Construction and characterization of a BAC library from a gynogenetic channel catfish Ictalurus punctatus

A bacterial artificial chromosome (BAC) library was constructed by cloning HindIII-digested high molecular weight DNA from a gynogenetic channel catfish, Ictalurus punctatus, into the vector pBeloBAC11. Approximately 53 500 clones were arrayed in 384-well plates and stored at -80°C (CCBL1), while clones from a smaller insert size fraction were stored at -80°C without arraying (CCBL2). Pulsed-field gel electrophoresis of 100 clones after NotI digestion revealed an average insert size of 165 kb for CCBL1 and 113 kb for CCBL2. Further characterization of CCBL1 demonstrated that 10% of the clones did not contain an insert. CCBL1 provides a 7.2-fold coverage of the channel catfish haploid genome. PCR-based screening demonstrated that 68 out of 74 unique loci were present in the library. This represents a 92% chance to find a unique sequence. These libraries will be useful for physical mapping of the channel catfish genome, and identification of genes controlling major traits in this economically important species

Intracranial arteriosclerosis and the risk of dementia:A population-based cohort study

BACKGROUNDThe impact of intracranial arteriosclerosis on dementia remains largely unclear.METHODSIn 2339 stroke-free and dementia-free participants (52.2% women, mean age 69.5 years) from the general population, we assessed intracranial carotid artery calcification (ICAC) and vertebrobasilar artery calcification (VBAC) as proxy for arteriosclerosis. Associations with dementia were assessed using Cox models. In addition, indirect effects through cerebral small vessel disease (cSVD) and subcortical brain structure volumes were assessed using causal mediation analyses.RESULTSDuring a median of 13.4 years (25th–75th percentiles 9.9–14.5) of follow-up, 282 participants developed dementia. Both ICAC presence (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: 1.00–2.32]) and volume (HR per standard deviation: 1.19, 95% CI: 1.01–1.40) increased dementia risk. For VBAC, severe calcifications increased dementia risk (HR for third vs first volume tertile: 1.89, 95% CI: 1.00–3.59). These effects were mediated partly through increased cSVD (percentage mediated for ICAC: 13% and VBAC: 24%).DISCUSSIONIntracranial arteriosclerosis increases the risk of dementia

Neurocognitive outcomes in neurofibromatosis clinical trials

Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials

The Outcome of the Axillofemoral Bypass: A Retrospective Analysis of 45 Patients

Purpose This study was designed to retrospectively analyze outcomes of axillofemoral bypass (AxFB) operations performed in patients with severe comorbidities. Methods All patients (n = 45) who received an AxFB between 1990 and 2005 for aortoiliac occlusive disease (AIOD, n = 35) or infectious aortic disease (IAD, n = 10) were included. Information on patency of the bypass and mortality was retrieved from patient records. A Kaplan-Meier survival analysis was performed to illustrate survival rates, limb salvage, and primary and secondary patency. Results Included patients had several comorbidities and a high operative risk. In this group, a 30-day mortality rate of 20% was found: 17% for the AIOD group, and 30% for the IAD group. During 5-year follow-up 20 patients died, of which 15 during the first year after operation. Survival rates were at 64 and 41% at 1 and 5 years and limb salvage rates were 84% for both these years. Primary patency rates at 1 and 5 years were 72 and 58%, respectively, and secondary patency rates were 86% at both time points. Conclusions High mortality rates were found in AIOD or IAD patients who received an AxFB. However, for high-risk patients with an already reduced life expectancy, the AxFB remains an alternative with acceptable patency rate

Social health and change in cognitive capability among older adults:findings from four European longitudinal studies

Introduction: In this study we examine whether social health markers measured at baseline are associated with differences in cognitive capability and in the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. Methods: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. Results: Pooled estimates show distinct relationships between markers of social health and cognitive domains e.g., a large network size (≥6 people vs none) was associated with higher executive function (0.17 SD[95%CI:0.0, 0.34], I2=27%) but not with memory (0.08 SD[95%CI: -0.02, 0.18], I2=19%). We also observed pooled associations between being married or cohabiting, having a large network size and participating in social activities with slower decline in cognitive capability, however estimates were close to zero e.g., 0.01SD/year [95%CI: 0.01 to 0.02] I2=19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous and results for average memory were the most heterogenous. Conclusion: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between study differences and considering context specificity of findings in developing and deploying any intervention

Mix of methods is needed to identify adverse events in general practice: A prospective observational study

Contains fulltext : 69425.pdf ( ) (Open Access)BACKGROUND: The validity and usefulness of incident reporting and other methods for identifying adverse events remains unclear. This study aimed to compare five methods in general practice. METHODS: In a prospective observational study, with five general practitioners, five methods were applied and compared. The five methods were physician reported adverse events, pharmacist reported adverse events, patients' experiences of adverse events, assessment of a random sample of medical records, and assessment of all deceased patients. RESULTS: A total of 68 events were identified using these methods. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number. No overlap between the methods was detected. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number. CONCLUSION: A mix of methods is needed to identify adverse events in general practice

On the Action of Methotrexate and 6-Mercaptopurine on M. avium Subspecies paratuberculosis

BACKGROUND: Clinical improvement in inflammatory bowel disease (IBD) treated with methotrexate and 6-mercaptopurine (6-MP) is associated with a decrease in pro-inflammatory cytokines. This has been presumed to indicate the mechanism of action of methotrexate and 6-MP. Although controversial, there are increasingly compelling data that Mycobacterium avium subspecies paratuberculosis (MAP) may be an etiological agent in some or all of IBD. We hypothesized that the clinical efficacy of methotrexate and 6-MP in IBD may be to simply inhibit the growth of MAP. METHODOLOGY: The effect on MAP growth kinetics by methotrexate and 6-MP were evaluated in cell culture of two strains each of MAP and M. avium using a radiometric ((14)CO(2) BACTEC®) detection system that quantifies mycobacterial growth as arbitrary “growth index units” (GI). Efficacy data are presented as “percent decrease in cumulative GI” (% −ΔcGI). PRINCIPAL FINDINGS: The positive control antibiotic (clarithromycin) has ≥85% −ΔcGI at a concentration of 0.5 µg/ml. The negative control (ampicillin) has minimal inhibition at 64 µg/ml. MAP ATCC 19698 shows ≥80% −ΔcGI for both agents by 4 µg/ml. With the other three isolates, although more effective than ampicillin, 6-MP is consistently less effective than methotrexate. CONCLUSIONS: We show that methotrexate and 6-MP inhibit MAP growth in vitro. Each of the four isolates manifests different % −ΔcGI. These data are compatible with the hypothesis that the clinical improvement in patients with IBD treated with methotrexate and 6-MP could be due to treating a MAP infection. The decrease in pro-inflammatory cytokines, thought to be the primary mechanism of action, may simply be a normal, secondary, physiological response. We conclude that henceforth, in clinical studies that evaluate the effect of anti-MAP agents in IBD, the use of methotrexate and 6-MP should be excluded from any control groups

Inclusive V0V^0 Production Cross Sections from 920 GeV Fixed Target Proton-Nucleus Collisions

Inclusive differential cross sections $d\sigma_{pA}/dx_F$ and $d\sigma_{pA}/dp_t^2$ for the production of \kzeros, \lambdazero, and \antilambda particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to $\sqrt {s} = 41.6$ GeV in the proton-nucleon system. The ratios of differential cross sections \rklpa and \rllpa are measured to be $6.2\pm 0.5$ and $0.66\pm 0.07$, respectively, for \xf $\approx-0.06$. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions $d\sigma_{pA}/dp_t^2$ also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections $\sigma_{pA}$ on the atomic mass $A$ of the target material is discussed, and the deduced cross sections per nucleon $\sigma_{pN}$ are compared with results obtained at other energies.Comment: 17 pages, 7 figures, 5 table

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT