bluuebunny/crossref_metadata_2025_split huggingface dataset:
Earnings Management and Measurement Error
Authors: Hofmann Christian 
Published: March 2014

AbstractIn this paper I consider the impact of a noisy indicator regarding a manager’s manipulative behavior on optimal effort incentives and the extent of earnings management. The analysis in this paper extends a two-task, single performance measure LEN model by including a binary random variable. I show that contracting on the noisy indicator variable is not always useful. More specifically, the principal uses the indicator variable to prevent earnings management only under conditions where manipulative behavior is not excessive. Thus, under conditions of excessive earnings management, accounting adjustments that yield a more congruent overall performance measure can be more effective than an appraisal of the existence of earnings management to mitigate the earnings management problem.
A Cooperative and Adaptive Variable Neighborhood Search for the Multi Depot Vehicle Routing Problem with Time Windows
Authors: Polacek Michael , Benkner Siegfried , Doerner Karl F. , Hartl Richard F. 
Published: March 2014

AbstractIn this paper we propose two cooperation schemes to compose new parallel variants of the Variable Neighborhood Search (VNS). On the one hand, a coarse-grained cooperation scheme is introduced which is well suited for being enhanced with a solution warehouse to store and manage the so far best found solutions and a self-adapting mechanism for the most important search parameters. This makes an a priori parameter tuning obsolete. On the other hand, a fine-grained scheme was designed to reproduce the successful properties of the sequential VNS. In combination with the use of parallel exploration threads all of the best solutions and 11 out of 20 new best solutions for the Multi Depot Vehicle Routing Problem with Time Windows were found.
A Clinical Pathway for Total Shoulder Arthroplasty—A Pilot Study
Authors: Goon Amanda K. , Dines David M. , Craig Edward V. , Gordon Michael A. , Goytizolo Enrique A. , Lin Yi , Lin Emily , YaDeau Jacques T. 
Published: March 2014

Background Appropriate pain management after total shoulder arthroplasty (TSA) facilitates rehabilitation and may improve clinical outcomes. Questions/purposes This prospective, observational study evaluated a multimodal analgesia clinical pathway for TSA. Methods Ten TSA patients received an interscalene nerve block (25 cm3 0.375% ropivacaine) with intraoperative general anesthesia. Postoperative analgesia included regularly scheduled non-opioid analgesics (meloxicam, acetaminophen, and pregabalin) and opioids on demand (oral oxycodone and intravenous patient-controlled hydromorphone). Patients were evaluated twice daily to assess pain, anterior deltoid strength, handgrip strength, and sensory function. Results The nerve block lasted an average of 18 h. Patients had minimal pain after surgery; 0 (median score on a 0–10 scale) in the Post-Anesthesia Care Unit (PACU) but increased on postoperative day (POD) 1 to 2.3 (0.0, 3.8; median (25%, 75%)) at rest and 3.8 (2.1, 6.1) with movement. Half of the patients activated the patient-controlled analgesia four or fewer times in the first 24 h after surgery. Operative anterior deltoid strength was 0 in the PACU but returned to 68% by POD 1. Operative hand strength was 0 (median) in the PACU, but the third quartile (75%) had normalized strength 49% of preoperative value. Conclusions Patients did well with this multimodal analgesic protocol. Pain scores were low, half of the patients used little or no intravenous opiate, and some patients had good handgrip strength. Future research can focus on increasing duration of analgesia from the nerve block, minimizing motor block, lowering pain scores, and avoiding intravenous opioids.
Genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in Alzheimer's disease
Authors: Morgen Katrin , Ramirez Alfredo , Frölich Lutz , Tost Heike , Plichta Michael M. , Kölsch Heike , Rakebrandt Fabian , Rienhoff Otto , Jessen Frank , Peters Oliver , Jahn Holger , Luckhaus Christian , Hüll Michael , Gertz Hermann‐Josef , Schröder Johannes , Hampel Harald , Teipel Stefan J. , Pantel Johannes , Heuser Isabella , Wiltfang Jens , Rüther Eckart , Kornhuber Johannes , Maier Wolfgang , Meyer‐Lindenberg Andreas 
Published: March 2014

AbstractBackgroundEvidence has emerged indicating that the ε4 allele of APOE and PICALM interact in conferring risk of Alzheimer's disease (AD). The biologic basis of this interaction is unclear, but it is likely to have phenotypic relevance and contribute to the structural and clinical heterogeneity of AD.MethodsThe aim of this study was to investigate interaction effects of the APOE ε4 allele and the alleles at the single‐nucleotide polymorphism rs3851179 located in the PICALM locus. We analyzed brain volumes and cognitive phenotypes of 165 patients with early AD dementia.ResultsThere was a synergistic adverse effect of homozygosity for the PICALM risk allele G in rs3851179 and APOE ε4 on volume in prefrontal and performance on the Trail Making Test A, which is sensitive to processing speed and working memory function.ConclusionsThe data suggest a neural mechanism for APOE–PICALM interactions in patients with manifest AD and indicate that the PICALM genotype modulates both brain atrophy and cognitive performance in APOE ε4 carriers.
Adverse events and dropouts in Alzheimer's disease studies: What can we learn?
Authors: Henley David B. , Sundell Karen L. , Sethuraman Gopalan , Schneider Lon S. 
Published: March 2014

AbstractBackgroundInterpreting Alzheimer's disease (AD) clinical trial (CT) outcomes is complicated by treatment dropouts and adverse events (AEs). In elderly participants, AE rates, dropouts, and deaths are important considerations as they may undermine the validity of clinical trials. Published discontinuation and safety data are limited.MethodsSafety data from 1054 placebo‐treated participants in IDENTITY and IDENTITY‐2, 76‐week, Phase 3 AD studies conducted in 31 countries, were pooled, annualized, and summarized overall, by country and age group.ResultsMedian age was 74.2 (interquartile range 67.9–79.5) years; 57.4% were female; and median observation time was 63.2 (interquartile range 41.6–77.4) weeks when study drug dosing was halted. Overall annualized rates for discontinuations, discontinuations due to AEs, serious adverse events (SAEs), and deaths were 21.6% (range 19.6%–24.0%), 8.2% (range 8.1%–8.3%), 12.0%, and 1.7%, respectively. AE and discontinuation rates varied by country and age groups. Fall, pneumonia, and atrial fibrillation AEs were more frequent in the oldest age group.ConclusionsThese annualized placebo safety data provide insight into the course of enrolled patients with mild‐to‐moderate AD, and are useful in planning longer term trials and in monitoring safety.
Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature
Authors: Antar A , El Hajj H , Jabbour M , Khalifeh I , EL-Merhi F , Mahfouz R , Bazarbachi A 
Published: March 2014

AbstractPrimary effusion lymphoma (PEL) is a rare aggressive subset of non-Hodgkin B-cell lymphoma. It is caused by Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8). It occurs mainly, but not exclusively, in HIV-positive patients. PEL predominantly develops in serous cavities and occasionally in extracavitary regions. PEL carries a very poor prognosis with a median survival time of <6 months. Indeed, currently used treatment modalities such as CHOP chemotherapy are far from achieving complete and sustainable remission. Therefore, there is no clear standard of care established in the treatment of PEL patients, stressing the need for novel-targeted approaches. Here, we have attempted a comprehensive assessment of the treatment of PEL, discussed avant-garde therapies and updated the state of preclinical research with promising clinical applications in the field. These include inhibitors of viral replication, modulators of cell signaling and inflammation, nuclear factor kappa B (NF-κB) and histone deacetylase inhibitors, and recently the combination of arsenic trioxide and interferon-alpha. Some of these targeted therapies have not yet reached clinical studies, although others were used in a few individual case reports with low numbers of patients. We also describe the first case of a 77-year-old, HIV-negative, HHV8-positive patient diagnosed with PEL limited to the pleural and peritoneal cavities. He received lenalidomide 25 mg/day for 21 days every 28 days. Treatment was well tolerated with no side effects. He rapidly improved after 1 month of treatment and progressively achieved complete remission persistent after 18 months of therapy. We believe that this review will bridge an important gap between classical chemotherapy and modern approaches of targeted therapy. Finally, our findings warrant further evaluation of lenalidomide in future prospective clinical studies.
The actin homologue MreB organizes the bacterial cell membrane
Authors: Strahl Henrik , Bürmann Frank , Hamoen Leendert W. 
Published: March 2014

AbstractThe eukaryotic cortical actin cytoskeleton creates specific lipid domains, including lipid rafts, which determine the distribution of many membrane proteins. Here we show that the bacterial actin homologue MreB displays a comparable activity. MreB forms membrane-associated filaments that coordinate bacterial cell wall synthesis. We noticed that the MreB cytoskeleton influences fluorescent staining of the cytoplasmic membrane. Detailed analyses combining an array of mutants, using specific lipid staining techniques and spectroscopic methods, revealed that MreB filaments create specific membrane regions with increased fluidity (RIFs). Interference with these fluid lipid domains (RIFs) perturbs overall lipid homeostasis and affects membrane protein localization. The influence of MreB on membrane organization and fluidity may explain why the active movement of MreB stimulates membrane protein diffusion. These novel MreB activities add additional complexity to bacterial cell membrane organization and have implications for many membrane-associated processes.
Miniature antennas embedded in electronic devices with micro‐SD card form factor for telemedicine applications
Authors: Hamouda H. , Le Thuc P. , Staraj R. , Kossiavas G. 
Published: March 2014

Two different types of inverted‐F antennas which can be integrated into a micro‐SD (μSD) card are presented. The antennas operate in the new band from 2.4835 to 2.5 GHz dedicated to medical applications. The volume available for the antenna in the μSD card is only 11 × 3 × 1 mm3. Performance in terms of bandwidth, the radiation efficiency and the gain of the two structures is compared and discussed. The μSD card is intended to fit multiple devices with different ground plane dimensions. As an example, the influence of the μSD card position on a standard printed circuit board of 100 × 40 mm² is also studied.
Size effect and stability of polarized fluid phases
Authors: Levesque D. , Weis J.-J. 
Published: March 2014

The existence of a ferroelectric fluid phase for systems of 1000–2000 dipolar hard or soft spheres is well established by numerical simulations. Theoretical approaches proposed to determine the stability of such a phase are either in qualitative agreement with the simulation results or disagree with them. Experimental results for systems of molecules or particles with large electric or magnetic dipole moments are also inconclusive. As a contribution to the question of existence and stability of a fluid ferroelectric phase this simulation work considers system sizes of the order of 10 000 particles, thus an order of magnitude larger than those used in previous studies. It shows that although ferroelectricity is not affected by an increase of system size, different spatial arrangements of the dipolar hard spheres in such a phase are possible whose free energies seem to differ only marginally.
Everolimus in Patients with Severe Pulmonary Hypertension: A Safety and Efficacy Pilot Trial
Authors: Seyfarth Hans‐Jürgen , Hammerschmidt Stefan , Halank Michael , Neuhaus Petra , Wirtz Hubert R. 
Published: March 2014

Despite the availability of vasodilating compounds, pulmonary hypertension (PH) of various origins remains a disease with a poor prognosis. In recent years, pulmonary arterial hypertension (PAH) has been recognized as a predominantly proliferative process. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), inhibits cellular protein synthesis and growth not only in lymphocytes but also in cells of the vascular wall. Ten patients suffering from PAH (n = 8) or chronic thromboembolic PH (n = 2) with progressive disease despite therapy with at least 2 vasodilating drugs were included in a prospective open‐label pilot study. All patients were treated with everolimus in addition to their prior medication. Safety and tolerability were observed throughout the study. Pulmonary vascular resistance (PVR) and 6‐minute walk distance (6MWD) were considered coprimary end points. In 2 patients, study medication was stopped prematurely because of an adverse event. One patient had acute bronchitis, and the other had right heart decompensation. The remaining 8 patients exhibited a significant 31% decrease in PVR (median [interquartile range], 1,012 [688–1,344] vs. 663 [546–860] dyn s cm−5; P = 0.018) and an increase in 6MWD (median [interquartile range], 236 [139–350] vs. 298 [207–450] m; P = 0.069) after 6 months of treatment with everolimus. In conclusion, in this pilot study antiproliferative therapy with everolimus was well tolerated in patients with PH. The observed improvements in PVR and 6MWD may stimulate further consideration of mTOR inhibition with everolimus for the treatment of PH.
Acute Effects of Sildenafil and Dobutamine in the Hypertrophic and Failing Right Heart in Vivo
Authors: Andersen Asger , Nielsen Jan M. , Rasalingam Sivagowry , Sloth Erik , Nielsen‐Kudsk Jens Erik 
Published: March 2014

The purpose of this study was to investigate whether acute intravenous administration of the phosphodiesterase type 5 (PDE‐5) inhibitor sildenafil in a single clinically relevant dose improves the in vivo function of the hypertrophic and failing right ventricle (RV). Wistar rats (n = 24) were subjected to pulmonary trunk banding (PTB) causing RV hypertrophy and failure. Four weeks after surgery, they were randomized to receive an intravenous bolus dose of sildenafil (1 mg/kg; n = 7), vehicle (n = 6), or dobutamine (10 μg/kg; n = 6). Invasive RV pressures were recorded continuously, and transthoracic echocardiography was performed 1, 5, 15, 25, 35, 50, 70, and 90 minutes after injecting the bolus. Cardiac function was compared to baseline measurements to evaluate the in vivo effects of each specific treatment. The PTB procedure caused significant hypertrophy, cardiac fibrosis, and reduction in RV function evaluated by echocardiography (TAPSE) and invasive pressure measurements. Sildenafil did not improve the function of the hypertrophic failing right heart in vivo, measured by TAPSE, RV systolic pressure (RVsP), and dp/dtmax. Dobutamine improved RV function 1 minute after injection measured by TAPSE (0.1242 ± 0.03 vs. 0.1565 ± 0.04 cm; P < 0.001), RVsP (83 ± 11 vs. 107 ± 11 mmHg; P < 0.001), and dp/dtmax (3, 136 ± 521 vs. 4, 489 ± 706 mmHg/s; P < 0.001). Acute administration of the PDE‐5 inhibitor sildenafil in a single clinically relevant dose did not modulate the in vivo function of the hypertrophic failing right heart of the rat measured by echocardiography and invasive hemodynamics. In the same model, dobutamine acutely improved RV function.
Anatomical Considerations for the Development of a New Transcatheter Aortopulmonary Shunt Device in Patients with Severe Pulmonary Arterial Hypertension
Authors: Guo Kenneth , Langleben David , Afilalo Jonathan , Shimony Avi , Leask Richard , Marelli Ariane , Martucci Giuseppe , Therrien Judith 
Published: March 2014

Morbidity from pulmonary arterial hypertension (PAH) ensues when the pulmonary pressure reaches suprasystemic levels. A transcatheter alternative to the Potts shunt would allow decompression of the right heart without the surgical risks. To aid development of a transcatheter aortopulmonary shunt (TAPS) device, we described the anatomic relationship between the left pulmonary artery (LPA) and the descending aorta (dAO) in adults with severe pulmonary hypertension. Adults with severe PAH (peak systolic pulmonary arterial pressure [PASP] ≥80 mmHg) who had computed tomography of the chest were enrolled. Measurements were taken on the axial plane at the level of the pulmonary artery bifurcation. Forty patients (male sex, 9 patients; median age ± standard deviation [SD], 59 ± 15 years; median PASP ± SD, 93 ± 12 mmHg) were identified. The mean distance (±SD) between the LPA and dAO was 2.3 ± 3.1 mm. The mean luminal dAO and LPA diameters (±SD) were 23.4 ± 3.8 mm and 25.5 ± 5.1 mm, respectively. The LPA and dAO approximated in 93% of patients, with 38% having aortic calcification at the contact site. The mean “landing zone” width and height (defining an area with distance <4 mm between the outer borders) of the two arteries were 15.7 ± 3.4 mm and 20.6 ± 4.3 mm, respectively, at a mean distance of 28.0 ± 7.6 mm from the main pulmonary artery bifurcation. This study shows that the landing zone is able to accommodate a TAPS device of up to 15 mm in diameter in the majority of patients with severe PAH.
Pulmonary 2‐Deoxy‐2‐[18F]‐Fluoro‐D‐Glucose Uptake is Low in Treated Patients with Idiopathic Pulmonary Arterial Hypertension
Authors: Ruiter Gerrina , Wong Yeun Ying , Raijmakers Pieter , Huisman Marc C. , Lammertsma Adriaan A. , Knaapen Paul , de Man Frances S. , Westerhof Nico , van der Laarse Willem J. , Vonk‐Noordegraaf Anton 
Published: March 2014

Glucose metabolism measurement using 2‐deoxy‐2‐[18F]‐fluoro‐D‐glucose (18FDG) positron emission tomography (PET) could provide in vivo information about pulmonary vascular remodeling. The purpose of this study was to assess whether pulmonary 18FDG uptake in idiopathic pulmonary arterial hypertension (IPAH) patients changes and, if so, to determine whether the change is related to disease severity and survival. Sixteen IPAH patients who were treated with IPAH‐specific therapy and 7 patients who had a myocardial infarction (MI) without pulmonary hypertension were included. IPAH disease severity was determined using the 6‐minute walk test and right heart catheterization 2 days before 18FDG PET. Regions of interest were defined for left and right lungs, and standardized uptake values (SUVs), normalized to body weight, injected dose, and plasma glucose level, were derived. Mean SUVs for IPAH left and right lungs were 0.40 ± 0.26 and 0.44 ± 0.18 (P = 0.32), respectively. In MI patients, SUVs were 0.38 ± 0.13 and 0.35 ± 0.10 (P = 0.24) in left and right lungs, respectively. Total lung SUVs were similar in IPAH and MI patients (0.41 ± 0.19 vs. 0.37 ± 0.11; P = 0.56). There was no correlation between SUV and IPAH disease severity parameters. In addition, lung SUV did not predict survival in IPAH patients (hazard ratio, 1.155; 95% confidence interval, 0.16–8.26; P = 0.88). In conclusion, pulmonary 18FDG uptake in treated IPAH patients is low and is not associated with disease severity and survival, thereby limiting its clinical use in patient care.
Induction of T-cell memory by a dendritic cell vaccine: a computational model
Authors: Pappalardo Francesco , Pennisi Marzio , Ricupito Alessia , Topputo Francesco , Bellone Matteo 
Published: March 2014

Abstract
Motivation: Although results from phase III clinical trials substantially support the use of prophylactic and therapeutic vaccines against cancer, what has yet to be defined is how many and how frequent boosts are needed to sustain a long-lasting and protecting memory T-cell response against tumor antigens. Common experience is that such preclinical tests require the sacrifice of a relatively large number of animals, and are particularly time- and money-consuming.
Results: As a first step to overcome these hurdles, we have developed an ordinary differential equation model that includes all relevant entities (such as activated cytotoxic T lymphocytes and memory T cells), and investigated the induction of immunological memory in the context of wild-type mice injected with a dendritic cell-based vaccine. We have simulated the biological behavior both in the presence and in the absence of memory T cells. Comparing results of ex vivo and in silico experiments, we show that the model is able to envisage the expansion and persistence of antigen-specific memory T cells. The model might be applicable to more complex vaccination schedules and substantially in any biological condition of prime-boosting.
Availability and implementation: The model is fully described in the article.
Contact: fp@francescopappalardo.net
Supplementary information: Supplementary data are available at Bioinformatics online.
PyRAD: assembly of
de novo
RADseq loci for phylogenetic analyses
Authors: Eaton Deren A. R. 
Published: March 2014

Abstract
Motivation:  Restriction-site–associated genomic markers are a powerful tool for investigating evolutionary questions at the population level, but are limited in their utility at deeper phylogenetic scales where fewer orthologous loci are typically recovered across disparate taxa. While this limitation stems in part from mutations to restriction recognition sites that disrupt data generation, an additional source of data loss comes from the failure to identify homology during bioinformatic analyses. Clustering methods that allow for lower similarity thresholds and the inclusion of indel variation will perform better at assembling RADseq loci at the phylogenetic scale.
Results:  PyRAD is a pipeline to assemble de novo RADseq loci with the aim of optimizing coverage across phylogenetic datasets. It uses a wrapper around an alignment-clustering algorithm, which allows for indel variation within and between samples, as well as for incomplete overlap among reads (e.g. paired-end). Here I compare PyRAD with the program Stacks in their performance analyzing a simulated RADseq dataset that includes indel variation. Indels disrupt clustering of homologous loci in Stacks but not in PyRAD , such that the latter recovers more shared loci across disparate taxa. I show through reanalysis of an empirical RADseq dataset that indels are a common feature of such data, even at shallow phylogenetic scales. PyRAD uses parallel processing as well as an optional hierarchical clustering method, which allows it to rapidly assemble phylogenetic datasets with hundreds of sampled individuals.
Availability :   Software is written in Python and freely available at http://www.dereneaton.com/software/
Contact:  daeaton.chicago@gmail.com
Supplementary Information:  Supplementary data are available at Bioinformatics online.
Frag’r’Us: knowledge-based sampling of protein backbone conformations for
de novo
structure-based protein design
Authors: Bonet Jaume , Segura Joan , Planas-Iglesias Joan , Oliva Baldomero , Fernandez-Fuentes Narcis 
Published: March 2014

Abstract
Motivation The remodeling of short fragment(s) of the protein backbone to accommodate new function(s), fine-tune binding specificities or change/create novel protein interactions is a common task in structure-based computational design. Alternative backbone conformations can be generated de novo or by redeploying existing fragments extracted from protein structures i.e. knowledge-based. We present Frag’r’Us, a web server designed to sample alternative protein backbone conformations in loop regions. The method relies on a database of super secondary structural motifs called s motifs. Thus, sampling of conformations reflects structurally feasible fragments compiled from existing protein structures.
Availability and implementation Frag’r’Us has been implemented as web application and is available at http://www.bioinsilico.org/FRAGRUS .
Contact narcis.fernandez@gmail.com or baldo.oliva@upf.edu
Supplementary information Supplementary data are available at Bioinformatics online.