Stroke Mortality, Clinical Presentation and Day of Arrival: The Atherosclerosis Risk in Communities (ARIC) Study

Background. Recent studies report that acute stroke patients who present to the hospital on weekends have higher rates of 28-day mortality than similar patients who arrive during the week. However, how this association is related to clinical presentation and stroke type has not been systematically investigated. Methods and Results. We examined the association between day of arrival and 28-day mortality in 929 validated stroke events in the ARIC cohort from 1987–2004. Weekend arrival was defined as any arrival time from midnight Friday until midnight Sunday. Mortality was defined as all-cause fatal events from the day of arrival through the 28th day of followup. The presence or absence of thirteen stroke signs and symptoms were obtained through medical record review for each event. Binomial logistic regression was used to estimate odds ratios and 95% confidence intervals (OR; 95% CI) for the association between weekend arrival and 28-day mortality for all stroke events and for stroke subtypes. The overall risk of 28-day mortality was 9.6% for weekday strokes and 10.1% for weekend strokes. In models controlling for patient demographics, clinical risk factors, and event year, weekend arrival was not associated with 28-day mortality (0.87; 0.51, 1.50). When stratified by stroke type, weekend arrival was not associated with increased odds of mortality for ischemic (1.17, 0.62, 2.23) or hemorrhagic (0.37; 0.11, 1.26) stroke patients. Conclusions. Presence or absence of thirteen signs and symptoms was similar for weekday patients and weekend patients when stratified by stroke type. Weekend arrival was not associated with 28-day all-cause mortality or differences in symptom presentation for strokes in this cohort

Southwest Pacific subtropics responded to last deglacial warming with changes in shallow water sources

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 29 (2014): 595–611, doi:10.1002/2013PA002584.This study examined sources of mixed layer and shallow subsurface waters in the subtropical Bay of Plenty, New Zealand, across the last deglaciation (~30–5 ka). δ18O and δ13C from planktonic foraminifera Globgerinoides bulloides and Globorotalia inflata in four sediment cores were used to reconstruct surface mixed layer thickness, δ18O of seawater (δ18OSW) and differentiate between high- and low-latitude water provenance. During the last glaciation, depleted planktonic δ18OSW and enriched δ13C (−0.4–0.1‰) indicate surface waters had Southern Ocean sources. A rapid δ13C depletion of ~1‰ in G. bulloides between 20 and 19 ka indicates an early, permanent shift in source to a more distal tropical component, likely with an equatorial Pacific contribution that persisted into the Holocene. At 18 ka, a smaller but similar shift in G. inflata δ13C depletion of ~0.3‰ suggests that deeper subsurface waters had a delayed reaction to changing conditions during the deglaciation. This contrasts with the isotopic records from nearby Hawke Bay, to the east of the North Island of New Zealand, which exhibited several changes in thermocline depth indicating switches between distal subtropical and proximal subantarctic influences during the early deglaciation ending only after the Antarctic Cold Reversal. Our results identify the midlatitude subtropics, such as the area around the North Island of New Zealand, as a key region to decipher high- versus low-latitude influences in Southern Hemisphere shallow water masses.Funding for this project came from NSF OCE-0823487 and 0823549-03.2014-12-1

新しい時代に対応した授業の在り方を考える：活用型学習活動の実践を通して（第53回（平成20年度）公開研究発表会 総論）

Background Overuse and inappropriate prescribing of antibiotics is driving antibiotic resistance. GPs often prescribe antibiotics for upper respiratory tract infections (URTIs) in young children despite their marginal beneficial effects. Aim To assess the quality of antibiotic prescribing for common infections in young children attending primary care and to investigate influencing factors. Design and setting An observational, descriptive analysis, including children attending primary care sites in England and Wales. Method The Diagnosis of Urinary Tract infection in Young children study collected data on 7163 children aged <5 years, presenting to UK primary care with an acute illness (<28 days). Data were compared with the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) disease-specific quality indicators to assess prescribing for URTIs, tonsillitis, and otitis media, against ESAC-Net proposed standards. Non-parametric trend tests and χ2 tests assessed trends and differences in prescribing by level of deprivation, site type, and demographics. Results Prescribing rates fell within the recommendations for URTIs but exceeded the recommended limits for tonsillitis and otitis media. The proportion of children receiving the recommended antibiotic was below standards for URTIs and tonsillitis, but within the recommended limits for otitis media. Prescribing rates increased as the level of deprivation decreased for all infections (P<0.05), and increased as the age of the child increased for URTIs and tonsillitis (P<0.05). There were no other significant trends or differences. Conclusion The quality of antibiotic prescribing in this study was mixed and highlights the scope for future improvements. There is a need to assess further the quality of disease-specific antibiotic prescribing in UK primary care settings using data representative of routine clinical practice

A temperate former West Antarctic ice sheet suggested by an extensive zone of bed channels

Several recent studies predict that the West Antarctic Ice Sheet will become increasingly unstable under warmer conditions. Insights on such change can be assisted through investigations of the subglacial landscape, which contains imprints of former ice-sheet behavior. Here, we present radio-echo sounding data and satellite imagery revealing a series of ancient large sub-parallel subglacial bed channels preserved in the region between the Möller and Foundation Ice Streams, West Antarctica. We suggest that these newly recognized channels were formed by significant meltwater routed along the icesheet bed. The volume of water required is likely substantial and can most easily be explained by water generated at the ice surface. The Greenland Ice Sheet today exemplifies how significant seasonal surface melt can be transferred to the bed via englacial routing. For West Antarctica, the Pliocene (2.6–5.3 Ma) represents the most recent sustained period when temperatures could have been high enough to generate surface melt comparable to that of present-day Greenland. We propose, therefore, that a temperate ice sheet covered this location during Pliocene warm periods

Low birth weight and markers of inflammation and endothelial activation in adulthood: The ARIC study

To investigate the hypothesis that intrauterine growth restriction might produce a longstanding pro-inflammatory tendency, we investigated the association of low birth weight with blood levels of markers of inflammation and endothelial activation in middle-aged adults

Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins

As core components of the microRNA-induced silencing complex (miRISC), Argonaute (AGO) proteins interact with TNRC6 proteins, recruiting other effectors of translational repression/mRNA destabilization. Here, we show that LIMD1 coordinates the assembly of an AGO-TNRC6 containing miRISC complex by binding both proteins simultaneously at distinct interfaces. Phosphorylation of AGO2 at Ser 387 by Akt3 induces LIMD1 binding, which in turn enables AGO2 to interact with TNRC6A and downstream effector DDX6. Conservation of this serine in AGO1 and 4 indicates this mechanism may be a fundamental requirement for AGO function and miRISC assembly. Upon CRISPR-Cas9-mediated knockout of LIMD1, AGO2 miRNA-silencing function is lost and miRNA silencing becomes dependent on a complex formed by AGO3 and the LIMD1 family member WTIP. The switch to AGO3 utilization occurs due to the presence of a glutamic acid residue (E390) on the interaction interface, which allows AGO3 to bind to LIMD1, AJUBA, and WTIP irrespective of Akt signaling

Medication, reperfusion therapy and survival in a community-based setting of hospitalised myocardial infarction

To examine the survival benefit of multiple medical therapies in a large, community-based population of validated myocardial infarction (MI) events

Temporal Trends in Medical Therapies for ST- and Non-ST Elevation Myocardial Infarction: (from the Atherosclerosis Risk in Communities [ARIC] Surveillance Study)

Reports from large studies using administrative datasets and event registries have characterized recent temporal trends and treatment patterns for AMI. However, few are population-based and fewer have examined differences in patterns of treatment for patients presenting with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). We examined 22-year trends in the use of 10 medical therapies and procedures by STEMI and NSTEMI classification in 30986 definite or probable MIs in the ARIC Community Surveillance Study from 1987 to 2008. We used weighted multivariable Poisson regression controlling for sex, race/center classification, age, and PREDICT score to estimate average annual percent changes in medical therapy use. From 1987 – 2008, 6106 (19.7%) hospitalized events were classified as STEMI, and 20302 (65.5%) were classified as NSTEMI. Among STEMI patients, increases (%; 95% CI) were noted in the use of ACE inhibitors (6.4; 5.7, 7.2), non-aspirin anti-platelets (5.0; 4.0, 6.0), lipid-lowering medications (4.5; 3.1, 5.8), beta blockers (2.7; 2.4, 3.0), aspirin (1.2; 1.0, 1.3), and heparin (0.8; 0.4, 1.3). Among NSTEMI patients, the use of ACE inhibitors (5.5; 5.0, 6.1), non-aspirin anti-platelets (3.7; 2.7, 4.7), lipid-lowering medications (3.0; 1.9, 4.1), beta blockers (4.2; 3.9, 4.4), aspirin (1.9, 1.6; 2.1), and heparin (1.7; 1.3, 2.1) increased. Among STEMI patients, we observed decreases in the use of thrombolytics (-7.2; -7.9, -6.6) and CABG (-2.4%; -3.6, -1.2). We noted similar increases in PCI and decreases in the use of thrombolytics and CABG among all patients. In conclusion, we found trends of increasing use of evidence-based therapies for both STEMI and NSTEMI patients over the past 22 years

Freezing of ridges and water networks preserves the Gamburtsev Subglacial Mountains for millions of years

Once an ice sheet grows beyond a critical thickness, the basal thermal regime favors melting and development of subglacial water networks. Subglacial water is necessary for bedrock erosion, but the exact mechanisms that lead to preservation of subglacial topography are unclear. Here we resolve the freezing mechanisms that lead to long-term, high-altitude preservation across the Gamburtsev Subglacial Mountains in East Antarctica. Analyses of a comprehensive geophysical data set reveal a large-scale water network along valley floors. The ice sheet often drives subglacial water up steep topography where it freezes along high ridges beneath thinner ice. Statistical tests of hypsometry show the Gamburtsevs resemble younger midlatitude mountains, indicating exceptional preservation. We conclude that the Gamburtsevs have been shielded from erosion since the latest Eocene (∼34 Ma). These freezing mechanisms likely account for the spatial and temporal patterns of erosion and preservation seen in other glaciated mountain ranges

Hormone replacement therapy and cardiovascular disease: A statement for healthcare professionals from the American Heart Association

For more than 50 million American women, and millions of women in other countries who are over the age of 50 years, the decision whether or not to use estrogen replacement therapy (ERT) for chronic disease prevention is often a difficult one. Established benefits of treatment for menopausal symptoms and prevention of osteoporosis must be weighed against documented risks of therapy, including venous thromboembolic events (VTE), gallbladder disease, and a possible increased risk of breast cancer. Unopposed ERT is also associated with an increased risk of endometrial cancer in women with a uterus. Therefore, it is typically combined with a progestin and is referred to as hormone replacement therapy (HRT). The impact of ERT/HRT on cardiovascular disease (CVD) is of great public health importance, because CVD is the leading cause of death and a major contributor to disability in women.1 The purpose of this advisory is to summarize the currently available data concerning potential CVD benefits and risks associated with ERT/HRT and to provide updated clinical recommendations regarding its use in the secondary and primary prevention of CVD