Earthquake early warning (EEW) entails detection of initial earthquake shaking and rapid estimation and notification to users prior to imminent, stronger shaking. EEW (ShakeAlert Phase 1, version ...2.0) went operational in California in October 2019 and is coming to the rest of the U.S. West Coast. But what are the technical and social challenges to delivering actionable information on earthquake shaking before it arrives? Although there will be tangible benefits, there are also limitations. Basic seismological principles, alert communication challenges, and potential response actions, as well as substantial lessons learned from the use of EEW in Japan, point to more limited opportunities to warn and protect than perhaps many expect. This is in part because potential warning times vary by region and are influenced by tectonic environment, hypocentral depth, and the fault’s proximity to the alert user. For the U.S. West Coast, particularly for crustal earthquakes, warning times are shorter—and possible mitigation actions are likely to be less effective—than often maintained. Nevertheless, EEW is an additional arrow in the quiver of earthquake information tools available in the service of earthquake risk reduction. What is called for, then, is transparency and balance in the EEW discussion: along with its potential, the acknowledgment of EEW’s inherent and practical limitations is needed. Recognizing these limitations could, in fact, make EEW implementation more successful as part of a holistic earthquake mitigation strategy, where its role among other earthquake information tools is quite natural.
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract Objective To quantify the incremental effect of combining blood pressure-lowering drugs from any 2 classes of thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium ...channel blockers over 1 drug alone and to compare the effects of combining drugs with doubling dose. Methods Meta-analysis of factorial trials in which participants were randomly allocated to 1 drug alone, another drug alone, both drugs together, or a placebo. Results We identified 42 trials (10,968 participants). With a thiazide used alone, the mean placebo-subtracted reduction in systolic blood pressure was 7.3 mm Hg and 14.6 mm Hg combined with a drug from another class. The corresponding reductions were 9.3 mm Hg and 18.9 mm Hg with a beta-blocker, 6.8 mm Hg and 13.9 mm Hg with an angiotensin-converting enzyme, and 8.4 mm Hg and 14.3 mm Hg with a calcium channel blocker. The expected blood pressure reduction from 2 drugs together, assuming an additive effect, closely predicted the observed blood pressure reductions. The ratios of the observed to expected incremental blood pressure reductions from combining each class of drug with any other over that from 1 drug were, respectively, for thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers: 1.04 (95% confidence interval CI, 0.88-1.20), 1.00 (95% CI, 0.76-1.24), 1.16 (95% CI, 0.93-1.39), and 0.89 (95% CI, 0.69-1.09); the overall average was 1.01 (95% CI, 0.90-1.12). Comparison of our results with those of a published meta-analysis of different doses of the same drug showed that doubling the dose of 1 drug had approximately one fifth of the equivalent incremental effect (0.22 95% CI, 0.19-0.25). Conclusion Blood pressure reduction from combining drugs from these 4 classes can be predicted on the basis of additive effects. The extra blood pressure reduction from combining drugs from 2 different classes is approximately 5 times greater than doubling the dose of 1 drug.
Patients with acute STEMI were randomly assigned to undergo infarct-vessel-only PCI or preventive PCI (PCI to noninfarct arteries with stenoses). The rate of the primary outcome of cardiac death, ...myocardial infarction, or refractory angina was lower with preventive PCI.
Patients with acute ST-segment elevation myocardial infarction (STEMI) are effectively treated with emergency angioplasty, hereafter called percutaneous coronary intervention (PCI), to restore blood flow to the coronary artery that is judged to be causing the myocardial infarction (infarct artery, also known as culprit artery).
1
–
5
These patients may have major stenoses in coronary arteries that were not responsible for the myocardial infarction,
6
but the value of performing PCI in such arteries for the prevention of future cardiac events is not known.
Some physicians have taken the view that stenoses in noninfarct arteries may cause serious adverse cardiac events that could . . .
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK ...cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma. This microenvironment ultimately limits the clinical efficacy of NK cell therapy. In this study, we examined the use of a TGF-beta receptor kinase inhibitor, LY2157299, in preserving the cytotoxic function of ex vivo expanded, highly activated NK cells following sustained exposure to pathologic levels of TGF-beta in vitro and in a liver metastases model of colon cancer. Using myeloid leukemia and colon cancer cell lines, we show that the TGF-beta driven impairment of NK cell cytotoxicity is mitigated by LY2157299. We demonstrate this effect using quantitative cytotoxicity assays as well as by showing a preserved activated phenotype with high NKG2D/CD16 expression and enhanced cytokine production. In a mouse liver metastases model of colon cancer, we observed significantly improved eradication of liver metastases in mice treated with adoptive NK cells combined with LY2157299 compared with mice receiving NK cells or TGF beta inhibition alone. We propose that the therapeutic efficacy of adoptive NK cell therapy clinically will be markedly enhanced by complementary approaches targeting TGF-beta signaling in vivo.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study assessed child–parent screening for familial hypercholesterolemia in primary care practices. For every 1000 children screened, 8 persons who had positive screening results for familial ...hypercholesterolemia were identified.
Population-based child–parent screening has been proposed to detect familial hypercholesterolemia.
1
The method screens two generations; the child provides the screening entry point, at an age when the measurement of cholesterol is most discriminatory.
1
If a child with familial hypercholesterolemia is identified, the parent with familial hypercholesterolemia may then be identified. Adults 20 to 39 years of age who were classified as having familial hypercholesterolemia were found to have a risk of a coronary heart disease event at a young age that was 100 times that of a person who did not have familial hypercholesterolemia.
2
Identification of children and most parents . . .
We describe and present a new model of global subduction zone geometries, called Slab1.0. An extension of previous efforts to constrain the two‐dimensional non‐planar geometry of subduction zones ...around the focus of large earthquakes, Slab1.0 describes the detailed, non‐planar, three‐dimensional geometry of approximately 85% of subduction zones worldwide. While the model focuses on the detailed form of each slab from their trenches through the seismogenic zone, where it combines data sets from active source and passive seismology, it also continues to the limits of their seismic extent in the upper‐mid mantle, providing a uniform approach to the definition of the entire seismically active slab geometry. Examples are shown for two well‐constrained global locations; models for many other regions are available and can be freely downloaded in several formats from our new Slab1.0 website, http://on.doi.gov/d9ARbS. We describe improvements in our two‐dimensional geometry constraint inversion, including the use of ‘average’ active source seismic data profiles in the shallow trench regions where data are otherwise lacking, derived from the interpolation between other active source seismic data along‐strike in the same subduction zone. We include several analyses of the uncertainty and robustness of our three‐dimensional interpolation methods. In addition, we use the filtered, subduction‐related earthquake data sets compiled to build Slab1.0 in a reassessment of previous analyses of the deep limit of the thrust interface seismogenic zone for all subduction zones included in our global model thus far, concluding that the width of these seismogenic zones is on average 30% larger than previous studies have suggested.
Key Points
Introduces a new set of detailed 3D global subduction zone models
Focuses on the shallow seismogenic zone (unrepresented in previous models)
Allows for improved finite‐fault, seismic and tsunami hazard calculations
A Polypill is proposed for the primary prevention of cardiovascular disease in people judged to be at risk on account of their age alone. Its efficacy in reducing cholesterol and blood pressure is ...uncertain.
We conducted a randomized double-blind placebo-controlled crossover trial of a Polypill among individuals aged 50+ without a history of cardiovascular disease and compared the reductions with those predicted from published estimates of the effects of the individual drugs. Participants took the Polypill (amlodipine 2.5 mg, losartan 25 mg, hydrochlorothiazide 12.5 mg and simvastatin 40 mg) each evening for 12 weeks and a placebo each evening for 12 weeks in random sequence. The mean within-person differences in blood pressure and low density lipoprotein (LDL) cholesterol at the end of each 12 week period were determined.
84 out of 86 participants completed both treatment periods. The mean systolic blood pressure was reduced by 17.9 mmHg (95% CI, 15.7-20.1) on the Polypill, diastolic blood pressure by 9.8 mmHg (8.1-11.5), and LDL cholesterol by 1.4 mmol/L (1.2-1.6), reductions of 12%, 11%, and 39% respectively. The results were almost identical to those predicted; 18.4 mmHg, 9.7 mmHg, and 1.4 mmol/L respectively.
The Polypill resulted in the predicted reductions in blood pressure and LDL cholesterol. Long term reductions of this magnitude would have a substantial effect in preventing heart attacks and strokes.
Controlled-Trials.com ISRCTN36672232.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objective Combination therapy, specifically with aspirin, cholesterol and blood pressure-lowering drugs, substantially reduces the risk of coronary heart disease, but the full preventive ...effect is only realized if treatment continues indefinitely. Our objective was to provide a summary estimate of adherence to drugs that prevent coronary heart disease, according to drug class and use in people who have had a myocardial infarction (secondary prevention) and people who have not (primary prevention). Methods A meta-analysis of data on 376,162 patients from 20 studies assessing adherence using prescription refill frequency for the following 7 drug classes was performed: aspirin, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-channel blockers, thiazides, and statins. Meta-regression was used to examine the effects of age, payment, and treatment duration. Results The summary estimate for adherence across all studies was 57% (95% confidence interval CI, 50-64) after a median of 24 months. There were statistically significant differences in adherence between primary and secondary prevention: 50% (CI, 45-56) and 66% (CI, 56-75), respectively ( P =. 012). Adherence was lower for thiazides (42%) than for angiotensin receptor blockers (61%) in primary prevention ( P =. 02). There were no other statistically significant differences between any of the drug classes in primary or secondary prevention studies. Adherence decreased by 0.15% points/month ( P = .07) and was unrelated to age or whether patients paid for their pills. Conclusion Adherence to preventive treatment is poor and little related to class of drug, suggesting that side effects are not the main cause. General, rather than class-specific, measures at improving adherence are needed.
About one third of patients prescribed blood pressure or lipid-lowering drugs for the prevention of coronary heart disease and stroke do not take their medication as prescribed. We conducted a ...randomized trial to evaluate text messaging as a means of improving adherence to cardiovascular disease preventive treatment.
303 patients taking blood pressure and/or lipid-lowering medications were randomly assigned to being sent text messages (Text group, 151) or not being sent them (No text group, 152). Texts were sent daily for 2 weeks, alternate days for 2 weeks and weekly thereafter for 22 weeks (6 months overall), using an automated computer programme. Patients were asked to respond on whether they had taken their medication, whether the text reminded them to do so if they had forgotten, and if they had not taken their medication to determine if there was a reason for not doing so. At 6 months, use of medication was assessed.
Two patients were lost to follow-up, providing data on 301 for analysis. In the No text group 38/151 (25%) took less than 80% of the prescribed regimen (ie. stopped medication completely or took it on fewer than 22 of the last 28 days of follow-up) compared to 14/150 patients (9%) in the Text group - an improvement in adherence affecting 16 per 100 patients (95% CI 7 to 24), p<0.001. The texts reminded 98/151 patients (65%) to take medication on at least one occasion and lead to 20/151 (13%) who stopped taking medication because of concern over efficacy or side-effects, resuming treatment.
In patients taking blood pressure or lipid-lowering treatment for the prevention of cardiovascular disease, text messaging improved medication adherence compared with no text messaging.
Controlled-Trials.com ISRCTN74757601.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Results from genetic epidemiological studies suggest that raised serum homocysteine is a cause of ischaemic heart disease, but the results of randomised trials suggest otherwise. We aimed to update ...meta-analyses on each type of study using the latest published data and test a hypothesis based on antiplatelet therapy use in the trials to explain the discrepancy.
Meta-analyses of ischaemic heart disease using (i) 75 studies in which the prevalence of a mutation (CT) in the MTHFR gene (which increases homocysteine) was determined in cases (22,068) and controls (23,618), and (ii) 14 randomised trials (39,597 participants) of homocysteine lowering and ischaemic heart disease events. The summary estimates from the two analyses were compared. Meta-analysis of the MTHFR studies showed a statistically significantly increased risk of ischaemic heart disease in TT compared with CC homozygotes; odds ratio 1.16 (1.04 to 1.29) for a 1.9 µmol/L homocysteine difference (TT minus CC). Meta-analysis of randomised trials showed no significant reduction in IHD risk from folic acid; relative risk 1.00 (0.93 to 1.08), despite a reduction in homocysteine of 3.3 µmol/L. There was a statistically significant difference in risk reduction between the 5 trials with the lowest prevalence of antiplatelet therapy (60% on average, usually aspirin), RR 0.93 (0.84 to 1.05) and the 5 trials with the highest prevalence (91% on average), RR 1.09 (1.00 to 1.19), p = 0.037 for the difference.
Discordant results from MTHFR studies and randomised trials could be explained by aspirin reducing or negating the anti-platelet effect of lowering homocysteine. On this basis, folic acid would have a role in the primary prevention of ischaemic heart disease, when aspirin is not taken routinely, but not in secondary prevention, when it is routine.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
