they cannot be the result of the same vicariance events, a result that is independent of molecular dating. Interpretations of the cladogenetic events in the seahorse phylogeny based purely on vicariance biogeographic hypotheses are problematic. We conclude that the evolution of the circumglobally distributed seahorse lineage was strongly influenced by founder dispersal, and suggest that this mode of speciation may be particularly important in marine organisms that lack a pelagic dispersal phase and instead disperse by means of rafting.


The evidence-based use of FFP and cryoprecipitate for abnormalities of coagulation tests and clinical coagulopathy.
There continues to be a general but unfounded enthusiasm for fresh frozen plasma (FFP) or frozen plasma (FP) usage across a range of clinical specialties in hospital practice. Plasma for transfusion is most often used where there are abnormal coagulation screening tests, either therapeutically in the face of bleeding, or prophylactically in nonbleeding patients prior to invasive procedures or surgery. Little evidence exists to inform best therapeutic transfusion practice, and most studies describe plasma use in a prophylactic setting. Laboratory abnormalities of coagulation are considered by many clinicians to be a predictive risk factor for bleeding prior to invasive procedures or in other clinical situations where bleeding risk exists, and plasma for transfusion is presumed to improve the laboratory results and reduce this risk. However, most guideline indications for the prophylactic use of plasma for transfusion are not supported by evidence from good-quality randomized trials. Arguably, the strongest randomized controlled trial (RCT) evidence indicates that prophylactic plasma for transfusion is not effective across a range of different clinical settings, and this is supported by data from nonrandomized studies in patients with mild to moderate abnormalities in coagulation tests. There is a need to undertake new trials evaluating the efficacy and adverse effects of plasma, both in bleeding and non-bleeding patients, to understand whether the presumed benefits outweigh the real risks. In addition, new hemostatic tests that better define the risk of bleeding and monitor the effectiveness of the use of FFP should be validated. Last, there is an opportunity to develop effective educational strategies aimed at addressing understanding and compliance with recommendations in guidelines.


Intensified preparative regimens and allogeneic transplantation in refractory or relapsed intermediate and high grade non-Hodgkin's lymphoma.
Between September 1986 and June 1998, 32 patients with relapsed or refractory intermediate or high grade lymphoma received intensified preparative therapy and underwent allogeneic transplantation at a single institution. Patients were considered for allogeneic transplantation if they failed to respond to initial therapy, failed to respond to salvage therapy, relapsed after autologous transplantation, had bone marrow involvement, or failed attempts to harvest autologous stem cells. Patients had a median age of 39 years and had generally received at least two chemotherapy regimens. Five year actuarial survival (S) was 16% +/- 6%; median survival was 4 months. Survival was significantly worse in patients who had received high intensity brief duration chemotherapy prior to transplantation and was also significantly worse in patients who did not receive total body irradiation (TBI). This likely reflects the fact that the patients with the most resistant disease had required local radiotherapy and could not receive TBI. While treatment related mortality played a major role in limiting the effectiveness of allogeneic transplantation, in this heavily pre-treated population of patients with resistant disease, only 39% of patients achieved a complete response following allogeneic transplantation, and in only 40% of that group was long term disease free survival achieved.


Visual adaptation to goal-directed hand actions.
Prolonged exposure to visual stimuli, or adaptation, often results in an adaptation "aftereffect" which can profoundly distort our perception of subsequent visual stimuli. This technique has been commonly used to investigate mechanisms underlying our perception of simple visual stimuli, and more recently, of static faces. We tested whether humans would adapt to movies of hands grasping and placing different weight objects. After adapting to hands grasping light or heavy objects, subsequently perceived objects appeared relatively heavier, or lighter, respectively. The aftereffects increased logarithmically with adaptation action repetition and decayed logarithmically with time. Adaptation aftereffects also indicated that perception of actions relies predominantly on view-dependent mechanisms. Adapting to one action significantly influenced the perception of the opposite action. These aftereffects can only be explained by adaptation of mechanisms that take into account the presence/absence of the object in the hand. We tested if evidence on action processing mechanisms obtained using visual adaptation techniques confirms underlying neural processing. We recorded monkey superior temporal sulcus (STS) single-cell responses to hand actions. Cells sensitive to grasping or placing typically responded well to the opposite action; cells also responded during different phases of the actions. Cell responses were sensitive to the view of the action and were dependent upon the presence of the object in the scene. We show here that action processing mechanisms established using visual adaptation parallel the neural mechanisms revealed during recording from monkey STS. Visual adaptation techniques can thus be usefully employed to investigate brain mechanisms underlying action perception.


The clinical significance of quality-of-life results: practical considerations for specific audiences.
This is the sixth article in a series intended to summarize the state of the science for assessing the clinical significance of quality-of-life (QOL) assessments. The previous 5 articles dealt with specific methodological issues, whereas this article addresses practical considerations in implementing the methods and presenting the results to various audiences with differing perspectives. Proposals for how to interpret the "clinical significance" or "clinical meaningfulness" of changes in QOL scores were addressed in previous articles within this series. Within this article, 4 audiences-patients and physicians, clinical researchers, health policymakers, and private- and public-sector employees who work in health-related fields-are examined because each is a unique stakeholder with a distinct vantage point and each can interpret QOL outcomes differently. A clinician may attempt to explain to a patient potential treatment alternatives for his or her QOL; a health policymaker may try to describe to elected officials the financial impact on a patient population with reduced QOL; a researcher may try to obtain the vital messages from a clinical trial that included QOL end points; and a regulatory agency and/or pharmaceutical company may try to ascertain the appropriate level of evidence required for a successful research study. For each of the 4 audiences, concrete examples and practical guidelines are offered by which changes in QOL outcomes can be interpreted meaningfully. Ultimately, both determining and disseminating the meaning of clinical significance are functions of the outlook of the audience because the perspective of the audience determines its ability to comprehend, evaluate, and convey the context within which such outcomes appear meaningful. Among the audiences described within this article, a commonality of interests exist that mandates a careful exposition of the scientific rigor involved in describing the clinical significance of QOL assessments. Collectively, this series attempts to provide methods and means for making such determinations.


Food processing and cancer risk in Europe: results from the prospective EPIC cohort study.
Food processing has been hypothesised to play a role in cancer development; however, data from large-scale epidemiological studies are scarce. This study investigated the association between dietary intake according to amount of food processing and risk of cancer at 25 anatomical sites using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This study used data from the prospective EPIC cohort study, which recruited participants between March 18, 1991, and July 2, 2001, from 23 centres in ten European countries. Participant eligibility within each cohort was based on geographical or administrative boundaries. Participants were excluded if they had a cancer diagnosis before recruitment, had missing information for the NOVA food processing classification, or were within the top and bottom 1% for ratio of energy intake to energy requirement. Validated dietary questionnaires were used to obtain information on food and drink consumption. Participants with cancer were identified using cancer registries or during follow-up from a combination of sources, including cancer and pathology centres, health insurance records, and active follow-up of participants. We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional hazard models. 521 324 participants were recruited into EPIC, and 450 111 were included in this analysis (318 686 [70·8%] participants were female individuals and 131 425 [29·2%] were male individuals). In a multivariate model adjusted for sex, smoking, education, physical activity, height, and diabetes, a substitution of 10% of processed foods with an equal amount of minimally processed foods was associated with reduced risk of overall cancer (hazard ratio 0·96, 95% CI 0·95-0·97), head and neck cancers (0·80, 0·75-0·85), oesophageal squamous cell carcinoma (0·57, 0·51-0·64), colon cancer (0·88, 0·85-0·92), rectal cancer (0·90, 0·85-0·94), hepatocellular carcinoma (0·77, 0·68-0·87), and postmenopausal breast cancer (0·93, 0·90-0·97). The substitution of 10% of ultra-processed foods with 10% of minimally processed foods was associated with a reduced risk of head and neck cancers (0·80, 0·74-0·88), colon cancer (0·93, 0·89-0·97), and hepatocellular carcinoma (0·73, 0·62-0·86). Most of these associations remained significant when models were additionally adjusted for BMI, alcohol and dietary intake, and quality. This study suggests that the replacement of processed and ultra-processed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types. Cancer Research UK, l'Institut National du Cancer, and World Cancer Research Fund International.


Is developmental change in gender-typed behavior associated with adult sexual orientation?
The goal of this article was to examine gender-typed behavior longitudinally and to consider its relationship with sexual orientation in adulthood. Data were from 10,624 respondents who completed Wave 1 (adolescence), Wave 3 (emerging adulthood), and Wave 4 (early adulthood) of the National Longitudinal Study of Adolescent to Adult Health. First, we described the distributions of gender-typed behavior by adult sexual orientation at each of the three developmental stages. Next, we performed multilevel mixed regression models to assess longitudinal variation in gender-typed behavior from adolescence to adulthood within sexual orientation groups. Results showed that gender-typed behavior varied both within and between sexual orientation groups, as well as over time. For males, the differences in gender-typed behavior among the sexual orientation groups were relatively consistent at each stage, whereas differences in gender-typed behavior among sexual orientation groups varied more at each stage among females. Longitudinal models exhibited curvilinear patterns, such that gender-typed behavior strengthened from adolescence to early adulthood but peaked in emerging adulthood. To our knowledge, this is the first study to use population representative data to study gender-typed behavior both prospectively and at multiple time points from adolescence to adulthood, and to consider how such behavior is related to adult sexual orientation. This research contributes to a growing body of prospective literature on the link between gendered behavior and sexual orientation and provides further justification for more age- and cohort-specific measures of gender-typed behavior in future research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Bcl6 mediates the development of T follicular helper cells.
A fundamental function of CD4+ helper T (T(H)) cells is the regulation of B cell-mediated humoral immunity. Development of T follicular helper (T(FH)) cells that provide help to B cells is mediated by the cytokines interleukin-6 and interleukin-21 but is independent of TH1, TH2, and TH17 effector cell lineages. Here, we characterize the function of Bcl6, a transcription factor selectively expressed in T(FH) cells. Bcl6 expression is regulated by interleukin-6 and interleukin-21. Bcl6 overexpression induced T(FH)-related gene expression and inhibited other T(H) lineage cell differentiation in a DNA binding-dependent manner. Moreover, Bcl6 deficiency in T cells resulted in impaired T(FH) cell development and germinal center reactions, and altered production of other effector T cell subsets. Our data thus illustrate that Bcl6 is required for programming of T(FH) cell generation.


Cellular analogs of visual cortical epigenesis. I. Plasticity of orientation selectivity.
A differential pairing procedure was applied in vivo to individual neurons in the primary visual cortex of anesthetized paralyzed cats, in order to produce changes in their relative orientation preference. While we recorded from a single cell, its visual response to a light bar was driven iontophoretically to a "high" level when stimulating with an initially nonpreferred orientation (S+), and alternately reduced to a "low" level when stimulating with the preferred orientation (S). This associative procedure was devised to test the possible role of neuronal coactivity in controlling the plasticity of orientation selectivity. Among 87 cells tested, 35 (40%) showed significant long-lasting changes, either in the relative orientation preference for the two "paired" stimuli S+ and S-, in the global orientation tuning profile, or in both. Measurements of relative orientation preference demonstrated significant effects in 27 cells (31%), all in favor of the positively reinforced orientation (S+). Modifications of orientation selectivity (studied over the entire orientation spectrum in 45 of the conditioned cells) usually consisted (21 out of 25 modified cells) of a competitive reorganization of the orientation tuning curve: the preferred orientation shifted toward S+, and a loss of relative visual responsiveness was observed for orientations close to the negatively reinforced orientation (S-). The largest changes were found in deprived kittens at the peak of the critical period, although the probability of inducing a significant change studied during the first year of postnatal life was independent of age. These functional modifications demonstrated at the cellular level are analogous to those induced by a global manipulation of the visual environment, when only a restricted spectrum of orientations is experienced during the critical period. Our results support the hypothesis that covariance levels between pre- and postsynaptic activity determine the sign and the amplitude of the modification of efficacy of cortical synapses.


Long-Term Skeletal Muscle Mitochondrial Dysfunction is Associated with Hypermetabolism in Severely Burned Children.
The long-term impact of burn trauma on skeletal muscle bioenergetics remains unknown. Here, the authors determined respiratory capacity and function of skeletal muscle mitochondria in healthy individuals and in burn victims for up to 2 years postinjury. Biopsies were collected from the m. vastus lateralis of 16 healthy men (26 ± 4 years) and 69 children (8 ± 5 years) with burns encompassing ≥30% of their total BSA. Seventy-nine biopsies were collected from cohorts of burn victims at 2 weeks (n = 18), 6 months (n = 18), 12 months (n = 25), and 24 months (n = 18) postburn. Hypermetabolism was determined by the difference in predicted and measured metabolic rate. Mitochondrial respiration was determined in saponin-permeabilized myofiber bundles. Outcomes were modeled by analysis of variance, with differences in groups assessed by Tukey-adjusted contrasts. Burn patients were hypermetabolic for up to 2 years postinjury. Coupled mitochondrial respiration was lower at 2 weeks (17 [8] pmol/sec/mg; P < .001), 6 months (41 [30] pmol/sec/mg; P = .03), and 12 months (35 [14] pmol/sec/mg; P < .001) postburn compared with healthy controls (58 [13] pmol/sec/mg). Coupled respiration was greater at 6, 12, and 24 months postburn vs 2 weeks postburn (P < .001). Mitochondrial adenosine diphosphate and oligomycin sensitivity (measures of coupling control) were lower at all time-points postburn vs control (P < .05), but greater at 6, 12, and 24 months postburn vs 2 weeks postburn (P < .05). Muscle mitochondrial respiratory capacity remains significantly lower in burn victims for 1-year postinjury. Mitochondrial coupling control is diminished for up to 2 years postinjury in burn victims, resulting in greater mitochondrial thermogenesis. These quantitative and qualitative derangements in skeletal muscle bioenergetics likely contribute to the long-term pathophysiological stress response to burn trauma.


Cardiac Effects of Mad Honey Poisoning and Its Management in Emergency Department: A Review from Turkey.
Mad honey poisoning occurs when honey containing grayanotoxin is digested. The most common clinical signs and symptoms of poisoning involve findings of digestive system irritation, severe bradycardia and hypotension and central nervous system reaction. In this review, we aimed to underline the cardiac effects of mad honey poisoning. We also aimed to raise the awareness of physicians about early diagnosis and treatment of this rare entity.


A randomised controlled trial of the effect of laryngeal mask airway manometry on postoperative sore throat in spontaneously breathing adult patients presenting for surgery at a university teaching hospital.
Laryngeal mask airways (LMAs) are widely used in anaesthesia and are considered to be generally safe. Postoperative sore throat (POST) is a frequent complication following LMA use and can be very distressing to patients. The use of an LMA cuff pressure of between 30 and 32cm of H2O in alleviating post-operative sore throat has not been investigated. To compare the occurrence of POST between the intervention group in which LMA cuff pressures were adjusted to 30-32cm of H2O and the control group in which only monitoring of LMA cuff pressures was done, to compare the severity of POST between the two study groups and to compare the LMA cuff pressures between the two study groups. Eighty consenting adult patients scheduled to receive general anaesthesia with use of an LMA were randomized into two groups of 40 patients each. Intervention group: LMA airway cuff pressures were adjusted to 30 to 32cm of H2O. Control group: Only had LMA cuff pressures monitored throughout the surgery. All patients were interviewed postoperatively at two, six and twelve hours. Data of their baseline characteristics, occurrence and severity of POST was collected. If POST was present; a Numerical Rating Scale (NRS) was used to assess the severity. Cuff pressures between the two study groups were also determined. The baseline demographic characteristics of the participants were similar. The use of manometry to limit LMA AMBU® AuraOnce™ intracuff pressure to 30-32cm H2O reduced POST in surgical patient's by 62% at 2 hours and 6 hours (Risk Ratio 0.38 95%CI 0.21-0.69)in the intervention group. The median POST pain score in the intervention group was significantly lower than the control group with scores of 0 at 2, 6 and 12 hours post operatively. Routine practice of LMA cuff inflation by anesthesiologists is variable, and the intracuff pressures in the control group were higher than in the intervention group. (P<0.001). Among this population, reduction of LMA AMBU® AuraOnce™ intracuff pressure to 30-32cm H2O reduces the occurrence and severity of POST. The LMA cuff pressures should be measured routinely using manometry and reducing the intracuff pressures to 30-32 cm of H2O recommended as best practice.


Neutralization of IFNgamma defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice.
Hereditary haemophagocytic lymphohistiocytosis (HLH) is a fatal inflammatory disease and treatments currently may lead to serious side effects. There is a pressing need for effective, less toxic treatments for this disease. Previous reports have suggested that interferon gamma (IFNgamma) has a role in the pathogenesis of HLH. Here, we report that blocking IFNgamma had a therapeutic effect in two different murine models of human hereditary HLH (perforin-deficient and Rab27a-deficient mice, both infected with lymphocytic choriomeningitis virus). Therapeutic administration of an anti-IFNgamma antibody induced recovery from haemophagocytosis in both genetic models, as evidenced by increased survival in perforin-deficient mice and correction of blood cytopenia, moderation of body temperature changes, decreased cytokinaemia, restoration of splenic architecture and reduced haemophagocytosis in the liver of both murine models. Involvement of the central nervous system in Rab27a-deficient mice was prevented by anti-IFNgamma therapy. Hepatic T-cell infiltrates and virus persisted, with no detectable harm during the time course of these studies. These data strongly suggest that neutralization of IFNgamma could be used in humans to safely alleviate the clinical manifestations of haemophagocytosis.


Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of Saccharomyces cerevisiae.
Exonuclease I was originally identified as a 5' --> 3' deoxyribonuclease present in fractionated extracts of Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genetic analysis of exo1 mutants of both yeasts revealed no major defect in meiosis, suggesting that exonuclease I is unlikely to be the primary activity that processes meiosis-specific double-strand breaks (DSBs). We report here that exo1 mutants of S. cerevisiae exhibit subtle but complex defects in meiosis. Diploids containing a homozygous deletion of EXO1 show decreased spore viability associated with an increase in meiosis I nondisjunction, while intergenic recombination is reduced about twofold. Exo1p functions in the same pathway as Msh5p for intergenic recombination. The length of heteroduplex tracts within the HIS4 gene is unaffected by the exo1 mutation. These results suggest that Exo1p is unlikely to play a major role in processing DSBs to form single-stranded tails at HIS4, but instead appears to promote crossing over to ensure disjunction of homologous chromosomes. In addition, our data indicate that exonuclease I may have a minor role in the correction of large DNA mismatches that occur in heteroduplex DNA during meiotic recombination at the HIS4 locus.


Predictors and outcomes of acute respiratory failure in hospitalised patients with acute pancreatitis.
Acute pancreatitis (AP) is associated with organ failures and systemic complications, most commonly acute respiratory failure (ARF) and acute kidney injury. So far, no studies have analysed the predictors and hospitalisation outcomes, of patients with AP who developed ARF. The aim of this study was to measure the prevalence of ARF in AP and to determine the clinical predictors for ARF and mortality in AP. This is a retrospective cohort study using the Nationwide Inpatient Sample database from the year 2005-2014. The study population consisted of all hospitalisations with a primary or secondary discharge diagnosis of AP, which is further stratified based on the presence of ARF. The outcome measures include in-hospital mortality, hospital length of stay and hospitalisation cost. In our study, about 5.4% of patients with AP had a codiagnosis of ARF, with a mortality rate of 26.5%. The significant predictors for ARF include sepsis, pleural effusion, pneumonia and cardiogenic shock. Key variables that were associated with a higher risk of mortality include mechanical ventilation, age more than 65 years, sepsis and cancer (excluding pancreatic cancer). The presence of ARF increased hospital stay by 8.3 days and hospitalisation charges by US$103 460. In this study, we demonstrate that ARF is a significant risk factor for increased hospital mortality, greater length of stay and higher hospitalisation charges in patients with AP. This underlines significantly higher resource utilisation in patients with a dual diagnosis of AP-ARF.


Chemical communication and host search in Galerucella leaf beetles.
Herbivore insects use a variety of search cues during host finding and mate recognition, including visual, gustatory, and olfactory stimuli, leaving multiple traits for evolution to act upon. However, information about differences or similarities in search pattern amongst closely related insect herbivore species is still scarce. Here, we study the production of and the response to pheromone in Galerucella (Coleoptera: Chrysomelidae) to investigate the beetles' search behaviour. Males of G. pusilla and G. calmariensis, two closely related species, are known to produce the aggregation pheromone dimethylfuran-lactone when feeding on their host plant, whereas no pheromones have been identified in other Galerucella species. We show that dimethylfuran-lactone is produced also by males of G. tenella, a species phylogenetically close to G. pusilla and G. calmariensis, whereas the more distantly related species G. lineola and G. sagittariae were not found to produce the same compound. To investigate the beetles' behavioural response to dimethylfuran-lactone, the pheromone was synthesized using a partly novel method and tested in olfactometers, showing that G. pusilla, G. calmariensis, and G. tenella were all attracted to the pheromone, whereas G. lineola and G. sagittariae did not respond. This suggests that the production of and the response to pheromone could be linked to the phylogenetic relatedness between the species.


Diffusion of multiple species with excluded-volume effects.
Stochastic models of diffusion with excluded-volume effects are used to model many biological and physical systems at a discrete level. The average properties of the population may be described by a continuum model based on partial differential equations. In this paper we consider multiple interacting subpopulations/species and study how the inter-species competition emerges at the population level. Each individual is described as a finite-size hard core interacting particle undergoing brownian motion. The link between the discrete stochastic equations of motion and the continuum model is considered systematically using the method of matched asymptotic expansions. The system for two species leads to a nonlinear cross-diffusion system for each subpopulation, which captures the enhancement of the effective diffusion rate due to excluded-volume interactions between particles of the same species, and the diminishment due to particles of the other species. This model can explain two alternative notions of the diffusion coefficient that are often confounded, namely collective diffusion and self-diffusion. Simulations of the discrete system show good agreement with the analytic results.


Attentional modulation of unconscious "automatic" processes: evidence from event-related potentials in a masked priming paradigm.
Automatic processes are usually thought to occur independently of any cognitive resources. This traditional view has been recently challenged by showing that temporal attention to a target stimulus is a prerequisite for "automatic" response priming. The event-related potential (ERP) study reported here extends this research by pursuing a somewhat different approach. In two experiments, it was investigated whether masked semantic priming effects can be modulated by temporal attention to the prime using a cueing procedure. We hypothesized that masked priming is amplified when attention is directed to the stimulus stream in the time window of masked prime presentation, even in the absence of any prime awareness. ERPs were recorded while subjects performed a primed lexical decision task. Target words were preceded by semantically related or unrelated masked prime words, which were not consciously identified. A cue stimulus prompted subjects to direct their attention to the stimulus stream either shortly before the masked prime (short cue interval) or a long time interval before. Priming affected the amplitude of the N400 ERP component, an electrophysiological index of semantic processing. Unrelated prime-target pairs elicited a larger N400 than related pairs (N400 priming effect). Most importantly, this masked N400 priming effect was strongest when the cue interval and the stimulus onset asynchronies were short. The present results show that temporal attention to the prime is a prerequisite for obtaining masked N400 priming effects. They also demonstrate that unconscious automatic processes are susceptible to attentional modulation.


Long-Read Single Molecule Sequencing to Resolve Tandem Gene Copies: The Mst77Y Region on the Drosophila melanogaster Y Chromosome.
The autosomal gene Mst77F of Drosophila melanogaster is essential for male fertility. In 2010, Krsticevic et al. (Genetics 184: 295-307) found 18 Y-linked copies of Mst77F ("Mst77Y"), which collectively account for 20% of the functional Mst77F-like mRNA. The Mst77Y genes were severely misassembled in the then-available genome assembly and were identified by cloning and sequencing polymerase chain reaction products. The genomic structure of the Mst77Y region and the possible existence of additional copies remained unknown. The recent publication of two long-read assemblies of D. melanogaster prompted us to reinvestigate this challenging region of the Y chromosome. We found that the Illumina Synthetic Long Reads assembly failed in the Mst77Y region, most likely because of its tandem duplication structure. The PacBio MHAP assembly of the Mst77Y region seems to be very accurate, as revealed by comparisons with the previously found Mst77Y genes, a bacterial artificial chromosome sequence, and Illumina reads of the same strain. We found that the Mst77Y region spans 96 kb and originated from a 3.4-kb transposition from chromosome 3L to the Y chromosome, followed by tandem duplications inside the Y chromosome and invasion of transposable elements, which account for 48% of its length. Twelve of the 18 Mst77Y genes found in 2010 were confirmed in the PacBio assembly, the remaining six being polymerase chain reaction-induced artifacts. There are several identical copies of some Mst77Y genes, coincidentally bringing the total copy number to 18. Besides providing a detailed picture of the Mst77Y region, our results highlight the utility of PacBio technology in assembling difficult genomic regions such as tandemly repeated genes.