bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discussion: Statistics Research in Business and Industry ‐ The General Electric Experience
Authors: Hahn Gerald J. , Hoerl Roger , Doganaksoy Necip , Gardner Martha 
Published: October 2013

SummaryFor over 60 years, the statistics group at General Electric (GE) has used statistical methods to successfully address key company issues, both reactively and in recent years more and more proactively and holistically. Much of this work invariably calls for some degree of statistics research, including what we now call statistical engineering. We briefly review the history of research at GE, describe the accomplishments, research, and evolution of the GE statistics group over time, and present our views on the state of statistics research in business and industry.
Applications of the Likelihood Theory in Finance: Modelling and Pricing
Authors: Janssen Arnold , Tietje Martin 
Published: October 2013

SummaryThis paper discusses the connection between mathematical finance and statistical modelling which turns out to be more than a formal mathematical correspondence. We like to figure out how common results and notions in statistics and their meaning can be translated to the world of mathematical finance and vice versa. A lot of similarities can be expressed in terms of LeCam’s theory for statistical experiments which is the theory of the behaviour of likelihood processes. For positive prices the arbitrage free financial assets fit into statistical experiments. It is shown that they are given by filtered likelihood ratio processes. From the statistical point of view, martingale measures, completeness, and pricing formulas are revisited. The pricing formulas for various options are connected with the power functions of tests. For instance the Black–Scholes price of a European option is related to Neyman–Pearson tests and it has an interpretation as Bayes risk. Under contiguity the convergence of financial experiments and option prices are obtained. In particular, the approximation of Itô type price processes by discrete models and the convergence of associated option prices is studied. The result relies on the central limit theorem for statistical experiments, which is well known in statistics in connection with local asymptotic normal (LAN) families. As application certain continuous time option prices can be approximated by related discrete time pricing formulas.
The Two Functional Enoyl-Acyl Carrier Protein Reductases of Enterococcus faecalis Do Not Mediate Triclosan Resistance
Authors: Zhu Lei , Bi Hongkai , Ma Jincheng , Hu Zhe , Zhang Wenbin , Cronan John E. , Wang Haihong 
Published: October 2013

ABSTRACT

Enoyl-acyl carrier protein (enoyl-ACP) reductase catalyzes the last step of the elongation cycle in the synthesis of bacterial fatty acids. The
Enterococcus faecalis
genome contains two genes annotated as enoyl-ACP reductases, a FabI-type enoyl-ACP reductase and a FabK-type enoyl-ACP reductase. We report that expression of either of the two proteins restores growth of an
Escherichia coli
fabI
temperature-sensitive mutant strain under nonpermissive conditions.
In vitro
assays demonstrated that both proteins support fatty acid synthesis and are active with substrates of all fatty acid chain lengths. Although expression of
E. faecalis fabK
confers to
E. coli
high levels of resistance to the antimicrobial triclosan, deletion of
fabK
from the
E. faecalis
genome showed that FabK does not play a detectable role in the inherent triclosan resistance of
E. faecalis
. Indeed, FabK seems to play only a minor role in modulating fatty acid composition. Strains carrying a deletion of
fabK
grow normally without fatty acid supplementation, whereas
fabI
deletion mutants make only traces of fatty acids and are unsaturated fatty acid auxotrophs.

IMPORTANCE
The finding that exogenous fatty acids support growth of
E. faecalis
strains defective in fatty acid synthesis indicates that inhibitors of fatty acid synthesis are ineffective in countering
E. faecalis
infections because host serum fatty acids support growth of the bacterium.
Clinical staff perceptions of palliative care-related quality of care, service access, education and training needs and delivery confidence in an acute hospital setting
Authors: Frey Rosemary , Gott Merryn , Raphael Deborah , O'Callaghan Anne , Robinson Jackie , Boyd Michal , Laking George , Manson Leigh , Snow Barry 
Published: October 2013

ContextCentral to appropriate palliative care management in hospital settings is ensuring an adequately trained workforce. In order to achieve optimum palliative care delivery, it is first necessary to create a baseline understanding of the level of palliative care education and support needs among all clinical staff (not just palliative care specialists) within the acute hospital setting.ObjectivesThe objectives of the study were to explore clinical staff: perceptions concerning the quality of palliative care delivery and support service accessibility, previous experience and education in palliative care delivery, perceptions of their own need for formal palliative care education, confidence in palliative care delivery and the impact of formal palliative care training on perceived confidence.MethodsA purposive sample of clinical staff members (598) in a 710-bed hospital were surveyed regarding their experiences of palliative care delivery and their education needs.ResultsOn average, the clinical staff rated the quality of care provided to people who die in the hospital as ‘good’ (x̄=4.17, SD=0.91). Respondents also reported that 19.3% of their time was spent caring for end-of-life patients. However, only 19% of the 598 respondents reported having received formal palliative care training. In contrast, 73.7% answered that they would like formal training. Perceived confidence in palliative care delivery was significantly greater for those clinical staff with formal palliative care training.ConclusionsFormal training in palliative care increases clinical staff perceptions of confidence, which evidence suggests impacts on the quality of palliative care provided to patients. The results of the study should be used to shape the design and delivery of palliative care education programmes within the acute hospital setting to successfully meet the needs of all clinical staff.
Intestinal GUCY2C Prevents TGF-β Secretion Coordinating Desmoplasia and Hyperproliferation in Colorectal Cancer
Authors: Gibbons Ahmara V. , Lin Jieru E. , Kim Gilbert W. , Marszalowicz Glen P. , Li Peng , Stoecker Brian A. , Blomain Erik S. , Rattan Satish , Snook Adam E. , Schulz Stephanie , Waldman Scott A. 
Published: October 2013

Abstract
Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to secrete hepatocyte growth factor (HGF), reciprocally driving colon cancer cell proliferation through cMET-dependent signaling. Elimination of GUCY2C signaling in mice (Gucy2c−/−) produces intestinal desmoplasia, with increased reactive myofibroblasts, which is suppressed by anti-TGF-β antibodies or genetic silencing of Akt. Thus, GUCY2C coordinates intestinal epithelial–mesenchymal homeostasis through reciprocal paracrine circuits mediated by TGF-β and HGF. In that context, GUCY2C signaling constitutes a direct link between the initiation of colorectal cancer and the induction of its associated desmoplastic stromal niche. The recent regulatory approval of oral GUCY2C ligands to treat chronic gastrointestinal disorders underscores the potential therapeutic opportunity for oral GUCY2C hormone replacement to prevent remodeling of the microenvironment essential for colorectal tumorigenesis. Cancer Res; 73(22); 6654–66. ©2013 AACR.
CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients
Authors: Ott Patrick A. , Hodi F. Stephen , Robert Caroline 
Published: October 2013

Abstract
Immune checkpoint blockade with monoclonal antibodies directed at the inhibitory immune receptors CTLA-4, PD-1, and PD-L1 has emerged as a successful treatment approach for patients with advanced melanoma. Ipilimumab is the first agent associated with a documented improved overall survival benefit in this patient population. A striking attribute of CTLA-4 blockade is the durability of objective responses, leading to speculation of a possible cure for some patients. Many tumor responses achieved with PD-1 and PD-L1 inhibition were durable in the phase I trials and were seen in a higher proportion of patients with melanoma than typically observed with ipilimumab. Biomarker development to identify the subset of patients with melanoma who will achieve durable clinical benefit with checkpoint blockade is critical; tumor PD-L1 expression has been promising in early studies. The contrast between unprecedented response rates but limited durability of responses achieved with BRAF and MEK inhibition in BRAFV600-mutated melanoma and the impressive durability but relatively low rate of response achieved with immune checkpoint blockade is striking. Preclinical data on potential synergies between CTLA-4/PD-1/PD-L1 inhibition and MAPK-targeted therapy is emerging, and combined immune checkpoint blockade and MAPK inhibition are being explored in clinical trials. Other promising approaches to increase the number of patients with melanoma who benefit from durable responses with immune checkpoint blockade include concurrent or sequenced CTLA-4 and PD-1/PD-L1 inhibition and combination with other immunotherapeutic strategies. Clin Cancer Res; 19(19); 5300–9. ©2013 AACR.
Adoptive T-cell Transfer Therapy and Oncogene-Targeted Therapy for Melanoma: The Search for Synergy
Authors: Kwong Mei Li M. , Neyns Bart , Yang James C. 
Published: October 2013

Abstract
The clinical strengths of immunotherapy and small-molecule inhibitors targeting the mitogen-activated protein kinase (MAPK) pathway appear to be largely complementary for the treatment of advanced melanoma. In current practice, most patients with BRAF V600 mutant melanomas will see both modalities. Several in vitro and in vivo studies suggest that combining immunotherapy with MAPK inhibition may have synergistic effects. First, mouse models show that adoptive cell therapy (ACT) can be enhanced by vaccination. Rapid tumor destruction by vemurafenib could provide a vaccine-like stimulus to adoptively transferred T cells. Second, both in mice and in early clinical trials, melanoma metastases treated with MAPK inhibitors seem to display increased T-cell infiltrates. Third, MAPK inhibition upregulates the expression of some melanoma antigens and, therefore, may enhance T-cell recognition of vemurafenib-treated melanomas. Fourth, vemurafenib may sensitize tumor cells to immune destruction. Finally, some investigators have found that an optimal antitumor effect from MAPK inhibition is dependent on an intact host immune response. Currently, the Surgery Branch of the National Cancer Institute has initiated a phase II trial combining the BRAF inhibitor vemurafenib with ACT using tumor-infiltrating lymphocytes in patients with BRAF-mutant tumors to investigate the safety and efficacy of this combination. The proposed mechanisms for synergy between these two modalities can be complex, and their optimal combination may require testing a variety of sequences and schedules. Clin Cancer Res; 19(19); 5292–9. ©2013 AACR.
New Strategies in Endometrial Cancer: Targeting the PI3K/mTOR Pathway—The Devil Is in the Details
Authors: Myers Andrea P. 
Published: October 2013

Abstract
Endometrial cancer is the most common gynecologic malignancy in the developed world and affects approximately 40,000 women in the United States each year. The phosphoinositide 3-kinase (PI3K) signaling pathway regulates key aspects of cancer biology including glucose uptake and metabolism, cellular growth, and survival. Endometrial cancers harbor the highest rates of PI3K pathway alterations reported to date. The PI3K pathway is highly druggable and several classes of agents are in clinical development including rapalogs, pan-PI3K inhibitors, PI3K isoform-specific inhibitors, dual PI3K/mTOR catalytic inhibitors, mTOR-specific catalytic inhibitors, and AKT inhibitors. It has been 10 years since the initiation of the first studies of rapalogs as anticancer agents. There are more than 20 registered clinical trials of PI3K/mTOR inhibitors as single agents or in therapeutic combinations for the treatment of endometrial cancers. What have we learned from the completed studies? What can we expect to learn from ongoing studies? What should we anticipate moving forward? Clin Cancer Res; 19(19); 5264–74. ©2013 AACR.
Lycopene Metabolite, Apo-10′-Lycopenoic Acid, Inhibits Diethylnitrosamine-Initiated, High Fat Diet–Promoted Hepatic Inflammation and Tumorigenesis in Mice
Authors: Ip Blanche C. , Hu Kang-Quan , Liu Chun , Smith Donald E. , Obin Martin S. , Ausman Lynne M. , Wang Xiang-Dong 
Published: October 2013

Abstract
Obesity is associated with increased risk in hepatocellular carcinoma (HCC) development and mortality. An important disease control strategy is the prevention of obesity-related hepatic inflammation and tumorigenesis by dietary means. Here, we report that apo-10′-lycopenoic acid (APO10LA), a cleavage metabolite of lycopene at its 9′,10′-double bond by carotene-9′,10′-oxygenase, functions as an effective chemopreventative agent against hepatic tumorigenesis and inflammation. APO10LA treatment on human liver THLE-2 and HuH7 cells dose dependently inhibited cell growth and upregulated sirtuin 1 (SIRT1), a NAD+-dependent protein deacetylase that may suppress hepatic carcinogenesis. This observed SIRT1 induction was associated with decreased cyclin D1 protein, increased cyclin-dependent kinase inhibitor p21 protein expression, and induced apoptosis. APO10LA supplementation (10 mg/kg diet) for 24 weeks significantly reduced diethylnitrosamine-initiated, high fat diet (HFD)–promoted hepatic tumorigenesis (50% reduction in tumor multiplicity; 65% in volume) and lung tumor incidence (85% reduction) in C57Bl/6J mice. The chemopreventative effects of APO10LA were associated with increased hepatic SIRT1 protein and deacetylation of SIRT1 targets, as well as with decreased caspase-1 activation and SIRT1 protein cleavage. APO10LA supplementation in diet improved glucose intolerance and reduced hepatic inflammation [decreased inflammatory foci, TNFα, interleukin (IL)-6, NF-κB p65 protein expression, and STAT3 activation] in HFD-fed mice. Furthermore, APO10LA suppressed Akt activation, cyclin D1 gene, and protein expression and promoted PARP protein cleavage in transformed cells within liver tumors. Taken together, these data indicate that APO10LA can effectively inhibit HFD-promoted hepatic tumorigenesis by stimulating SIRT1 signaling while reducing hepatic inflammation. Cancer Prev Res; 6(12); 1304–16. ©2013 AACR.
Impact of age on the efficacy and safety of extended-duration thromboprophylaxis in medical patients
Authors: Hull Russell D. , Schellong Sebastian M. , Tapson Victor F. , Monreal Manuel , Samama Meyer-Michel , Chen Min , Deslandes Bruno , Turpie Alexander G. G. , Yusen Roger D. 
Published: October 2013

SummaryThe EXCLAIM study enrolled hospitalised acutely ill medical patients with age >40 years and recently-reduced mobility into a trial of extended-duration anticoagulant thromboprophylaxis. This post-hoc analysis evaluated the impact of age on patient outcomes. After completion of open-label therapy with enoxaparin 40 mg once-daily (10 ± 4 days), eligible patients underwent randomisation to receive double-blind therapy of enoxaparin (n=2,975) or placebo (n=2,988) for 28 ± 4 days. During follow-up, the venous thromboembolism (VTE) risk increased with age in both treatment groups. In patients with age >75 years, those who received extended-duration enoxaparin had lower incidence of VTE (2.5% vs 6.7%; absolute difference [AD] [95% confidence interval]: −4.2% [−6.5, −2.0]), proximal deep-vein thrombosis (2.5% vs 6.6%; AD −4.1 % [−6.2, −2.0]), and symptomatic VTE (0.3% vs 1.5%; AD −1.2% [−2.2, −0.3]), in comparison to those who received placebo. In patients with age ≤75 years, those who received enoxaparin had reduced VTE (2.4% vs 2.8%; AD −0.4% [−1.5, 0.7]) and symptomatic VTE (0.2% vs 0.7%; AD −0.6% [−1.0, −0.1]) in comparison to those who received placebo. In both age subgroups, patients who received enoxaparin had increased rates of major bleeding versus those who received placebo: age >75 years (0.6% vs 0.2%; AD +0.3% [−0.2, 0.9], respectively); age ≤75 years (0.7% vs 0.2%; AD +0.5% [0.1, 0.9]). Patients in both age subgroups that received enoxaparin had similar low bleeding rates (0.6% and 0.7%, respectively). VTE risk increased with age, though the bleeding risk did not. Patients with age >75 years had a more favourable benefit-to-harm profile than younger patients.
Prognostic significance of free-floating right heart thromboemboli in acute pulmonary embolism
Authors: Becattini Cecilia , Guglielmelli Emanuele , Floriani Irene , Morrone Vincenzo , Caponi Carla , Pizzorno Luigi , Masotti Luca , Bongarzoni Amedeo , Pignataro Luigi , Casazza Franco 
Published: October 2013

SummaryThe exact prevalence of mobile right heart thromboemboli (RHTh) in patients with pulmonary embolism (PE) is unknown, depending upon PE severity and the use of early echocardiography. Similarly, the mortality rate is variable, though RHTh detection appears to substantially increase the risk of death in patients with PE. The aim of this study was to assess the prevalence of RHTh in different risk categories in a wide series of patients with PE, and to analyse the effect of RHTh on in-hospital mortality. Among 1,716 patients enrolled in the Italian Pulmonary Embolism Registry, 1,275 (13.3% at high risk, 59.3% at intermediate risk and 27.4% at low risk) had echocardiography within 48 hours from hospital admission and entered the study. Overall, RHTh were detected in 57 patients (4.5%, at admission echocardiography in 88%): in 27/169 (16%) high-risk, in 29/756 (3.8%) intermediate-risk and 1/350 (0.3%) low-risk patients, respectively. At multivariate analysis, only advanced age (odds ratio [OR] 1.61, 95% confidence [CI] 1.27–2.03, p<0.0001), high-risk category (OR vs low-risk category 37.82, 95% CI 11.26–127.06, p<0.0001) and recurrent PE (OR 45.92, 95%CI 15.19–139.96, p<0.0001) showed a statistically significant effect on mortality. The presence of RHTh significantly increased the risk of dying (OR 3.89, 95%CI 1.98–7.67, p=0.0001) at univariate analysis, but this result was not mantained in the multivariate model (OR 1.64, 95%CI 0.75–3.60, p=0.216). In conclusion, though patients with RHTh had a more severe presentation of PE, this study did not detect an association between RHTh and prognosis.
Three monoclonal antibodies against the serpin protease nexin-1 prevent protease translocation
Authors: Kousted Tina M. , Skjoedt Karsten , Petersen Steen V. , Koch Claus , Vitved Lars , Sochalska Maja , Lacroix Céline , Andersen Lisbeth M. , Wind Troels , Andreasen Peter A. , Jensen Jan K. 
Published: October 2013

SummaryProtease nexin-1 (PN-1) belongs to the serpin family and is an inhibitor of thrombin, plasmin, urokinase-type plasminogen activator, and matriptase. Recent studies have suggested PN-1 to play important roles in vascular-, neuro-, and tumour-biology. The serpin inhibitory mechanism consists of the serpin presenting its so-called reactive centre loop as a substrate to its target protease, resulting in a covalent complex with the inactivated enzyme. Previously, three mechanisms have been proposed for the inactivation of serpins by monoclonal antibodies: steric blockage of protease recognition, conversion to an inactive conformation or induction of serpin substrate behaviour. Until now, no inhibitory antibodies against PN-1 have been thoroughly characterised. Here we report the development of three monoclonal antibodies binding specifically and with high affinity to human PN-1. The antibodies all abolish the protease inhibitory activity of PN-1. In the presence of the antibodies, PN-1 does not form a complex with its target proteases, but is recovered in a reactive centre cleaved form. Using site-directed mutagenesis, we mapped the three overlapping epitopes to an area spanning the gap between the loop connecting α-helix F with β-strand 3A and the loop connecting α-helix A with β-strand 1B. We conclude that antibody binding causes a direct blockage of the final critical step of protease translocation, resulting in abortive inhibition and premature release of reactive centre cleaved PN-1. These new antibodies will provide a powerful tool to study the in vivo role of PN-1’s protease inhibitory activity.
Flow Reversal Versus Filter Protection
Authors: de Castro-Afonso Luis Henrique , Abud Lucas Giansante , Rolo Jaicer Gonçalves , dos Santos Antônio Carlos , de Oliveira Lívia , Barreira Clara Monteiro Antunes , Velasco Tonicarlo Rodrigues , Pontes-Neto Octávio Marques , Abud Daniel Giansante 
Published: October 2013

Background—
Carotid artery stenting (CAS) has become an alternative treatment for patients presenting symptomatic carotid artery stenosis. The improvement in clinical outcomes with CAS has been associated with the development of embolic protection devices. The trial aim is to compare flow reversal versus filter protection during CAS through femoral access.

Methods and Results—

Patients were randomly enrolled in CAS using flow reversal or filter protection. The primary end points were the incidence, number, and size of new ischemic brain lesions after CAS. The secondary end points included major adverse cardiac and cerebrovascular events, transient ischemic attack, and definitive ischemic brain lesions on fluid-attenuated inversion recovery magnetic resonance image at a 3-month follow-up. Ischemic brain lesions were assessed by a 3T magnetic resonance image. Neurological outcomes were evaluated by means of the National Institutes of Health Stroke Scale and the modified Rankin Scale (mRS). Forty consecutive patients were randomly assigned. Compared with flow reversal (n=21), filter protection (n=19) resulted in a significant reduction in the incidence (15.8% versus 47.6%,
P
=0.03), number (0.73 versus 2.6,
P
=0.05), and size (0.81 versus 2.23 mm,
P
=0.05) of new ischemic brain lesions. Two patients, 1 from each group, presented transient ischemic attack at 3-month follow-up. There were no major adverse cardiac and cerebrovascular events in the hospital or at 3-month follow-up.

Conclusions—
In this small sample size trial, filter protection was more effective than flow reversal in reducing ischemic brain lesions during CAS through femoral approach.

Clinical Trial Registration—

URL:
http://portal2.saude.gov.br/sisnep/
. Unique identifier: 0538.0.004.000-10.