bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ceiling of care decisions at an older person's mental health unit in Gloucestershire
Authors: Slack Philip , Rose Anneka 
Published: February 2015

AbstractThis quality improvement project was inspired as an answer to a problem that many fellow psychiatric trainees had been struggling with while on-call covering the old age mental health hospital which includes a specialist dementia ward. The issue was that decisions around ceilings of care for patients were often not discussed or at least recorded in the electronic notes and as a result when reviewing deteriorating patients out of hours trainees would find themselves without any guidance on the treating medics opinion on what was in the best interests of the patient. This led to situations where unnecessary transfers to the acute hospital would occur overnight which could have been avoided with more consistent planning.Prior to initiating the changes it was recorded that nine out of 47 inpatients had documented decisions on ceiling of care of treatment in the consultant’s ward round entries. Next policies from acute hospitals were reviewed, opinions were discussed in departmental meetings, and eventually there was agreed a change in procedure with the consultant on the dementia ward around resuscitation and ceiling of care status and consistent recording of this.Following the intervention there was seen an improvement in the recording of decisions around treatment and transfer of patients on the dementia ward of 80% (4/5) fully compliant with new criteria and then 71% (5/7) in successive cycles. Further communication both with relevant professionals on the old age ward and with the trainees on the on-call rota will be necessary to sustain any change but the centralised recording of resuscitation status and ceiling of care in the ward round entries have provided much more guidance than was previously available. In the future it may be possible to spread this policy throughout the entire old age mental health unit.
Visual assessment of Ki67 using a 5-grade scale (Eye-5) is easy and practical to classify breast cancer subtypes with high reproducibility
Authors: Hida Akira I , Bando Kenji , Sugita Atsuro , Maeda Toshiharu , Ueda Norifumi , Matsukage Shoichi , Nakanishi Mamoru , Kito Katsumi , Miyazaki Tatsuhiko , Ohtsuki Yuji , Oshiro Yumi , Inoue Hiromichi , Kawaguchi Hidetoshi , Yamashita Natsumi , Aogi Kenjiro , Moriya Takuya 
Published: February 2015

AimsPersonalised breast cancer therapy requires pathological characterisation of tumours. The proliferative index, based on Ki67, is pivotal, but a standard method has not been established. Here we look for an easy and practical way to evaluate Ki67.MethodsImmunohistochemical staining of estrogen receptors, progesterone receptors, HER2 and Ki67 (MIB-1) was performed on resected specimens from 406 primary invasive ductal carcinomas. Ki67 labelling index (LI) from manual counting was compared with visual assessment using a 5-grade scale (Eye-5). Next, 10 pathologists evaluated 100 samples with marked hot spots by using Eye-5. Another 100 samples without marking were also assessed by eight pathologists. One year later, two pathologists reviewed 222 cases with Eye-5. Prognosis was analysed among estrogen receptor-positive cases with postoperative endocrine therapy.ResultsEye-5 showed good correlation to LI. All 136 cases of score 4–5 had LI >20% and all 56 cases of score 1 had LI<20%, which means that manual counting was not necessary for about half of the cases. Interobserver and intraobserver variability was low even when a hot spot was not fixed. Eye-5 also correlated with histological grade and lymph node metastasis. Combining Eye-5 and histological grade created a new algorism to predict LI, which allows 80% of all cases (74% of luminal cases) without manual counting. Cases of Eye-5 score 1–2 had significantly better survival than score 3–5.ConclusionsVisual assessment of Ki67 by a 5-grade scale (Eye-5) is fast, easy, and reliable with acceptably low interobserver and intraobserver variability. Eye-5 can replace LI in many luminal tumours, and is a strong candidate as a standard method of evaluating Ki67.
Balancing Load via Small Coalitions in Selfish Ring Routing Games
Authors: Chen Xujin , Hu Xiaodong , Ma Weidong 
Published: February 2015

This paper concerns the asymmetric atomic selfish routing game for load balancing in ring networks. In the selfish routing, each player selects a path in the ring network to route one unit traffic between its source and destination nodes, aiming at a minimum maximum link load along its own path. The selfish path selections by individuals ignore the system objective of minimizing the maximum load over all network links. This selfish ring load (SRL) game arises in a wide variety of applications in decentralized network routing, where network performance is often measured by the price of anarchy (PoA), the worst-case ratio between the maximum link loads in an equilibrium routing and an optimal routing. It has been known that the PoA of SRL with respect to classical Nash Equilibrium (NE) cannot be upper bounded by any constant, showing large loss of efficiency at some NE outcome. In an effort to improve the network performance in the SRL game, we generalize the model to so-called SRL with collusion (SRLC) which allows coordination within any coalition of up to k selfish players on the condition that every player of the coalition benefits from the coordination. We prove that, for m-player game on n-node ring, the PoA of SRLC is n - 1 when k ≤ 2, drops to 2 when k = 3 and is at least 1 + 2/m for k ≥ 4. Our study shows that on one hand, the performance of ring networks, in terms of maximum load, benefits significantly from coordination of self-interested players within small-sized coalitions; on the other hand, the equilibrium routing in SRL might not reach global optimum even if any number of players can coordinate.
Repeated Sequential Prisoner's Dilemma: The Stackleberg Variant
Authors: Qu Xing-Long , Cao Zhi-Gang , Mu Yi-Fen , Yang Xiao-Guang 
Published: February 2015

We study the Stackleberg variant of the repeated Sequential Prisoner's Dilemma (SPD). The game goes in two stages, and the two players, the leader and the follower, are asymmetric in both stages. In the first stage of the game, the leader chooses a strategy (for the repeated SPD of the second stage), which is immediately known to the follower. In the second stage, they play repeated SPD: In each round the follower moves after observing the leader's action. Assuming complete rationality, we find some extraordinary properties of this model. (i) The (subgame perfect) equilibrium payoff profile is unique, which lies on the corner of the region predicted by classical folk theorems: It is best for the leader and at the same time worst for the follower, (ii) the leader has simple optimal strategies that are one-step memory and stationary. These features are in great contrast with classical results, where either uniqueness cannot be guaranteed and equilibrium strategies are often quite complicated, or bounded rationality is required. Although full cooperation, i.e., the outcome is always (cooperate, cooperate), is not attainable in our model, at least a half of the optimal social welfare can be guaranteed. We also do a non-equilibrium analysis which makes the usual equilibrium analysis more convincing.
Topic Categorization of Biomedical Abstracts
Authors: Kanavos Andreas , Makris Christos , Theodoridis Evangelos 
Published: February 2015

Nowadays, people frequently use search engines in order to find the information they need on the Web. Especially, Web search constitutes of a basic tool used by million researchers in their everyday work. A very popular indexing engine, concerning life sciences and biomedical research, is PubMed. PubMed is a free database accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The present search engines usually return search results in a global ranking, making it difficult for the users to browse in different topics or subtopics. In this work we propose a novel system to address the issues of clustering biomedical search engine results according to their topic. A methodology that exploits semantic text clustering techniques in order to group biomedical document collections in homogeneous topics, is presented and evaluated. In order to provide more accurate clustering results, we utilize various biomedical ontologies, likeMeSH and GeneOntology. Finally, we embed the proposed methodology in an online system that post-processes the PubMed online database so as to provide users the retrieved results according to well formed topics. So as to expose our method as an online real-time service with reasonable response times, we performed a wide range of engineering optimizations along with experimentation on preprocessing time to precision of results trade off.
From tourism to geotourism: a few historical cases from the French Alpine foreland
Authors: Cayla Nathalie , Gauchon Christophe , Hobléa Fabien 
Published: February 2015

Abstract
This paper traces the touristic trajectories of three spectacular gorges located in the Alpine foreland and the southern Jura: the gorges of the upper Rhône (Ain/Haute-Savoie), the Sierroz (Savoie) and the Fier (Haute-Savoie). All three are located within a distance of 50 km from each other. The upper Rhône gorge, already famous at the end of the eighteenth century, was drowned under the floodwaters of the Génissiat dam in 1948; only a significant iconography remains of two centuries of (geo)tourism. The Sierroz gorge, close to the spa resort of Aix-les-Bains, became famous after the dramatic and tragic death in 1810 of a young noblewoman. Following that event many tourists staying on the shore of the lake Bourget visited the gorge until 1970 when it was closed to the public. Since then, the gorge has gradually become a touristic wasteland. The Fier gorge near Annecy became a tourist attraction in 1869 with the opening of the nearby railway station of Lovagny; since then, visitors have been attracted to it in increasing numbers. The history of these three gorges illustrates how tourism and heritage are in constant interaction; however, the development of the one will not always ensure the protection of the other. Today, geoheritage assessment is based upon criteria that are as objective as is possible. The intrinsic geological and geomorphological characteristics are the initial geoheritage values, to which can be added the cultural value elements. Associated with the development of geotourism and geoparks, this new approach should ensure a better and sustainable use of these sites in the long term.
Structural model creation: the impact of data type and creative space on geological reasoning and interpretation
Authors: Bond C. E. , Johnson G. , Ellis J. F. 
Published: February 2015

Abstract

Interpretation of sparse or incomplete datasets is a fundamental part of geology, particularly when building models of the subsurface. Available geological data are often remotely sensed (seismic data) or very limited in spatial extent (borehole data). Understanding how different datasets are interpreted and what makes an interpreter effective is critical if accurate geological models are to be created. A comparison of the interpretation outcome and techniques used by two cohorts interpreting different geological datasets of the same model, an inversion structure, was made. The first cohort consists of interpreters of the synthetic seismic image data in Bond
et al.
(‘What do you think this is?: “Conceptual uncertainty” in geoscience interpretation’,
GSA Today
, 2007,
17
, 4–10,
http://dx.doi.org/10.1130/GSAT01711A.1
); the second cohort is new and interpreted borehole data. The outcomes of the borehole interpretation dataset support earlier findings that technique use, specifically evidence of geological evolution thought processes, results in more effective interpretation. The results also show that the borehole interpreters were more effective at arriving at the correct interpretation. Analysis of their final interpretations in the context of psychological and medical image analysis research suggests that the clarity of the original dataset, the amount of noise and white space may play a role in interpretation outcome, through enforced geological reasoning during data interpretation.
Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β
Authors: Alamino Vanina A. , Mascanfroni Iván D. , Montesinos María M. , Gigena Nicolás , Donadio Ana C. , Blidner Ada G. , Milotich Sonia I. , Cheng Sheue-yann , Masini-Repiso Ana M. , Rabinovich Gabriel A. , Pellizas Claudia G. 
Published: February 2015

Abstract
Bidirectional cross-talk between the neuroendocrine and immune systems orchestrates immune responses in both physiologic and pathologic settings. In this study, we provide in vivo evidence of a critical role for the thyroid hormone triiodothyronine (T3) in controlling the maturation and antitumor functions of dendritic cells (DC). We used a thyroid hormone receptor (TR) β mutant mouse (TRβPV) to establish the relevance of the T3-TRβ system in vivo. In this model, TRβ signaling endowed DCs with the ability to stimulate antigen-specific cytotoxic T-cell responses during tumor development. T3 binding to TRβ increased DC viability and augmented DC migration to lymph nodes. Moreover, T3 stimulated the ability of DCs to cross-present antigens and to stimulate cytotoxic T-cell responses. In a B16-OVA mouse model of melanoma, vaccination with T3-stimulated DCs inhibited tumor growth and prolonged host survival, in part by promoting the generation of IFNγ-producing CD8+ T cells. Overall, our results establish an adjuvant effect of T3-TRβ signaling in DCs, suggesting an immediately translatable method to empower DC vaccination approaches for cancer immunotherapy. Cancer Res; 75(7); 1265–74. ©2015 AACR.
VEGF-A Expression Correlates with TP53 Mutations in Non–Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy
Authors: Schwaederlé Maria , Lazar Vladimir , Validire Pierre , Hansson Johan , Lacroix Ludovic , Soria Jean-Charles , Pawitan Yudi , Kurzrock Razelle 
Published: February 2015

Abstract
Bevacizumab is one of the most widely used antiangiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the tumor suppressor gene TP53, which occur frequently in many human malignancies. In this study, we present a multiple regression analysis of transcriptomic data in 123 patients with non–small cell lung cancer (NSCLC) showing that TP53 mutations are associated with higher VEGF-A expression (P = 0.006). This association was interesting given a recent retrospective study showing longer progression-free survival in patients with diverse tumors who receive bevacizumab, if tumors harbor mutant TP53 instead of wild-type TP53. Thus, our current findings linking TP53 mutation with VEGF-A upregulation offered a mechanistic explanation for why patients exhibit improved outcomes after bevacizumab treatment when their tumors harbor mutant TP53 versus wild-type TP53. Overall, this work warrants further evaluation of TP53 as a ready biomarker to predict bevacizumab response in NSCLC and possibly other tumor types. Cancer Res; 75(7); 1187–90. ©2015 AACR.
Atg7 Overcomes Senescence and Promotes Growth of BrafV600E-Driven Melanoma
Authors: Xie Xiaoqi , Koh Ju Yong , Price Sandy , White Eileen , Mehnert Janice M. 
Published: February 2015

Abstract
Macroautophagy (autophagy hereafter) may promote survival and growth of spontaneous tumors, including melanoma. We utilized a genetically engineered mouse model of melanoma driven by oncogenic BrafV600E and deficiency in the Pten tumor suppressor gene in melanocytes to test the functional consequences of loss of the essential autophagy gene autophagy-related-7, Atg7. Atg7 deficiency prevented melanoma development by BrafV600E and allelic Pten loss, indicating that autophagy is essential for melanomagenesis. Moreover, BrafV600E-mutant, Pten-null, Atg7-deficient melanomas displayed accumulation of autophagy substrates and growth defects, which extended animal survival. Atg7-deleted tumors showed increased oxidative stress and senescence, a known barrier to melanomagenesis. Treatment with the BRAF inhibitor dabrafenib decreased tumor growth and induced senescence that was more pronounced in tumors with Atg7 deficiency. Thus, Atg7 promotes melanoma by limiting oxidative stress and overcoming senescence, and autophagy inhibition may be of therapeutic value by augmenting the antitumor activity of BRAF inhibitors.
Significance: The essential autophagy gene Atg7 promotes development of BrafV600E-mutant, Pten-null melanomas by overcoming senescence, and deleting Atg7 facilitated senescence induction and antitumor activity of BRAF inhibition. This suggests that combinatorial BRAFV600E and autophagy inhibition may improve therapeutic outcomes in patients whose tumors have BRAFV600E/K mutations, an approach currently being explored in clinical trials. Cancer Discov; 5(4); 410–23. ©2015 AACR.
See related commentary by Thorburn and Morgan, p. 353
This article is highlighted in the In This Issue feature, p. 333
Assessing the Effects of Concurrent versus Sequential Cisplatin/Radiotherapy on Immune Status in Lung Tumor–Bearing C57BL/6 Mice
Authors: Kao Chiao-Jung , Wurz Gregory T. , Lin Yi-Chen , Vang Daniel P. , Griffey Stephen M. , Wolf Michael , DeGregorio Michael W. 
Published: February 2015

Abstract
Concurrent and sequential cisplatin-based chemoradiotherapy regimens are standard therapeutic approaches in cancer treatment. Recent clinical data suggest that these different dosing schedules may adversely affect antigen-specific immunotherapy. The goal of the present preclinical study was to explore the effects of concurrent and sequential cisplatin/radiotherapy on immune status in a lung cancer mouse model. A total of 150 C57BL/6 mice were randomized into six treatment groups: control; 8 Gy thoracic radiotherapy (dose schedules 1 and 2); cisplatin 2.5 mg/kg i.p.; cisplatin + radiotherapy (concurrent); and cisplatin + radiotherapy (sequential; n = 25, all groups). At the end of the study (week 41), serum cytokines were assessed by multiplex immunoassay, surface markers of spleen-derived lymphocytes were assessed by immunostaining and flow cytometry, lung tumor expression of programmed death ligands 1 and 2 (PD-L1/2) was evaluated by immunohistochemistry, and miRNA profiling was performed in serum and lymphocytes by quantitative real-time PCR. Lung whole mounts were prepared to assess treatment effects on lung tumor foci formation. The results showed that sequential chemoradiotherapy (two cycles of cisplatin followed by 8 Gy radiotherapy) had equivalent antitumor activity as concurrent therapy. However, sequential cisplatin/radiotherapy resulted in significant differences in several immune response biomarkers, including regulatory T cells, miR-29c, expression of costimulatory molecule CD28, and serum IFNγ. PD-L1 and PD-L2 were strongly expressed in tumor foci, but no trend was seen between groups. These results suggest that monitoring immune status may be necessary when designing treatment regimens combining immunotherapy with chemoradiotherapy. Cancer Immunol Res; 3(7); 741–50. ©2015 AACR.
Arrhythmogenic Remodeling of β
2
Versus β
1
Adrenergic Signaling in the Human Failing Heart
Authors: Lang Di , Holzem Katherine , Kang Chaoyi , Xiao Mengqian , Hwang Hye Jin , Ewald Gregory A. , Yamada Kathryn A. , Efimov Igor R. 
Published: February 2015

Background—
Arrhythmia is the major cause of death in patients with heart failure, for which β-adrenergic receptor blockers are a mainstay therapy. But the role of β-adrenergic signaling in electrophysiology and arrhythmias has never been studied in human ventricles.

Methods and Results—

We used optical imaging of action potentials and [Ca
2+
]
i
transients to compare the β
1
- and β
2
-adrenergic responses in left ventricular wedge preparations of human donor and failing hearts. β
1
-Stimulation significantly increased conduction velocity, shortened action potential duration, and [Ca
2+
]
i
transients duration (CaD) in donor but not in failing hearts, because of desensitization of β
1
-adrenergic receptor in heart failure. In contrast, β
2
-stimulation increased conduction velocity in both donor and failing hearts but shortened action potential duration only in failing hearts. β
2
-Stimulation also affected transmural heterogeneity in action potential duration but not in [Ca
2+
]
i
transients duration. Both β
1
- and β
2
-stimulation augmented the vulnerability and frequency of ectopic activity and enhanced substrates for ventricular tachycardia in failing, but not in donor, hearts. Both β
1
- and β
2
-stimulation enhanced Purkinje fiber automaticity, whereas only β
2
-stimulation promoted Ca-mediated premature ventricular contractions in heart failure.

Conclusions—

During end-stage heart failure, β
2
-stimulation creates arrhythmogenic substrates via conduction velocity regulation and transmurally heterogeneous repolarization. β
2
-Stimulation is, therefore, more arrhythmogenic than β
1
-stimulation. In particular, β
2
-stimulation increases the transmural difference between [Ca
2+
]
i
transients duration and action potential duration, which facilitates the formation of delayed afterdepolarizations.
The Amazon Dense GNSS Meteorological Network: A New Approach for Examining Water Vapor and Deep Convection Interactions in the Tropics
Authors: Adams David K. , Fernandes Rui M. S. , Holub Kirk L. , Gutman Seth I. , Barbosa Henrique M. J. , Machado Luiz A. T. , Calheiros Alan J. P. , Bennett Richard A. , Kursinski E. Robert , Sapucci Luiz F. , DeMets Charles , Chagas Glayson F. B. , Arellano Ave , Filizola Naziano , Amorim Rocha Alciélio A. , Silva Rosimeire Araújo , Assunção Lilia M. F. , Cirino Glauber G. , Pauliquevis Theotonio , Portela Bruno T. T. , Sá André , de Sousa Jeanne M. , Tanaka Ludmila M. S. 
Published: February 2015

Abstract
The complex interactions between water vapor fields and deep atmospheric convection remain one of the outstanding problems in tropical meteorology. The lack of high spatial–temporal resolution, all-weather observations in the tropics has hampered progress. Numerical models have difficulties, for example, in representing the shallow-to-deep convective transition and the diurnal cycle of precipitation. Global Navigation Satellite System (GNSS) meteorology, which provides all-weather, high-frequency (5 min), precipitable water vapor estimates, can help. The Amazon Dense GNSS Meteorological Network experiment, the first of its kind in the tropics, was created with the aim of examining water vapor and deep convection relationships at the mesoscale. This innovative, Brazilian-led international experiment consisted of two mesoscale (100 km × 100 km) networks: 1) a 1-yr (April 2011–April 2012) campaign (20 GNSS meteorological sites) in and around Manaus and 2) a 6-week (June 2011) intensive campaign (15 GNSS meteorological sites) in and around Belem, the latter in collaboration with the Cloud Processes of the Main Precipitation Systems in Brazil: A Contribution to Cloud-Resolving Modeling and to the Global Precipitation Measurement (CHUVA) Project in Brazil. Results presented here from both networks focus on the diurnal cycle of precipitable water vapor associated with sea-breeze convection in Belem and seasonal and topographic influences in and around Manaus. Ultimately, these unique observations may serve to initialize, constrain, or validate precipitable water vapor in high-resolution models. These experiments also demonstrate that GNSS meteorology can expand into logistically difficult regions such as the Amazon. Other GNSS meteorology networks presently being constructed in the tropics are summarized.