Stable two-element control of dTph1 transposition in mutator strains of Petunia by an inactive ACT1 introgression from a wild species

The high copy dTph1 transposon system of Petunia (Solanaceae) is one of the most powerful insertion mutagens in plants, but its activity cannot be controlled in the commonly used mutator strains. We analysed the regulation of dTph1 activity by QTL analysis in recombinant inbred lines of the mutator strain W138 and a wild species (P. integrifolia spp. inflata). Two genetic factors were identified that control dTph1 transposition. One corresponded to the ACT1 locus on chromosome I. A second, previously undescribed locus ACT2 mapped on chromosome V. As a 6-cM introgression in W138, the P. i. inflata act1(S6) allele behaved as a single recessive locus that fully eliminated transposition of all dTph1 elements in all stages of plant development and in a heritable fashion. Weak dTph1 activity was restored in act1(S6)/ACT2(S6) double introgression lines, indicating that the P. i. inflata allele at ACT2 conferred a low level of transposition. Thus, the act1(S6) allele is useful for simple and predictable control of transposition of the entire dTph1 family when introgressed into an ultra-high copy W138 mutator strain. We demonstrate the use of the ACT1(W138)/act1(S6) allele pair in a two-element dTph1 transposition system by producing 10 000 unique and fixed dTph1 insertions in a population of 1250 co-isogenic lines. This Petunia system produces the highest per plant insertion number of any known two-element system, providing a powerful and logistically simple tool for transposon mutagenesis of qualitative as well as quantitative traits.

Chlamydia Control: A Comparative Review from the USA and UK

Chlamydia trachomatis infection (chlamydia) is the most common notifiable bacterial sexually transmitted infection (STI) worldwide. In the United States of America (USA) in 2009, 1,244,180 cases of chlamydia were reported to the Centers for Disease Control and Prevention (CDC), the largest number of cases ever reported to CDC for any notifiable disease [1]. It has been estimated, from population prevalence surveys, that approximately 2 % of sexually active adults aged 18–44 years old in the UK [2] and 2.2 % (CI, 1.8–2.8 %) of the US population aged 14–39 years [3] are infected with chlamydia. This level of prevalence in the USA translates into an estimated 2,291,000 (95 % confidence interval, CI, 1,857,000–2,838,000) chlamydia infections each year [3]. Globally, the World Health Organization (WHO) estimates that there are about 92 million new cases of chlamydia each year [4].

Virological outcome and management of persistent low-level viraemia in HIV-1-infected patients: 11 years of the Swiss HIV Cohort Study

BACKGROUND Management of persistent low-level viraemia (pLLV) in patients on combined antiretroviral therapy (cART) with previously undetectable HIV viral loads (VLs) is challenging. We examined virological outcome and management among patients enrolled in the Swiss HIV Cohort Study (SHCS). METHODS In this retrospective study (2000-2011), pLLV was defined as a VL of 21-400 copies/mL on ≥3 consecutive plasma samples with ≥8 weeks between first and last analyses, in patients undetectable for ≥24 weeks on cART. Control patients had ≥3 consecutive undetectable VLs over ≥32 weeks. Virological failure (VF), analysed in the pLLV patient group, was defined as a VL>400 copies/mL. RESULTS Among 9972 patients, 179 had pLLV and 5389 were controls. Compared to controls, pLLV patients were more often on unboosted PI-based (adjusted odds ratio, aOR, [95%CI] 3.2 [1.8-5.9]) and NRTI-only combinations (aOR 2.1 [1.1-4.2]) than on NNRTI and boosted PI-based regimens. At 48 weeks, 102/155 pLLV patients (66%) still had pLLV, 19/155 (12%) developed VF, and 34/155 (22%) had undetectable VLs. Predictors of VF were previous VF (aOR 35 [3.8-315]), unboosted PI-based (aOR 12.8 [1.7-96]) or NRTI-only combinations (aOR 115 [6.8-1952]), and VLs>200 during pLLV (aOR 3.7 [1.1-12]). No VF occurred in patients with persistent very LLV (pVLLV, 21-49 copies/mL; N=26). At 48 weeks, 29/39 patients (74%) who changed cART had undetectable VLs, compared to 19/74 (26%) without change (P<0.001). CONCLUSIONS Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL ≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV >200 copies/ml.

Electrophysiological indices of response inhibition in a Go/NoGo task predict self-control in a social context.

Recent research demonstrates that response inhibition-a core executive function-may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test). Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes-two established electrophysiological indices of response inhibition-both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.

[Helminth control in the adult horse: the need for a re-orientation].

The epidemiological situation of strongyle infections in adult horses in Switzerland is characterized by a strong dominance of small strongyles (Cyathostominae) and an overall low level of egg shedding in the faeces. The prevailing attitude towards anthelmintic therapy considers neither husbandry conditions nor pasture hygiene measures. Instead, calendar-based routine medication, comprising usually 3 to 4 annual treatments, is the typical strategy. Such an approach, however, often results in an excessive administration of anthelmintics. With respect to the continuous spread of drug resistant cyathostomins a change of strategy seems inevitable. A consensus has been agreed on between equine parasitologists and clinicians of the Vetsuisse Faculty in Zurich and Berne to focus on the concept of a selective control approach, based on individual faecal egg counts as the central element. It is now recommended that clinically healthy horses (> 4 y) are treated only when their strongyle egg count is equal to or higher than 200 eggs per gram of faeces. A regular analysis of the strongyle population based on larval cultures, the control of drug efficacy, and quarantine measures for incoming horses are mandatory components of the concept. Recent experiences in several pilot farms have indicated that only 4 % of the McMaster analyses resulted in a deworming treatment. For horses that did not receive any nematicidal anthelmintic during the current season, a "safety" treatment is recommended at the end of the grazing period.

Resisting the power of temptations: the right prefrontal cortex and self-control.

Imagine you are overweight and you spot your favorite pastry in the storefront of a bakery. How do you manage to resist this temptation? Or to give other examples, how do you manage to restrain yourself from overspending or succumbing to sexual temptations? The present article summarizes two recent studies stressing the fundamental importance of inhibition in the process of decision making. Based on the results of these studies, we dare to claim that the capacity to resist temptation depends on the activity level of the right prefrontal cortex (PFC).

Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019)

BACKGROUND Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa-the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)-includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort. OBJECTIVE Describe survival outcomes, along with current treatment standards and factors associated with prognosis, to inform future trial design in this patient group. DESIGN, SETTING, AND PARTICIPANTS STAMPEDE trial control arm comprising men newly diagnosed with M1 disease who were recruited between October 2005 and January 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Overall survival (OS) and failure-free survival (FFS) were reported by primary disease characteristics using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (CIs) were derived from multivariate Cox models. RESULTS AND LIMITATIONS A cohort of 917 men with newly diagnosed M1 disease was recruited to the control arm in the specified interval. Median follow-up was 20 mo. Median age at randomisation was 66 yr (interquartile range [IQR]: 61-71), and median prostate-specific antigen level was 112 ng/ml (IQR: 34-373). Most men (n=574; 62%) had bone-only metastases, whereas 237 (26%) had both bone and soft tissue metastases; soft tissue metastasis was found mainly in distant lymph nodes. There were 238 deaths, 202 (85%) from PCa. Median FFS was 11 mo; 2-yr FFS was 29% (95% CI, 25-33). Median OS was 42 mo; 2-yr OS was 72% (95% CI, 68-76). Survival time was influenced by performance status, age, Gleason score, and metastases distribution. Median survival after FFS event was 22 mo. Trial eligibility criteria meant men were younger and fitter than general PCa population. CONCLUSIONS Survival remains disappointing in men presenting with M1 disease who are started on only long-term ADT, despite active treatments being available at first failure of ADT. Importantly, men with M1 disease now spend the majority of their remaining life in a state of castration-resistant relapse. PATIENT SUMMARY Results from this control arm cohort found survival is relatively short and highly influenced by patient age, fitness, and where prostate cancer has spread in the body.

Invisible social control as predictor of daily negative affect and smoking after a self-set quit date

The dual-effects model of social control proposes that social control leads to increased psychological distress but also to better health practices. However, findings are inconsistent, and recent research suggests that the most effective control is unnoticed by the receiver (i. e., invisible). Yet, investigations of the influence of invisible control on daily negative affect and smoking have been limited. Using daily diaries, we investigated how invisible social control was associated with negative affect and smoking. Overall, 100 smokers (72.0 % men, age M = 40.48, SD = 9.82) and their nonsmoking partners completed electronic diaries from a self-set quit date for 22 consecutive days, reporting received and provided social control, negative affect, and daily smoking. We found in multilevel analyses of the within-person process that on days with higher-than-average invisible control, smokers reported more negative affect and fewer cigarettes smoked. Findings are in line with the assumptions of the dual-effects model of social control: Invisible social control increased daily negative affect and simultaneously reduced smoking at the within-person level.

Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of incident gout: a population-based case-control study

OBJECTIVE The aim of this study was to explore the risk of incident gout in patients with type 2 diabetes mellitus (T2DM) in association with diabetes duration, diabetes severity and antidiabetic drug treatment. METHODS We conducted a case-control study in patients with T2DM using the UK-based Clinical Practice Research Datalink (CPRD). We identified case patients aged ≥18 years with an incident diagnosis of gout between 1990 and 2012. We matched to each case patient one gout-free control patient. We used conditional logistic regression analysis to calculate adjusted ORs (adj. ORs) with 95% CIs and adjusted our analyses for important potential confounders. RESULTS The study encompassed 7536 T2DM cases with a first-time diagnosis of gout. Compared to a diabetes duration <1 year, prolonged diabetes duration (1-3, 3-6, 7-9 and ≥10 years) was associated with decreased adj. ORs of 0.91 (95% CI 0.79 to 1.04), 0.76 (95% CI 0.67 to 0.86), 0.70 (95% CI 0.61 to 0.86), and 0.58 (95% CI 0.51 to 0.66), respectively. Compared to a reference A1C level of <7%, the risk estimates of increasing A1C levels (7.0-7.9, 8.0-8.9 and ≥9%) steadily decreased with adj. ORs of 0.79 (95% CI 0.72 to 0.86), 0.63 (95% CI 0.55 to 0.72), and 0.46 (95% CI 0.40 to 0.53), respectively. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. CONCLUSIONS Increased A1C levels, but not use of antidiabetic drugs, was associated with a decreased risk of incident gout among patients with T2DM.

Examining invisible social control as predictor of daily smoking and negative affect after a self-set quit date

Objectives: The dual-effects model of social control proposes that social control leads to better health practices, but also arouses psychological distress. However, findings are inconsistent in relation to health behavior and psychological distress. Recent research suggests that the most effective control is unnoticed by the receiver (i.e., invisible). There is some evidence that invisible social control is beneficial for positive and negative affective reactions. Yet, investigations of the influence of invisible social control on daily smoking and distress have been limited. In daily diaries, we investigated how invisible social control is associated with number of cigarettes smoked and negative affect on a daily basis. Methods: Overall, 99 smokers (72.0% men, mean age M = 40.48, SD = 9.82) and their non-smoking partners completed electronic diaries from a self-set quit date for 22 consecutive days within the hour before going to bed, reporting received and provided social control, daily number of cigarettes smoked, and negative affect. Results: Multilevel analyses indicated that between-person levels of invisible social control were associated with lower negative affect, whereas they were unrelated to number of cigarettes smoked. On days with higher-than-average invisible social control, smokers reported less cigarettes smoked and more negative affect. Conclusions: Between-person level findings indicate that invisible social control can be beneficial for negative affect. However, findings on the within-person level are in line with the assumptions of the dual-effects model of social control: Invisible social control reduced daily smoking and simultaneously increased daily negative affect within person.

Impact of development of job control and task-related stressors on resigned job attitude.

With more experience in the labor market, some job characteristics increase, some decrease. For example, among young employees who just entered the labor market, job control may initially be low but increase with more routine and experience. Job control is a job resource that is valued in itself and is positively associated with job satisfaction; but job control also helps dealing with stressors at work. There is little research on correlated changes, but the existing evidence suggests a joint development over time. However, even less is known about the relevance of such changes for employees. Usually, research tends to use mean levels to predict mean levels in outcomes but development in job control and stressors may be as relevant for job satisfaction as having a certain level in those job characteristics. Job satisfaction typically is regarded as a positive attitude towards one’s work. What has received less attention is that some employees may lower their expectations if their job situation does not reflect their needs, resulting in a resigned attitude towards one’s job. The present study investigates the development of job control and task-related stressors over ten years and tests the predictive value of changes in job control and task-related stressors for resigned attitude towards one’s job. We used data from a Swiss panel study (N=356) ranging over ten years. Job control, task-related stressors (an index consisting of time pressure, concentration demands, performance constraints, interruptions, and uncertainty about tasks), and resigned attitude towards one’s job were assessed in 1998, 1999, 2001, and 2008. Latent growth modeling revealed that growth rates of job control and task-related stressors were not correlated with one another. We predicted resigned attitude towards one’s job in 2008 a) by initial levels, and b) by changes in job control and stressors, controlling for resigned attitude in 1998. There was some prediction by initial levels (job control: β = -.15, p < .05; task-related stressors: β = .12, p = .06). However, as expected, changes in control and stressors predicted resigned attitude much better, with β = -.37, p < .001, for changes in job control, and β = .31, p < .001, for changes in task-related stressors. Our data confirm the importance of having low levels of task-related stressors and higher levels of job control for job attitudes. However, development in these job characteristics seems even more important than initial levels.

Service Level Agreements-Driven Management of Distributed Applications in Cloud Computing Environments

Cloud Computing enables provisioning and distribution of highly scalable services in a reliable, on-demand and sustainable manner. However, objectives of managing enterprise distributed applications in cloud environments under Service Level Agreement (SLA) constraints lead to challenges for maintaining optimal resource control. Furthermore, conflicting objectives in management of cloud infrastructure and distributed applications might lead to violations of SLAs and inefficient use of hardware and software resources. This dissertation focusses on how SLAs can be used as an input to the cloud management system, increasing the efficiency of allocating resources, as well as that of infrastructure scaling. First, we present an extended SLA semantic model for modelling complex service-dependencies in distributed applications, and for enabling automated cloud infrastructure management operations. Second, we describe a multi-objective VM allocation algorithm for optimised resource allocation in infrastructure clouds. Third, we describe a method of discovering relations between the performance indicators of services belonging to distributed applications and then using these relations for building scaling rules that a CMS can use for automated management of VMs. Fourth, we introduce two novel VM-scaling algorithms, which optimally scale systems composed of VMs, based on given SLA performance constraints. All presented research works were implemented and tested using enterprise distributed applications.

Ego depletion and attention regulation under pressure: Is a temporary loss of self-control strength indeed related to impaired attention regulation?

In the current study we investigated whether ego depletion negatively affects attention regulation under pressure in sports by assessing participants' dart throwing performance and accompanying gaze behavior. According to the strength model of self-control, the most important aspect of self-control is attention regulation. Because higher levels of state anxiety are associated with impaired attention regulation, we chose a mixed design with ego depletion (yes vs. no) as between-subjects and anxiety level (high vs. low) as within-subjects factor. Participants performed a perceptual-motor task requiring selective attention, namely, dart throwing. In line with our expectations, depleted participants in the high-anxiety condition performed worse and displayed a shorter final fixation on bull's eye, demonstrating that when one's self-control strength is depleted, attention regulation under pressure cannot be maintained. This is the first study that directly supports the general assumption that ego depletion is a major factor in influencing attention regulation under pressure.

Ego depletion and attention regulation under pressure: Is a temporary loss of self-control strength indeed related to impaired attention regulation?

In the present study we investigated whether ego depletion negatively affects attention regulation under pressure in sports by assessing participants’ dart throwing performance and accompanying gaze behavior. According to the strength model of self-control the most important aspect of self-control is attention regulation (Schmeichel & Baumeister, 2010). As higher levels of state anxiety are associated with impaired attention regulation (Nieuwenhuys & Oudejans, 2012) we chose a mixed design with ego depletion (yes vs. no) as between-subjects and anxiety level (high vs. low) as within-subjects factor. A total of 28 right-handed students participated in our study (Mage = 23.4, SDage = 2.5; 10 female; no professional dart experience). Participants performed a perceptual-motor task requiring selective attention, namely, dart throwing. The task was performed while participants were positioned high and low on a climbing wall (i.e., with high and low levels of anxiety). In line with our expectations, a mixed-design ANOVA revealed that depleted participants in the high anxiety condition performed worse (p < .001) and displayed a shorter final fixation on bull’s eye (p < .01) than in the low anxiety condition, demonstrating that when one is depleted attention regulation under pressure cannot be maintained. This is the first study that directly supports the general assumption that ego depletion is a major factor in influencing attention regulation under pressure.