bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoscopic Repair of Gluteus Medius Tendon Tears of the Hip
Authors: Voos James E. , Shindle Michael K. , Pruett Arianna , Asnis Peter D. , Kelly Bryan T.
Published: February 2009

Background

Tears of the gluteus medius tendon at the greater trochanter have been termed “rotator cuff tears of the hip.” Previous reports have described the open repair of these lesions.

Hypothesis

Endoscopic repair of gluteus medius tears results in successful clinical outcomes in the short term.

Study Design

Case series; Level of evidence, 4.

Methods

Of 482 consecutive hip arthroscopies performed by the senior author, 10 patients with gluteus medius tears repaired endoscopically were evaluated prospectively. Perioperative data were analyzed on this cohort of patients. There were 8 women and 2 men, with an average age of 50.4 years (range, 33-66 years). Patients had persistent lateral hip pain and abductor weakness despite extensive conservative measures. Diagnosis was made by physical examination and magnetic resonance imaging and was confirmed at the time of endoscopy in all cases. At the most recent follow-up, patients completed the Modified Harris Hip Score and Hip Outcomes Score surveys.

Results

At an average follow-up of 25 months (range, 19-38 months), all 10 patients had complete resolution of pain; 10 of 10 regained 5 of 5 motor strength in the hip abductors. Modified Harris Hip Scores at 1 year averaged 94 points (range, 84-100), and Hip Outcomes Scores averaged 93 points (range, 85-100). There were no adverse complications after abductor repairs. Seven of 10 patients said their hip was normal, and 3 said their hip was nearly normal.

Conclusion

With short-term follow-up, endoscopic repair of gluteus medius tendon tears of the hip appears to provide pain relief and return of strength in select patients who have failed conservative measures. Further long-term follow-up is warranted to confirm the clinical effectiveness of this procedure.
Using the Concrete-Representational-Abstract Sequence to Teach Subtraction With Regrouping to Students at Risk for Failure
Authors: Flores Margaret M.
Published: February 2009

This study investigated the effects of the concrete—representational—abstract (CRA) instructional sequence on the subtraction performance of students identified as at-risk for mathematics failure. Although the CRA sequence has been demonstrated as effective for teaching a variety of mathematical skills and processes its effects when used to teach subtraction with regrouping have not been studied. This study examined the effects of CRA instruction on elementary students’ fluency in computing subtraction problems with regrouping in the tens place as well as regrouping in both the tens and hundreds places. The study also investigated the effects of CRA instruction on students’ maintenance of regrouping skills. A multiple probe across students with embedded changing behaviors design was employed. A functional relation between CRA instruction and subtraction with regrouping was demonstrated across all students. The results and their implications are discussed further.
Dyke-Davidoff-Masson Syndrome in Postcerebral Malaria
Authors: Karuppiah Sabesan , Rodgman Christopher , Lombard Jay
Published: February 2009

Dyke-Davidoff-Masson syndrome is a disorder involving hemiatrophy or hypoplasia of 1 cerebral hemisphere secondary to an insult in the developing brain. Often this will manifest with seizures, hemiparesis, mental retardation, and facial changes. Associated with this pathology are the radiologically evident changes, such as thickening of the calvarium, hyperpneumatization of the sinuses, and dilation of the ipsilateral lateral ventricle among others. The following is a case presentation of an 18-year-old female emigrating from Ghana who presented to the emergency department with complaints of seizures diagnosed as being caused by cerebral malaria at 13 years of age. We hypothesize that the cerebral malaria and related vascular occlusion are the causes of her acquired cerebral changes. Included are computed tomography images.
C-Graft in Regeneration of Periodontal Tissue in Intrabony Periodontal Defect in Dog
Authors: Nakanishi Shinsuke , Ota Mikio , Shibukawa Yoshihiro , Yamada Satoru
Published: February 2009

The aim of this study was to investigate the effect of C-Graft particles on formation of new cementum and bone in periodontal bone defects in dog. Healing and tissue change were histologically determined at 2, 4, 8, and 16 weeks. Little bone or cementum formation was observed in the control group. A statistically significant increase in bone and cementum formation was seen in the C-Graft group compared to the control group (75.4% vs. 44.9%, p<50.01, 80.4% vs. 46.7%, p<50.05, respectively). These findings suggest that C-Graft particles provide a scaffold for the regeneration of new bone and cementum.
Semi-active Vibration Control of a Composite Beam by Adaptive Synchronized Switching on Voltage Sources Based on LMS Algorithm
Authors: Hongli Ji  , Jinhao Qiu  , Badel Adrien , Yuansheng Chen  , Kongjun Zhu
Published: February 2009

In this article, an adaptive semi-active SSDV (Synchronized Switch Damping on Voltage) method based on the LMS algorithm is proposed and applied to the vibration control of a composite beam. In the SSDV method, the value of voltage source in the switching circuit is critical to its control performance. In the adaptive approach proposed in this study, the voltage source is adjusted adaptively using the LMS algorithm. Two cases of the adjustment are considered. In the first case, as an improvement to the enhanced SSDV, the voltage coefficient is adjusted by the LMS algorithm. In the second case, as an improvement to the classical SSDV, the voltage value is adjusted directly. The new adaptive approach is compared with the derivative-based adaptive SSDV proposed in the former study in the control of the first mode of a composite beam. The control results show that adaptive adjustment of voltage value and adaptive adjustment of voltage coefficient are equally effective in the vibration control of the composite beam and that LMS-based approach is slightly better than the derivative-based approach.
Nonverbal Communication
Authors: Battersby Sharyn L.
Published: February 2009

As busy music teachers, we try to strike a balance between everything that we want to accomplish in a lesson and the constraints of our own teaching circumstances. What is sometimes overlooked in our efforts to fulfill our expectations is how our students really see us and what we are communicating to them with our bodies. Nonverbal exchanges such as hand gestures or facial expressions between a teacher and students can impact learning experiences in music classrooms or rehearsals. Being aware of our nonverbal output will help us to be more consistent and effective communicators and to create environments that are conducive to positive learning experiences and exciting classrooms.
Confirmatory Factor Analysis of a Family Quality of Life Scale for Families of Kindergarten Children Without Disabilities
Authors: Zuna Nina I. , Selig James P. , Summers Jean Ann , Turnbull Ann P.
Published: February 2009

Recently, within the field of special education, attention has been accorded to the conceptualization and measurement of family outcomes. The Family Quality of Life (FQOL) Scale is an instrument that can be used to measure family outcomes for families who have children with disabilities, and it has been demonstrated to have psychometric validity. To expand the usability of the FQOL Scale, the authors tested its measurement properties for families of kindergarten children without disabilities. Results from this new population of interest indicated adequate fit of the sample data to the theoretical model. Policy and program implications are discussed.
Development of an Intervention Program for Alzheimer's Family Caregivers Following Diagnostic Disclosure
Authors: Ducharme Francine , Beaudet Line , Legault Alain , Kergoat Marie-Jeanne , Lévesque Louise , Caron Chantal
Published: February 2009

The purpose of this qualitative study was to develop a pro-active psycho-educational intervention program for Alzheimer's family caregivers following diagnostic disclosure. Based on a theoretical model of role transitions and a participatory approach, the study comprised four steps: (a) exploring caregiver needs; (b) developing and validating a program proposal based on caregiver-expressed needs; (c) formalizing program through intervention mapping; and (d) testing and qualitatively evaluating the program. The psycho-educational program consisted of seven individual sessions aimed at fostering knowledge and skills required to ensure successful transition to the caregiver role. The approach used in this study can serve as a guide for the development of nursing intervention programs. Intervention mapping allowed, in particular, integrating theoretical and empirical elements in a formal intervention model.
Maternal Health and Child Asthma Health Services Use
Authors: Kaiser Katherine Laux , Barry Teresa L. , Mason Andrea
Published: February 2009

The primary purpose of this pilot study was to examine the influence of maternal health status on health services use in children with the diagnosis of asthma. A secondary purpose was to assess both preventive and illness-related child health services use patterns. Fifty-two asthmatic children and 43 mothers met the inclusion criteria. The majority of mothers (72%, n = 31/43) rated their own overall health as good to excellent. Eighty-six percent ( n = 38/44) of the children had a medical home, 20% had peak flow meters, 26% had been to see a specialist, and 4% were currently under the care of a specialist. This pilot study raises important questions about the influence of maternal health on child health services use patterns for asthmatic children from low-income families. Understanding the influence of maternal health on health-seeking patterns for children with asthma is important for nursing intervention.
Parent and Community Participation in Program Design
Authors: Uding Nancy , Kieckhefer Gail M. , Trahms Cristine M.
Published: February 2009

Parents of children with chronic illnesses face many challenges not faced by other parents. A family-centered parent support and education program, Building on Family Strengths (BFS), was designed to help parents meet these challenges by gaining new skills and learning new ways to support their children. BFS researchers involved potential participant families in the refinement of the BFS curriculum to make it truly family centered. The article reports major feedback received from parent focus groups, leaders in several cultural communities, and participants in a pilot class as BFS underwent final refinement. This feedback greatly influences the development of the BFS curriculum, as without it the final product going into a randomized clinical trial would be less attuned to the needs of parents of children with chronic illnesses. Other researchers and family educators may find this feedback useful as they improve their own research and program offerings.
Transforming Music Teacher Education Through Service Learning
Authors: Burton Suzanne , Reynolds Alison
Published: February 2009

Service-learning initiatives have become prevalent on the campuses of higher education. In teacher education, preservice teachers involved in educational partnerships that are service-learning based respond to the needs of a community partner, apply pedagogical knowledge and skills they have acquired in their coursework to real-world problems, and engage in critical reflection. Service-learning offers preservice teachers increased opportunities to develop their teaching practice and teacher identities and provides a backdrop for preservice teachers to develop personally and become socially integrated into the field of teacher education. In this article, we provide descriptions of four service-learning contexts for music teacher preparation. We discuss the role of service-learning in transforming preservice music teachers, their music teaching practice, and the community partners they served. Finally we present challenges to engaging in service learning in music teacher preparation, characteristics of meaningful service learning work, and discuss the transformative potential of service-learning in music teacher preparation.
Data Foundations for Sustainability
Authors: Whitford Andrew B. , Wong Karen
Published: February 2009

The authors respond to Richard York's main concerns about their approach to assessing the impact of federalism and democratization on environmental sustainability, as measured by the Environmental Sustainability Index.
The Family and Consumer Sciences Body of Knowledge and the Cultural Kaleidoscope: Research Opportunities and Challenges
Authors: Nickols Sharon Y. , Ralston Penny A. , Anderson Carol , Browne Lorna , Schroeder Genevieve , Thomas Sabrina , Wild Peggy
Published: February 2009

As a profession established during the Progressive Era when industrialization, immigration, urbanization, and other social forces were prevalent, family and consumer sciences is once again faced with similar social, economic, and technological societal conditions. This article addresses how family and consumer sciences, through its body of knowledge, is positioned to address the social changes of the 21st century. In particular, the article examines the family and consumer sciences body of knowledge in light of the growth in diversity or the cultural kaleidoscope by (a) providing a historical context for the body of knowledge for the profession, (b) presenting the current body of knowledge for family and consumer sciences and highlighting related research, and (c) discussing opportunities and challenges for applications in the body of knowledge for broadening the scope of research and practice to embrace the cultural kaleidoscope. The article not only contributes to the intellectual foundations of the field but also makes recommendations and identifies implications for research and practice.
Design Thinking: Promoting Diversity Through Global Immersion
Authors: Beacham Cindy , MacDonald Nora M. , Yoo Jeong‐Ju , McFall Barbara S.
Published: February 2009

Students must experience diversity if they are to embrace it. This article describes the process of integrating a required global experience into two design units and recommends integration strategies for other family and consumer sciences programs. The global focus began in 2000 with Interior Design's participation in a Fund for the Improvement of Postsecondary Education grant. Semester student exchanges over 3 years were between Mexico, Canada, and the United States. The Interior Design and Fashion Design and Merchandising units then partnered with a Milan, Italy, design school for students to experience Italian culture, design, and language. Curricula were revised to allow for international semester programs, to enhance students' diversity sensitivity. Pedagogical considerations included philosophy identification, program design, and interdisciplinary collaborations.
TransCent: Computational enzyme design by transferring active sites and considering constraints relevant for catalysis
Authors: Fischer André , Enkler Nils , Neudert Gerd , Bocola Marco , Sterner Reinhard , Merkl Rainer
Published: February 2009

Background

Computational enzyme design is far from being applicable for the general case. Due to computational complexity and limited knowledge of the structure-function interplay, heuristic methods have to be used.

Results

We have developed TransCent, a computational enzyme design method supporting the transfer of active sites from one enzyme to an alternative scaffold. In an optimization process, it balances requirements originating from four constraints. These are 1) protein stability, 2) ligand binding, 3) pKa values of active site residues, and 4) structural features of the active site. Each constraint is handled by an individual software module. Modules processing the first three constraints are based on state-of-the-art concepts, i.e. RosettaDesign, DrugScore, and PROPKA. To account for the fourth constraint, knowledge-based potentials are utilized. The contribution of modules to the performance of TransCent was evaluated by means of a recapitulation test. The redesign of oxidoreductase cytochrome P450 was analyzed in detail. As a first application, we present and discuss models for the transfer of active sites in enzymes sharing the frequently encountered triosephosphate isomerase fold.

Conclusion

A recapitulation test on native enzymes showed that TransCent proposes active sites that resemble the native enzyme more than those generated by RosettaDesign alone. Additional tests demonstrated that each module contributes to the overall performance in a statistically significant manner.
NITPICK: peak identification for mass spectrometry data
Authors: Renard Bernhard Y , Kirchner Marc , Steen Hanno , Steen Judith AJ , Hamprecht Fred A
Published: February 2009

Background

The reliable extraction of features from mass spectra is a fundamental step in the automated analysis of proteomic mass spectrometry (MS) experiments.

Results

This contribution proposes a sparse template regression approach to peak picking called NITPICK. NITPICK is a Non-greedy, Iterative Template-based peak PICKer that deconvolves complex overlapping isotope distributions in multicomponent mass spectra. NITPICK is based onfractional averagine, a novel extension to Senko's well-known averagine model, and on a modified version of sparse, non-negative least angle regression, for which a suitable, statistically motivated early stopping criterion has been derived. The strength of NITPICK is the deconvolution of overlapping mixture mass spectra.

Conclusion

Extensive comparative evaluation has been carried out and results are provided for simulated and real-world data sets. NITPICK outperforms pepex, to date the only alternate, publicly available, non-greedy feature extraction routine. NITPICK is available as software package for the R programming language and can be downloaded fromhttp://hci.iwr.uni-heidelberg.de/mip/proteomics/.
Spinocerebellar ataxia type 8 larger triplet expansion alters histone modification and induces RNA foci
Authors: Chen I-Cheng , Lin Hsuan-Yuan , Lee Ghin-Chueh , Kao Shih-Huan , Chen Chiung-Mei , Wu Yih-Ru , Hsieh-Li Hsiu-Mei , Su Ming-Tsan , Lee-Chen Guey-Jen
Published: February 2009

Background

Spinocerebellar ataxia type 8 (SCA8) involves the expression of an expanded CTG/CAG combined repeats (CR) from opposite strands producing CUG expansion transcripts (ataxin 8 opposite strand, ATXN8OS) and a polyglutamine expansion protein (ataxin 8, ATXN8). The pathogenesis of SCA8 is complex and the spectrum of clinical presentations is broad.

Results

Using stably induced cell models expressing 0, 23, 88 and 157 CR, we study the role of ATXN8OS transcripts in SCA8 pathogenesis. In the absence of doxycycline, the stable ATXN8OS CR cell lines exhibit low levels of ATXN8OS expression and a repeat length-related increase in staurosporine sensitivity and in the number of annexin positive cells. A repeat length-dependent repression of ATXN8OS expression was also notable. Addition of doxycycline leads to 25~50 times more ATXN8OS RNA expression with a repeat length-dependent increase in fold of ATXN8OS RNA induction. ChIP-PCR assay using anti-dimethyl-histone H3-K9 and anti-acetyl-histone H3-K14 antibodies revealed increased H3-K9 dimethylation and reduced H3-K14 acetylation around the ATXN8OS cDNA gene in 157 CR line. The repeat length-dependent increase in induction fold is probably due to the increased RNA stability as demonstrated by monitoring ATXN8OS RNA decay in cells treated with the transcriptional inhibitor, actinomycin D. In cells stably expressing ATXN8OS, RNA FISH experiments further revealed ribonuclear foci formation in cells carrying expanded 88 and 157 CR.

Conclusion

The present study demonstrates that the expanded CUG-repeat tracts are toxic to human cells and may affect ATXN8OS RNA expression and stability through epigenetic and post-transcriptional mechanisms.
Quality improvement in small office settings: an examination of successful practices
Authors: Wolfson Daniel , Bernabeo Elizabeth , Leas Brian , Sofaer Shoshanna , Pawlson Gregory , Pillittere Donna
Published: February 2009

Background

Physicians in small to moderate primary care practices in the United States (U.S.) (<25 physicians) face unique challenges in implementing quality improvement (QI) initiatives, including limited resources, small staffs, and inadequate information technology systems 23,36. This qualitative study sought to identify and understand the characteristics and organizational cultures of physicians working in smaller practices who are actively engaged in measurement and quality improvement initiatives.

Methods

We undertook a qualitative study, based on semi-structured, open-ended interviews conducted with practices (N = 39) that used performance data to drive quality improvement activities.

Results

Physicians indicated that benefits to performing measurement and QI included greater practice efficiency, patient and staff retention, and higher staff and clinician satisfaction with practice. Internal facilitators included the designation of a practice champion, cooperation of other physicians and staff, and the involvement of practice leaders. Time constraints, cost of activities, problems with information management and or technology, lack of motivated staff, and a lack of financial incentives were commonly reported as barriers.

Conclusion

These findings shed light on how physicians engage in quality improvement activities, and may help raise awareness of and aid in the implementation of future initiatives in small practices more generally.
Heat Shock Protein-27, -60 and -90 expression in gastric cancer: association with clinicopathological variables and patient survival
Authors: Giaginis Constantinos , Daskalopoulou Stella S , Vgenopoulou Stephanie , Sfiniadakis Ioannis , Kouraklis Gregorios , Theocharis Stamatios E
Published: February 2009

Background

Heat shock proteins (HSPs) are ubiquitous, highly conserved proteins across all the species and play essential roles in maintaining protein stability within the cells under normal conditions, while preventing stress-induced cellular damage. HSPs were also overexpressed in various types of cancer, being associated with tumor cell proliferation, differentiation and apoptosis. The aim of the present study was to evaluate the clinical significance of HSP -27, -60, and -90 expression in gastric carcinoma.

Methods

HSP -27, -60, and -90 proteins expression was assessed immunohistochemically in tumoral samples of 66 gastric adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological characteristics, tumor proliferative capacity and patients' survival.

Results

HSP-27, -60, -90 proteins were abundantly expressed in gastric adenocarcinoma cases examined. HSP-27 expression was significantly associated with tumor size (pT, P = 0.026), the presence of organ metastases (pM, P = 0.046) and pStage (P = 0.041), while HSP-27 staining intensity with nodal status (pN, P = 0.042). HSP-60 expression was significantly associated with patients' sex (P = 0.011), while HSP-60 staining intensity with patients' age (P = 0.027) and tumor histopathological grade (P = 0.031). HSP-90 expression was not associated with any of the clinicopathological parameters examined; however, HSP-90 staining intensity was significantly associated with tumor size (pT, P = 0.020). High HSP-90 expression was significantly associated with longer overall survival times in univariate analysis (log-rank test, P = 0.033), being also identified as an independent prognostic factor in multivariate analysis (P = 0.026).

Conclusion

HSP-27, -60, and -90 were associated with certain clinicopathological parameters which are crucial for the management of gastric adenocarcinoma patient. HSP-90 expression may also be an independent prognostic indicator in gastric adenocarcinoma patients.
Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of diabetic peripheral neuropathic pain
Authors: Quilici Sibilia , Chancellor Jeremy , Löthgren Mickael , Simon Dominique , Said Gérard , Le Trong Kim , Garcia-Cebrian Ana , Monz Brigitta
Published: February 2009

Background

Few direct head-to-head comparisons have been conducted between drugs for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB), gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using placebo as a common comparator.

Methods

We searched PubMed, EMBASE, CENTRAL databases and regulatory websites for randomized, double-blind, placebo-controlled, parallel group or crossover clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using approved dosages with assessments after 5–13 weeks were eligible. Efficacy criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs, and response rate (≥ 50% pain reduction) and Patient Global Impression of Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence. Direct comparisons versus placebo were conducted with pooled fixed – and random-effects analyses on endpoints reported in at least two studies of each drug. Indirect comparisons were performed between DLX and each of PGB and GBP using Bayesian simulation.

Results

Three studies of DLX, six of PGB, two of GBP and none of AMT met the inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and GBP, all were superior to placebo for all efficacy parameters, with some tolerability trade-offs. Indirect comparison of DLX with PGB found no differences in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no statistically significant differences.

Conclusion

From the few available studies suitable for indirect comparison, DLX shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine provides an important treatment option for this disabling condition.
Perinatal outcomes in a South Asian setting with high rates of low birth weight
Authors: George Kuryan , Prasad Jasmin , Singh Daisy , Minz Shanthidani , Albert David S , Muliyil Jayaprakash , Joseph K S , Jayaraman Jyothi , Kramer Michael S
Published: February 2009

Background

It is unclear whether the high rates of low birth weight in South Asia are due to poor fetal growth or short pregnancy duration. Also, it is not known whether the traditional focus on preventing low birth weight has been successful. We addressed these and related issues by studying births in Kaniyambadi, South India, with births from Nova Scotia, Canada serving as a reference.

Methods

Population-based data for 1986 to 2005 were obtained from the birth database of the Community Health and Development program in Kaniyambadi and from the Nova Scotia Atlee Perinatal Database. Menstrual dates were used to obtain comparable information on gestational age. Small-for-gestational age (SGA) live births were identified using both a recent Canadian and an older Indian fetal growth standard.

Results

The low birth weight and preterm birth rates were 17.0% versus 5.5% and 12.3% versus 6.9% in Kaniyambadi and Nova Scotia, respectively. SGA rates were 46.9% in Kaniyambadi and 7.5% in Nova Scotia when the Canadian fetal growth standard was used to define SGA and 6.7% in Kaniyambadi and < 1% in Nova Scotia when the Indian standard was used. In Kaniyambadi, low birth weight, preterm birth and perinatal mortality rates did not decrease between 1990 and 2005. SGA rates in Kaniyambadi declined significantly when SGA was based on the Indian standard but not when it was based on the Canadian standard. Maternal mortality rates fell by 85% (95% confidence interval 57% to 95%) in Kaniyambadi between 1986–90 and 2001–05. Perinatal mortality rates were 11.7 and 2.6 per 1,000 total births and cesarean delivery rates were 6.0% and 20.9% among live births ≥ 2,500 g in Kaniyambadi and Nova Scotia, respectively.

Conclusion

High rates of fetal growth restriction and relatively high rates of preterm birth are responsible for the high rates of low birth weight in South Asia. Increased emphasis is required on health services that address the morbidity and mortality in all birth weight categories.
Time-frequency component analysis of somatosensory evoked potentials in rats
Authors: Zhang Zhi-Guo , Yang Jun-Lin , Chan Shing-Chow , Luk Keith Dip-Kei , Hu Yong
Published: February 2009

Background

Somatosensory evoked potential (SEP) signal usually contains a set of detailed temporal components measured and identified in a time domain, giving meaningful information on physiological mechanisms of the nervous system. The purpose of this study is to measure and identify detailed time-frequency components in normal SEP using time-frequency analysis (TFA) methods and to obtain their distribution pattern in the time-frequency domain.

Methods

This paper proposes to apply a high-resolution time-frequency analysis algorithm, the matching pursuit (MP), to extract detailed time-frequency components of SEP signals. The MP algorithm decomposes a SEP signal into a number of elementary time-frequency components and provides a time-frequency parameter description of the components. A clustering by estimation of the probability density function in parameter space is followed to identify stable SEP time-frequency components.

Results

Experimental results on cortical SEP signals of 28 mature rats show that a series of stable SEP time-frequency components can be identified using the MP decomposition algorithm. Based on the statistical properties of the component parameters, an approximated distribution of these components in time-frequency domain is suggested to describe the complex SEP response.

Conclusion

This study shows that there is a set of stable and minute time-frequency components in SEP signals, which are revealed by the MP decomposition and clustering. These stable SEP components have specific localizations in the time-frequency domain.
Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer
Authors: Guardiola Emmanuel , Delroeux Delphine , Heyd Bruno , Combe Marielle , Lorgis Veronique , Demarchi Martin , Stein Ulrich , Royer Bernard , Chauffert Bruno , Pivot Xavier
Published: February 2009

Background

Intra-peritoneal (i.p.) chemotherapy is an encouraging treatment option for ovarian cancer with peritoneum involvement in addition with intravenous (i.v.) chemotherapy. Intra-operative i.p. chemotherapy is an interesting method of administration by enhancing the diffusion of chemotherapy. This study had assessed the feasibility of intra-operative i.p. chemotherapy in patients with peritoneal carcinoma of ovarian cancer.

Methods

From January 2003 to February 2006, 47 patients with stage III ovarian cancer were treated with standard paclitaxel carboplatin intravenous chemotherapy and debulking surgery with intra-operative i.p. chemotherapy. After optimal cytoreductive surgery, defined by no unresectable residual disease > 1 cm, i.p. chemotherapy was performed during surgery. The peritoneal cavity was filled by 3 litres of isotonic saline pre-heated at 37 degrees and 90 mg of cisplatin. The sequence was repeated twice during 2 hours based on previous published studies which optimized the cisplatin dosage and exposure duration. Optimal diffusion was obtained by stirring by hands during the 2 hours.

Results

Median age was 59.6 years. No severe haematological or non-haematological toxicity induced by intra operative i.p. chemotherapy was reported. No patient died due to the complications of surgery or the i.p. chemotherapy. No neurotoxicity occurred, and one patients had renal impairment.

Conclusion

This study demonstrates the feasibility of intra-operative i.p. chemotherapy with cisplatin after optimal resection of peritoneal tumor nodules. Further randomized trials are planned to investigate the clinical benefit of this therapeutic modality.
Cathepsin D expression level affects alpha-synuclein processing, aggregation, and toxicity in vivo
Authors: Cullen Valerie , Lindfors Maria , Ng Juliana , Paetau Anders , Swinton Erika , Kolodziej Piotr , Boston Heather , Saftig Paul , Woulfe John , Feany Mel B , Myllykangas Liisa , Schlossmacher Michael G , Tyynelä Jaana
Published: February 2009

Background

Elevated SNCA gene expression and intracellular accumulation of the encoded α-synuclein (aSyn) protein are associated with the development of Parkinson disease (PD). To date, few enzymes have been examined for their ability to degrade aSyn. Here, we explore the effects of CTSD gene expression, which encodes the lysosomal protease cathepsin D (CathD), on aSyn processing.

Results

Over-expression of human CTSD cDNA in dopaminergic MES23.5 cell cultures induced the marked proteolysis of exogenously expressed aSyn proteins in a dose-dependent manner. Unexpectedly, brain extractions, Western blotting and ELISA quantification revealed evidence for reduced levels of soluble endogenous aSyn in ctsd knock-out mice. However, these CathD-deficient mice also contained elevated levels of insoluble, oligomeric aSyn species, as detected by formic acid extraction. In accordance, immunohistochemical studies of ctsd-mutant brain from mice, sheep and humans revealed selective synucleinopathy-like changes that varied slightly among the three species. These changes included intracellular aSyn accumulation and formation of ubiquitin-positive inclusions. Furthermore, using an established Drosophila model of human synucleinopathy, we observed markedly enhanced retinal toxicity in ctsd-null flies.

Conclusion

We conclude from these complementary investigations that: one, CathD can effectively degrade excess aSyn in dopaminergic cells; two, ctsd gene mutations result in a lysosomal storage disorder that includes microscopic and biochemical evidence of aSyn misprocessing; and three, CathD deficiency facilitates aSyn toxicity. We therefore postulate that CathD promotes 'synucleinase' activity, and that enhancing its function may lower aSyn concentrations in vivo.
Guidelines for Human Epidermal Growth Factor Receptor 2 Testing: Biologic and Methodologic Considerations
Authors: Sauter Guido , Lee James , Bartlett John M.S. , Slamon Dennis J. , Press Michael F.
Published: February 2009

The goal of this review is to systematically address a number of issues raised in the American Society of Clinical Oncology–College of American Pathologists (ASCO-CAP) guidelines on testing for the human epidermal growth factor receptor 2 (HER-2) alteration. A group of investigators who are experienced in the conduct and interpretation of HER-2 assay methods reviewed the ASCO-CAP guidelines and address several areas of the HER-2 testing guidelines with a particular emphasis on biologic and methodologic considerations. Although HER-2 status determined by immunohistochemistry (IHC) and the status determined by fluorescent in situ hybridization (FISH) are significantly correlated, we feel that standard considerations of laboratory testing, including test accuracy, reproducibility, and precision, as well as the current data favor FISH over IHC assay methods for determining HER-2 status. These considerations are clearly important in clinical practice because HER2 amplification is directly linked to protein expression levels in breast cancer. However, this protein is not consistently analyzed in formalin-fixed tissues as a result of variability in fixation methods and times and the impact of fixation on HER-2 protein antigenicity. Conversely, gene amplification and FISH are significantly less dependent on tissue fixation methods, making this assay more reproducible between central and peripheral laboratories than IHC. Moreover, review of the existing data demonstrate that FISH is more strongly correlated with responsiveness to either trastuzumab or lapatinib treatment. Until other methods achieve similar test accuracy, reproducibility, and predictive value, we suggest FISH as the primary HER-2 testing modality for women with breast cancer who are candidates for HER-2–targeted therapies.
Beyond Li Fraumeni Syndrome: Clinical Characteristics of Families With p53 Germline Mutations
Authors: Gonzalez Kelly D. , Noltner Katie A. , Buzin Carolyn H. , Gu Dongqing , Wen-Fong Cindy Y. , Nguyen Vu Q. , Han Jennifer H. , Lowstuter Katrina , Longmate Jeffrey , Sommer Steve S. , Weitzel Jeffrey N.
Published: February 2009

Purpose

A clinical testing cohort was used to gain a broader understanding of the spectrum of tumors associated with germline p53 mutations to aid clinicians in identifying high-risk families.

Patients and Methods

Full sequencing of the coding exons (2 to 11) and associated splice junctions of the p53 gene was performed on 525 consecutive patients whose blood samples were submitted for diagnostic testing. Clinical features of p53 germline carriers in this cohort were characterized, clinical referral schemes based on reported p53-associated family phenotypes were evaluated, and practical mutation prevalence tables were generated.

Results

Mutations were identified in 91 (17%) of 525 patients submitted for testing. All families with a p53 mutation had at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC). Every individual with a choroid plexus tumor (eight of eight) and 14 of 21 individuals with a childhood ACC had a mutation regardless of family history. Based on reported personal and family history, 95% of patients (71 of 75) with a mutation met either classic Li Fraumeni syndrome (LFS) or Chompret criteria. A simplified prevalence table provides a concise summary of individual and family characteristics associated with p53 mutations.

Conclusion

This is, to our knowledge, the largest single report of diagnostic testing for germline p53 mutations, yielding practical mutation prevalence tables and suggesting clinical utility of classic LFS and Chompret criteria for identifying a subset of cancer-prone families with p53 germline mutations, with important implications for diagnosis and management.
Intratumoral Epidermal Growth Factor Receptor Antisense DNA Therapy in Head and Neck Cancer: First Human Application and Potential Antitumor Mechanisms
Authors: Lai Stephen Y. , Koppikar Priya , Thomas Sufi M. , Childs Erin E. , Egloff Ann Marie , Seethala Raja R. , Branstetter Barton F. , Gooding William E. , Muthukrishnan Ashok , Mountz James M. , Lui Vivian W.Y. , Shin Dong M. , Agarwala Sanjiv S. , Johnson Rita , Couture Larry A. , Myers Eugene N. , Johnson Jonas T. , Mills Gordon , Argiris Athanassios , Grandis Jennifer R.
Published: February 2009

Purpose

Squamous cell carcinoma of the head and neck (SCCHN) is characterized by upregulation of the epidermal growth factor receptor (EGFR). We developed a novel strategy to target EGFR by using a therapeutic gene that consisted of an EGFR antisense (AS) gene sequence under U6 promoter control. A phase I clinical trial was conducted to evaluate the safety and biologic effects of EGFR AS.

Patients and Methods

Patients with advanced SCCHN who were refractory to standard therapies and who had at least one assessable and accessible lesion were enrolled. The EGFR AS dose was escalated in successive cohorts (six dose levels; 60 to 1,920 μg/injection). Patients received four weekly intratumoral EGFR AS injections. Tumor biopsies were performed before and after completion of therapy. Treatment response was assessed by tumor volume measurements (positron emission tomography/computed tomography), and levels of target proteins were assessed by immunohistochemistry.

Results

Seventeen assessable patients were treated. No grades 3 to 4 or dose-limiting toxicities were noted, and a maximum-tolerated dose was not reached. Five patients (29%) achieved a clinical response, which included two complete responses (CRs) and three partial responses (PRs); two additional patients had stable disease (SD) as the best response. Patients with disease control (CR + PR + SD) had tumors with higher EGFR and lower STAT3 expression at baseline compared with patients who had progressive disease (P = .0312 and P = .095, respectively).

Conclusion

Intratumoral EGFR AS was safe and resulted in antitumor activity in patients with advanced SCCHN. Baseline levels of high EGFR and low STAT3 may be associated with antitumor effects.
Supervised Risk Predictor of Breast Cancer Based on Intrinsic Subtypes
Authors: Parker Joel S. , Mullins Michael , Cheang Maggie C.U. , Leung Samuel , Voduc David , Vickery Tammi , Davies Sherri , Fauron Christiane , He Xiaping , Hu Zhiyuan , Quackenbush John F. , Stijleman Inge J. , Palazzo Juan , Marron J.S. , Nobel Andrew B. , Mardis Elaine , Nielsen Torsten O. , Ellis Matthew J. , Perou Charles M. , Bernard Philip S.
Published: February 2009

Purpose

To improve on current standards for breast cancer prognosis and prediction of chemotherapy benefit by developing a risk model that incorporates the gene expression–based “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like.

Methods

A 50-gene subtype predictor was developed using microarray and quantitative reverse transcriptase polymerase chain reaction data from 189 prototype samples. Test sets from 761 patients (no systemic therapy) were evaluated for prognosis, and 133 patients were evaluated for prediction of pathologic complete response (pCR) to a taxane and anthracycline regimen.

Results

The intrinsic subtypes as discrete entities showed prognostic significance (P = 2.26E-12) and remained significant in multivariable analyses that incorporated standard parameters (estrogen receptor status, histologic grade, tumor size, and node status). A prognostic model for node-negative breast cancer was built using intrinsic subtype and clinical information. The C-index estimate for the combined model (subtype and tumor size) was a significant improvement on either the clinicopathologic model or subtype model alone. The intrinsic subtype model predicted neoadjuvant chemotherapy efficacy with a negative predictive value for pCR of 97%.

Conclusion

Diagnosis by intrinsic subtype adds significant prognostic and predictive information to standard parameters for patients with breast cancer. The prognostic properties of the continuous risk score will be of value for the management of node-negative breast cancers. The subtypes and risk score can also be used to assess the likelihood of efficacy from neoadjuvant chemotherapy.
Phase II Trial of Irinotecan and Carboplatin for Extensive or Relapsed Small-Cell Lung Cancer
Authors: Chen Gigi , Huynh Minh , Fehrenbacher Lou , West Howard , Lara Primo N. , Yavorkovsky Leonid L. , Russin Michael , Goldstein Desiree , Gandara David , Lau Derick
Published: February 2009

Purpose

The regimens of weekly irinotecan with platinum have been used for treatment of metastatic small-cell lung cancer (SCLC). We conducted a multi-institution phase II trial to evaluate a novel 21-day schedule of irinotecan and carboplatin in patients with relapsed or extensive SCLC.

Patients and Methods

Eighty patients were enrolled with the following characteristics: 39 male patients, 41 female patients; median age, 65 years; and Zubrod performance status, 0 to 1 in 85% and 2 in 15% of patients. Dosing schemas were based on the maximum-tolerated dose derived in a previous phase I study. Chemotherapy-naive patients with extensive SCLC were treated with irinotecan 200 mg/m2 and carboplatin area under the curve (AUC) of 5 (arm A). Patients, who had previously been treated with chemotherapy and had relapsed disease received irinotecan 150 mg/m2 and carboplatin AUC of 5 (arm B). In each study arm, the treatment was given every 21 days for up to six cycles.

Results

The most common grade 3 to 4 toxicities included neutropenia (54%), thrombocytopenia (22%), anemia (13%), diarrhea (22%), and nausea/emesis (11%) in both study arms. There were three treatment-related deaths owing to neutropenic sepsis. Among 72 assessable patients, response rates of 65% and 50% were observed, respectively, for arm A and arm B. The median survival for both study arms was identical at 10 months (95% CI, 6 to 14 months). A response rate of 65% was observed in the intracranial disease of 14 patients with known brain metastases.

Conclusion

This 21-day regimen of irinotecan and carboplatin seems promising for the treatment of relapsed SCLC.
Effect of blank shapes on the crashworthiness of stamped parts
Authors: Shim H B
Published: February 2009

The forming histories of stamped products, such as the strain hardening and thickness changes used, are dependent on various process parameters including the blank shape. In view of this, it is clear that stamped products using different blank shapes must have different forming histories. This paper is concerned with the effect of blank shape on the crashworthiness of stamped parts, to show an additional advantage to the already well-known advantages of using optimal blanks for realizing material saving and better formability. In order to study the effect of blank shape, a deformation analysis, followed by crash analysis considering the forming history, has been carried out using two kinds of blank shape, namely an optimal blank and another reference blank. For an objective comparison, the results of the deformation analysis were trimmed off to give the part the same contour shape before the crash analysis. Nevertheless, the results provide no firm evidence of increased crashworthiness, so that the effect of blank shape on the resulting crashworthiness properties of stamped parts has been found to be insignificant.
Validating the dynamic coefficients of bearing pedestals in a multi-mode rotor—bearing system
Authors: Lim T M , Chai G B
Published: February 2009

Over the years, methods have been developed to estimate the dynamic coefficients of bearings based on parameter identification techniques. The stage where the estimated coefficients obtained from these methods need to be validated on actual operating machines, especially those operating at hypercritical speeds, has been reached. This article extended the frequency domain parameter estimation technique normally used on bearings to extract the dynamic coefficients of the bearing pedestals in isolation. It is demonstrated here that by using only a single forcing mechanism located at an angle to the bearing pedestal, the eight possible stiffness and damping coefficients can be estimated accurately. An on-line frequency domain algorithm for estimating these coefficients was developed and tested in the laboratory for this purpose. Its ability to reduce testing time and to produce reliable coefficient estimates from structural spurious resonance is observed. Validations of the dynamic coefficients of the bearing pedestals were carried out by comparing the experimental and computer simulated responses and resonance frequencies of the arrangement of two multi-mode rotor—bearing-system's configurations. By using ANSYS Inc. finite element software as a comparison tool, the results indicated that a nine stations rotor model formulated by the stiffness coefficient method is highly accurate at predicting the rotor—bearing system's responses and resonance frequencies. The results also confirmed that rotor bearing's synchronous response is insensitive with respect to individual estimated parameters that have been determined by statistical hypothesis test to be insignificant.