bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restricted maximum likelihood estimation of joint mean‐covariance models
Authors: Papageorgiou Georgios 
Published: May 2012

AbstractThe class of joint mean‐covariance models uses the modified Cholesky decomposition of the within subject covariance matrix in order to arrive to an unconstrained, statistically meaningful reparameterisation. The new parameterisation of the covariance matrix has two sets of parameters that separately describe the variances and correlations. Thus, with the mean or regression parameters, these models have three sets of distinct parameters. In order to alleviate the problem of inefficient estimation and downward bias in the variance estimates, inherent in the maximum likelihood estimation procedure, the usual REML estimation procedure adjusts for the degrees of freedom lost due to the estimation of the mean parameters. Because of the parameterisation of the joint mean covariance models, it is possible to adapt the usual REML procedure in order to estimate the variance (correlation) parameters by taking into account the degrees of freedom lost by the estimation of both the mean and correlation (variance) parameters. To this end, here we propose adjustments to the estimation procedures based on the modified and adjusted profile likelihoods. The methods are illustrated by an application to a real data set and simulation studies.The Canadian Journal of Statistics40: 225–242; 2012 © 2012 Statistical Society of Canada
Regression analysis for a summed missing data problem under an outcome‐dependent sampling scheme
Authors: Ding Jieli , Liu Yanyan , Peden David B. , Kleeberger Steven R. , Zhou Haibo 
Published: May 2012

AbstractIn this paper, we consider a regression analysis for a missing data problem in which the variables of primary interest are unobserved under a general biased sampling scheme, an outcome‐dependent sampling (ODS) design. We propose a semiparametric empirical likelihood method for accessing the association between a continuous outcome response and unobservable interesting factors. Simulation study results show that ODS design can produce more efficient estimators than the simple random design of the same sample size. We demonstrate the proposed approach with a data set from an environmental study for the genetic effects on human lung function in COPD smokers. The Canadian Journal of Statistics 40: 282–303; 2012 © 2012 Statistical Society of Canada
Phase 1 dose‐escalation trial evaluating the combination of the selective MET (mesenchymal‐epithelial transition factor) inhibitor tivantinib (ARQ 197) plus erlotinib
Authors: Goldman Jonathan W. , Laux Isett , Chai Feng , Savage Ronald E. , Ferrari Dora , Garmey Edward G. , Just Richard G. , Rosen Lee S. 
Published: May 2012

AbstractBACKGROUND:Amplification of the mesenchymal‐epithelial transition factor (MET) gene can promote tumor resistance to epidermal growth factor receptor (EGFR) inhibition. Dual EGFR‐MET inhibition may overcome this resistance. Tivantinib (ARQ 197) is a selective, oral, non–ATP‐competitive, small‐molecule inhibitor of the MET receptor tyrosine kinase. This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of tivantinib combined with the EGFR inhibitor erlotinib.METHODS:Patients with advanced solid malignancies were administered oral tivantinib at escalating doses of 120, 240, 360, and 480 mg twice daily (BID) plus 150 mg erlotinib once daily (QD). Single or multiple intrapatient dose escalation was planned in the absence of dose‐limiting toxicity in the first cycle of therapy (21 days).RESULTS:Thirty‐two patients received combination treatment. Tivantinib serum concentrations were not dose‐proportional. The most common (≥20%) adverse events (AEs) regardless of causality included rash (n = 17), fatigue (n = 12), nausea (n = 10), abdominal pain (n = 10), diarrhea (n = 9), bradycardia (n = 9), and anemia (n = 7). AEs considered related to study treatment occurred in 28 patients (87.5%), and 5 patients (15.6%) had treatment‐related serious AEs, including neutropenia, leukopenia, syncope, sinus bradycardia, and sick sinus syndrome. Fifteen of 32 patients (46.8%) had a partial response (n = 1) or stable disease (n = 14) as assessed by Response Evaluation Criteria in Solid Tumors. Six of 8 patients with nonsmall cell lung cancer achieved stable disease. The recommended phase 2 dose is tivantinib 360 mg BID plus erlotinib 150 mg QD.CONCLUSIONS:Tivantinib plus erlotinib was well tolerated with encouraging clinical activity, especially in patients with nonsmall cell lung cancer. Cancer 2012. © 2012 American Cancer Society.
Long‐term incidence of breast cancer by trial arm in one county of the Swedish Two‐County Trial of mammographic screening
Authors: Yen Amy Ming‐Fang , Duffy Stephen W. , Chen Tony Hsiu‐Hsi , Chen Li‐Sheng , Chiu Sherry Yueh‐Hsia , Fann Jean Ching‐Yuan , Wu Wendy Yi‐Ying , Su Chiu‐Wen , Smith Robert A. , Tabár Lászlo 
Published: May 2012

AbstractBACKGROUND:This study estimated the excess incidence (overdiagnosis) of breast cancer associated with starting mammographic screening at an earlier age, by using data from the Dalarna County component of the Swedish Two‐County Trial of breast cancer screening.METHODS:In Dalarna County, Sweden, 38,589 women aged 40 to 74 years were randomized to invitation to regular mammographic screening (active study population [ASP]) and 18,582 women to usual care (passive study population [PSP]). After 3 screening rounds (6‐8 years after randomization), the PSP was invited to screening. The cumulative incidence of breast cancer was calculated in the ASP and PSP from randomization to 29 years later. In addition, cumulative incidence was calculated for invasive cancers, advanced invasive cancers (≥2 cm in maximum diameter or node‐positive), and nonadvanced cancers (<2 cm and node negative).RESULTS:There was no excess of cancers in the ASP at 29 year follow‐up (relative risk, 1.00; 95% confidence interval, 0.92‐1.08). Cumulative incidence in the 2 arms approximately equalized at the conclusion of the first round of screening of the PSP. There was an excess of nonadvanced cancers and a deficit of advanced cancers in the ASP, both of which persisted to 29 years.CONCLUSIONS:There was no additional breast cancer incidence associated with 100,000 additional screens in the ASP. Results suggest that overdiagnosis is small and largely confined to the prevalence screen. Cancer 2012. © 2012 American Cancer Society.
The prostate cancer conundrum revisited
Authors: Etzioni Ruth , Gulati Roman , Tsodikov Alex , Wever Elisabeth M. , Penson David F. , Heijnsdijk Eveline A.M. , Katcher Jeffrey , Draisma Gerrit , Feuer Eric J. , de Koning Harry J. , Mariotto Angela B. 
Published: May 2012

AbstractBACKGROUND:Prostate cancer mortality rates in the United States declined by >40% between 1991 and 2005. The impact of changes in primary treatment and adjuvant and neoadjuvant hormone therapy on this decline is unknown.METHODS:The authors applied 3 independently developed models of prostate cancer natural history and disease detection under common assumptions about treatment patterns, treatment efficacy, and survival in the population. Primary treatment patterns were derived from the Surveillance, Epidemiology, and End Results registry; data on the frequency of hormone therapy were obtained from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) database; and treatment efficacy was based on estimates from randomized trials and comparative effectiveness studies of treatment alternatives. The models projected prostate cancer mortality without prostate‐specific antigen screening and in the presence and absence of treatment benefit. The impact of primary treatment was expressed as a fraction of the difference between observed mortality and projected mortality in the absence of treatment benefit.RESULTS:The 3 models projected that changes in treatment explained 22% to 33% of the mortality decline by 2005. These contributions were accounted for mostly by surgery and radiation therapy, which increased in frequency until the 1990s, whereas hormone therapies contributed little to the mortality decline by 2005. Assuming that treatment benefit was less for older men, changes in treatment explained only 16% to 23% of the mortality decline by 2005.CONCLUSIONS:Changes in primary treatment explained a minority of the observed decline in prostate cancer mortality. The remainder of the decline probably was because of other interventions, such as prostate‐specific antigen screening and advances in the treatment of recurrent and progressive disease. Cancer 2012. © 2012 American Cancer Society.
The economic impact of a patient navigator program to increase screening colonoscopy
Authors: Elkin Elena B. , Shapiro Ephraim , Snow Jacqueline G. , Zauber Ann G. , Krauskopf Marian S. 
Published: May 2012

AbstractBACKGROUND:Patient navigation can increase colorectal cancer screening rates. The net economic impact of a colonoscopy patient navigator program was evaluated in an urban public hospital setting.METHODS:Cost, cost‐effectiveness, and cost‐benefit analyses were performed of a colonoscopy patient navigation program at 3 urban public hospitals in the period from 2003 to 2007. Program effectiveness was assessed in a 2‐group, pre‐ and post‐program, nonrandomized evaluation, comparing program hospitals with comparison hospitals that served similar populations. Costs were assessed from the provider's perspective. Outcomes included colonoscopy volume, colonoscopy completion rate, program cost, incremental cost‐effectiveness, and net monetary benefit.RESULTS:Patient navigation was associated with a 61% increase in average monthly colonoscopy volume at program hospitals, from 114 procedures to 184 procedures, compared with a 12% increase at comparison hospitals. Adjusted for other factors, the navigator program increased colonoscopy volume by 44 to 67 additional procedures per month. Average program cost varied from $50 to $300 per patient referred to a navigator. Incremental cost‐effectiveness varied from $200 to $700 per additional colonoscopy. At 2 hospitals, net revenue associated with increased colonoscopy volume exceeded the program cost per additional colonoscopy, yielding a net financial benefit; at the third hospital, the program yielded a net cost. Variation between hospitals in the program's economic impact was primarily attributable to differences in personnel costs.CONCLUSIONS:Economic evaluation of this colonoscopy patient navigator program in an urban public hospital setting suggests that such programs can be a cost‐effective use of limited resources and yield a net financial benefit for providers. Cancer 2012. © 2012 American Cancer Society.
Gain of chromosome 8q is associated with metastases and poor survival of patients with clear cell renal cell carcinoma
Authors: Klatte Tobias , Kroeger Nils , Rampersaud Edward N. , Birkhäuser Frédéric D. , Logan Joshua E. , Sonn Geoffrey , Riss Joseph , Rao P. Nagesh , Kabbinavar Fairooz F. , Belldegrun Arie S. , Pantuck Allan J. 
Published: May 2012

AbstractBACKGROUND:The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease‐specific survival (DSS).METHODS:The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated.RESULTS:Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes (P = .030). Patients with gain of 8q had a 3.22‐fold increased risk of death from CCRCC (P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain (P = .0015).CONCLUSIONS:Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto‐oncogene c‐MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c‐MYC inhibitors or agents that target the MAPK/ERK (mitogen‐activated protein kinase) pathway. Cancer 2012. © 2012 American Cancer Society.
Late dysphagia after radiotherapy‐based treatment of head and neck cancer
Authors: Hutcheson Katherine A. , Lewin Jan S. , Barringer Denise A. , Lisec Asher , Gunn G.Brandon , Moore Michael W.S. , Holsinger F. Christopher 
Published: May 2012

AbstractBACKGROUND:Changing trends in head and neck cancer (HNC) merit an understanding of the late effects of therapy, but few studies examine dysphagia beyond 2 years of treatment.METHODS:A case series was examined to describe the pathophysiology and outcomes in dysphagic HNC survivors referred for modified barium swallow (MBS) studies ≥5 years after definitive radiotherapy or chemoradiotherapy (January 2001 through May 2011). Functional measures included the penetration‐aspiration scale (PAS), performance status scale–head and neck (PSS‐HN), National Institutes of Health Swallowing Safety Scale (NIH‐SSS), and MBS impairment profile (MBSImp).RESULTS:Twenty‐nine patients previously treated with radiotherapy (38%) or chemoradiotherapy (62%) were included (median years posttreatment, 9; range, 5‐19). The majority (86%) had oropharyngeal cancer; 52% were never‐smokers. Seventy‐five percent had T2 or T3 tumors; 52% were N+. The median age at diagnosis was 55 (range, 38‐72). Abnormal late examination findings included: dysarthria/dysphonia (76%), cranial neuropathy (48%), trismus (38%), and radionecrosis (10%). MBS studies confirmed pharyngeal residue and aspiration in all dysphagic cases owing to physiologic impairment (median PAS, 8; median NIH‐SSS, 10; median MBSImp, 18), whereas stricture was confirmed endoscopically in 7 (24%). Twenty‐five (86%) developed pneumonia, half requiring hospitalization. Swallow postures/strategies helped 69% of cases, but no patient achieved durable improvement across functional measures at last follow‐up. Ultimately, 19 (66%) were gastrostomy‐dependent.CONCLUSIONS:Although functional organ preservation is commonly achieved, severe dysphagia represents a challenging late effect that may develop or progress years after radiation‐based therapy for HNC. These data suggest that novel approaches are needed to minimize and better address this complication that is commonly refractory to many standard dysphagia therapies. Cancer 2012. © 2012 American Cancer Society.
Fibroblast growth factor 2 regulates adequate nigrostriatal pathway formation in mice
Authors: Baron Olga , Ratzka Andreas , Grothe Claudia 
Published: May 2012

AbstractFibroblast growth factor 2 (FGF‐2) is an important neurotrophic factor that promotes survival of adult mesencephalic dopaminergic (mDA) neurons and regulates their adequate development. Since mDA neurons degenerate in Parkinson's disease, a comprehensive understanding of their development and maintenance might contribute to the development of causative therapeutic approaches. The current analysis addressed the role of FGF‐2 in mDA axonal outgrowth, pathway formation, and innervation of respective forebrain targets using organotypic explant cocultures of ventral midbrain (VM) and forebrain (FB). An enhanced green fluorescent protein (EGFP) transgenic mouse strain was used for the VM explants, which allowed combining and distinguishing of individual VM and FB tissue from wildtype and FGF‐2‐deficient embryonic day (E)14.5 embryos, respectively. These cocultures provided a suitable model to study the role of target‐derived FB and intrinsic VM‐derived FGF‐2. In fact, we show that loss of FGF‐2 in both FB and VM results in significantly increased mDA fiber outgrowth compared to wildtype cocultures, proving a regulatory role of FGF‐2 during nigrostriatal wiring. Further, we found in heterogeneous cocultures deficient for FGF‐2 in FB and VM, respectively, similar phenotypes with wider fiber tracts compared to wildtype cocultures and shorter fiber outgrowth distance than cocultures completely deficient for FGF‐2. Additionally, the loss of target‐derived FGF‐2 in FB explants resulted in decreased caudorostral glial migration. Together these findings imply an intricate interplay of target‐derived and VM‐derived FGF signaling, which assures an adequate nigrostriatal pathway formation and target innervation. J. Comp. Neurol. 520:3949–3961, 2012. © 2012 Wiley Periodicals, Inc.
Cadherin expression delineates the divisions of the postnatal and adult mouse amygdala
Authors: Hertel Nicole , Redies Christoph , Medina Loreta 
Published: May 2012

AbstractThe amygdaloid complex represents a group of telencephalic nuclei and cortical areas that control emotional and social behavior. Amygdalar development is poorly understood. It is generally accepted that the structures of the amygdala originate from the neuroepithelium at both sides of the pallial–subpallial boundary. In the present study, we mapped the expression of 13 members of the cadherin superfamily of cell adhesion molecules, which provide an adhesive code for the development and maintenance of functional structures in the central nervous system (CNS). Five classic cadherins (Cdh4, Cdh6, Cdh7, Cdh8, Cdh11) and eight delta‐protocadherins (Pcdh1, Pcdh7, Pcdh8, Pcdh9, Pcdh10, Pcdh11, PCdh17, PCdh19) were studied by in situ hybridization in the postnatal (P5) and adult mouse amygdala. In the different parts of the amygdala, each of these (proto‐) cadherins shows a distinct and spatially restricted expression pattern that is highly similar at postnatal and adult stages. The combinatorial expression of (proto‐) cadherins allows the distinction of multiple molecular subdivisions within the amygdala that partially coincide with previously described morphological divisions. Beyond these expected results, a number of novel molecular subdivisions and subpopulations of cells were identified; for example, additional molecular subdomains, patches, or cell aggregates with distinct (proto‐) cadherin expression in several nuclei/areas of the amygdala. We also show that several cadherins are molecular markers for particular functional subsystems within the amygdala, such as in the olfactory projections. In summary, (proto‐) cadherins provide a code of potentially adhesive cues that can aid the understanding of functional organization in the amygdala. J. Comp. Neurol. 520:3982–4012, 2012. © 2012 Wiley Periodicals, Inc.
Peripheral axons of the adult zebrafish maxillary barbel extensively remyelinate during sensory appendage regeneration
Authors: Moore Alex C. , Mark Tiffany E. , Hogan Ann K. , Topczewski Jacek , LeClair Elizabeth E. 
Published: May 2012

AbstractMyelination is a cellular adaptation allowing rapid conduction along axons. We have investigated peripheral axons of the zebrafish maxillary barbel (ZMB), an optically clear sensory appendage. Each barbel carries taste buds, solitary chemosensory cells, and epithelial nerve endings, all of which regenerate after amputation (LeClair and Topczewski [2010] PLoS One 5:e8737). The ZMB contains axons from the facial nerve; however, myelination within the barbel itself has not been established. Transcripts of myelin basic protein (mbp) are expressed in normal and regenerating adult barbels, indicating activity in both maintenance and repair. Myelin was confirmed in situ by using toluidine blue, an anti‐MBP antibody, and transmission electron microscopy (TEM). The adult ZMB contains ∼180 small‐diameter axons (<2 μm), approximately 60% of which are myelinated. Developmental myelination was observed via whole‐mount immunohistochemistry 4–6 weeks postfertilization, showing myelin sheaths lagging behind growing axons. Early‐regenerating axons (10 days postsurgery), having no or few myelin layers, were disorganized within a fibroblast‐rich collagenous scar. Twenty‐eight days postsurgery, barbel axons had grown out several millimeters and were organized with compact myelin sheaths. Fiber types and axon areas were similar between normal and regenerated tissue; within 4 weeks, regenerating axons restored ∼85% of normal myelin thickness. Regenerating barbels express multiple promyelinating transcription factors (sox10, oct6 = pou3f1; krox20a/b = egr2a/b) typical of Schwann cells. These observations extend our understanding of the zebrafish peripheral nervous system within a little‐studied sensory appendage. The accessible ZMB provides a novel context for studying axon regeneration, Schwann cell migration, and remyelination in a model vertebrate. J. Comp. Neurol. 520:4184–4203, 2012. © 2012 Wiley Periodicals, Inc.
Computational representation of a realistic head and brain volume conductor model: electroencephalography simulation and visualization study
Authors: Kybartaite Asta 
Published: May 2012

SUMMARYComputational head and brain volume conductor modeling is a practical and non‐invasive method to investigate neuroelectrical activity in the brain. Anatomical structures included in a model affect the flow of volume currents and the resulting scalp surface potentials. The influence of different tissues within the head on scalp surface potentials was investigated by constructing five highly detailed, realistic head models from segmented and processed Visible Human Man digital images. The models were: (1) model with 20 different tissues, that is, skin, dense connective tissue (fat), aponeurosis (muscle), outer, middle and inner tables of the scalp, dura matter, arachnoid layer (including cerebrospinal fluid), pia matter, six cortical layers, eye tissue, muscle around the eye, optic nerve, temporal muscle, white matter and internal air, (2) model with three main inhomogeneities, that is, scalp, skull, brain, (3) model with homogeneous scalp and remaining inhomogeneities, (4) model with homogeneous skull and remaining inhomogeneities, and (5) model with homogeneous brain matter and remaining inhomogeneities. Scalp potentials because of three different dipolar sources in the parietal‐occipital lobe were computed for all five models. Results of a forward solution revealed that tissues included in the model and the dipole source location directly affect the simulated scalp surface potentials. The major finding indicates that significant change in the scalp surface potentials is observed when the brain's distinctions are removed. The other modifications, for example, layers of the scalp and skull are important too, but they have less effect on the overall results. Copyright © 2012 John Wiley & Sons, Ltd.
Juvenile, but not adult exposure to high‐fat diet impairs relational memory and hippocampal neurogenesis in mice
Authors: Boitard Chloe , Etchamendy Nicole , Sauvant Julie , Aubert Agnes , Tronel Sophie , Marighetto Aline , Layé Sophie , Ferreira Guillaume 
Published: May 2012

AbstractIncreased consumption of high‐fat diet (HFD) leads to obesity and adverse neurocognitive outcomes. Childhood and adolescence are important periods of brain maturation shaping cognitive function. These periods could consequently be particularly sensitive to the detrimental effects of HFD intake. In mice, juvenile and adulthood consumption of HFD induce similar morphometric and metabolic changes. However, only juvenile exposure to HFD abolishes relational memory flexibility, assessed after initial radial‐maze concurrent spatial discrimination learning, and decreases neurogenesis. Our results identify a critical period of development covering adolescence with higher sensitivity to HFD‐induced hippocampal dysfunction at both behavioral and cellular levels. © 2012 Wiley Periodicals, Inc.