Abstract Objective: To create a risk score for death from cardiovascular disease that can be easily used. Design: Data from eight randomised controlled trials of antihypertensive treatment. Setting: ...Europe and North America. Participants: 47 088 men and women from trials that had differing age ranges and differing eligibility criteria for blood pressure. Main outcome measure: 1639 deaths from cardiovascular causes during a mean 5.2 years of follow up. Results: Baseline factors were related to risk of death from cardiovascular disease using a multivariate Cox model, adjusting for trial and treatment group (active versus control). A risk score was developed from 11 factors: age, sex, systolic blood pressure, serum total cholesterol concentration, height, serum creatinine concentration, cigarette smoking, diabetes, left ventricular hypertrophy, history of stroke, and history of myocardial infarction. The risk score is an integer, with points added for each factor according to its association with risk. Smoking contributed more in women and in younger age groups. In women total cholesterol concentration mattered less than in men, whereas diabetes had more of an effect. Antihypertensive treatment reduced the score. The five year risk of death from cardiovascular disease for scores of 10, 20, 30, 40, 50, and 60 was 0.1%, 0.3%, 0.8%, 2.3%, 6.1%, and 15.6%, respectively. Age and sex distributions of the score from the two UK trials enabled individual risk assessment to be age and sex specific. Risk prediction models are also presented for fatal coronary heart disease, fatal stroke, and all cause mortality. Conclusion: The risk score is an objective aid to assessing an individual's risk of cardiovascular disease, including stroke and coronary heart disease. It is useful for physicians when determining an individual's need for antihypertensive treatment and other management strategies for cardiovascular risk. What is already known on this topic Many other factors are known to affect the risk of cardiovascular disease in patients with raised blood pressure A patient's overall risk should be taken into account when determining their need for antihypertensive drugs and other strategies for improving cardiovascular health What this study adds A new score uses 11 risk factors to quantify an adult's risk of death from cardiovascular disease, including stroke and coronary heart disease The score is based on a large cohort of participants in controlled trials of antihypertensive drugs An individual's risk can be readily assessed as high or low compared with others of the same age and sex The website http://www.riskscore.org.uk/ is available for users of the risk score
We investigate the solar cycle modulation of the quasi‐biennial oscillation (QBO) in stratospheric zonal winds and its impact on stratospheric ozone with an updated version of the zonally averaged ...CHEM2D middle atmosphere model. We find that the duration of the westerly QBO phase at solar maximum is 3 months shorter than at solar minimum, a more robust result than in an earlier CHEM2D study due to reduced Rayleigh friction drag in the present version of the model. The modeled solar cycle ozone response, determined via multiple linear regression, is compared with observational estimates from the combined Solar Backscattered Ultraviolet (SBUV/2) data set for the period 1979–2003. We find that a model simulation including imposed solar UV variations, the zonal wind QBO, and an imposed 11‐year variation in planetary wave 1 amplitude produces a lower stratospheric ozone response of ∼2.5% between 0 and 20°S and an upper stratospheric ozone response of ∼1% between 45 and 55 km, in good agreement with the SBUV‐derived ozone response. This simulation also produces an (enhancement/reduction) in the (lower/upper) stratospheric temperature response at low latitudes compared to the effects of solar UV variations alone, which are consistent with model vertical velocity anomalies produced by the solar‐modulated QBO and imposed changes in planetary wave forcing.
We have investigated the 5 day wave in both temperature and water vapor in the stratosphere and mesosphere as seen in the Navy Operational Global Atmospheric Prediction System–Advanced Level Physics ...High Altitude (NOGAPS‐ALPHA) analysis fields for summer 2007. We have compared these fields and the derived saturation ratios with polar mesospheric cloud (PMC) measurements from the AIM satellite. We find that the 5 day wave is variable in both time and space, with significant amplitudes in the temperature wave in August (up to ∼6 K). By contrast, the 5 day wave–induced water vapor anomalies remain at a near‐constant level throughout the season. During August, the 5 day wave in the NOGAPS‐ALPHA saturation ratio and in the occurrence of clouds in the AIM data shows a clear anticorrelation with bright PMCs forming in the trough of the temperature wave. The analysis shows that the August enhancement in the 5 day wave amplitude acts to extend the PMC season past the time when zonal mean temperatures are saturated with respect to ice. The increased wave amplitude in August is attributed to in situ wave generation and amplification due to baroclinic instability of mean winds at around 0.1–0.01 hPa. The late‐season extension of cloud occurrence due to the 5 day wave may explain previous ground‐based reports of bright noctilucent cloud displays in August.
PS-341, a selective inhibitor of the proteasome, currently is under evaluation as an anticancer agent in multiple phase I clinical trials. In animal-model studies, PS-341 was rapidly removed from the ...vascular compartment and distributed widely, quickly approaching the limits of detection. An accurate pharmacodynamic assay has been developed as an alternative or complement to pharmacokinetic measurements.
Fluorogenic kinetic assays for both the chymotryptic and tryptic activities of the proteasome have been optimized for both whole blood and blood cells. Using the ratio of these activities and the catalytic mechanism of the proteasome, we developed a novel method of calculating percentage of inhibition, using two structurally unrelated inhibitors (PS-341 and lactacystin).
This ratio method was demonstrated to be sensitive (detection limit of 13% inhibition with 10 microgram of cell lysate), specific to the proteasome (PS-341 provides >98% inhibition), accurate (112% analyte recovery), and precise (0% +/- 5% inhibition at 0 nmol/L PS-341 and 74.5% +/- 1.7% inhibition at 200 nmol/L PS-341). Using these assays, we found that both erythrocytes and leukocytes contain proteasome at 3 micromol/L. Pharmacodynamic results for PS-341 obtained from the whole-blood ratio method were comparable to those using leukocytes determined by another method.
The described assay provides a reliable method for studying the pharmacodynamics of proteasome inhibitors and is now in use in concurrent phase I clinical trials with PS-341.
There is currently an ambiguity in what controls polar mesospheric cloud (PMC) periodicities near 83 km altitude. This is primarily because satellite and ground‐based data sets cannot resolve global ...mesospheric temperature variability over the diurnal cycle. To address this limitation, we employ a global meteorological analysis and forecast system that assimilates mesospheric satellite data with two significant advances. The first is that we use output at a more rapid one hourly cadence, allowing for a quantitative description of diurnal (24 h), semidiurnal (12 h), and terdiurnal oscillations. The second is that the output drives a simple PMC parameterization which depends only on the local temperature, pressure, and water vapor concentrations. Our study focuses on results from July 2009 in the Northern Hemisphere and January 2008 in the Southern Hemisphere. We find that the 24 h migrating temperature tide as well as the 12 h and 24 h nonmigrating tides dominate northern PMC oscillations whereas the 12 h and 24 h nonmigrating tides dominate southern oscillations. Monthly averaged amplitudes for each of these components are generally 2–6 K with the larger amplitudes at lower PMC latitudes (50°). The 2 day and 5 day planetary waves also contribute in both hemispheres, with monthly averaged amplitudes from 1 to 3 K although these amplitudes can be as high as 4–6 K on some days. Over length scales of ~1000 km and timescales of ~1 week, we find that local temperature oscillations adequately describe midlatitude PMC observations.
Key Points
Solar temperature tides and the 2 day and 5 day planetary waves are quantified throughout the northern and southern PMC regions
The impact of these periodicities on PMC frequency and ice water content are determined
PMC results are compared directly to two independent satellite data sets
A decadal variation of tropical lower stratospheric ozone and temperature has previously been identified that correlates positively with the 11 year solar activity cycle. However, the El ...Niño–Southern Oscillation (ENSO) also influences lower stratospheric ozone and temperature. It is therefore legitimate to ask whether quasi‐decadal ENSO variability can contribute to this apparent solar cycle variation, either accidentally because of the short measurement record or physically because solar variability affects ENSO. Here we present multiple regression analyses of available data records to compare differences in results obtained with and without including an ENSO term in the statistical model. In addition, simulations are performed using the NRL NOGAPS‐ALPHA GCM for warm/cold ENSO conditions to test for consistency with the ENSO regression results. We find only very minor changes in annual mean solar regression coefficients when an ENSO term is included. However, the observed tropical ENSO response provides useful insights into the origin of the unexpected vertical structure of the tropical solar cycle ozone response. In particular, the ENSO ozone response is negative in the lower stratosphere due to increased upwelling but changes sign, becoming positive in the middle stratosphere (5–10 hPa) due mainly to advective decreases of temperature and NOx, which photochemically increase ozone. A similar mechanism may explain the observed lower stratospheric solar cycle ozone and temperature response and the absence of a significant response in the tropical middle stratosphere.
The zonally averaged CHEM2D photochemical‐dynamical middle atmosphere model is used to investigate the effect of the 11‐year cycle in solar ultraviolet (UV) irradiance on the quasi‐biennial ...oscillation (QBO) in equatorial lower stratospheric zonal wind. Model calculations show the duration of the westerly (easterly) phase of the modeled QBO is ∼1 month shorter (longer) at solar maximum than at solar minimum. This effect is most apparent when the modeled QBO period is 28 months, and it is dependent on the magnitude of the imposed solar UV variations. The model results also show that a realistic simulation of the semi‐annual oscillation in equatorial zonal wind is necessary to produce solar cycle changes in QBO behavior. This is the first fully interactive modeling study to show that changes in solar UV can influence the behavior of the QBO, and lends support to the current working theory of sun‐climate connections.
Previous modeling studies have found significant differences in winter extratropical stratospheric temperatures depending on the presence or absence of zonally asymmetric ozone heating (ZAOH), yet ...the physical mechanism causing these differences has not been fully explained. The present study describes the effect of ZAOH on the dynamics of the Northern Hemisphere extratropical stratosphere using an ensemble of free‐running atmospheric general circulation model simulations over the 1 December ‐ 31 March period. We find that the simulations including ZAOH produce a significantly warmer and weaker stratospheric polar vortex in mid‐February due to more frequent major stratospheric sudden warmings compared to the simulations using only zonal mean ozone heating. This is due to regions of enhanced Eliassen‐Palm flux convergence found in the region between 40°N–70°N latitude and 10–0.05 hPa. These results are consistent with changes in the propagation of planetary waves in the presence of ZAOH predicted by an ozone‐modified refractive index.
ObjectiveTo investigate current Down syndrome live birth and death rates, and childhood hospitalisations, compared with peers.SettingGeneral community.ParticipantsAll live births with Down syndrome, ...1990–2015, identified via Scottish regional cytogenetic laboratories, each age–sex–neighbourhood deprivation matched with five non-Down syndrome controls. Record linkage to Scotland’s hospital admissions and death data.Primary outcomeHRs comparing risk of first hospitalisation (any and emergency), readmission for children with Down syndrome and matched controls were calculated using stratified Cox proportional hazards (PH) model, and length of hospital stay was calculated using a conditional log-linear regression model.Results689/1479 (46.6%) female and 769/1479 (51.9%) male children/young people with Down syndrome were identified (1.0/1000 births, with no reduction over time); 1235 were matched. 92/1235 (7.4%) died during the period, 18.5 times more than controls. More of the Down syndrome group had at least one admission (incidence rate ratio(IRR) 72.89 (68.72–77.32) vs 40.51 (39.15–41.92); adjusted HR=1.84 (1.68, 2.01)) and readmissions (IRR 54.85 (51.46–58.46) vs 15.06 (14.36–15.80); adjusted HR=2.56 (2.08, 3.14)). More of their admissions were emergencies (IRR 56.78 (53.13–60.72) vs 28.88 (27.73–30.07); first emergency admission adjusted HR=2.87 (2.61, 3.15)). Children with Down syndrome had 28% longer first admission after birth. Admission rate increased from 1990–2003 to 2004–2014 for the Down syndrome group (from 90.7% to 92.2%) and decreased for controls (from 63.3% to 44.8%).ConclusionsWe provide contemporaneous statistics on the live birth rate of babies with Down syndrome, and their childhood death rate. They require more hospital admissions, readmissions emergency admissions and longer lengths of stays than their peers, which has received scant research attention in the past. This demonstrates the importance of statutory planning as well as informal support to families to avoid added problems in child development and family bonding over and above that brought by the intellectual disabilities associated with Down syndrome.
The atmosphere's response to the total solar eclipse of 4 December 2002 is studied using a prototype high‐altitude global numerical weather prediction model (NOGAPS‐ALPHA). Local reductions in solar ...ultraviolet (UV) radiation during the eclipse are estimated using astronomical calculations of umbral and penumbral surface trajectories and observed solar limb darkening at ∼200–300 nm. In NOGAPS‐ALPHA these UV eclipse shadows yield stratospheric radiative cooling rate footprints peaking near 27 K day−1, a value 2–3 times larger than assumed in previous modeling. Difference fields between NOGAPS‐ALPHA runs with and without this eclipse forcing reveal vertically deep middle atmospheric responses, with three‐dimensional horizontal structures very similar to the large‐scale “bow‐wave” response first proposed by Chimonas (1970). Such structure appears clearly only at later times when total eclipses have abated and gravity waves generated in the stratosphere have had time to propagate vertically. Bow‐wave amplitudes and direct thermal cooling responses are both small (≲1 K for temperature and ≲2–3 m s−1 for horizontal winds), contradicting some rocketsonde measurements that suggest much larger responses near 50–60 km altitude. We also find clear evidence of a bow‐wave‐like response in the model's surface pressure fields, with an amplitude ∼0.1–0.5 hPa, while surface air temperatures in NOGAPS‐ALPHA show ∼4 K cooling over Africa during the eclipse. Both findings are consistent with surface atmospheric data acquired during previous eclipse passages.
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