bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for hospital admission in the 28 days following a community-acquired pneumonia diagnosis in older adults, and their contribution to increasing hospitalisation rates over time: a cohort study
Authors: Millett Elizabeth R C , De Stavola Bianca L , Quint Jennifer K , Smeeth Liam , Thomas Sara L 
Published: December 2015

ObjectivesTo determine factors associated with hospitalisation after community-acquired pneumonia (CAP) among older adults in England, and to investigate how these factors have contributed to increasing hospitalisations over time.DesignCohort study.SettingPrimary and secondary care in England.Population39 211 individuals from the Clinical Practice Research Datalink, who were eligible for linkage to Hospital Episode Statistics and mortality data, were aged ≥65 and had at least 1 CAP episode between April 1998 and March 2011.Main outcome measuresThe association between hospitalisation within 28 days of CAP diagnosis (a ‘post-CAP’ hospitalisation) and a wide range of comorbidities, frailty factors, medications and vaccinations. We examined the role of these factors in post-CAP hospitalisation trends. We also looked at trends in post-CAP mortality and length of hospitalisation over the study period.Results14 comorbidities, 5 frailty factors and 4 medications/vaccinations were associated with hospitalisation (of 18, 12 and 7 considered, respectively). Factors such as chronic lung disease, severe renal disease and diabetes were associated with increased likelihood of hospitalisation, whereas factors such as recent influenza vaccination and a recent antibiotic prescription decreased the odds of hospitalisation. Despite adjusting for these and other factors, the average predicted probability of hospitalisation after CAP rose markedly from 57% (1998–2000) to 86% (2009–2010). Duration of hospitalisation and 28-day mortality decreased over the study period.ConclusionsThe risk factors we describe enable identification of patients at increased likelihood of post-CAP hospitalisation and thus in need of proactive case management. Our analyses also provide evidence that while comorbidities and frailty factors contributed to increasing post-CAP hospitalisations in recent years, the trend appears to be largely driven by changes in service provision and patient behaviour.
New Phenomena in the Spatial Isosceles Three-Body Problem with Unequal Masses
Authors: Yan Duokui , Liu Rongchang , Hu Xingwei , Mao Weize , Ouyang Tiancheng 
Published: December 2015

This work studies periodic orbits as action minimizers in the spatial isosceles three-body problem with mass [Formula: see text]. In each period, the body with mass [Formula: see text] moves up and down on a vertical line, while the other two bodies have the same mass [Formula: see text], and rotate about this vertical line symmetrically. For given [Formula: see text], such periodic orbits form a one-parameter set with a rotation angle [Formula: see text] as the parameter. [Formula: see text]Two new phenomena are found for this set. First, for each [Formula: see text], this set of periodic orbits bifurcate from a circular Euler (central configuration) orbit to a Broucke (collision) orbit as [Formula: see text] increases from [Formula: see text] to [Formula: see text]. There exists a critical rotation angle [Formula: see text], where the orbit is a circular Euler orbit if [Formula: see text]; a spatial orbit if [Formula: see text]; and a Broucke (collision) orbit if [Formula: see text]. The exact formula of [Formula: see text] is numerically proved to be [Formula: see text]. Second, oscillating behaviors occur at rotation angle [Formula: see text] for all [Formula: see text]. Actually, the orbit with [Formula: see text] runs on its initial periodic shape for only a few periods. It breaks the first periodic shape and becomes irregular in a moment. However, it runs close to a different periodic shape after a while. In a short time, it falls apart from the second periodic shape and runs irregularly again. Such oscillation continues as time [Formula: see text] increases. Up to [Formula: see text], the orbit is bounded and keeps oscillating between periodic shapes and irregular motions. Further study implies that, for each [Formula: see text], the angle between any two consecutive periodic shapes is a constant. When [Formula: see text], similar oscillating behaviors are expected.
Market Impacts and the Life Cycle of Investors Orders
Authors: Bacry Emmanuel , Iuga Adrian , Lasnier Matthieu , Lehalle Charles-Albert 
Published: December 2015

This study is the first to decipher market impact at all time scales on the same database, from a trade-by-trade scale to a daily one. Moreover, the very concentrated nature of the database (400,000 metaorders issued by investors, electronically traded, during one year—2010—, on European market all regulated by the same directive—MiFID—) ensures investors did not change their habits during the study. At the intraday scale, we confirm a square root temporary impact in the daily participation, and we shed light on a duration factor in [Formula: see text] with [Formula: see text]. Including this factor in the fits reinforces the square root shape of impact. We observe a power-law for the transient impact with an exponent between [Formula: see text] (for long metaorders) and [Formula: see text] (for shorter ones). Moreover, we show that the market does not anticipate the size of the metaorders. The intraday decay seems to exhibit two regimes (though hard to identify precisely): a “slow” regime right after the execution of the metaorder followed by a faster one. At the daily time scale, we show price moves after a metaorder can be split between realizations of expected returns that have triggered the investing decision and an idiosynchratic impact that slowly decays to zero. Moreover, we propose a class of toy models based on Hawkes processes (the Hawkes Impact Model, HIM) to illustrate our reasoning. We show how the Impulsive-HIM model, despite its simplicity, embeds appealing features like transience and decay of impact. The latter is parametrized by a parameter C having a macroscopic interpretation: the ratio of contrarian reaction (i.e., impact decay) and of the “herding” reaction (i.e., impact amplification).
A Supplemented High-Fat Low-Carbohydrate Diet for the Treatment of Glioblastoma
Authors: Martuscello Regina T. , Vedam-Mai Vinata , McCarthy David J. , Schmoll Michael E. , Jundi Musa A. , Louviere Christopher D. , Griffith Benjamin G. , Skinner Colby L. , Suslov Oleg , Deleyrolle Loic P. , Reynolds Brent A. 
Published: December 2015

Abstract
Purpose: Dysregulated energetics coupled with uncontrolled proliferation has become a hallmark of cancer, leading to increased interest in metabolic therapies. Glioblastoma (GB) is highly malignant, very metabolically active, and typically resistant to current therapies. Dietary treatment options based on glucose deprivation have been explored using a restrictive ketogenic diet (KD), with positive anticancer reports. However, negative side effects and a lack of palatability make the KD difficult to implement in an adult population. Hence, we developed a less stringent, supplemented high-fat low-carbohydrate (sHFLC) diet that mimics the metabolic and antitumor effects of the KD, maintains a stable nutritional profile, and presents an alternative clinical option for diverse patient populations.
Experimental Design: The dietary paradigm was tested in vitro and in vivo, utilizing multiple patient-derived gliomasphere lines. Cellular proliferation, clonogenic frequency, and tumor stem cell population effects were determined in vitro using the neurosphere assay (NSA). Antitumor efficacy was tested in vivo in preclinical xenograft models and mechanistic regulation via the mTOR pathway was explored.
Results: Reducing glucose in vitro to physiologic levels, coupled with ketone supplementation, inhibits proliferation of GB cells and reduces tumor stem cell expansion. In vivo, while maintaining animal health, the sHFLC diet significantly reduces the growth of tumor cells in a subcutaneous model of tumor progression and increases survival in an orthotopic xenograft model. Dietary-mediated anticancer effects correlate with the reduction of mTOR effector expression.
Conclusions: We demonstrate that the sHFLC diet is a viable treatment alternative to the KD, and should be considered for clinical testing. Clin Cancer Res; 22(10); 2482–95. ©2015 AACR.
Targeting MYCN-Driven Transcription By BET-Bromodomain Inhibition
Authors: Henssen Anton , Althoff Kristina , Odersky Andrea , Beckers Anneleen , Koche Richard , Speleman Frank , Schäfers Simon , Bell Emma , Nortmeyer Maike , Westermann Frank , De Preter Katleen , Florin Alexandra , Heukamp Lukas , Spruessel Annika , Astrahanseff Kathy , Lindner Sven , Sadowski Natalie , Schramm Alexander , Astorgues-Xerri Lucile , Riveiro Maria E. , Eggert Angelika , Cvitkovic Esteban , Schulte Johannes H. 
Published: December 2015

Abstract
Purpose: Targeting BET proteins was previously shown to have specific antitumoral efficacy against MYCN-amplified neuroblastoma. We here assess the therapeutic efficacy of the BET inhibitor, OTX015, in preclinical neuroblastoma models and extend the knowledge on the role of BRD4 in MYCN-driven neuroblastoma.
Experimental Design: The efficacy of OTX015 was assessed in in vitro and in vivo models of human and murine MYCN-driven neuroblastoma. To study the effects of BET inhibition in the context of high MYCN levels, MYCN was ectopically expressed in human and murine cells. The effect of OTX015 on BRD4-regulated transcriptional pause release was analyzed using BRD4 and H3K27Ac chromatin immunoprecipitation coupled with DNA sequencing (ChIP-Seq) and gene expression analysis in neuroblastoma cells treated with OTX015 compared with vehicle control.
Results: OTX015 showed therapeutic efficacy against preclinical MYCN-driven neuroblastoma models. Similar to previously described BET inhibitors, concurrent MYCN repression was observed in OTX015-treated samples. Ectopic MYCN expression, however, did not abrogate effects of OTX015, indicating that MYCN repression is not the only target of BET proteins in neuroblastoma. When MYCN was ectopically expressed, BET inhibition still disrupted MYCN target gene transcription without affecting MYCN expression. We found that BRD4 binds to super-enhancers and MYCN target genes, and that OTX015 specifically disrupts BRD4 binding and transcription of these genes.
Conclusions: We show that OTX015 is effective against mouse and human MYCN-driven tumor models and that BRD4 not only targets MYCN, but specifically occupies MYCN target gene enhancers as well as other genes associated with super-enhancers. Clin Cancer Res; 22(10); 2470–81. ©2015 AACR.
The impact of statin therapy on plasma levels of von Willebrand factor antigen
Authors: Sahebkar Amirhossein , Serban Corina , Ursoniu Sorin , Mikhailidis Dimitri P. , Undas Anetta , Lip Gregory Y. H. , Bittner Vera , Ray Kausik K. , Watts Gerald F. , Hovingh G. Kees , Rysz Jacek , Kastelein John J. P. , Banach Maciej ,   Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
Published: December 2015

SummaryIncreased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A systematic multiple-database search was carried out to identify randomized controlled trials (RCTs) that investigated the effect of statins on plasma vWF:Ag levels. Random-effect meta-analysis of 21 treatment arms revealed a significant decrease in plasma vWF:Ag levels following statin therapy (SMD: −0.54, 95 %CI: −0.87, −0.21, p=0.001). In subgroup analyses, the greatest effect was observed with simvastatin (SMD: −1.54, 95 %CI: −2.92, −0.17, p=0.028) and pravastatin (SMD: −0.61, 95 %CI: −1.18, −0.04, p=0.035), but not with fluvastatin (SMD: −0.34, 95 %CI: −0.69, 0.02, p=0.065), atorvastatin (SMD: −0.23, 95 %CI: −0.57, 0.11, p=0.179) and rosuvastatin (SMD: −0.20, 95 %CI: −0.71, 0.30, p=0.431). The lowering effect of statins on plasma vWF:Ag levels was greater in the subset of studies lasting ≥ 12 weeks (SMD: −0.70, 95 %CI: −1.19, −0.22, p=0.005) compared with that of studies lasting > 12 weeks (SMD: −0.34, 95 %CI: −0.67, 0.003, p=0.052). Finally, low-intensity statin therapy was not associated with a significant reduction in vWF:Ag levels (SMD: −0.28, 95 %CI: −0.82, 0.27, p=0.320), but a significant effect was observed in high-intensity statin trials (SMD: −0.66, 95 %CI: −1.07, −0.24, p=0.002). This meta-analysis of available RCTs demonstrates a significant reduction in plasma vWF:Ag levels following statin therapy.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.
Increased inhibitor incidence in severe haemophilia A since 1990 attributable to more low titre inhibitors
Authors: Fischer Kathelijn , Petrini Pia , Ljung Rolf , Rafowicz Anne , Carcao Manuel , Auerswald Günter , Kurnik Karin , Kenet Gili , Santagostino Elena , Berg H. Marijke van den , Hashemi S. Mojtaba ,   for the PedNet Study group
Published: December 2015

SummaryMany studies have reported an increased incidence of inhibitors in previously untreated patients (PUPs) with severe haemophilia A after the introduction of recombinant products. It was the objective of this study to investigate whether the inhibitor incidence has increased between 1990 and 2009 in an unselected cohort of PUPs with severe haemophilia A (FVIII < 1 %). Patients were consecutively recruited from 31 haemophilia treatment centres in 16 countries and followed until 50 exposure days or until inhibitor development. Inhibitor development was studied in five-year birth cohorts comparing cumulative incidences. Furthermore the risk for inhibitor development per five-year birth cohort was studied using multivariable Cox regression, adjusting for potential genetic and treatment-related confounders. A total of 926 PUPs were included with a total cumulative inhibitor incidence of 27.5 %. The inhibitor incidence increased from 19.5 % in 1990-1994 (lowest) to 30.9 % in 2000-2004 (highest; p-value 0.011). Low titre inhibitor incidence increased from 3.1 % in 1990-1994 to 10.5 % in 2005-2009 (p-value 0.009). High titre inhibitor incidences remained stable over time. After 2000, risk of all inhibitor development was increased with adjusted hazard ratios 1.96 (95 % CI 1.06-2.83) in 2000-2004 and 2.34 (1.42-4.92) in 2005-2009. Screening for inhibitors was intensified over this 20-year study period from a median of 1.9 to 2.9 tests/year before 2000 to 2.7 to 4.3 tests/ year after 2000. In conclusion, the cumulative inhibitor incidence has significantly increased between 1990 and 2009. The high titre inhibitor incidence has remained stable.
Revisiting Place-Pitch Match in CI Recipients Using 3D Imaging Analysis
Authors: Devocht Elke M.J. , Dees Guido , Arts Remo A.G.J. , Smits Jeroen J. , George Erwin L.J. , van Hoof Marc , Stokroos Robert J. 
Published: December 2015

Objective: To improve the estimation of the perceived pitch in a single-sided deaf cochlear implant (CI) listener by using accurate 3-dimensional (3D) image analysis of the cochlear electrode positions together with the predicted tonotopical function for humans. Methods: An SSD CI user underwent a Cone-Beam computed tomography (CBCT) scan. Electrode contacts were marked in 3D space in relation to the nearest point on the cochlear lateral wall. Distance to the base of the lateral wall was calculated and plotted against the place-pitch function for humans. An adaptive procedure was used to elicit the perceived pitch of electrically evoked stimulation by matching it with a contralateral acoustic pitch. Results: The electrically evoked pitch percept matched well with the calculated frequency. The median mismatch in octaves was 0.12 for our method in comparison to 0.69 using the conventional Stenvers view. Conclusion: A method of improved image analysis is described that can be used to predict the pitch percept on corresponding cochlear electrode positions. This method shows the potential of 3D imaging in CI fitting optimization.
Suicidal ideation, suicide attempts and non-suicidal self-injury among lesbian, gay, bisexual and heterosexual adults: Findings from an Australian national study
Authors: Swannell Sarah , Martin Graham , Page Andrew 
Published: December 2015

Objectives: This study investigated associations between sexual orientation and measures of suicidality and non-suicidal self-injury in Australian adults. Previous studies of sexual orientation and suicidality have been limited by unclear conceptualisations of suicidal intent, failure to differentiate between homosexuality and bisexuality, inattention to gender differences and use of convenience-based samples. Methods: A large ( N = 10,531) representative national sample of Australian adults was used to investigate associations between sexual orientation (heterosexual, homosexual, bisexual) and (1) suicidal ideation, (2) attempted suicide and (3) non-suicidal self-injury, for males and females separately, in a series of sequentially adjusted logistic regression models. Results: Sexual minority participants were at greater risk of suicidality and self-injury than heterosexuals, after adjusting for age and other covariates, with patterns of risk differing by sexual orientation and gender. Compared with their heterosexual counterparts, gay men, but not bisexual men, were more likely to report suicidal ideation (odds ratio = 3.05, 95% confidence interval = [1.65, 5.60]) and suicide attempts (odds ratio = 4.16, confidence interval = [2.18, 7.93]). Bisexual women, but not lesbian women, were more likely to report suicidal ideation (odds ratio = 4.40, confidence interval = [3.00, 6.37]) and suicide attempts (odds ratio = 4.46, confidence interval = [2.41, 8.24]). Neither bisexual nor gay men were more likely than heterosexual men to report self-injury. However, bisexual women, but not lesbian women, were more likely than heterosexual women to report self-injury (odds ratio = 19.59, confidence interval = [9.05, 42.40]). Overall, bisexual females were at greatest risk of suicidality and self-injury. Conclusion: Clinicians working with sexual minority populations are encouraged to openly discuss suicidal and self-injurious thoughts and behaviours with their clients and may consider using therapeutic strategies to reduce internalised stigma and enhance personal and social resources.
Improved Visualization of Artificial Pulmonary Nodules with a New Subvolume Rendering Technique
Authors: Abildgaard A. , Karlsen J. Skaarud , Heiberg L. , Bosse G. , Hol P. K. 
Published: December 2015

Background: The detection of small nodules in pulmonary multidetector computed tomography (MDCT) data sets is challenging, and there is a need for visualization techniques that can improve reader sensitivity and efficiency. We have developed a subvolume rendering technique (“Softslice”) with nonlinear, symmetrical modulation of the relative signal intensity along the viewing direction. Our hypothesis was that this technique might provide an advantageous visual differentiation between nodules and overlapping vessels in pulmonary MDCT subvolumes. Purpose: To compare the Softslice subvolume rendering technique and maximum intensity projection (MIP) rendering for visualization of artificial pulmonary nodules in MDCT data sets. Material and Methods: Virtual, artificial pulmonary nodules were created with custom-made software. The nodules had the same signal intensity as pulmonary vessels. Approximately 50 nodules with diameter 2–7 mm were inserted in the Digital Imaging and Communications in Medicine (DICOM) image files of pulmonary MDCT data sets obtained without intravenous contrast. Each data set contained approximately 300 slices with 1-mm slice spacing. Four types of subvolumes were rendered: MIP with 10- and 20-mm subvolume thickness, and Softslice with 20- and 30-mm subvolume thickness. Three radiologists performed readings with free scrolling using 1-, 4- or 8-mm increments between subvolume positions. Results: No significant differences in the number of detected nodules were found between the different renderings with free scrolling using 1- and 4-mm increments. When 8-mm increment was used, nodule detection with the 30-mm Softslice rendering was significantly superior to the other renderings ( P = 0.012 vs. MIP 10 mm, P = 0.018 vs. MIP 20 mm, P = 0.021 vs. Softslice 20 mm). When the subvolume increments were changed from 4 mm to 8 mm, the most marked reduction in the number of detected nodules was seen for MIP subvolumes with 10-mm thickness ( P = 0.018). Conclusion: The Softslice rendering technique is promising for the detection of pulmonary nodules in MDCT data sets, and may allow more efficient reading than the standard MIP subvolume technique. With 10-mm MIP rendering, the detection rate for small pulmonary nodules substantially influenced by the incremental distance between subvolumes positions.
Occupation-focused health promotion for well older people — A cost-effectiveness analysis
Authors: Zingmark Magnus , Nilsson Ingeborg , Fisher Anne G , Lindholm Lars 
Published: December 2015

Introduction The aim of this study was to evaluate three occupational therapy interventions, focused on supporting continued engagement in occupation among older people, to determine which intervention was most cost effective, evaluated as the incremental cost/quality adjusted life year gained. Method The study was based on an exploratory randomized controlled trial. Participants were 77–82 years, single living and without home help. One hundred and seventy seven persons were randomized to an individual intervention, an activity group, a discussion group or a no intervention control group. All interventions focused on supporting the participants to maintain or improve occupational engagement. Outcomes were evaluated at baseline, three and 12 months and included general health and costs (intervention, municipality and health care). Based on linear regression models, we evaluated how outcomes had changed at each follow-up for each intervention group in relation to the control group. Results Both group interventions resulted in quality adjusted life years gained at three months. A sustained effect on quality adjusted life years gained and lower total costs indicated that the discussion group was the most cost-effective intervention. Conclusion Short-term, occupation-focused occupational therapy intervention delivered in group formats for well older people resulted in quality-adjusted life years gained. A one-session discussion group was most cost effective.
Cultural diversity and mental health
Authors: Gopalkrishnan Narayan , Babacan Hurriyet 
Published: December 2015

Objective: Cultural diversity and its impact on mental health has become an increasingly important issue in a globalised world where the interactions between cultures continue to grow exponentially. This paper presents critical areas in which culture impacts on mental health, such as how health and illness are perceived, coping styles, treatment-seeking patterns, impacts of history, racism, bias and stereotyping, gender, family, stigma and discrimination. Conclusions: While cultural differences provide a number of challenges to mental health policy and practice they also provide a number of opportunities to work in unique and effective ways towards positive mental health. Ethno-specific approaches to mental health that incorporate traditional and community-based systems can provide new avenues for working with culturally diverse populations.