bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prescribing of antipsychotics in UK primary care: a cohort study
Authors: Marston Louise , Nazareth Irwin , Petersen Irene , Walters Kate , Osborn David P J 
Published: December 2014

ObjectiveTo examine the recorded indication for antipsychotic prescriptions in UK primary care.DesignCohort study.SettingPrimary care.ParticipantsIndividuals prescribed antipsychotics between 2007 and 2011.MeasuresThe proportion of individuals prescribed antipsychotics with a diagnosis of (1) psychosis and bipolar disorder, (2) other diagnoses including depression, anxiety and dementia and (3) none of these diagnoses.ResultsWe identified 47 724 individuals prescribed antipsychotic agents. 13 941 received first-generation agents and 27 966 received second-generation agents. The rates of prescribing were higher in females (incidence rate ratio (IRR) 1.092 (95% CI 1.088 to 1.095), older people (80+ vs 40–49; IRR 2.234 (2.222 to 2.246)) and in those from the most deprived areas (most deprived vs least deprived IRR 3.487 (3.567 to 3.606). Of those receiving first-generation antipsychotics, less than 50% had a diagnosis of psychosis/bipolar disorder. For the second-generation agents, the numbers ranged from 4824 (36%) for quetiapine to 7094 (62%) for olanzapine. In patients without psychosis/bipolar disorder, common diagnoses included anxiety, depression, dementia, sleep and personality disorders. For example, in risperidone users, 14% had an anxiety code, 22% depression, 12% dementia, 11% sleep disorder and 4% personality disorder. The median daily doses and duration of treatment were greater in those with schizophrenia (eg, risperidone median daily dose 4 mg; IQR 2–6: median duration 1.2 years) than in those with non-psychotic/bipolar disorders such as depression or anxiety (eg, risperidone 1 mg; IQR 1–2: 0.6 years). A relatively large proportion (between 6% and 17%) of people receiving individual antipsychotics had none of the diagnoses stated above.ConclusionsIn UK primary care, a large proportion of people prescribed antipsychotics have no record of psychotic or bipolar disorder. They are often older people with conditions including dementia, non-psychotic depression, anxiety and sleep disorders.
Age before acuity: the drivers of demand for emergency department services in the Greater Sydney Area
Authors: Dinh Michael M , Bein Kendall J , Latt Mark , Chalkley Dane , Muscatello David 
Published: December 2014

ObjectiveTo contrast long-term population-based trends in general practice (GP) presentations and acute inpatient admissions from the emergency department (ED) in the elderly population within the Greater Sydney Area.MethodsThis was a retrospective analysis of population-based ED presentation data over 11 years, between January 2001 and December 2011, conducted within the Greater Sydney Area in Australia. De-identified data were obtained from the New South Wales Emergency Department Data Collection database on all patients presenting to 30 public hospital EDs located within the Greater Sydney Area. The outcomes of interest were GP presentations to ED (triage category 4 or 5, self-referred and discharged from ED) and of acute inpatient admissions from ED per 1000 population.ResultsOver 11 million presentations were identified. Around 40% of presentations were classified as a GP presentation and 23% were classified as acute inpatient admissions. There was a 2.9% per annum increase in acute inpatient admissions per 1000 population in those ≥80 years of age and no appreciable change in other age groups. Rates of GP presentations were higher in those <65 years of age. GP presentations increased 1.9% per annum in those aged <65 years of age.ConclusionsThe increase in ED demand appears to be driven by the elderly presenting with acute problems requiring inpatient admission. There has been a modest increase in the rate of GP presentations to ED.
eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor Cells
Authors: Avdulov Svetlana , Herrera Jeremy , Smith Karen , Peterson Mark , Gomez-Garcia Jose R. , Beadnell Thomas C. , Schwertfeger Kathryn L. , Benyumov Alexey O. , Manivel J. Carlos , Li Shunan , Bielinsky Anja-Katrin , Yee Douglas , Bitterman Peter B. , Polunovsky Vitaly A. 
Published: December 2014

Abstract
Translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when overexpressed. The mechanisms by which eIF4E directs such distinct biologic outputs remain unknown. We found that mouse mammary morphogenesis during pregnancy and lactation is accompanied by increased cap-binding capability of eIF4E and activation of the eIF4E-dependent translational apparatus, but only subtle oscillations in eIF4E abundance. Using a transgenic mouse model engineered so that lactogenic hormones stimulate a sustained increase in eIF4E abundance in stem/progenitor cells of lactogenic mammary epithelium during successive pregnancy/lactation cycles, eIF4E overexpression increased self-renewal, triggered DNA replication stress, and induced formation of premalignant and malignant lesions. Using complementary in vivo and ex vivo approaches, we found that increasing eIF4E levels rescued cells harboring oncogenic c-Myc or H-RasV12 from DNA replication stress and oncogene-induced replication catastrophe. Our findings indicate that distinct threshold levels of eIF4E govern its biologic output in lactating mammary glands and that eIF4E overexpression in the context of stem/progenitor cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints activated by oncogenic stimuli. Maintaining eIF4E levels below its proneoplastic threshold is an important anticancer defense in normal cells, with important implications for understanding pregnancy-associated breast cancer. Cancer Res; 75(4); 687–97. ©2014 AACR.
Assays of fibrin network properties altered by VKAs in atrial fibrillation – importance of using an appropriate coagulation trigger
Authors: Ząbczyk Michal , Blombäck Margareta , Majewski Jacek , Karkowski Grzegorz , Wallen Hakan N. , Undas Anetta , He Shu 
Published: December 2014

SummaryAtrial fibrillation (AF) is a prothrombotic condition, involving increased thrombin generation and fibrinogen concentrations. Vitamin K antagonists (VKAs) prevent arterial thromboembolism if optimal anticoagulation is achieved by individualised drug doses, assessed by determining the Prothrombin time-related International Normalized Ratio (Pt-INR). There is evidence that formation of tight-laced fibrin networks is pathogenic in prothrombotic diseases. This study was performed among AF patients, to test whether long-term treatment with VKAs affects the structure of fibrin networks, and whether the effect is altered by employing different coagulation triggers: exogenous thrombin (1 IU/ml), 10 pM tissue factor (TF) or a commercial Pt-INR reagent (containing 400-fold more TF). In the thrombin-based method, fibrin network porosity (scanning electron microscopy) and liquid permeability (flow measurements) correlated inversely to fibrinogen concentrations, while positive correlations to the degree of anticoagulation were shown with the Pt-INR reagent. In the method with 10 pM TF, the two above relationships were detected, though the influence of Pt-INR was more profound than that of fibrinogen concentrations. Moreover, greater shortening of clot lysis time (CLT) arose from more permeable clots. As a coagulation trigger, 10 pM TF vs exogenous thrombin or the Pt-INR reagent is more informative in reflecting the in vivo process from thrombin generation to fibrin formation. Since fibrin network permeability rose in parallel to elevations of INR and shortening of CLT in AF patients, antithrombotic effects on prevention of thrombotic complications may be achieved from impairment of thrombin generation, resulting in formation of permeable clots susceptible to fibrinolysis.
Cluster of Differentiation 43 Deficiency in Leukocytes Leads to Reduced Atherosclerosis—Brief Report
Authors: Meiler Svenja , Baumer Yvonne , McCurdy Sara , Lee Bog-Hieu , Kitamoto Shiro , Boisvert William A. 
Published: December 2014

Objective—
The aim of this study was to investigate the role of cluster of differentiation 43 (CD43), an integral membrane glycoprotein with both proadhesive and antiadhesive activities, in atherosclerosis.

Approach and Results—

Low-density lipoprotein receptor–deficient mice were lethally irradiated and reconstituted with either bone marrow from
CD43
−/−
mice or from wild-type controls. We found that mice lacking the CD43 on their leukocytes had significantly less severe atherosclerosis and that, contrary to our expectation, macrophage infiltration into the vessel wall was not affected by the lack of CD43 in the leukocytes. However, we found that CD43 mediates cholesterol homeostasis in macrophages by facilitating cholesterol efflux. This resulted in a significant reduction in storage of cholesterol in the aorta of mice lacking CD43 in the leukocytes.

Conclusions—
CD43 may be an important mediator of macrophage lipid homeostasis, thereby affecting macrophage foam cell formation and ultimately atherosclerotic plaque development.
White Matter Ischemic Changes in Hyperacute Ischemic Stroke
Authors: Nael Kambiz , Trouard Theodore P , Lafleur Scott R. , Krupinski Elizabeth A. , Salamon Noriko , Kidwell Chelsea S. 
Published: December 2014

Background and Purpose—
The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis.

Methods—
In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA.

Results—

There was an overall significant mean difference (
P
<0.001) for the apparent diffusion coefficient, Tmax, and FA values between the normal, hypoperfused, and infarcted WM. The mean±SD of FA was significantly higher (
P
<0.001) in hypoperfused WM (0.397±0.019) and lower (
P
<0.001) in infarcted WM (0.313±0.037) when compared with normal WM (0.360±0.020). Regression tree analysis of hypoperfused WM showed the largest mean FA difference at Tmax above versus below 5.4 s with a mean difference of 0.033 (
P
=0.0096).

Conclusions—
Diffusion tensor imaging-FA was decreased in regions of WM infarction and increased in hypoperfused WM in patients with hyperacute acute ischemic stroke. The significantly increased FA values in the hypoperfused WM with Tmax≥5.4 s are suggestive of early ischemic microstructural changes.
Use of Follow-Up Imaging in Isolated Perimesencephalic Subarachnoid Hemorrhage
Authors: Kalra Vivek B. , Wu Xiao , Matouk Charles C. , Malhotra Ajay 
Published: December 2014

Background and Purpose—
Multiple studies have shown that negative computed tomographic angiograms (CTAs) are reliable in excluding aneurysms in patients with isolated perimesencephalic subarachnoid hemorrhage (pSAH). We evaluate the use of digital subtraction angiography versus CTA for initial diagnosis and of angiographic follow-ups in patients with pSAH by performing an institutional analysis and a meta-analysis of literature.

Methods—
Retrospective institutional analysis of patients with pSAH was performed from 2008 to 2014. The number and types of follow-up imaging studies were tabulated. Initial and follow-up studies were evaluated by an experienced neuroradiologist for intracranial aneurysm. Meta-analysis of literature was performed to assess the use of initial digital subtraction angiography and of follow-up imaging.

Results—
Our institutional review revealed no additional use of initial digital subtraction angiography or of any angiographic follow-up after initial negative CTA in patients with pSAH on noncontrast CT. Meta-analysis of 40 studies yielded a total of 1031 patients. Only 8 aneurysms were first diagnosed on follow-ups (0.78%). Careful review showed that some of these aneurysms reported on follow-up are of questionable validity. Initial digital subtraction angiography and follow-up imaging after a negative initial CTA showed no statistically significant benefits.

Conclusions—
In patients meeting the strict imaging criteria of pSAH, initial negative CTA is reliable in excluding aneurysms. A critical review of the literature through meta-analysis shows no foundation for multiple follow-up studies in patients with pSAH.
MicroRNA-424 Protects Against Focal Cerebral Ischemia and Reperfusion Injury in Mice by Suppressing Oxidative Stress
Authors: Liu Ping , Zhao Haiping , Wang Rongliang , Wang Peng , Tao Zhen , Gao Li , Yan Feng , Liu Xiangrong , Yu Shun , Ji Xunming , Luo Yumin 
Published: December 2014

Background and Purpose—
We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress–induced neuronal injury.

Methods—

Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion). The miR-424 level in the peri-infarct cortex was quantified. Mice were also administered miR-424 angomir by intracerebroventricular injection. Cerebral infarct volume, neuronal apoptosis, and levels of oxidative stress markers and antioxidants were evaluated. In an in vitro experiment, primary cortical neurons were exposed to H
2
O
2
and treated with miR-424 angomir, nuclear factor erythroid 2-related factor 2 siRNA, and superoxide dismutase (SOD) inhibitor; cell activity, lactate dehydrogenase release, malondialdehyde level, and manganese (Mn)SOD activity were then evaluated.

Results—

MiR-424 levels in the peri-infarct cortex increased at 1 and 4 hours then decreased 24 hours after reperfusion. Treatment with miR-424 decreased infarct volume and inhibited neuronal apoptosis after ischemia/reperfusion, reduced reactive oxygen species and malondialdehyde levels in the cortex, and increased the expression and activation of MnSOD as well as the expression of extracellular SOD and the redox-sensitive transcription factor nuclear factor erythroid 2-related factor. In neuronal cultures, miR-424 treatment abrogated H
2
O
2
-induced injury, as evidenced by decreased lactate dehydrogenase leakage and malondialdehyde level and increased cell viability and MnSOD activity; the protective effects of miR-424 against oxidative stress were reversed by nuclear factor erythroid 2-related factor knockdown and SOD inhibitor treatment.

Conclusions—
MiR-424 protects against transient cerebral ischemia/reperfusion injury by inhibiting oxidative stress.
Bright Vessel Appearance on Arterial Spin Labeling MRI for Localizing Arterial Occlusion in Acute Ischemic Stroke
Authors: Yoo Roh-Eul , Yun Tae Jin , Rhim Jung Hyo , Yoon Byung-Woo , Kang Koung Mi , Choi Seung Hong , Kim Ji-Hoon , Kim Jeong Eun , Kang Hyun-Seung , Sohn Chul-Ho , Han Moon Hee 
Published: December 2014

Background and Purpose—
The purpose of this study was to evaluate whether bright vessel appearance on arterial spin labeling (ASL) MRI can help localize arterial occlusion sites in patients with acute ischemic stroke.

Methods—
Patients who underwent MRI for suspected acute ischemic stroke, as identified by an area of restricted diffusion, were included. All images were visually analyzed for the presence or absence of (1) arterial occlusion on time-of-flight MR angiography, (2) bright vessel appearance on ASL images, and (3) susceptibility vessel sign. McNemar 2-tailed test was used to compare the sensitivities of ASL and susceptibility-weighted imaging for the detection of arterial occlusion, using MR angiography as the reference standard.

Results—

ASL bright vessel appearance was significantly more common in the group with occlusion than in the group without occlusion (94% [33 of 35] versus 21% [17 of 82], respectively;
P
<0.001). The bright vessel appearance, when present, was seen proximal or distal to the occlusion site. The bright vessel appearance had a significantly higher sensitivity for the detection of occlusion than the susceptibility vessel sign (94% [33 of 35] versus 66% [23 of 35], respectively;
P
=0.002). In cases with negative MR angiography, the bright vessel appearance helped identify more additional arterial occlusions than the susceptibility vessel sign (21% [17 of 82] versus 10% [8 of 82], respectively;
P
=0.012).

Conclusions—
The bright vessel appearance on ASL imaging can provide an important diagnostic clue for the detection and localization of arterial occlusion sites in patients with acute ischemic stroke.
Effects of Stroke Education of Junior High School Students on Stroke Knowledge of Their Parents
Authors: Matsuzono Kosuke , Yokota Chiaki , Takekawa Hidehiro , Okamura Tomonori , Miyamatsu Naomi , Nakayama Hirofumi , Nishimura Kunihiro , Ohyama Satoshi , Ishigami Akiko , Okumura Kosuke , Toyoda Kazunori , Miyamoto Yoshihiro , Minematsu Kazuo ,   Participating Investigators of Tochigi Junior High School Stroke Education Group, Sugiyama Daisuke , Nagao Masanori , Morimoto Akiko , Kadota Aya , Takizawa Nobue , Ieiri Kayo , Watanabe Teruki 
Published: December 2014

Background and purpose—
Educating the youth about stroke is a promising approach for spreading stroke knowledge. The aim of this study was to verify communication of stroke knowledge to parents by educating junior high school students about stroke.

Methods—
We enrolled 1127 junior high school students (age, 13–15 years) and their parents in the Tochigi prefecture, Japan. All students received a stroke lesson, watched an animated cartoon, and read the related Manga comic as educational aids. The students took back home the Manga and discussed what they learned with their parents. Questionnaires on stroke knowledge were given to all at baseline and immediately after the lesson.

Results—
A total of 1125 students and 915 parents answered the questionnaires. In the students, the frequency of correct answers increased significantly for all questions on stroke symptoms except for headache, and for all questions on risk factors after the lesson. In the parents, the correct answer rates increased for stroke symptoms except for headache and numbness in one side of the body, and for all questions on risk factors except for hypertension. Ninety-one percent of students and 92.7% of parents correctly understood the Face, Arm, Speech, and Time (FAST) mnemonic after the lesson.

Conclusions—
Improvement of stroke knowledge immediately after the stroke lesson was observed in parents as well as their children, which indicated that our teaching materials using the Manga was effective in delivering the stroke knowledge to parents through their children.
Reduced Risk of North American Cold Extremes due to Continued Arctic Sea Ice Loss
Authors: Screen James A. , Deser Clara , Sun Lantao 
Published: December 2014

Abstract
In early January 2014, an Arctic air outbreak brought extreme cold and heavy snowfall to central and eastern North America, causing widespread disruption and monetary losses. The media extensively reported the cold snap, including debate on whether human-induced climate change was partly responsible. Related to this, one particular hypothesis garnered considerable attention: that rapid Arctic sea ice loss may be increasing the risk of cold extremes in the midlatitudes. Here we use large ensembles of model simulations to explore how the risk of North American daily cold extremes is anticipated to change in the future, in response to increases in greenhouse gases and the component of that response solely due to Arctic sea ice loss. Specifically, we examine the changing probability of daily cold extremes as (un)common as the 7 January 2014 event. Projected increases in greenhouse gases decrease the likelihood of North American cold extremes in the future. Days as cold or colder than 7 January 2014 are still projected to occur in the mid-twenty-first century (2030–49), albeit less frequently than in the late twentieth century (1980–99). However, such events will cease to occur by the late twenty-first century (2080–99), assuming greenhouse gas emissions continue unabated. Continued Arctic sea ice loss is a major driver of decreased—not increased—North America cold extremes. Projected Arctic sea ice loss alone reduces the odds of such an event by one-quarter to one-third by the mid-twenty-first century, and to zero (or near zero) by the late twenty-first century.
Sudden Track Changes of Tropical Cyclones in Monsoon Gyres: Full-Physics, Idealized Numerical Experiments*
Authors: Liang Jia , Wu Liguang 
Published: December 2014

Abstract
Tropical cyclones (TCs) in the eastern semicircle of large-scale monsoon gyres (MGs) were observed to take either a northward (sudden northward and northward without a sharp turn) or a westward TC turn, but only the northward turn was previously simulated in a barotropic model. To understand what controls TC track types in MGs, idealized numerical experiments are performed using the full-physics Weather Research and Forecasting (WRF) Model. These experiments indicate that TCs initially located in the eastern semicircle of MGs can generally take three types of tracks: a sudden northward track, a westward track, and a northward track without a sharp turn. The track types depend upon the TC movement relative to the MG center.
In agreement with barotropic simulations, the WRF simulation confirms that approaching and being collocated with the MG center is crucial to the occurrence of sudden northward TC track changes and that sudden northward track changes can be generally accounted for by changes in the steering flow. TCs that take westward tracks and northward tracks without a sharp turn do not experience such a coalescence process. Westward TCs move faster than MGs and are then located to the west of the MG center, while TCs move more slowly than MGs and then take a northward track without a sharp turn. This study reveals that the specific TC track in the eastern semicircle of an MG is sensitive to the initial wind profiles of both MGs and TCs, suggesting that improvement in the observation of TC and MG structures is very important for predicting TC track types in MGs.