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Founder populations are of special interest to both evolutionary and conservation biologists, but the detection of genetic signals of selection in these populations is challenging due to their demographic history. Geographically separated founder populations likely to have been subjected to similar selection pressures provide an ideal but rare opportunity to overcome these challenges. Here we take advantage of such a situation generated when small, isolated founder populations of reindeer were established on the island of South Georgia, and using this system we look for empirical evidence of selection overcoming strong genetic drift. We generated a 70 k ddRADseq single nucleotide polymorphism database for the two parallel reindeer founder populations and screened for signatures of soft sweeps. We find evidence for a genomic region under selection shared among the two populations, and support our findings with Wright–Fisher model simulations to assess the power and specificity of interpopulation selection scans—namely Bayescan, OutFLANK, PCadapt and a newly developed scan called Genome Wide Differentiation Scan (GWDS)—in the context of pairwise source–founder comparisons. Our simulations indicate that loci under selection in small founder populations are most probably detected by GWDS, and strengthen the hypothesis that the outlier region represents a true locus under selection. We explore possible, relevant functional roles for genes in linkage with the detected outlier loci.

To foster teamwork, improve clinical excellence, and promote a culture of safety, perioperative leaders should have a clear understanding of the dynamics that affect clinician communication in the OR. We used social network analysis to characterize the typical OR clinician communication patterns at a military surgery center and determine how clinician relationships influenced individual behavior. We surveyed 50 surgical teams and used the data to develop six relational networks and a clinician communication effectiveness index. The study results showed that communication effectiveness increased in networks in which clinicians reported interacting frequently, having close working relationships, socializing, and seeking advice and providing advice to others. Increases in individual clinician centrality were associated with increased communication effectiveness. Participants rated anesthesia professionals as the most effective communicators, followed by perioperative nurses, surgeons, and surgical technologists. Perioperative leaders should consider surgical team familiarity as a potential option to optimize surgical care and improve communication effectiveness.

Contains fulltext : 203443.pdf (Publisher’s version ) (Open Access) Introduction and Aims: Cognitive impairments in substance use disorder predict treatment outcome and are assumed to differ between substances. They often go undetected, thus the current study focuses on the prevalence of and differences in cognitive functioning across substances by means of a cognitive screen at the early stage of addiction treatment. Design and Methods: The Montreal Cognitive Assessment was administered to outpatients seeking treatment for substance use disorder. Patient characteristics (age, years of regular use, polysubstance use, severity of dependence/abuse, depression, anxiety and stress) were also taken into account. Results: A total of 656 patients were included (n = 391 used alcohol, n = 123 used cannabis, n = 100 used stimulants and n = 26 used opioids). The prevalence of cognitive impairments was 31%. Patients using alcohol had a lower total- and memory domain score than those using cannabis. Patients using opioids scored lower on visuospatial abilities than those using cannabis or stimulants. Younger patients scored higher than older patients. No effect was found for the other investigated characteristics. Discussion and Conclusions: Given the high prevalence of cognitive impairments, standard screening at an early stage of treatment is important to determine the course of treatment and maximise treatment outcome. Caution is needed in interpreting results about opioids due to an underrepresentation of this patient group, and more research is needed on the effect of age on Montreal Cognitive Assessment performance. 8 p.

SNP data sets can be used to infer a wealth of information about natural populations, including information about their structure, genetic diversity, and the presence of loci under selection. However, SNP data analysis can be a time-consuming and challenging process, not in the least because at present many different software packages are needed to execute and depict the wide variety of mainstream population-genetic analyses. Here, we present SambaR, an integrative and user-friendly R package which automates and simplifies quality control and population-genetic analyses of biallelic SNP data sets. SambaR allows users to perform mainstream population-genetic analyses and to generate a wide variety of ready to publish graphs with a minimum number of commands (less than 10). These wrapper commands call functions of existing packages (including adegenet, ape, LEA, poppr, pcadapt and StAMPP) as well as new tools uniquely implemented in SambaR. We tested SambaR on online available SNP data sets and found that SambaR can process data sets of over 100,000 SNPs and hundreds of individuals within hours, given sufficient computing power. Newly developed tools implemented in SambaR facilitate optimization of filter settings, objective interpretation of ordination analyses, enhance comparability of diversity estimates from reduced representation library SNP data sets, and generate reduced SNP panels and structure-like plots with Bayesian population assignment probabilities. SambaR facilitates rapid population genetic analyses on biallelic SNP data sets by removing three major time sinks: file handling, software learning, and data plotting. In addition, SambaR provides a convenient platform for SNP data storage and management, as well as several new utilities, including guidance in setting appropriate data filters. The SambaR source script, manual and example data set are distributed through GitHub: https://github.com/mennodejong1986/SambaR.

Background and aim Biologicals are potent drugs for immune mediated inflammatory diseases (IMIDs). After discontinuation or switch of therapy, many patients have unused biological injectors left. We aimed to evaluate potential redistribution of unused injectors to prevent spillage of these costly drugs by assessing 1) the quality of transport and home storage through the proportion of injectors stored within the recommended temperature range (2°C-8°C) and 2) acceptance of redistribution by patients. Methods All golimumab users, irrespective of the indication, at Maastricht University Medical Center were eligible for inclusion. Patients received golimumab in a sealed bag containing a validated temperature sensor, measuring temperature every 5 minutes. Patients were asked to store their medication as usual. Deviations from the recommended range were defined as any duration below 0°C and >30 minutes below 2°C or above 8°C. After 3 months, patients completed a questionnaire on their opinion towards potential redistribution of unused biologicals. Results Fifty patients (42.0% male, mean age 53.2±14.3 years) received 276 injectors. The mean storage time was 30.9±33.1 days. Only 11.6% of the injectors were stored within the recommended temperature range. In addition, 11.2% were stored >30 minutes below 0°C and 33.2% were stored > 1 week above 8°C. Of all patients, 95% would accept redistributed medication when product quality is ensured. conclusions During transport and home-storage, only one in eight biological injectors was stored within the recommended temperature range. This hinders redistribution of unused injectors, but also raises concern regarding drug effectiveness in IMID-patients.

Summary Crossings between the diploid wild Brassica rapa (AA, 2n=20) and the tetraploid cultivar B. napus (AACC, 2n=38) can readily be made. Backcrosses to the wild B. rapa (BC1) produce aneuploids with variable chromosome numbers between 20 and 29. How does survival and performance relate to DNA content of plants? Growth of the BC1 plants was measured in the lab. One plant in the F1 self-pollinated spontaneously and produced abundant F2 seeds that were also examined. The number of C-chromosomes was estimated from DNA-values obtained with flow cytometry. Average DNA value of the BC1 was similar to that of the parents, which shows that C-chromosomes do not reduce success of pollen or embryos. The average DNA value in the F2 was 13% higher than in the F1, suggesting that extra C-chromosomes facilitated gamete success and/or embryo survival. Under both optimal and drought stress conditions growth and survival of BC1 hybrids was similar to that of B. rapa. No significant correlations existed between growth or survival and DNA value. Aneuploid plants were not inferior under the conditions of the growth room and may persist in nature. We discuss other factors, such as herbivory, that could prevent hybrid establishment in the field. This article is protected by copyright. All rights reserved.

Increasing evidence shows that sensitivity to reward (SR) and punishment (SP) may be involved in eating disorders (EDs). Most studies used self-reported positive/negative effect in rewarding/punishing situations, whereas the implied proneness to detect signals of reward/punishment is largely ignored. This pilot study used a spatial orientation task to examine transdiagnostic and interdiagnostic differences in SR/SP. Participants (14-29 years) were patients with anorexia nervosa of restricting type (AN-R, n = 20), binge/purge ED group [AN of binge/purge type and bulimia nervosa (n = 16)] and non-symptomatic individuals (n = 23). Results revealed stronger difficulties to redirect attention away from signals of rewards in AN-R compared with binge/purge EDs, and binge/purge EDs showed stronger difficulties to direct attention away from signals of punishment compared with AN-R. Findings demonstrate interdiagnostic differences and show that the spatial orientation task is sensitive for individual differences in SP/SR within the context of EDs, thereby sustaining its usefulness as behavioural measure of reinforcement sensitivity. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Slugs feed on some plant species but not on others for reasons that are not yet fully understood. We re-examined the two largest studies on the preference of Arion lusitanicus for different plant species. Briner & Frank (1998) measured the consumption index of slugs (CIB) based on the dry leaf mass eaten per day per gram of slug mass. Kozlowski & Kozlowska (2009) also measured a consumption index of slugs (CIK) but on the basis of the area eaten per day per gram of slug mass. The two indices showed a moderate positive rank correlation. Briner & Frank (1998) found that slugs preferred annual to perennial plants and crops rather than wild species. On the other hand, Kozlowski & Kozlowska (2009) found no statistically significant difference in slug preference for annuals, biennials or perennials. Using botanical databases we selected plant traits related to slug herbivory and analysed 141 species. We first analysed the two data sets separately and found that CIB was higher for seedlings with a higher relative growth rate although this result was only marginally statistically significant. In addition, we found that annuals were consumed more than perennials and that cultivated plants were consumed more than wild plants. This is in agreement with the conclusions of Briner & Frank (1998). For CIK slugs consumed less from plants with high dry matter content (DMC). The use of classification and regression tree models solves the problem of analysing datasets with missing values. Regarding CIB, the tree models indicated that life cycle was the major branch. Within perennials, cultivated/wild origin of plants was the most important predictor of slug feeding. Within wild perennials slugs ate more from plants with low specific leaf area (SLA), i.e. relatively thick leaves. Within annuals we found the unexpected result that slugs ate more from plant species with either alkaloids or glucosinolates than from species without one of these compounds. For CIK, the results of tree models showed that slugs preferred shade-intolerant plants to shade-tolerant plant species. Within the shade-tolerant group slugs fed more on leaves with low DMC. We only partially understand which factors make plants acceptable to slugs. We discuss this issue along with the pros and cons of the two methods used to calculate CI.

CE-MS can be considered a useful analytical technique for the global profiling of (highly) polar and charged metabolites in various samples. Over the past few years, significant advancements have been made in CE-MS approaches for metabolomics studies. In this paper, which is a follow-up of a previous review paper covering the years 2012-2014 (Electrophoresis 2015, 36, 212-224), recent CE-MS strategies developed for metabolomics covering the literature from July 2014 to June 2016 are outlined. Attention will be paid to new CE-MS approaches for the profiling of anionic metabolites and the potential of SPE coupled to CE-MS is also demonstrated. Representative examples illustrate the applicability of CE-MS in the fields of biomedical, clinical, microbial, plant, and food metabolomics. A complete overview of recent CE-MS-based metabolomics studies is given in a table, which provides information on sample type and pretreatment, capillary coatings, and MS detection mode. Finally, general conclusions and perspectives are given.

An overview of the design and application of coupled solid-phase extraction-capillary electrophoresis (SPE-CE) systems reported in the literature between July 2013 and June 2015 is provided in this paper. The present article is a continuation of our previous review papers on this topic which covered the time period 2000-2013 (Electrophoresis 2008, 29, 108-128; Electrophoresis 2010, 31, 44-54; Electrophoresis 2012, 33, 243-250; Electrophoresis 2014, 35, 128-137). The use of in-line and on-line SPE-CE approaches is treated and outlined in this review. Recent advancements, such as, for example, the use of aptamers as affinity material for in-line SPE-CE, the use of a bead string design for in-line fritless SPE-CE, and new interfacing techniques for the on-line coupling of SPE to CE, are outlined. Selected examples demonstrate the applicability of the coupled SPE-CE systems for biomedical, pharmaceutical, environmental, and food studies. A complete overview of the recent SPE-CE studies is given in table format, providing information on sample type, SPE sorbent, coupling mode, detection mode, and LOD. Finally, some general conclusions and perspectives are provided.

BACKGROUND. Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.8-39.1% of patients previously treated with docetaxel (Doc) and AA do respond to Enz. These responders have not been characterized. METHODS. 102 Enz treated mCRPC patients after AA and Doc treatment were included in this study. Differences in patient characteristics and previous treatment outcomes between PSA responders and non-responders on Enz were evaluated. RESULTS. Median Progression-Free Survival was 12.2 weeks (95% CI 11.7-14.3) and Overall Survival 43.5 weeks (95% CI 37.4-61.2). There were 26 (25%) Enz-responders and 76 (75%) non-responders. Significant higher percentages of Gleason scores >= 8 and PSA doubling times (PSA-DT) = 40 (68 patients) revealed significant differences in baseline PSA levels, PSA-DT = 8 and IAE's between Enz responders and non-responders. CONCLUSIONS. PSA response to Enz after previous AA and Doc treatment was associated with a longer IAE, a higher Gleason score and a PSA-DT

Blushing-fearful individuals often expect that others will judge them negatively. In two studies, we tested if this could be explained by having relatively strict beliefs about what is appropriate social behaviour. Study 1 used a student sample (n = 74), whereas study 2 compared a clinical treatment-seeking sample of blushing-fearful individuals (n = 33) with a non-anxious control group (n = 31). In both studies, participants were asked to read descriptions of common behaviours that could be considered as breaching the prevailing social norms but not necessarily so. Participants indicated (i) to what extent they considered these behaviours as violating the prevailing norm and (ii) their expectation of observers' judgments. Study 1 showed that strict norms were indeed related to fear of blushing and that the tendency of fearful participants to expect negative judgments could at least partly explain this relationship. Study 2 showed that high-fearful and low-fearful individuals do indeed differ in the strictness of their norms and that especially the norms that individuals apply to themselves might be relevant. These findings may provide fresh clues for improving available treatment options. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Messages Blushing-fearful individuals attribute relatively strict social norms to other people about which behaviours are appropriate and which are not and have stricter personal norms as well. Blushing-fearful individuals' tendency to expect overly negative judgments in ambivalent social situations can partly be explained by their relatively strict social norms. Having relatively strict social norms may (also) explain why blushing-fearful individuals report to blush often and intensely. It may be worthwhile to address strict social norms in therapy for fear of blushing.

Mainstream teachers throughout the world are increasingly expected to differentiate instruction for primary-grade students with diverse learning needs, including second or English language learners (ELLs). Does teacher preparation translate into instructional practices for English language development? What do graduates of those programs do differently, if anything, for ELLs in their classrooms? This mixed-methods study examined the beliefs and practices of two focal teacher graduates of a teacher preparation program that included second language training. Findings show that teacher graduates working with ELLs in primary classrooms with low numbers of ELLs used some generic accommodation strategies and just-in-time scaffolding techniques, but they rarely instituted specific ELL practices to facilitate the English language development of ELLs. The authors discuss implications for second language educators.

In the field of metabolomics, CE-MS is now regarded as a useful complementary analytical technique for the profiling of (highly) polar ionogenic metabolites in biological samples. Over the past few years, significant advancements have been made in CE-MS approaches for metabolic profiling studies. This paper, which is a follow-up of three previous review papers covering the years 2000-2012 [Electrophoresis 2009, 30, 276-291; Electrophoresis 2011, 32, 52-65; Electrophoresis 2013, 34, 86-98], provides an update of these developments covering the scientific literature from July 2012 to June 2014. Attention will be paid to novel interfacing techniques for coupling CE to MS and their implications for metabolomics studies. The potential of CEC-MS and MEKC-MS are also considered, and CE-MS systems for high-throughput metabolic profiling are discussed. The applicability of CE-MS for metabolomics studies is demonstrated by representative examples in the fields of biomedical, clinical, microbial, plant, environmental, and food metabolomics. An overview of recent CE-MS-based metabolomics studies is given in a table, which provides information on sample type and pretreatment, capillary coatings, and MS detection mode. Finally, general conclusions and perspectives are given.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Infliximab is an effective treatment for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis and national and international guidelines have been developed for each indication. WHAT THIS STUDY ADDS: This study is the first study which compared current international, national and local guidelines from the medical specialties involved in the treatment with infliximab on the following topics: indication, dosage, synergy and monitoring of vital signs. AIMS: Infliximab, an anti-TNF biologic agent, is currently indicated and reimbursed for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis. Development of national and international guidelines for rheumatology, gastroenterology and dermatology, was mostly based on clinical studies and expert opinion. The aim of this study was to compare available guidelines and local protocols for rheumatology, dermatology and gastroenterology, regarding dosage of infliximab, synergy of infliximab with concomitant medication and monitoring of vital signs during infliximab administration, for achieving optimal care. METHODS: Current international, national and local guidelines on the use of infliximab were reviewed and compared, differences and shortcomings were identified, and optimal treatment schedules discussed during a meeting (July 2008) of clinical experts and researchers from three departments of a Dutch university hospital. RESULTS: Recommended dosages of infliximab are not equal for different indications. Loss of response to infliximab is a common problem encountered within the three medical specialties, but indications for adjustments in treatment schedules are lacking in all of the guidelines. Monitoring of vital signs (blood pressure, pulse, temperature) during infusion with infliximab is common practice and recommended by some guidelines. Routine measurement of vital signs is not of any value in predicting or recognizing acute infusion reactions, in our experience, and this is confirmed by literature on inflammatory bowel disease. CONCLUSION: Different indications encompass different dosing schedules. National and internal guidelines do not provide advice regarding loss of response. Routine measurement of vital signs during infusion is not valuable in detecting acute infusion reactions and should only be performed in case of an acute infusion reaction. These topics need to be studied in future studies and covered in future guidelines.

Background: Cognitive–behavioural models of chronic pain predict that dysfunctional assumptions about harmfulness of activities may maintain pain-related fear and disability. To assess perceived harmfulness in adolescents, the Photograph Series of Daily Activities for youth (PHODA-youth) was developed. Information concerning its methodological quality is currently lacking. Objective: To investigate psychometric characteristics (factor structure, test–retest reliability, construct validity) and feasibility of the PHODA-youth in adolescents with chronic musculoskeletal pain. Study design: Test–retest design. Study population: Adolescents aged 13–21 years with chronic nonspecific musculoskeletal pain. Methods: Participants filled in an electronic version of the PHODA-youth including 89 items twice with a 4-week interval. The instrument’s factor structure was determined by a factor analysis. Construct validity was studied with criterion variables: catastrophizing (Pain Catastrophizing Scale for Children), pain intensity (visual analogue scale), depression (Children’s Depression Inventory) and pain-related disability (Functional Disability Inventory) using regression analysis. Test–retest reliability was evaluated based on the Pearson correlation coefficient. Feasibility was studied with self-constructed questions. Results: Seventy-one adolescents participated. Results show a three-factor structure for the PHODA-youth including 51 items with subscales labelled as: ‘activities of daily life’, ‘intensive physical activities’ and ‘social activities’. Total and subscale scores showed a high internal consistency. Its test–retest reliability was good (r = 0.94) and its construct validity is supported by the finding that both catastrophizing ( β= 0.25; p = 0.02) and disability ( β= 0.71; p < 0.001) were uniquely related to the PHODA-youth. In addition, feasibility appeared adequate. Conclusion: The findings support the PHODA-youth as a valid and reliable measure of the perceived harmfulness of activities in adolescents with musculoskeletal pain.

Our study assessed whether rising age, socioeconomic status (SES) and the presence of serious comorbidity affected treatment choice and survival in a population-based series of patients with muscle-invasive bladder cancer (MIBC) in The Netherlands. Therefore, a consecutive series was studied, including all patients diagnosed with MIBC between 1995 and 2009 in the Eindhoven Cancer Registry, preceding centralization of cystectomy. The independent effects of age, SES and serious comorbidity on therapy choice and their effects on overall survival were estimated by multivariate logistic regression and multivariate Cox proportional hazard analyses, respectively. Out of the 2,445 patients, 38% were aged ≥ 75 years at diagnosis and 63% had at least one serious comorbid condition. Higher age and serious comorbidity were independent predictors for abstaining from cystectomy, where SES was not (61-74 vs. ≤ 60: odds ratio [OR], 0.8; 95% confidence interval [CI], 0.6-1.0; ≥ 75 vs. ≤ 60: OR, 0.1; 95% CI,0.1-0.2; one comorbid condition vs. none: OR, 0.7; 95% CI, 0.5-0.9; two vs. none: OR, 0.6; 95% CI, 0.5-0.8). Patients undergoing cystectomy, external beam radiotherapy or interstitial radiotherapy survived longer independent of age, SES and serious comorbidity (hazard ratio [HR]: 0.4; 95% CI: 0.4-0.5; HR: 0.8; 95% CI: 0.7-0.9; HR: 0.4; 95% CI: 0.3-0.5, respectively). Consequently, preceding centralization of cystectomy, higher age and serious comorbidity were independent predictors for abstaining from cystectomy owing to an expected high rate of short-term medical problems. As cystectomy is associated with a better survival, independently of age, SES and serious comorbidity, it can be questioned whether cystectomy has been underutilised in elderly and in patients with serious comorbidity. Centralization might be a solution for this suggested underutilisation.

BACKGROUND: Enzalutamide (Enz) and abiraterone acetate (AA) are hormone treatments that have a proven survival advantage in patients with metastatic, castration-resistant prostate cancer who previously received docetaxel (Doc). Recently, limited activity of AA after Enz and of Enz after AA was demonstrated in small cohort studies. Here, the authors present the activity and tolerability of Enz in patients who previously received AA and Doc in the largest cohort to date. METHODS: The efficacy and tolerability of Enz were investigated in men with progressive, metastatic, castrate-resistant prostate cancer who previously received Doc and AA. Toxicity, progression-free survival, time to prostate-specific antigen (PSA) progression, and overall survival were retrospectively evaluated. RESULTS: Sixty-one patients were included in the analysis. The median age was 69 years (interquartile range [IQR], 64-74 years), 57 patients (93%) had an Eastern Cooperative Oncology Group performance status from 0 to 2, 48 patients (79%) had bone metastases, 33 patients (54%) had lymph node metastases, and 13 patients (21%) had visceral metastases. The median duration of Enz treatment was 14.9 weeks (IQR, 11.1-20.0 weeks), and 13 patients (21%) had a maximum PSA decline >/=50%. The median progression-free survival was 12.0 weeks (95% confidence interval [CI], 11.1-16.0 weeks), the median time to PSA progression was 17.4 weeks (95% CI, >16.0 weeks), and the median overall survival was 31.6 weeks (95% CI, >28.7 weeks). Enz was well tolerated, and fatigue and musculoskeletal pain were the most frequent grade >/=2 adverse events. The PSA response to Doc and AA did not predict the PSA response to Enz. CONCLUSIONS: Enz has modest clinical activity in patients with metastatic, castrate-resistant prostate cancer who previously received Doc and AA. PSA response to Doc and AA does not predict for PSA response to ENz. Cancer 2014;120:968-975. (c) 2013 American Cancer Society.

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This article presents an overview of the design and application of coupled SPE-CE systems that have been reported in the literature between January 2011 and June 2013. The present paper is an update of three previous review papers covering the years 2000-2011 (Electrophoresis 2008, 29, 108-128; Electrophoresis 2010, 31, 44-54; Electrophoresis 2012, 33, 243-250). The use of in-line and on-line SPE-CE approaches is described in this review. Emerging technological developments, such as the use of in-line frit-free SPE and chip-based SPE for extraction of sample components prior to CE analysis, are outlined. Selected examples illustrate the applicability of SPE-CE in biomedical, pharmaceutical, and environmental analysis. A complete overview of recent SPE-CE studies is given in table format, providing information on sample type, SPE sorbent, coupling mode, detection mode, and LOD. Finally, some general conclusions and future perspectives are provided.

A new MEKC-ESI-MS method for the analysis of amino acids (AAs) in human urine was developed employing ammonium perfluorooctanoate (APFO) as volatile surfactant. The influence of APFO on the MS signal of AAs was evaluated by infusion experiments, which showed that APFO hardly affects analyte responses and presents significantly less ion suppression than equal concentrations of ammonium acetate. In order to obtain efficient separation of AAs, MEKC parameters such as the pH and APFO concentration of the BGE, were optimized. Optimum AA resolution, including baseline separation of leucine and isoleucine, was obtained using 150 mM APFO (pH 9.0) as BGE, representing a considerable selectivity improvement over CE using 50 mM ammonium acetate (pH 9.0). Optimization of CE-MS parameters, such as sheath liquid composition and flow rate, and ESI and MS settings, led to LODs ranging from 9 to 26 ng/mL for the 20 tested AAs, which is highly favorable for an MEKC-MS method. Good linearity (r(2) > 0.99) and repeatability were obtained for all AAs tested with RSD values of 3.0-6.7% for peak area and

Blushing is restricted to the facial area that is uncovered and in the center of social attention. Together with the observation that blushing typically occurs in interpersonal situations, it has been proposed that the blush might have acquired signaling properties with relevant social implications. Following such a functional perspective, this article evaluates the signal value and social effects of the blush. First, it is argued that the blush fulfils all criteria for being a reliable social signal. It seems impossible to fake or to suppress, and it seems to co-occur with a specific mental state: The acute awareness that one’s goal of esteem before others is at stake. Second, it is illustrated that the social effects of the blush may greatly vary as a function of context. In contexts that clearly imply some kind of misbehavior, the blush has face-saving properties. Yet, in many other contexts, such as merely being the center of attention or situations that are ambiguous with regard to the blushing actors’ antecedent behaviors, the blush may have undesirable effects. Third, it is illustrated that the signal value of the blush not only affects the observers but also the blushing actors. It is shown that the anticipated influence of one’s blushing on other people’s judgments may help explain why actors often consider blushing as a highly undesirable response, and why some people may even develop a phobic fear of blushing.

CE-MS has emerged as a powerful technique for the profiling of (highly) polar and charged metabolites in biological samples. This review provides an update of the most recent developments in CE-MS for metabolomics covering the scientific literature from July 2010 to June 2012. The present paper is an update of two previous review papers covering the years 2000-2010 (Electrophoresis 2009, 30, 276-291; Electrophoresis 2011, 32, 52-65). Emerging technological developments used in CE-MS for metabolomics are discussed, such as the use of novel interfacing techniques for coupling CE to MS. Representative examples illustrate the applicability of CE-MS in the fields of biomedical, clinical, microbial, plant, environmental and food metabolomics. Concerning targeted and non-targeted approaches, a comprehensive overview of recent CE-MS-based metabolomics studies is given in a table. Information on sample type and pretreatment, capillary coatings and MS detection mode is provided. Finally, general conclusions and perspectives are provided. © 2012.

Since its introduction in 1987, CE-MS has become an increasingly important technique for the analysis of biomolecules. Since our previous update on CE-MS methods within the field of intact protein analysis (Electrophoresis 2011, 32, 66-82), a variety of interesting methodological improvements and applications have been reported in literature. Therefore, this article presents an overview of the development and application of CE-MS for intact protein analysis as published between June 2010 and June 2012. The article is divided in sections that treat CE coupled to MS through ESI, MALDI, and ICP ionization, respectively. In the section about CE-ESI-MS, technological developments with respect to CE-MS interfacing, prevention of protein adsorption, and chip-based CE-MS are treated in more detail. Novel interfacing strategies and the development of improved capillary coating strategies appeared to be the major developments. Furthermore, in all sections, the applicability of CE-MS for intact protein analysis is demonstrated by representative examples, including important developments in the fields of biopharmaceutical characterization and the analysis of proteins in biological samples. Finally, some general conclusions and future perspectives are given. © 2012.

Hybridisation and subsequent introgression have recently received much attention in the context of genetically modified crops. But crop-wild hybrid detection in the field can be difficult, as most domestication traits seem to be recessive, and the hybrid phenotype may also depend on the direction of the cross or environmental factors. Our aim was to develop a reliable set of morphological markers that differ between two wild and 13 cultivated carrots (Daucus carota L.) and to evaluate their inheritance in hybrid lines. We then examined these morphological markers in four F1 hybrids obtained by fertilising plants from the two wild accessions with pollen from two common carrot cultivars. Of the 16 traits that differed between the two carrot subspecies, three took intermediate values in the hybrids, eight resembled the cultivar parent (dominant domestication traits), two resembled the wild parent (domestication traits recessive), and three were not significant or growth condition-dependent. Root:shoot ratio was seven times higher for cultivars than for wild plants, while still attaining equivalent total dry weight, which shows that dry matter production by the shoot is much higher in cultivars than in wild plants. High root:shoot ratios were also present in the hybrids. While we found no maternal effects, the type of cultivar used for pollination had an impact on hybrid characteristics. The morphological markers developed here provide insights into the mode of inheritance of ecologically relevant traits and can be useful for pre-screening wild populations for hybrid detection prior to genetic analysis.

The potential of CE with native fluorescence detection (Flu) for the profiling of the therapeutic protein erythropoietin (EPO) was studied. EPO is a highly heterogeneous glycoprotein comprising a large number of isoforms. CE was applied to induce separation among the various glycoforms. Native Flu of EPO provided high detection selectivity yielding good signal-to-noise ratios and stable baselines, particularly when compared to conventional UV absorbance detection. In order to enhance EPO isoform resolution, CE was performed using a capillary with a neutral coating in combination with a simple BGE of 2.0 M acetic acid (pH 2.1). CE-Flu analysis of the EPO biological reference preparation of the European Pharmacopeia resulted in a highly detailed glycoform profile. Migration time RSDs for selected EPO isoforms were less than 0.22% and 0.80% for intraday and interday repeatability, respectively. RSDs for relative peak intensity of the major EPO isoforms were less than 3%. The achieved resolution, migration time stability, and sensitivity allowed discrimination of different EPO products (EPO-α and EPO-β) based on the recorded glycoform pattern. The developed CE-Flu method is relatively straightforward, and shows potential for quality control in biopharmaceutical production.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants, with remarkable variability in disease severity. An exaggerated proinflammatory response and influx of leukocytes is part of the pathogenesis of severe RSV disease. Here, we show an increase in proinflammatory cytokine production by human immune cells after stimulation with RSV and muramyl dipeptide (MDP), which is recognized by nucleotide-binding oligomerization domain containing 2 (NOD2). PBMCs from Crohn's disease patients homozygous for the 3020insC mutation in the NOD2 gene did not show a synergistic response to stimulation with RSV and MDP, suggesting that NOD2 is essential for the observed synergy. Further experiments aimed at identifying the viral ligand indicated that viral RNA plays an essential role in the recognition of RSV. Stimulation with RSV or Poly(I:C) induced IFN-β expression, which resulted in an increased expression of the viral receptors TLR3 and RIG-I, as well as an increased NOD2 expression. Our data indicate that IFN-β induction by viral RNA is an essential first step in the increased proinflammatory response to MDP. We hypothesize that the enhanced proinflammatory response to MDP following RSV infection may be an important factor in determining the outcome of the severity of disease.

Summary •Pollen of the crop oilseed rape (Brassica napus, AACC) can cross-fertilize ovules of Brassica rapa (AA), which leads to an influx of unpaired C-chromosomes into wild B. rapa populations. The presence of such extra chromosomes is thought to be an indicator of introgression. Backcrosses and F1 hybrids were found in Danish populations but, surprisingly, only F1 hybrids were found in the UK and the Netherlands. •Here, a model tests how the level of selection and biased vs unbiased transmission affect the population frequency of C-chromosomes. In the biased-transmission scenario the experimental results of the first backcross are extrapolated to estimate survival of gametes with different numbers of C-chromosomes from all crosses in the population. •With biased transmission, the frequency of C-chromosomes always rapidly declines to zero. With unbiased transmission, the continued presence of plants with extra C-chromosomes depends on selection in the adult stage and we argue that this is the most realistic option for modeling populations. •We suggest that selection in the field against plants with unpaired C-chromosomes is strong in Dutch and UK populations. The model highlights what we do not know and makes suggestions for further research on introgression.

Study Type – Diagnostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? So far, few publications have shown that a prediction model influences the behaviour of both physicians and patients. To our knowledge, it was unknown whether urologists and patients are compliant with the recommendations of a prostate cancer risk calculator and their reasons for non-compliance. Recommendations of the European Randomized study of Screening for Prostate Cancer risk calculator (ERSPC RC) about the need of a prostate biopsy were followed in most patients. In most cases of non-compliance with ‘no biopsy’ recommendations, a PSA level ≥3 ng/mL was decisive to opt for biopsy. Before implementation of the ERSPC RC in urological practices at a large scale, it is important to obtain insight into the use of guidelines that might counteract the adoption of the use of the RC as a result of opposing recommendations. OBJECTIVES • To assess both urologist and patient compliance with a ‘no biopsy’ or ‘biopsy’ recommendation of the European Randomized study of Screening for Prostate Cancer (ERSPC) Risk Calculator (RC), as well as their reasons for non-compliance. • To assess determinants of patient compliance. PATIENTS AND METHODS • The ERSPC RC calculates the probability on a positive sextant prostate biopsy (Pposb) using serum prostate-specific antigen (PSA) level, outcomes of digital rectal examination and transrectal ultrasonography, and ultrasonographically assessed prostate volume. A biopsy was recommended if Pposb≥20%. • Between 2008 and 2011, eight urologists from five Dutch hospitals included 443 patients (aged 55–75 years) after a PSA test with no previous biopsy. • Urologists calculated the Pposb using the RC in the presence of patients and completed a questionnaire about compliance. • Patients completed a questionnaire about prostate cancer knowledge, attitude towards prostate biopsy, self-rated health (12-Item Short Form Health Survey), anxiety (State Trait Anxiety Inventory-6, Memorial Anxiety Scale for Prostate Cancer) and decision-making measures (Decisional Conflict Scale). RESULTS • Both urologists and patients complied with the RC recommendation in 368 of 443 (83%) cases. • If a biopsy was recommended, almost all patients (96%; 257/269) complied, although 63 of the 174 (36%) patients were biopsied against the recommendation of the RC. • Compliers with a ‘no biopsy’ recommendation had a lower mean Pposb than non-compliers (9% vs 14%; P < 0.001). • Urologists opted for biopsies against the recommendations of the RC because of an elevated PSA level (≥3 ng/mL) (78%; 49/63) and patients because they wanted certainty (60%; 38/63). CONCLUSIONS • Recommendations of the ERSPC RC on prostate biopsy were followed in most patients. • The RC hence may be a promising tool for supporting clinical decision-making.

The clinical impression is that people who fear blushing do not easily seek psychological help for their complaints. Therefore, we designed a low-threshold psychoeducational group intervention to reduce fear of blushing. The intervention followed a cognitivebehavioural approach, but in a course setting, e.g., with participants and teachers instead of patients and therapists. The effectiveness of the course in reducing fear of blushing and social anxiety was tested in a group of blushing-fearful individuals (n?=?47) by using an uncontrolled study design. The course consisted of six weekly sessions and one booster session 3?months after the last regular session. Assessments took place upon application, immediately before the intervention, after the sixth session, before the booster session, and at 1-year follow-up. Results showed that the course was effective in reducing fear of blushing as well as symptoms of social anxiety. The positive effect of the course on anxiety measures suggests that it might be a promising approach for treating fear of blushing. Copyright (c) 2011 John Wiley & Sons, Ltd. Key Practitioner Message The course dealing with fear of blushing is a cognitivebehavioural group intervention in a course setting, e.g., with participants and teachers instead of patients and therapists. The course was effective in reducing anxiety complaints. An effect size of 1.4 and a reduction of approximately 30 points on this Blushing, Trembling and Sweating Questionnaire are comparable with what was reported for individual cognitivebehavioural treatments. Participants evaluated the course positively.

A goal in proteomics is the analysis of proteins by LC-MS. The proteins are enzymatically digested and the resulting peptides are chromatographically separated and introduced into a tandem MS. The obtained MS data are used for a search in sequence databases, providing identification scores for the proteins. A method to improve that score is to increase the chromatographic separation and peak capacity. In this study, the chromatographic conditions were optimized for a relatively large gradient time by varying the flow rate and gradient composition. The influence of the monolithic column length (15 and 64 cm) and particle diameter (1.8 μm; 15-cm length) on the sample peak capacity, productivity and identification score was studied. For comparison of gradient systems, a scaling factor was introduced to normalize the properties/performance of columns for material, diameter and length. As model proteins/digests, a simple (myoglobin) and a larger (BSA) protein were used. The smallest peak width, highest identification scores (54 and 89% for BSA and myoglobin, respectively) and productivity (5.0 and 4.0, respectively) were obtained for the 15-cm particulate column. The study also demonstrates that a further increase in the chromatographic performance is beneficial for BSA but hardly increases the identification score for the relatively small myoglobin.

Who is in control of seed size, and do some fathers sire bigger seeds than others? We used isogenic male-sterile genotypes of the Arabidopsis thaliana accessions Col and Ler. By fertilising flowers side-by-side with either pollen from the same accession (‘self-pollination’) or pollen from another accession (outcrossing), we compared, on the same mother plant, seed set of flowers that were very similar in resource status. Some paternal genotypes had a significant effect on seed mass, with the most extreme father siring seeds 15.3% heavier than seeds resulting from ‘self-pollination’. There was no correlation between seed mass of paternal parents and the seeds they sired. We discuss the evolution of seed size as a tug-of-war between parent and offspring.

The heat of dissociation of hexaphenylethane in m-xylene as a solvent, measured by means of electron spin resonance, amounts to 10.9 ± 0.29 (2.7%) kcal/mol. The ESR method appears to have important advantages over other techniques for this purpose.

The heats of dissociation of some ortho alkyl-substituted tetraphenylethanes which show reversible thermal dissociation in solution at room temperature, were measured by means of ESR. The values found are 22.0, 19.7 and 12.0 kcal/mole for symm.tetra(2,6-dimethylphenyl)ethane, symm.tetra(2-tert-butyl-phenyl)ethane and symm.tetra(2,6-diethylphenyl)ethane, respectively.

De meme que la benzylallylsulfone3), ses derives methyles en position α et β s'isomerisent sous l'influence d'un accepteur de protons, la double liaison se rapprochant du groupe sulfonyle. L'isomerisation de la benzylcrotylsulfone ne reussit pas dans les memes conditions. A moins qu'un substituant en position α n'encombre l'addition, les sulfones α-olefiniques qui resultent de l'isomerisation fixent des reactifs nucleophiles, ainsi que l'eau, l'alcool, le phenol et les mercaptannes en solution alcaline et la piperidine. Le mecanisme des reactions d'isomerisation et d'addition est etudie et discute en rapport avec les reactions analogues que presentent les sulfones cycliques des butadienes.

The ESR spectra of four ortho-alkyl-substituted diphenylmethyl radicals have been measured in solutions of m-xylene. The proton coupling constants were assigned experimentally such that the reconstructions of the spectra agreed with the recorded tracings. The spin densities were calculated assuming proportionality between proton coupling constant and spin density on the adjacent carbon atom. The relation between spin distribution and steric configuration of the radicals is considered on a qualitative basis.

Various compounds with the system and have been converted into conjugated trienes by means of potassium tert-butoxide in dimethyl sulfoxide (DMSO). Aromatization has been observed with compounds possessing the systems

A lamp-based fluorescence detection (Flu) system for CE was extended with a wavelength-resolved (WR) detector to allow recording of full protein emission spectra. WRFlu was achieved using a fluorescence cell that employs optical fibres to lead excitation light from a Xe-Hg lamp to the capillary window and protein fluorescence emission to a spectrograph equipped with a CCD. A 280 nm band pass filter etc. together with a 300 nm short pass cut-off filter was used for excitation. A capillary cartridge was modified to hold the detection cell in a commercial CE instrument enabling WRFlu in routine CE. The performance of the WRFlu detection was evaluated and optimised using lysozyme as model protein. Based on reference spectral data, a signal-intensity adjustment was introduced to correct for transmission losses in the detector optics that occurred for lower protein emission wavelengths. CE-WRFlu of lysozyme was performed using BGEs of 50 mM sodium phosphate (pH 6.5 or 3.0) and a charged-polymer coated capillary. Using the 3-D data set, signal averaging over time and emission-wavelength intervals was carried out to improve the S/N of emission spectra and electropherograms. The detection limit for lysozyme was 21 nM, providing sufficient sensitivity to obtain spectral information on protein impurities.

Phobic individuals expect aversive UCS's following encounters with phobic stimuli. Previous research using a thought-experiment procedure showed that contamination rather than harm-related outcome expectancies differentiated best between high and low spider fearful undergraduates. This study investigated the alleged role of these UCS-expectancy biases in the maintenance of phobic complaints. First, this study sought to replicate these earlier findings in a community sample of high spider fearful individuals who applied for treatment (n = 60) and a sample of low spider fear controls (n = 30). Second, the present study tested if UCS-expectancies disappear following successful treatment and whether there were any differences between harm and contamination-related UCS expectancies in this respect. If contamination-and/or harm-related UCS-expectancy biases play a critical role in the maintenance of spider fear, these biases should be substantially reduced after successful treatment. The results showed that spider fearful individuals associated spiders relatively strongly with both harm-and contamination-related outcomes. Consistent with the alleged reciprocal relationship between phobic fear and UCS expectancy bias, both types of biased expectancies were effectively reduced following treatment. Copyright (C) 2010 John Wiley & Sons, Ltd.

Pupae of apple leaf rollers (Lepidoptera, Tortricidae) in the Netherlands. The cremaster and the spines on the dorsal side of the abdomen of the pupa seem imminently suitable for the spines on the dorsal side of the abdomen of the pupa seem imminently suitable for distinguishing genera and species of Tortricidae. A key is given for identifying pupae of 17 Dutch species whose caterpillars feed on apple leaves. These species are described briefly. The pupae of only a few could not be distinguished. Zusammenfassung Der Kremaster und die Dornen der Dorsalseite des Abdomens der Puppen geben besonders gute Merkmale fur die Unterscheidung der Gattungen und Arten der Blattwickler. Es wird eine Bestimmungstabelle fur die Puppen von 17 Arten vorgelegt, deren Raupen oder Puppen zwischen zusammengesponnenen Apfelblattern gesammelt wurden. Die Arten werden alle beschrieben. Nur die Puppen weniger Arten konnten nicht eindeutig unterschieden werden.