Passive chevron replicator

There is described a passive replicator device to be used in magnetic bubble domain systems. The replicator is passive, i.e., does not require an active element such as a current source or the like, and both propagates and replicates bubble domains. In a preferred embodiment, the replicator uses chevron type elements arranged in an appropriate pattern so as to interact with a pair of propagation paths wherein bubble domains are propagated. A bubble in one propagation path is routinely transferred therealong and, concurrently, replicated by the instant device into another propagation path. A plurality of elements arranged in juxtaposition to the chevrons assists in controlling the propagation of the bubbles through the respective propagation paths and, at the appropriate time, provides a cutting action wherein a bubble which is elongated between the chevrons of the two propagation paths is split into two separate bubbles

Stroke impact on mortality and psychologic morbidity within the Childhood Cancer Survivor Study.

BackgroundPoor socioeconomic and health-related quality of life (HRQOL) outcomes in survivors of childhood cancer can lead to distress and overall negatively impact the lives of these individuals. The current report has highlighted the impact of stroke and stroke recurrence on mortality, psychological HRQOL, and socioeconomic outcomes within the Childhood Cancer Survivor Study (CCSS).MethodsThe CCSS is a retrospective cohort study with longitudinal follow-up concerning survivors of pediatric cancer who were diagnosed between 1970 and 1986. Mortality rates per 100 person-years were calculated across 3 periods: 1) prior to stroke; 2) after first stroke and before recurrent stroke; and 3) after recurrent stroke. Socioeconomic outcomes, the standardized Brief Symptoms Inventory-18, the Medical Outcomes Study 36-Item Short Form Health Survey, and the CCSS-Neurocognitive Questionnaire also were assessed.ResultsAmong 14,358 participants (median age, 39.7 years), 224 had a stroke after their cancer diagnosis (single stroke in 161 patients and recurrent stroke in 63 patients). Based on 2636 deaths, all-cause late mortality rates were 0.70 (95% CI, 0.68-0.73) prior to stroke, 1.03 (95% CI, 0.73-1.46) after the first stroke, and 2.42 (95% CI, 1.48-3.94) after the recurrent stroke. Among 7304 survivors, those with stroke were more likely to live with a caregiver (single stroke odds ratio [OR], 2.3 [95% CI, 1.4-3.8]; and recurrent stroke OR, 5.3 [95% CI, 1.7-16.8]) compared with stroke-free survivors. Stroke negatively impacted task efficiency (single stroke OR, 2.4 [95% CI, 1.4-4.1] and recurrent stroke OR, 3.3 [95% CI, 1.1-10.3]) and memory (single stroke OR, 2.1 [95% CI, 1.2-3.7]; and recurrent stroke OR, 3.5 [95% CI, 1.1-10.5]).ConclusionsStroke and stroke recurrence are associated with increased mortality and negatively impact HRQOL measures in survivors of pediatric cancer

Preferences for long-term follow-up care in childhood cancer survivors

Follow-up care is important for childhood cancer survivors to facilitate early detection and treatment of late effects. We aimed to describe preferences for different organisational aspects and models of follow-up care among Swiss childhood cancer survivors, and characteristics associated with preferences for different models. We contacted 720 survivors aged 18+ years, diagnosed with cancer after 1990 (age 0-16 years), registered in the Swiss Childhood Cancer Registry (SCCR), and Swiss resident, who previously participated in a baseline survey. They received questionnaires to assess attendance and preferences for follow-up (rated on 4-point scales, 0-3). Clinical information was available from the SCCR. Survivors (n = 314: response rate 43.6%; 47.8% still attended follow-up) rated clinical reasons for follow-up higher than supportive reasons (p < .001). They rated checking for cancer recurrence (mean = 2.78, SD = 0.53) and knowing about risks for my children most important (mean = 2.22, SD = 0.83). They preferred to attend a children's hospital (mean = 1.94, SD = 1.11), adult hospital (mean = 1.86, SD = 0.98) or general practitioner (mean = 1.86, SD = 1.01) rather than a central specialised late effects clinic (mean = 1.25, SD = 1.06, p < .001), and be seen by paediatric (mean = 2.24, SD = 0.72) or medical oncologist (mean = 2.17, SD = 0.69). Survivors preferred decentralised clinic-based follow-up, rather than one central specialised late effects clinic. Survivors' preferences should be considered to ensure future attendance

Sumoylation of the THO complex regulates the biogenesis of a subset of mRNPs

International audienceAssembly of messenger ribonucleoparticles (mRNPs) is a pivotal step in gene expression, but only a few molecular mechanisms contributing to its regulation have been described. Here, through a comprehensive proteomic survey of mRNP assembly, we demonstrate that the SUMO pathway specifically controls the association of the THO complex with mRNPs. We further show that the THO complex, a key player in the interplay between gene expression, mRNA export and genetic stability, is sumoylated on its Hpr1 subunit and that this modification regulates its association with mRNPs. Altered recruitment of the THO complex onto mRNPs in sumoylation-defective mutants does not affect bulk mRNA export or genetic stability, but impairs the expression of acidic stress-induced genes and, consistently, compromises viability in acidic stress conditions. Importantly, inactivation of the nuclear exosome suppresses the phenotypes of the hpr1 non-sumoylatable mutant, showing that SUMO-dependent mRNP assembly is critical to allow a specific subset of mRNPs to escape degradation. This article thus provides the first example of a SUMO-dependent mRNP-assembly event allowing a refined tuning of gene expression, in particular under specific stress conditions

A cluster of ribosome synthesis factors regulate pre-rRNA folding and 5.8S rRNA maturation by the Rat1 exonuclease

The 5′-exonuclease Rat1 degrades pre-rRNA spacer fragments and processes the 5′-ends of the 5.8S and 25S rRNAs. UV crosslinking revealed multiple Rat1-binding sites across the pre-rRNA, consistent with its known functions. The major 5.8S 5′-end is generated by Rat1 digestion of the internal transcribed spacer 1 (ITS1) spacer from cleavage site A(3). Processing from A(3) requires the ‘A(3)-cluster' proteins, including Cic1, Erb1, Nop7, Nop12 and Nop15, which show interdependent pre-rRNA binding. Surprisingly, A(3)-cluster factors were not crosslinked close to site A(3), but bound sites around the 5.8S 3′- and 25S 5′-regions, which are base paired in mature ribosomes, and in the ITS2 spacer that separates these rRNAs. In contrast, Nop4, a protein required for endonucleolytic cleavage in ITS1, binds the pre-rRNA near the 5′-end of 5.8S. ITS2 was reported to undergo structural remodelling. In vivo chemical probing indicates that A(3)-cluster binding is required for this reorganization, potentially regulating the timing of processing. We predict that Nop4 and the A(3) cluster establish long-range interactions between the 5.8S and 25S rRNAs, which are subsequently maintained by ribosomal protein binding

School-aged children after the end of successful treatment of non-central nervous system cancer: Longitudinal assessment of health-related quality of life, anxiety and coping

Contains fulltext : 81585.pdf (publisher's version ) (Closed access)The aim of the study was to investigate: (1) health-related quality of life (HRQoL) and anxiety in school-aged cancer survivors during the first 4 years of continuous remission after the end of treatment; and (2) correlations of disease-related coping with HRQoL and anxiety. A total of 76 survivors aged 8-15 years completed questionnaires about HRQoL, anxiety and disease-related cognitive coping at one to five measurement occasions. Their HRQoL was compared with norm data, 2 months (n = 49) and 1 year (n = 41), 2 years (n = 41), 3 years (n = 42) and 4 years (n = 27) after treatment. Through longitudinal mixed models analyses it was investigated to what extent disease-related cognitive coping was associated with HRQoL and anxiety over time, independent of the impact of demographic and medical variables. Survivors reported worse Motor Functioning (HRQoL) 2 months after the end of treatment, but from 1 year after treatment they did no longer differ from the norm population. Lower levels of anxiety were associated with male gender, being more optimistic about the further course of the disease (predictive control) and less searching for information about the disease (interpretative control). Stronger reliance on the physician (vicarious control) was associated with better mental HRQoL. As a group, survivors regained good HRQoL from 1 year after treatment. Monitoring and screening survivors are necessary to be able to trace the survivors at risk of worse HRQoL

Antibiotics for acute bronchitis.

BACKGROUND: The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. OBJECTIVES: To assess the effects of antibiotics in improving outcomes and assess adverse effects of antibiotic therapy for patients with a clinical diagnosis of acute bronchitis. SEARCH METHODS: We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January week 1, 2014), EMBASE (1974 to January 2014) and LILACS (1982 to January 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in patients without underlying pulmonary disease. DATA COLLECTION AND ANALYSIS: At least two review authors extracted data and assessed trial quality. MAIN RESULTS: Seventeen trials with 3936 participants were included in the primary analysis. The quality of trials was generally good. There was limited evidence to support the use of antibiotics in acute bronchitis. At follow-up, there was no difference in participants described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15; number needed to treat for an additional beneficial outcome (NNTB) 22. Participants given antibiotics were less likely to have a cough (four studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; NNTB 6); have a night cough (four studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7) and a shorter mean cough duration (seven studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated patients were more likely to be unimproved according to clinician\u27s global assessment (six studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 25); have an abnormal lung exam (five studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB 6); have a reduction in days feeling ill (five studies with 809 participants, MD -0.64 days, 95% CI -1.16 to -0.13) and a reduction in days with limited activity (six studies with 767 participants MD -0.49 days, 95% CI -0.94 to -0.04). The differences in proportions with activity limitations at follow-up did not reach statistical significance. There was a significant trend towards an increase in adverse effects in the antibiotic group (12 studies with 3496 participants) (RR 1.20, 95% CI 1.05 to 1.36; NNT for an additional adverse effect 5). AUTHORS\u27 CONCLUSIONS: There is limited evidence to support the use of antibiotics in acute bronchitis. Antibiotics may have a modest beneficial effect in some patients such as frail, elderly people with multimorbidity who may not have been included in trials to date. However, the magnitude of this benefit needs to be considered in the broader context of potential side effects, medicalisation for a self-limiting condition, increased resistance to respiratory pathogens and cost of antibiotic treatment

Purification of Nuclear Poly(A)-binding Protein Nab2 Reveals Association with the Yeast Transcriptome and a Messenger Ribonucleoprotein Core Structure

Nascent mRNAs produced by transcription in the nucleus are subsequently processed and packaged into mRNA ribonucleoprotein particles (messenger ribonucleoproteins (mRNPs)) before export to the cytoplasm. Here, we have used the poly(A)-binding protein Nab2 to isolate mRNPs from yeast under conditions that preserve mRNA integrity. Upon Nab2-tandem affinity purification, several mRNA export factors were co-enriched (Yra1, Mex67, THO-TREX) that were present in mRNPs of different size and mRNA length. High-throughput sequencing of the co-precipitated RNAs indicated that Nab2 is associated with the bulk of yeast transcripts with no specificity for different mRNA classes. Electron microscopy revealed that many of the mRNPs have a characteristic elongated structure. Our data suggest that mRNPs, although associated with different mRNAs, have a unifying core structure