Randomised controlled trial of a Calcium Channel or Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Regime to Reduce Blood Pressure Variability following Ischaemic Stroke (CAARBS): a protocol for a feasibility study

Introduction Raised blood pressure (BP) is common after stroke and is associated with a poor prognosis, yet trials of BP lowering in the immediate poststroke period have not demonstrated a benefit. One possible explanation for this may be that BP variability (BPV) rather than absolute levels predicts outcome, as BPV is increased after stroke and is associated with poor outcomes. Furthermore, there is evidence of distinct antihypertensive class effects on BPV despite similar BP-lowering effects. However, whether BPV in the immediate poststroke period is a therapeutic target has not been prospectively investigated. The objectives of this trial are to assess the feasibility and safety of recruiting patients following an acute ischaemic stroke or transient ischaemic attack (TIA) to an interventional randomised controlled trial comparing the effects of two different antihypertensive drug classes on BPV. Secondary exploratory objectives are to assess if different therapeutic strategies have diverse effects on levels of BPV and if this has an impact on outcomes. Methods 150 adult patients with first-ever ischaemic stroke or TIA who require antihypertensive therapy for secondary prevention will be recruited within 7 days of the event from stroke services across three sites. After baseline assessments they will be randomly assigned to treatment with a calcium channel blocker or ACE inhibitor/angiotensin receptor blocker-based regimen and followed up for a period of three months. Ethics and dissemination Ethical and regulatory approvals have been granted. Dissemination is planned via publication in peer-reviewed medical journals and presentation at relevant conferences. Trial registration number ISRCTN10853487

Oschersleben, 11 January 1944

Abstract: On 11 January 1944 the US 8th Air Force mounted a maximum effort raid on targets deep in Germany in the vicinity of Brunswick. As the Strike Force moved over the continent, weather conditions, both over continent and the home bases in England began deteriorating rapidly. A recall was sent out to all Wings, except those of the 1st Air Division and the 4th Combat Wing of the 3rd Air Division. Those Wings were closing in on their targets and were allowed to proceed. Because of weather conditions, of the three Fighter Groups assigned to cover the target area, only the 354th Fighter Group, of 49 P-51s, went on to provide cover over the target area. Upon the abort of most of the Strike Force, German fighters were able to concentrate the greatest number of aircraft on the 1 Air Division since October. The ensuing three and one half hour air battle was one of the most harrowing of the war. Sixty B-17s were lost, the number equaling each of the two Schweinfurt missions of the previous August and October. For its action that day, the entire 1st Air Division was awarded the Distinguished Unit Citation.Ope

Flamingo Vol. II N 3

Punch Bowl. A Previous Engagement . Prose. 1. Burr. Untitled. Prose. 1. Ubersax, Delmar. Untitled. Picture. 4. Mather, William G. Shelf 378C . Prose. 5. Bennett, G.W. Esotery . Poem. 6. W.A.V. Untitled. Poem. 6. Anonymous. Approved Subjects of Conversation . Poem. 7. Anonymous. Pipe Up . Prose. 7. Anonymous. Denison\u27s Hall of Fame: Francis W. Shepardson . Prose. 8 M.E. Percy . Poem. 9.; A.F.T. Triolet . Poem. 9. Anonymous. Untitled. Picture. 9. W.G.K. The Message of a Leader-Autobiographical . Prose. 9. Keeler, Clyde. Untitled. Picture. 10. Anonymous. Untitled. Prose. 10. Potter, W.M. Prose Fiction . Poem. 11. Keeler, Clyde. Untitled. Picture. 11. Anonymous. The Night After Christmas . Prose. 11. Anonymous. Untitled. Prose. 11. Anonymous. Popular Illusions Shattered . Prose. 11. Anonymous. Throw Him Into The Green River! . Poem. 12. Anonymous. Candid . Prose. 12. Holt, Kilburn. Favorite Poems (Revised Edition) . Poem. 12. Anonymous. Untitled. Prose. 14. Anonymous. Proof that Winter is Here . Cartoon. 16. F. The Inefficiency Medal . Prose. 18. Anonymous. Untitled. Picture. 18. Anonymous. Untitled. Prose. 18. Ed. A Pathetic Fallacy . Poem. 19. Ubersax, Delmar. Untitled. Picture. 19. Anonymous. Untitled. Prose. 19. Anonymous. Untitled. Picture. 19. Oh Min. The Baliff and The Bunk . Prose. 20. Anonymous. Reservoir . Prose. 20. Anonymous. Untitled. Prose. 20. Ed. and Delmar Ubersax. A Lass and a Lack . Picture. 20. Anonymous. Thrice Told Tales . Prose. 21. Anonymous. Untitled. Prose. 21. Anonymous. Untitled. Prose. 22. Keeler, Clyde. Untitled. Picture. 22. R. The Lover Sings . Poem. 23. Anonymous. Untitled. Prose. 23. Anonymous. Untitled. Picture. 23. Octopus. Untitled. Prose. 23. Anonymous. Untitled. Picture. 24. Anonymous. Untitled. Prose. 24. Keeler, Clyde. Untitled. Picture. 25. Anonymous. Untitled. Prose. 25. Punch Bowl. Untitled. Prose. 26. Orange Peel. Untitled. Prose. 26. Lampoon. Untitled. Prose. 26. Octopus. Untitled. Prose. 26. Sun Dodger. Untitled. Prose. 27. Phoenix. Untitled. Prose. 27. Dirge. Untitled. Prose. 27. Lampoon. Untitled. Prose. 27. Siren. Untitled. Prose. 27. Jester. Untitled. prose. 29. Frivol. Untitled. Prose. 29. Voo-Doo. Untitled. Prose. 29. Lampoon. Untitled. Prose. 29. Royal Gaboon. Untitled. Prose. 30. Octopus. Untitled. Prose. 30. Anonymous. Page Mr. Volstead . Prose. 30. Chaparral. Missing Cylinder . Prose. 30. Frivol. Untitled. Prose. 31. Widow. Bubbling over . Prose. 31. Juggler. The Order of The Bawth . Prose. 31. Tiger. Untitled. Prose. 31

Leaf-litter leachate is distinct in optical properties and bioavailability to stream heterotrophs

Dissolved organic C (DOC) leached from leaf litter contributes to the C pool of stream ecosystems and affects C cycling in streams. We studied how differences in leaf-litter chemistry affect the optical properties and decomposition of DOC. We used 2 species of cottonwoods (Populus) and their naturally occurring hybrids that differ in leaf-litter phytochemistry and decomposition rate. We measured DOC and nutrient concentration in leaf leachates and determined the effect of DOC quality on heterotrophic respiration in 24-h incubations with stream sediments. Differences in DOC composition and quality were characterized with fluorescence spectroscopy. Rapidly decomposing leaves with lower tannin and lignin concentrations leached ~40 to 50% more DOC and total dissolved N than did slowly decomposing leaves. Rates of heterotrophic respiration were 25 to 50% higher on leachate from rapidly decomposing leaf types. Rates of heterotrophic respiration were related to metrics of aromaticity. Specifically, rates of respiration were correlated negatively with the Fluorescence Index and positively with Specific Ultraviolet Absorbance (SUVA254) and T280 tryptophan-like fluorescence peak. These results reveal that leaf-litter DOC is distinctly different from ambient streamwater DOC. The relationships between optical characteristics of leaf leachate and bioavailability are opposite those found in streamwater DOC. Differences in phytochemistry among leaf types can influence stream ecosystems with respect to DOC quantity, composition, and rates of stream respiration. These patterns suggest that the relationship between the chemical structure of DOC and its biogeochemistry is more complex than previously recognized. These unique properties of leaf-litter DOC will be important when assessing the effects of terrestrial C on aquatic ecosystems, especially during leaf fall

Spectroscopy of Broad Line Blazars from 1LAC

We report on optical spectroscopy of 165 Flat Spectrum Radio Quasars (FSRQs) in the Fermi 1LAC sample, which have helped allow a nearly complete study of this population. Fermi FSRQ show significant evidence for non-thermal emission even in the optical; the degree depends on the gamma-ray hardness. They also have smaller virial estimates of hole mass than the optical quasar sample. This appears to be largely due to a preferred (axial) view of the gamma-ray FSRQ and non-isotropic (H/R ~ 0.4) distribution of broad-line velocities. Even after correction for this bias, the Fermi FSRQ show higher mean Eddington ratios than the optical population. A comparison of optical spectral properties with Owens Valley Radio Observatory radio flare activity shows no strong correlation.Comment: Accepted for publication in Ap

Spectroscopy of the Largest Ever γ-Ray-selected BL Lac Sample

We report on spectroscopic observations covering most of the 475 BL Lacs in the second Fermi Large Area Telescope (LAT) catalog of active galactic nuclei (AGNs). Including archival measurements (correcting several erroneous literature values) we now have spectroscopic redshifts for 44% of the BL Lacs. We establish firm lower redshift limits via intervening absorption systems and statistical lower limits via searches for host galaxies for an additional 51% of the sample leaving only 5% of the BL Lacs unconstrained. The new redshifts raise the median spectroscopic z from 0.23 to 0.33 and include redshifts as large as z = 2.471. Spectroscopic redshift minima from intervening absorbers have z = 0.70, showing a substantial fraction at large z and arguing against strong negative evolution. We find that detected BL Lac hosts are bright ellipticals with black hole masses M_• ~ 10^(8.5) – 10^9, substantially larger than the mean of optical AGNs and LAT Flat Spectrum Radio Quasar samples. A slow increase in M_• with z may be due to selection bias. We find that the power-law dominance of the optical spectrum extends to extreme values, but this does not strongly correlate with the γ-ray properties, suggesting that strong beaming is the primary cause of the range in continuum dominance

A calcium channel or angiotensin converting enzyme inhibitor/angiotensin receptor blocker regime to reduced blood pressure variability in acute ischaemic stroke (CAARBS): A feasibility trial

Background: Trials of lowering blood pressure in patients with acute ischaemic stroke not undergoing thrombolysis have not demonstrated improved outcomes with intervention. Rather than absolute levels, it may be that blood pressure variability is important. However, there are no prospective randomised trials investigating the benefit of reducing blood pressure variability in this patient group. Aims: The primary aim of this trial was to determine the feasibility of recruitment to a randomised trial investigating the effect of different antihypertensive medications on blood pressure variability. Methods: CAARBS was a multi-centre, open-label, randomised parallel group controlled feasibility trial. Adults with a first mild-moderate ischaemic stroke or transient ischaemic attack, requiring antihypertensive therapy for secondary prevention, were randomised to a calcium channel blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Blood pressure and variability were measured at baseline, three weeks, and three months. Compliance with measurements and treatment was monitored. Results: Fourteen patients were recruited to the trial (0.6% of those screened), nine of whom completed follow-up. The majority of patients screened (98.1%) were ineligible. Compliance with the intervention was good, as were measurement completion rates (88.9% or higher in all cases except ambulatory measurements). No major adverse events were recorded. Conclusions: Recruitment to the trial was difficult due to patient ineligibility, suggesting that the current protocol is unlikely to be successful if scaled for a definitive trial. However, the intervention was safe, and compliance was good, suggesting a future trial with modified eligibility criteria could be successful. Trial registration: ISRCTN10853487

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Self-Monitoring and Management of Blood Pressure in Patients with Stroke or TIA: An Economic Evaluation of TEST-BP, A Randomised Controlled Trial

Abstract: Background: Prevention of secondary stroke following initial ictus is an important focus of after-stroke care. Blood pressure (BP) is a key risk factor, so usual care following stroke or transient ischaemic attack includes regular BP checks and monitoring of anti-hypertensive medication. This is traditionally carried out in primary care, but the evidence supporting self-monitoring and self-guided management of BP in the general population with hypertension is growing. Objective: Our objective was to estimate the cost effectiveness of treatment as usual (TAU) versus (1) self-monitoring of BP (S-MON) and (2) self-monitoring and guided self-management of anti-hypertensive medication (S-MAN). Methods: This was a within-trial economic evaluation of a randomised controlled trial estimating the incremental cost per 1 mmHg BP reduction and per quality-adjusted life-year (QALY) gained over a 6-month time horizon from the perspective of the UK National Health Service (NHS). Results: Data were evaluable for 140 participants. Costs per patient were £473, £853 and £1035; mean reduction in systolic BP (SBP) was 3.6, 6.7 and 6.1 mmHg, and QALYs accrued were 0.427, 0.422 and 0.423 for TAU, S-MON and S-MAN, respectively. No statistically significant differences in incremental costs or outcomes were detected. On average, S-MAN was dominated or extended dominated. The incremental cost per 1 mmHg BP reduction from S-MON versus TAU was £137. Conclusion: On average, S-MAN is an inefficient intervention. S-MON may be cost effective, depending on the willingness to pay for a 1 mmHg BP reduction, although it yielded fewer QALYs over the within-trial time horizon. Decision modelling is required to explore the longer-term costs and outcomes