bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Outcomes and Prognostic Factors in Mexican Patients with Endometrial Carcinoma with Emphasis on Patients Receiving Radiotherapy after Surgery: An Institutional Perspective
Authors: Flores Christian , Mariscal Carlos , Celis Alfredo , Balcázar Nidia M. , Meneses Abelardo , Mohar Alejandro , Mota Aida , Trejo Elizabeth
Published: May 2012

Aim. To analyze the clinical characteristics and treatment outcomes in patients with endometrial carcinoma treated in a Latin American institute with emphasis in patients receiving adjuvant radiotherapy. Methods. A total of 412 patients with endometrial carcinoma admitted to our hospital between 1998 and 2008 were evaluated, retrospectively. The mean age was 55 years (28–87). Two hundred seventy patients received RT following surgery. Stage distribution was as follows: 221 patients (54%) stage I, 86 patients (21%) stage II, and 103 patients (24.5%) stage III and 2 patients (0.5%) stage IVA. Results. Overall survival rate was 95% at 2 years, 84% at 5 years, and 79% at 10 years. By the end of followup, 338 patients (82%) were disease-free, and 13 (3%) were alive with disease. Univariate and multivariate analyses identified age, grade, serosal and adnexial involvement as significant predictors for overall survival. Conclusion. The results of our study suggests that early-stage, low-grade endometrial cancer with no risk factors should not receive external beam radiotherapy, intermediate risk patients should receive only vaginal vault brachytherapy, and the use of chemotherapy with radiotherapy for patients high-risk and advanced-stage carcinoma the addition of radiotherapy is associated with a better survival being an effective therapeutic option.
Minimally Invasive Surgical Therapies for Atrial Fibrillation
Authors: Nakamura Yoshitsugu , Kiaii Bob , Chu Michael W. A.
Published: May 2012

Atrial fibrillation is the most common sustained arrhythmia and is associated with significant risks of thromboembolism, stroke, congestive heart failure, and death. There have been major advances in the management of atrial fibrillation including pharmacologic therapies, antithrombotic therapies, and ablation techniques. Surgery for atrial fibrillation, including both concomitant and stand-alone interventions, is an effective therapy to restore sinus rhythm. Minimally invasive surgical ablation is an emerging field that aims for the superior results of the traditional Cox-Maze procedure through a less invasive operation with lower morbidity, quicker recovery, and improved patient satisfaction. These novel techniques utilize endoscopic or minithoracotomy approaches with various energy sources to achieve electrical isolation of the pulmonary veins in addition to other ablation lines. We review advancements in minimally invasive techniques for atrial fibrillation surgery, including management of the left atrial appendage.
High-Purity Nanopowders for Laser Applications
Authors: Ganta Deepak , Venugopal Ganesh , Hunt Andrew T. , Sapp Michael
Published: May 2012

We have successfully developed high-quality laser-grade yttrium aluminum garnet (YAG), and lutetium oxide (Lu2O3), using a novel combustion chemical vapor condensation (CCVC) technique based on a proprietary NanoSpray Combustion process. The purity of the nanopowders was >99%. Nanopowders with different dopants have been synthesized over a 10–200 nm size range, with low-cost, high-purity precursors that are viable for large-scale production. Great strides have also been made in developing highly dense (>99% theoretical density) polycrystalline Nd-doped YAG pellets using vacuum sintering and hot isostatic pressing (HIP). This method is an alternative to the Czochralski method for making single-crystal ceramic bodies, which has several disadvantages including high cost, size, shape restrictions, and limitations in Nd concentrations (∼1 at %). Nanomaterials also enable higher percentages of Nd to be incorporated into the YAG lattice which improves laser efficiency and >85% near IR transmission, thereby reducing scattering losses associated with larger grain-size polycrystalline materials.
A Review of Fetal Scarless Healing
Authors: Rolfe K. J. , Grobbelaar A. O.
Published: May 2012

Wound healing is a complex process involving a number of processes. Fetal regeneration has been shown to have a number of differences compared to scar-forming healing. This review discusses the number of differences identified in fetal regeneration. Understanding these differences may result in new therapeutic targets which may reduce or even prevent scarring in adult healing.
Convergence and Divergence of Higher-Order Hermite or Hermite-Fejér Interpolation Polynomials with Exponential-Type Weights
Authors: Jung Hee Sun , Nakamura Gou , Sakai Ryozi , Suzuki Noriaki
Published: May 2012

Let and let , where and is an even function. Then we can construct the orthonormal polynomials of degree for . In this paper for an even integer
we investigate the convergence theorems with respect to the higher-order Hermite and Hermite-Fejér interpolation polynomials and related approximation process based at the zeros of . Moreover, for an odd integer , we give a certain divergence theorem with respect to the higher-order Hermite-Fejér interpolation polynomials based at the zeros of .
Facial Recognition Patterns of Children and Adults Looking at Robotic Faces
Authors: Park Eunil , Kim Ki Joon , del Pobil Angel P.
Published: May 2012

The present study investigates whether adults and children exhibit different eye-fixation patterns when they look at human faces, machinelike robotic faces, and humanlike robotic faces. The results from two between-subject experiments showed that children and adults did have different facial recognition patterns; children tended to fixate more on the mouth of both machinelike and humanlike robotic faces than they do on human faces, while adults focused more on the eyes. The implications of notable findings and the limitations of the experiment are discussed.
The Correction of a Secondary Bilateral Cleft Lip Nasal Deformity Using Refined Open Rhinoplasty with Reverse-U Incision, V-Y Plasty, and Selective Combination with Composite Grafting: Long-term Results
Authors: Cho Byung Chae , Choi Kang Young , Lee Jung Hun , Yang Jung Dug , Chung Ho Yun
Published: May 2012

Background This article presents long-term outcomes after correcting secondary bilateral cleft lip nasal deformities using a refined reverse-U incision and V-Y plasty or in combination with a composite graft in order to elongate the short columella.

Methods A total of forty-six patients underwent surgery between September 1996 and December 2008. The age of the patients ranged from 3 to 19 years of age. A bilateral reverse-U incision and V-Y plasty were used in 24 patients. A composite graft from the helical root was combined with a bilateral reverse-U incision in the 22 patients who possessed a severely shortened columella. The follow-up period ranged between 2 and 10 years.

Results A total of 32 patients out of 46 were evaluated postoperatively. The average columella length was significantly improved from an average of 3.7 mm preoperatively to 8.5 mm postoperatively. The average ratio of the columella height to the alar base width was 0.18 preoperatively and 0.29 postoperatively. The postoperative basal and lateral views revealed a better shape of the nostrils and columella. The elongated columella, combined with a composite graft, presented good maintenance of the corrected position with no growth disturbance. A composite graft showed color mismatching in several patients. Twenty-six patients demonstrated no alar-columella web deformity and satisfactory symmetry of the nostrils. Four patients experienced a drooping and overhanging of the corrected alar-columella web.

Conclusions A bilateral reverse-U incision with V-Y plasty or in combination with a composite graft was effective in correcting secondary bilateral cleft lip nasal deformity.
How Many Presentations Are Published as Full Papers?
Authors: Chung Kyu Jin , Lee Jun Ho , Kim Yong Ha , Kim Tae Gon , Ha Ju Ho
Published: May 2012

Background The publication rate of presentations at medical international meetings has ranged from 11% to 78% with an average of 45%. To date, there are no studies about the final rate of publications at scientific meetings associated with plastic surgery from Korea. The present authors investigated the publication rate among the presentations at meetings associated with plastic surgery.

Methods The titles and authors of the abstracts from oral and poster presentations were collected from the program books of the Congress of the Korean Society of Plastic and Reconstructive Surgeons (CKSPRS) for 2005 to 2007 (58th-63rd). All of the abstracts presented were searched for using PubMed, KoreaMed, KMbase, and Google Scholar. The titles, key words from the titles, and the authors' names were then entered in database programs. The parameters reviewed included the publication rate, type of presentation including running time, affiliation, subspecialty, time to publication, and publication journal.

Results A total of 1,176 abstracts presented at the CKSPRS from 2005 to 2007 were evaluated. 38.7% of the abstracts, of which oral presentations accounted for 41.0% and poster presentations 34.8%, were published as full papers. The mean time to publication was 15.04 months. Among journals of publication, the Journal of the Korean Society of Plastic and Reconstructive Surgeons was most used.

Conclusions Brilliant ideas and innovative approaches are being discussed at CKSPRS. The 38.7% publication rate found from this research appeared a bit lower than the average rate of medical meetings. If these valuable presentations are not available as full papers, the research would be a waste of time and effort.
A Case of Urethral Reconstruction Using a Superficial Circumflex Iliac Artery
Authors: Yoo Kun-Woon , Shin Hyun-Woo , Lee Hye Kyung
Published: May 2012

A radial forearm free flap has been conventionally used for urethral reconstruction. However, aesthetic and functional complications occur frequently at the donor site. The use of a superficial circumflex iliac artery perforator (SCIP) flap can resolve these disadvantages. Here, we report our case with a review of literature. A 69-year-old man visited our hospital with multiple contusions of the abdomen and genital amputation. After necrotic tissue debridement, the length of the residual corpus carvernosum was 1.5 cm and that of the corpus spongiosum and urethra was 1 cm. For the reconstruction of the penis, a SCIP flap and anterolateral thigh free flap was performed. The primary closure was performed at the donor site. Three weeks postoperatively, the patient had a urethral foley catheter removed. The neourethra was functioning well without stricture. Four months postoperatively, the patient had no complications such as urethral stricture. A good recovery was also achieved with no aesthetic deficits at the donor site. SCIP flap is appropriate for urethral reconstruction. Because of its proximity to the recipient sites, it makes surgical preparation easier and the primary closure at the donor site available. It is also advantageous in that its location is almost unnoticeable.
Tubularized Penile-Flap Urethroplasty Using a Fasciocutaneous Random Pedicled Flap for Recurrent Anterior Urethral Stricture
Authors: Lee Yong Jig , Lee Byung Kwon
Published: May 2012

This report describes the use of a tubularized random flap for the curative treatment of recurrent anterior urethral stricture. Under the condition of pendulous lithotomy and suprapubic cystostomy, the urethral stricture was removed via a midline ventral penile incision followed by elevation of the flap and insertion of an 18-Fr catheter. Subcutaneous buried interrupted sutures were used to reapproximate the waterproof tubularized neourethra and to coapt with the neourethra and each stump of the urethra, first proximally and then distally. The defect of the penile shaft was covered by advancement of the surrounding scrotal flap. The indwelling catheter was maintained for 21 days. A 9 month postoperative cystoscopy showed no flap necrosis, no mechanical stricture, and no hair growth on the lumen of the neourethra. The patient showed no voiding discomfort 6 months after the operation. The advantages of this procedure are the lack of need for microsurgery, shortening of admission, the use of only spinal anesthesia (no general anesthesia), and a relatively short operative time. The tubularized unilateral penile fasciocutaneous flap should be considered an option for initial flap urethroplasty as a curative technique.
Perspectiva generativa en la gestión de conflictos sociales
Authors: Fried Schnitman Dora
Published: May 2012

The effects of armed political conflict on civilian populations are very painful and involve not only the direct impact of violence but also the fragmentation it wages on the social tissue. This article presents some applications of the generative model and its methodologies for facing crisis and conflict. These applications can help people recover their resources, meanings and relationships, re-orient their lives and restore personal and social integrity. While the article recognizes the impact of traumatic situations, it understands that victims of violence were also capable of surviving and carrying on in the face of adversity. Indeed, they were often able to confront such adversity, appealing to their resources, and to detect and accept alliances and collaborations in order to find or build social conditions and networks that allowed them to re-orient their lives. This article suggests that this emphasis on resources and the joint construction of alternatives provides an approach to the study of these processes and facilitates spaces of recovery and coexistence. The article proposes that, when recognized as such, these survival strategies can be expanded to promote the transformation of identity and social bonds that go beyond that initial resources of these survivors to facilitate their transformation into citizens with full rights, and have an impact not only on their living conditions but also social and political agendas.
High‐Efficiency Transfection and siRNA‐Mediated Gene Knockdown in Human Pluripotent Stem Cells
Authors: Ma Yinghong , Lin Haifan , Qiu Caihong
Published: May 2012

This unit describes a protocol on how to achieve high transfection efficiency on human embryonic stem cells and induced pluripotent stem cells using the common transfection reagent Lipofectamine 2000 as a carrier instead of involving a virus, and/or expensive equipment and reagents. Applying this technique for siRNA‐mediated gene targeting to knockdown genes in the pluripotent stem cells, the expression of pluripotent genes, such as OCT4 and LIN28, was downregulated by more than 90% in multiple pluripotent cell lines. Beyond reaching high transfection efficiency on pluripotent cells, this protocol should also have application to primary cells that are traditionally difficult to transfect. Curr. Protoc. Stem Cell Biol. 21:5C.2.1‐5C.2.9. © 2012 by John Wiley & Sons, Inc.
Agroecosystems and Primate Conservation in The Tropics: A Review
Authors: ESTRADA ALEJANDRO , RABOY BECKY E. , OLIVEIRA LEONARDO C.
Published: May 2012

Agroecosystems cover more than one quarter of the global land area (ca. 50 million km2) as highly simplified (e.g. pasturelands) or more complex systems (e.g. polycultures and agroforestry systems) with the capacity to support higher biodiversity. Increasingly more information has been published about primates in agroecosystems but a general synthesis of the diversity of agroecosystems that primates use or which primate taxa are able to persist in these anthropogenic components of the landscapes is still lacking. Because of the continued extensive transformation of primate habitat into human‐modified landscapes, it is important to explore the extent to which agroecosystems are used by primates. In this article, we reviewed published information on the use of agroecosystems by primates in habitat countries and also discuss the potential costs and benefits to human and nonhuman primates of primate use of agroecosystems. The review showed that 57 primate taxa from four regions: Mesoamerica, South America, Sub‐Saharan Africa (including Madagascar), and South East Asia, used 38 types of agroecosystems as temporary or permanent habitats. Fifty‐one percent of the taxa recorded in agroecosystems were classified as least concern in the IUCN Red List, but the rest were classified as endangered (20%), vulnerable (18%), near threatened (9%), or critically endangered (2%). The large proportion of threatened primates in agroecosystems suggests that agroecosystems may play an important role in landscape approaches to primate conservation. We conclude by discussing the value of agroecosystems for primate conservation at a broad scale and highlight priorities for future research. Am. J. Primatol. 74:696‐711, 2012. © 2012 Wiley Periodicals, Inc.
Species Concept in Primates
Authors: GROVES COLIN
Published: May 2012

The way we view the Species category in Primates, as in other animals, especially other vertebrates, has been going through a revolution over the past 20 years or so. Much is wrong with the idea that we can define species according to whether or not they are “reproductively isolated”: this concept, the so‐called Biological Species Concept, has never offered any guidelines in the case of allopatric populations; this has now been shown to be simply wrong. Although other ways of looking at species – the Evolutionary, Recognition, Cohesion and Genetic Species Concepts – have all provided particular insights, the only proposal to offer a repeatable, falsifiable definition of species is the Phylogenetic Species Concept. This has been criticised for increasing the number of species to be recognised, although it is not clear why this should be a problem: indeed, it tells us that the world is far richer in biodiversity than we had conceived. Am. J. Primatol. 74:687‐691, 2012. © 2012 Wiley Periodicals, Inc.
Intelligent gels and cryogels with embedded emulsions of various oils
Authors: Komarova Galina A. , Starodubtsev Sergey G. , Lozinsky Vladimir V. , Nasimova Irina R. , Khokhlov Alexei R.
Published: May 2012

Thermo‐responsive gels and cryogels with embedded microdroplets of Vaseline, olive, peanut, and linseed oils and their mixtures with hydrophobic dye Sudan 3 have been synthesized and studied. These composite gel matrices were obtained by the three‐dimensional copolymerization of N‐isopropylacrylamide and N, N'‐bis(acryloyl)cystamine in the presence of oil emulsions stabilized with sodium dodecylsulfate or Span 80. Polymerization was performed at room temperature for conventional gels and at −15°C for cryogels. It was shown that all synthesized systems exhibit heat‐induced collapse at temperatures higher then 34°C. For conventional gels prepared at room temperature shrinking lasts within 20 to 80 min in accordance with gel composition. No squeezing of oil droplets was observed. In the case of cryogels, shrinking was accompanied by release of oils and response time was significantly shorter, about tens of seconds. Collapse character and release of lipophilic phase did not depend on the chemical nature of oils, dissolved compounds, and surfactant used for emulsion stabilization. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Improvement of interfacial shear strengths of polybenzobisoxazole fiber/epoxy resin composite by n‐TiO2 coating
Authors: Qian Jun , Wu Junling , Liu Xiaoyun , Zhuang Qixin , Han Zhewen
Published: May 2012

Smooth polybenzobisoxazole (PBO) fiber has limited interfacial interaction with resin matrix. In this article, nano‐TiO2 coating on PBO fiber is applied to improve the interfacial adhesion between PBO fiber and epoxy resin. The test results suggest that the PBO fiber had good interaction with epoxy resin matrix after its treatment with n‐TiO2 sol. Nano TiO2 particle embedded onto PBO fiber surface, acting as a chock, which made fiber implanted into the resin better. This greatly improved the shear strengths (IFSS) of PBO fiber/epoxy resin composite. It has been found that a 56% increase in interfacial IFSS has achieved without sacrificing mechanical properties of fiber. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Effects of substrate composition and roughness on mechanical properties and conformality of parylene C coatings
Authors: Verwolf Adrian , White Grady , Poling Chris
Published: May 2012

Nanoindentation was used to determine reduced elastic modulus Er and hardness H of 16 μm thick Parylene C coatings vapor‐deposited on mill‐finished samples of aluminum, copper, nickel steel, and stainless steel. Profilometry was used to compare average surface roughnesses of the polymeric coatings to the roughnesses of the underlying metals, thereby providing a quantitative index for determining conformality. Roughness, elasticity, and hardness of coatings were found to be affected by both chemical composition and surface roughness of four different metallic substrates. Standard nanoindentation evaluations of Er and H distributions for the various metals were found to be positively skewed, which precluded use of simple averages for purposes of comparison. However, analysis of the nanoindentation and profilometry data by use of alternative techniques indicated that coatings were consistently smoother and flatter than their underlying substrates, i.e., they were not truly conformal, and nanomechanical properties of Parylene C were affected by the chemical composition of the substrates independently of the effects of substrate roughness. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Effect of organoclay and silane grafting of polyethylene on morphology, barrierity, and rheological properties of HDPE/PA6 blends
Authors: Sharif‐Pakdaman Ali , Morshedian Jalil , Jahani Yousef
Published: May 2012

Silane‐grafted high‐density polyethylene (HDPE‐g‐Si) was prepared by reactive extrusion. The grafted polyethylene (PE) was then melt compounded with organically modified montmorillonite and polyamide‐6 (PA6) to form ternary nanocomposite. Fourier Transfer Infrared was used for investigation of grafting efficiency of specimens. Dispersion of clay in the blends and individual polymers were examined by X‐ray diffraction (SAXS) and transmission electron microscopy (TEM). Scanning electron microscopy and dynamic rheology were also used for further study of microstructure along with compatibilization effect of silane grafting and adding organoclay in the blends. SAXS and TEM study showed that nanoclay was delaminated by PA6 or HDPE‐g‐Si chains, whereas the intercalation of neat HDPE in clay layers was negligible especially in higher level of clay. The morphological studies indicated that silane‐grafted HDPE had hydrophilic characteristics and, therefore, was more compatible with PA6 than neat PE. Furthermore, in the same way adding nanoclay to this blends resulted in more uniform and finer morphology. And finally, results of oxygen and hydrocarbon permeability measurement demonstrated synergetic effect of silane grafting and presence of clay on barrierity improvement of samples. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Crystal phase of poly(vinylidene fluoride‐co‐trifluoroethylene) synthesized via hydrogenation of poly(vinylidene fluoride‐co‐chlorotrifluoroethylene)
Authors: Zhang Qiuping , Xia Weimin , Zhu Zhigang , Zhang Zhicheng
Published: May 2012

Trifluoroethylene addition and thermal treatment induced crystal phase transition in a series of poly(vinylidene fluoride‐co‐trifluoroethylene) [P(VDF‐co‐TrFE)] containing varied TrFE molar ratio (6, 9, 12, and 20 mol %) prepared from the hydrogenation of poly(vinylidene fluoride‐co‐chlorotrifluoroethylene have been investigated by means of Fourier transform infrared spectral (FTIR), X‐ray diffraction (XRD), and differential scanning calorimetry (DSC) analyses. The comprehensive applications of the three techniques could distinguish α, β and γ phase of P(VDF‐co‐TrFE) very well. The multipeak fitting technique of DSC is successfully applied to calculate the percentage of different phases in the samples, which allows us to investigate the phase transition process of P(VDF‐co‐TrFE) precisely. It is found that the crystal phase of P(VDF‐co‐TrFE) films is turned from α + γ phase (6 mol % TrFE) to α + γ + β phase (9 and 12 mol % TrFE) to β phase (20 mol % TrFE) at high temperature, and from α + γ phase (6 mol % TrFE) to γ + β phase (9 mol % TrFE) to β phase (>12 mol % TrFE) at low fabricated temperature. Both the fabrication conditions and TrFE addition are responsible for the crystal phase transition of the hydrogenised P(VDF‐co‐TrFE). © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
How do the shape of clay and type of modifier affect properties of polymer blends?
Authors: Gallego Raúl , García‐López David , Merino Juan Carlos , Pastor José María
Published: May 2012

Polyamide 6/ethylene–propylene–diene metallocene terpolymer/(ethylene–propylene–diene copolymer)‐graft‐(maleic anhydride) blends with clay (3 and 5 wt % depending on the formulation), different clays (montmorillonite and sepiolite) and different surface functionalization (ammonium salts and silanes) were studied to analyze the effect of the shape of clay and type of modifier on their properties. The results have shown that sepiolite has higher influence on the morphology and on the mechanical properties than montmorillonite. In that sense, blends with 3 wt % of sepiolite have reached the best balanced properties, i.e., tensile modulus and impact strength, than their homologous with montmorillonite. Furthermore, the blends with 3 wt % of sepiolite have reached the highest mechanical properties compared with blends with higher montmorillonite content. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Protective role of systemic furin in immune response–induced arthritis
Authors: Lin Hilène , Ah Kioon Marie‐Dominique , Lalou Claude , Larghero Jerome , Launay Jean‐Marie , Khatib Abdel‐Majid , Cohen‐Solal Martine
Published: May 2012

Objective

Rheumatoid arthritis (RA) is an autoimmune joint disease associated with chronic inflammation of the synovium that causes profound damage of joints. Inflammation results in part from the influx of immune cells secreting inflammatory cytokines and the reduction in the number of Treg cells. We undertook this study to assess the effect of furin, a proteinase implicated in the proteolytic activity of various precursor proteins and involved in the regulation of both proteinase maturation and immune cells, in an experimental model of RA.

Methods

The effect of furin and its inhibitor α1‐PDX was tested in mice with collagen‐induced arthritis (CIA). Joints were processed for histology and protein expression. Levels of cytokines were measured in joint tissue, and Treg cell numbers were measured in spleens.

Results

Furin expression and activity were high in the synovial pannus in RA patients and mice with CIA. Systemic administration of furin prevented increases in the arthritis score, joint destruction, and bone loss, in contrast to systemic administration of the furin inhibitor α1‐PDX, which enhanced these parameters. By preventing the development of synovial pannus, furin reduced the expression of metalloproteinases in the joints. In contrast, α1‐PDX enhanced synovial proliferation and the expression and activity of matrix metalloproteinases. Furthermore, furin reversed the local Th1/Th2 balance and restored the number of Treg cells in the spleen, indicating mediation by immune cells.

Conclusion

These findings show the protective role of exogenous furin against RA, mediated by an immune response. The data suggest the potential therapeutic use of furin or its derivatives in autoimmune diseases including RA.
Variable selection via the weighted group lasso for factor analysis models
Authors: Hirose Kei , Konishi Sadanori
Published: May 2012

We consider the problem of selecting variables in factor analysis models. The$L_1$regularization procedure is introduced to perform an automatic variable selection. In the factor analysis model, each variable is controlled by multiple factors when there are more than one underlying factor. We treat parameters corresponding to the multiple factors as grouped parameters, and then apply the group lasso. Furthermore, the weight of the group lasso penalty is modified to obtain appropriate estimates and improve the performance of variable selection. Crucial issues in this modeling procedure include the selection of the number of factors and a regularization parameter. Choosing these parameters can be viewed as a model selection and evaluation problem. We derive a model selection criterion for evaluating the factor analysis model via the weighted group lasso. Monte Carlo simulations are conducted to investigate the effectiveness of the proposed procedure. A real data example is also given to illustrate our procedure.The Canadian Journal of Statistics40: 345–361; 2012 © 2012 Statistical Society of Canada
Restricted maximum likelihood estimation of joint mean‐covariance models
Authors: Papageorgiou Georgios
Published: May 2012

The 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

In 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

BACKGROUND:

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

BACKGROUND:

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

BACKGROUND:

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

BACKGROUND:

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

BACKGROUND:

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

BACKGROUND:

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

Fibroblast 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

The 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.