bluuebunny/crossref_metadata_2025 huggingface dataset:
Endovascular Repair of Blunt Extremity Arterial Injury: Case Report
Authors: Zimmerman Pamela , d'Audiffret Alexandre , Pillai Lakshmikumar
Published: November 2008

Objective: Surgical revascularization is the standard treatment of complex blunt traumatic extremity vascular injuries. Limb salvage may be improved with minimally invasive endovascular therapies because of the ability to perform diagnostic and therapeutic intervention simultaneously. Two cases of acute limb-threatening arterial injuries successfully treated with percutaneous endovascular therapy are reported. Results: A skier suffered hemodynamic instability after shoulder reduction. An axillary arterial injury was suspected and confirmed with angiography. A covered stent successfully controlled the hemorrhage. A morbidly obese female sustained anterior dislocation of her left knee 7 years previously requiring repair. She developed recurrent knee dislocation with acute leg ischemia. Emergent fixation was performed followed by percutaneous angiography. Short segment thrombosis of the popliteal was noted. Wire recanalization of the thrombosed artery and stent placement restored 3-vessel runoff. Conclusion: Endovascular therapy can offer faster, easier access to the extremity vascular injury facilitating revascularization and avoiding long incisions and dissections.
Gait Speed in Relation to Categories of Functional Ambulation After Spinal Cord Injury
Authors: van Hedel Hubertus J. A.
Published: November 2008

Objective. The aim of the present study was to assess gait speeds that distinguished between levels of functional ambulation in subjects with a spinal cord injury. Methods. The data of 886 spinal cord injury subjects were derived from the European Multicenter Study for Human Spinal Cord Injury and analyzed at 1, 3, 6, and 12 months after injury. The indoor and outdoor mobility items from the Spinal Cord Independence Measure were combined into 5 clinically relevant categories: (1) wheelchair-dependent, (2) supervised walker with outdoor wheelchair dependency, (3) indoor walker with outdoor wheelchair dependency, (4) walker with aid, and (5) walker without aid. The preferred walking speed that distinguished between ambulation categories was derived from the 10-meter walking test and determined using receiver operating characteristic curves. Results. The walking speed correlated well (>0.84) with the ambulation categories. The average walking speed for each category was (1) 0.01 m/s, (2) 0.34 m/s, (3) 0.57 m/s, (4) 0.88 m/s, and (5) 1.46 m/s. The average (± SD) speed that distinguished between the categories was 0.09 ± 0.01 m/s (1 vs 2), 0.15 ± 0.08 m/s (2 vs 3), 0.44 ± 0.14 m/s (3 vs 4), and 0.70 ± 0.13 m/s (4 vs 5). The averaged sensitivity and specificity were above 0.98 and 0.94, respectively. Conclusion. In subjects with spinal cord injury, the preferred walking speed as assessed in the clinic can be used to estimate functional ambulation during daily life. The walking speed can distinguish between ambulation categories with high sensitivity and specificity.
Outcomes of Laparoscopic and Open Colectomy: A National Population-Based Comparison
Authors: Kemp Jason A. , Finlayson Samuel R. G.
Published: November 2008

Several recent clinical studies have demonstrated that laparoscopic colectomy is safe, feasible, and associated with many short-term benefits compared with open colectomy. It is unknown if outcomes observed in clinical trials can be achieved on a population level. The authors used the Nationwide Inpatient Sample to identify laparoscopic and open elective colon resections performed in the United States for each year from 2000 to 2004. They assessed differences in patient characteristics using demographic information and ICD-9 codes. They then used univariate and multiple logistic regression models to analyze the association between surgical approach and in-hospital morbidity, as well as in-hospital mortality and length of hospital stay. Patients undergoing laparoscopic colectomy tended to be younger (61 years vs 66 years, P < .001) and to have fewer comorbidities (Charlson score of 0 in 58.1% vs 37.0%, P < .001). After adjusting for patient characteristics and comorbidities, laparoscopic colectomy was associated with lower in-hospital mortality (0.6% vs 1.7%, P < .001), lower overall complication rate (32.1% vs 38.2%, P < .001), and shorter median hospital stay (5 vs 7 days, P < .001) compared with open colectomy. Significant benefits were observed in wound problems (0.8% vs 1.44%, P < .001); cardiovascular (12.5% vs 15.1%, P < .001), pulmonary (6.2% vs 8.7%, P < .001), and gastrointestinal (13.7% vs 16.1%, P < .001) morbidity; and reintervention rates (1.33% vs 1.66%, P = .02). Outcome benefits of laparoscopic colectomy previously demonstrated in clinical trials are observed on a population level.
Which College Students Are at Higher Health Risk?
Authors: Magnus Marcia H.
Published: November 2008

An electronic health risk appraisal was used to determine which demographic factors were associated with higher health risk among college students at an urban state university. Students’ real age was assessed as the primary indicator of health risk and it was associated to demographic characteristics. Real age represents the physiological age of the body based on lifestyle choices, and this is often different to chronological age. Approximately 26.0% of 576 students were more than 5 years older than their chronological age, 29.8% were 0 to 5 years older, 29.8% were 0 to 5 years younger, and 14.1% were more than 5 years younger than their chronological age. Students who were male, Black, and nonnutrition majors had significantly higher positive real age differentials: their bodies were more likely to be more than 5 years older than their chronological age. Students with significantly lower negative real age differential—those whose real age was lower than their chronological age—were female and nutrition majors. Students were significantly more likely to report that they were “very motivated” if they were female (88.6%), compared with male (66.7%). These data suggest that when health disparities are assessed at the level of real age differential and motivation to make lifestyle changes, male Black college students are at highest health risk and they are less likely to be “very motivated” to make lifestyle changes than their peers.
Benefits of Breakfast for Children and Adolescents: Update and Recommendations for Practitioners
Authors: Rampersaud Gail C.
Published: November 2008

A number of studies report health benefits for children and adolescents who consume breakfast. Breakfast skipping is fairly common in children and adolescents and increases as children age. Breakfast can enhance children's diets by positively contributing to daily nutrient intake, augmenting intake of key nutrients such as fiber and calcium, and provides an opportunity to help meet the recommendations of the Dietary Guidelines for Americans. Breakfast also is associated with more healthful food choices. Cross-sectional studies support that eating breakfast more often may help children and adolescents maintain a healthful weight. However, the results from longitudinal studies are inconclusive and suggest that more research is needed to clarify this relationship, including understanding the mediating effects of initial weight status, dieting behavior, and physical activity levels. Breakfast consumption may provide some benefit toward cognitive function and academic achievement, but more research is needed. Breakfast is one facet of a healthy lifestyle that may help contribute to the short- and long-term health and well-being of children and adolescents. Health practitioners can promote healthy breakfast consumption in children and adolescents by addressing barriers to eating breakfast and focusing on individuals who may be more likely to skip breakfast on a regular basis.
Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor
Authors: Reheman Adili , Yang Hong , Zhu Guangheng , Jin Wuxun , He Feng , Spring Christopher M. , Bai Xufang , Gross Peter L. , Freedman John , Ni Heyu
Published: November 2008

We previously showed that platelet aggregation and thrombus formation occurred in mice lacking both fibrinogen (Fg) and von Willebrand factor (VWF) and that plasma fibronectin (pFn) promoted thrombus growth and stability in injured arterioles in wild-type mice. To examine whether pFn is required for Fg/VWF-independent thrombosis, we generated Fg/VWF/conditional pFn triple-deficient (TKO; Cre+, Fnflox/flox, Fg/VWF−/−) mice and littermate control (Cre−, Fnflox/flox, Fg/VWF−/−) mice. Surprisingly, TKO platelet aggregation was not abolished, but instead was enhanced in both heparinized platelet-rich plasma and gel-filtered platelets. This enhancement was diminished when TKO platelets were aggregated in pFn-positive control platelet-poor plasma (PPP), whereas aggregation was enhanced when control platelets were aggregated in pFn-depleted TKO PPP. The TKO platelet aggregation can be completely inhibited by our newly developed mouse anti–mouse β3 integrin antibodies but was not affected by anti–mouse GPIbα antibodies. Enhanced platelet aggregation was also observed when heparinized TKO blood was perfused in collagen-coated perfusion chambers. Using intravital microscopy, we further showed that thrombogenesis in TKO mice was enhanced in both FeCl3-injured mesenteric arterioles and laser-injured cremaster arterioles. Our data indicate that pFn is not essential for Fg/VWF-independent thrombosis and that soluble pFn is probably an important inhibitory factor for platelet aggregation.
Platelets actively sequester angiogenesis regulators
Authors: Lakka Klement Giannoula , Yip Tai-Tung , Cassiola Flavia , Kikuchi Lena , Cervi David , Podust Vladimir , Italiano Joseph E. , Wheatley Erin , Abou-Slaybi Abdo , Bender Elise , Almog Nava , Kieran Mark W. , Folkman Judah
Published: November 2008

Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non–tumor-bearing animals. This process is selective, as platelets do not take up a proportional amount of other plasma proteins (eg, albumin), even though these may be present at higher concentrations. We also find that VEGF-enriched Matrigel pellets implanted subcutaneously into mice or the minute quantities of VEGF secreted by microscopic subcutaneous tumors (0.5-1 mm3) result in an elevation of VEGF levels in platelets, without any changes in its plasma levels. The profile of other angiogenesis regulatory proteins (eg, platelet-derived growth factor, basic fibroblast growth factor) sequestered by platelets also reflects the presence of tumors in vivo before they can be macroscopically evident. The ability of platelets to selectively take up angiogenesis regulators in cancer-bearing hosts may have implications for the diagnosis and management of many angiogenesis-related diseases and provide a guide for antiangiogenic therapies.
Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells
Authors: Otsu Keishi , Das Shonit , Houser Sandra D. , Quadri Sadiqa K. , Bhattacharya Sunita , Bhattacharya Jahar
Published: November 2008

Mesenchymal stem cells (MSCs), which potentially transdifferentiate into multiple cell types, are increasingly reported to be beneficial in models of organ system injury. However, the molecular mechanisms underlying interactions between MSCs and host cells, in particular endothelial cells (ECs), remain unclear. We show here in a matrigel angiogenesis assay that MSCs are capable of inhibiting capillary growth. After addition of MSCs to EC-derived capillaries in matrigel at EC:MSC ratio of 1:1, MSCs migrated toward the capillaries, intercalated between ECs, established Cx43-based intercellular gap junctional communication (GJC) with ECs, and increased production of reactive oxygen species (ROS). These events led to EC apoptosis and capillary degeneration. In an in vivo tumor model, direct MSC inoculation into subcutaneous melanomas induced apoptosis and abrogated tumor growth. Thus, our findings show for the first time that at high numbers, MSCs are potentially cytotoxic and that when injected locally in tumor tissue they might be effective antiangiogenesis agents suitable for cancer therapy.
RICD: A rice indicacDNA database resource for rice functional genomics
Authors: Lu Tingting , Huang Xuehui , Zhu Chuanrang , Huang Tao , Zhao Qiang , Xie Kabing , Xiong Lizhong , Zhang Qifa , Han Bin
Published: November 2008

Background

The Oryza sativa L. indica subspecies is the most widely cultivated rice. During the last few years, we have collected over 20,000 putative full-length cDNAs and over 40,000 ESTs isolated from various cDNA libraries of two indica varieties Guangluai 4 and Minghui 63. A database of the rice indica cDNAs was therefore built to provide a comprehensive web data source for searching and retrieving the indica cDNA clones.

Results

Rice Indica cDNA Database (RICD) is an online MySQL-PHP driven database with a user-friendly web interface. It allows investigators to query the cDNA clones by keyword, genome position, nucleotide or protein sequence, and putative function. It also provides a series of information, including sequences, protein domain annotations, similarity search results, SNPs and InDels information, and hyperlinks to gene annotation in both The Rice Annotation Project Database (RAP-DB) and The TIGR Rice Genome Annotation Resource, expression atlas in RiceGE and variation report in Gramene of each cDNA.

Conclusion

The online rice indica cDNA database provides cDNA resource with comprehensive information to researchers for functional analysis of indica subspecies and for comparative genomics. The RICD database is available through our website http://www.ncgr.ac.cn/ricd.
Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma
Authors: Shirasaki Takashi , Maruya Shin-ichiro , Mizukami Hiroki , Kakehata Seiji , Kurotaki Hidekachi , Yagihashi Soroku , Shinkawa Hideichi
Published: November 2008

Background

Thymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC).

Methods

An ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluatedin vitro. In addition, thein vivoeffect of TS siRNA on tumor progression was assessed using a xenograft model.

Results

Our results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model.

Conclusion

TS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.
Selective receptor expression restricts Nipah virus infection of endothelial cells
Authors: Erbar Stephanie , Diederich Sandra , Maisner Andrea
Published: November 2008

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes severe diseases in animals and humans. Endothelial cell (EC) infection is an established hallmark of NiV infection in vivo. Despite systemic virus spread via the vascular system, EC in brain and lung are preferentially infected whereas EC in other organs are less affected. As in vivo, we found differences in the infection of EC in cell culture. Only brain-derived primary or immortalized EC were found to be permissive to NiV infection. Using a replication-independent fusion assay, we could show that the lack of infection in non-brain EC was due to a lack of receptor expression. The NiV entry receptors ephrinB2 (EB2) or ephrinB3 were only expressed in brain endothelia. The finding that EB2 expression in previously non-permissive aortic EC rendered the cells permissive to infection then demonstrated that EB2 is not only necessary but also sufficient to allow the establishment of a productive NiV infection. This strongly suggests that limitations in receptor expression restrict virus entry in certain EC subsets in vivo, and are thus responsible for the differences in EC tropism observed in human and animal NiV infections.
Intrathecal synthesis of IgE in children with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis
Authors: Padilla-Docal Barbara , Dorta-Contreras Alberto J , Bu-Coifiu-Fanego Raisa , Hernández Hermes Fundora , Barroso Jesús Callol , Sanchez-Martinez Consuelo
Published: November 2008

Background

Eosinophilic meningoencephalitis caused by the helminthAngiostrongylus cantonensis, is an emerging infectious disease in America. The objective of this paper was to determine if the intrathecal synthesis of immunoglobulin E is produced during the acute phase of the disease.

Methods

Thirteen patients, mean age 4.5 years were studied; a diagnostic lumbar puncture was performed and serum samples taken. Immunoglobulin E (IgE) in serum and in cerebrospinal fluid (CSF) was quantified by nephelometry. Control patients had other infections or other neurological diseases.

Results

The mean cell count in the CSF was 500 × 10-6cells/L and of these 23% were eosinophils. In blood the eosinophils were 13%. The chief symptoms of the patients were migraine, vomiting and fever and 50% presented some meningeal signs. IgE intrathecal synthesis analyzed by the corresponding quotient diagram (Reibergram) was observed in all patients. No intrathecal IgE synthesis was seen in control patients.

Conclusion

Intrathecal synthesis of IgE demonstrates the participation of this immunoglobulin in the destruction of the third stage larvae of the parasite in the CSF. The test should be considered in our environment as a tool to aid diagnosis.
Trends towards an improved disease state in rheumatoid arthritis over time: influence of new therapies and changes in management approach: analysis of the EMECAR cohort
Authors: González-Alvaro Isidoro , Descalzo Miguel Angel , Carmona Loreto ,   the EMECAR Study Group
Published: November 2008

Introduction

The disease activity in patients with rheumatoid arthritis has improved during the past decade. The availability of new drugs and also a better assessment of the disease have been proposed to be responsible for this improvement. In the present work we estimate the effect of these factors on disease activity and function in patients with rheumatoid arthritis at the beginning of the new century.

Methods

The Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide (EMECAR) cohort was assembled in 2000 from the random sampling of rheumatoid arthritis patients registered in 34 centers. The cohort was composed of 789 patients who underwent a baseline assessment plus four annual follow-up visits in which functional ability (Health Assessment Questionnaire score), the disease activity score obtained from 28-joint count with three parameters (DAS28-3) and radiological progression (Larsen score) were recorded. The effect of the calendar year on the DAS28-3, the Health Assessment Questionnaire score, and the Larsen score was obtained from adjusted models in which all treatments were included as dummy variables.

Results

The effect of time as the β coefficient (95% confidence interval) for 2004, taking 2000 as a reference year, was -0.43 (-0.58 to -0.28) for the DAS28-3, 0.15 (0.07 to 0.22) for the Health Assessment Questionnaire score, and 4.4 (2.68 to 6.12) for the Larsen score. Treatment with new therapies, either leflunomide or TNF antagonists, increased in frequency from 1.1% (n = 8) in 2000 to 30.9% (n = 144) in 2004. Treatment with TNF antagonists (-0.28 (-0.5 to -0.05)) and with gold salts (-0.21 (-0.38 to -0.04)) was independently associated with a decrease in the DAS28-3 over time, whereas cyclosporin A treatment (0.45 (0.13 to 0.76)) was associated with an increase in disease activity.

Conclusions

The mean disease activity of rheumatoid arthritis has improved from 2000 to 2004. An explanation is the introduction of new therapies, but not solely. Other factors related to the calendar year, plausibly a better management of available drugs, show a greater effect on improvement than the drugs used.
Metformin-associated lactic acidosis in an intensive care unit
Authors: Peters Nicolas , Jay Nicolas , Barraud Damien , Cravoisy Aurélie , Nace Lionel , Bollaert Pierre-Edouard , Gibot Sébastien
Published: November 2008

Introduction

Metformin-associated lactic acidosis (MALA) is a classic side effect of metformin and is known to be a severe disease with a high mortality rate. The treatment of MALA with dialysis is controversial and is the subject of many case reports in the literature. We aimed to assess the prevalence of MALA in a 16-bed, university-affiliated, intensive care unit (ICU), and the effect of dialysis on patient outcome.

Methods

Over a five-year period, we retrospectively identified all patients who were either admitted to the ICU with metformin as a usual medication, or who attempted suicide by metformin ingestion. Within this population, we selected patients presenting with lactic acidosis, thus defining MALA, and described their clinical and biological features.

Results

MALA accounted for 0.84% of all admissions during the study period (30 MALA admissions over five years) and was associated with a 30% mortality rate. The only factors associated with a fatal outcome were the reason for admission in the ICU and the initial prothrombin time. Although patients who went on to haemodialysis had higher illness severity scores, as compared with those who were not dialysed, the mortality rates were similar between the two groups (31.3% versus 28.6%).

Conclusions

MALA can be encountered in the ICU several times a year and still remains a life-threatening condition. Treatment is restricted mostly to supportive measures, although haemodialysis may possess a protective effect.
Correlation of O6-Methylguanine Methyltransferase (MGMT) Promoter Methylation With Clinical Outcomes in Glioblastoma and Clinical Strategies to Modulate MGMT Activity
Authors: Hegi Monika E. , Liu Lili , Herman James G. , Stupp Roger , Wick Wolfgang , Weller Michael , Mehta Minesh P. , Gilbert Mark R.
Published: November 2008

Resistance to alkylating agents via direct DNA repair by O6-methylguanine methyltransferase (MGMT) remains a significant barrier to the successful treatment of patients with malignant glioma. The relative expression of MGMT in the tumor may determine response to alkylating agents, and epigenetic silencing of the MGMT gene by promoter methylation plays an important role in regulating MGMT expression in gliomas. MGMT promoter methylation is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome MGMT-mediated chemoresistance are being actively investigated. These include treatment with nontoxic pseudosubstrate inhibitors of MGMT, such as O6-benzylguanine, or RNA interference-mediated gene silencing of MGMT. However, systemic application of MGMT inhibitors is limited by an increase in hematologic toxicity. Another strategy is to deplete MGMT activity in tumor tissue using a dose-dense temozolomide schedule. These alternative schedules are well tolerated; however, it remains unclear whether they are more effective than the standard dosing regimen or whether they effectively deplete MGMT activity in tumor tissue. Of note, not all patients with glioblastoma having MGMT promoter methylation respond to alkylating agents, and even those who respond will inevitably experience relapse. Herein we review the data supporting MGMT as a major mechanism of chemotherapy resistance in malignant gliomas and describe ongoing studies that are testing resistance-modulating strategies.
Insulin-Like Growth Factor-I Activates Gene Transcription Programs Strongly Associated With Poor Breast Cancer Prognosis
Authors: Creighton Chad J. , Casa Angelo , Lazard ZaWaunyka , Huang Shixia , Tsimelzon Anna , Hilsenbeck Susan G. , Osborne Charles Kent , Lee Adrian V.
Published: November 2008

Purpose

Substantial evidence implicates insulin-like growth factor-I (IGF-I) signaling in the development and progression of breast cancer. To more clearly elucidate the role of IGF in human breast cancer, we identified and then examined gene expression patterns of IGF-I–treated breast cancer cells.

Methods

MCF-7 cells were stimulated with IGF-I for 3 or 24 hours and were profiled for greater than 22,000 RNA transcripts. We defined an IGF-I signature pattern of more than 800 genes that were up- or downregulated at both time points. The gene signature was examined in clinical breast tumors and in experimental models that represented other oncogenic pathways. The signature was correlated with clinical and pathologic variables and with patient outcome.

Results

IGF-I caused temporal changes in gene expression that were strongly associated with cell proliferation, metabolism, and DNA repair. Genes with early and sustained regulation by IGF-I were highly enriched for transcriptional targets of the estrogen receptor (ER), Ras/extracellular signal-related kinase 1/2, and phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathways. In three large, independent data sets of profiled human breast tumors, the IGF-I signature was manifested in the majority of ER-negative breast tumors and in a subset (approximately 25%) of ER-positive breast tumors. Patients who had tumors that manifested the IGF-I signature (including patients who did not receive adjuvant therapy) had a shorter time to a poor outcome event. The IGF gene signature was highly correlated with numerous poor prognostic factors and was one of the strongest indicators of disease outcome.

Conclusion

Transcriptional targets of IGF-I represent pathways of increased aggressiveness and possibly hormone independence in clinical breast cancers.
Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer
Authors: Litton Jennifer K. , Gonzalez-Angulo Ana M. , Warneke Carla L. , Buzdar Aman U. , Kau Shu-Wan , Bondy Melissa , Mahabir Somdat , Hortobagyi Gabriel N. , Brewster Abenaa M.
Published: November 2008

Purpose

To understand the mechanism through which obesity in breast cancer patients is associated with poorer outcome, we evaluated body mass index (BMI) and response to neoadjuvant chemotherapy (NC) in women with operable breast cancer.

Patients and Methods

From May 1990 to July 2004, 1,169 patients were diagnosed with invasive breast cancer at M. D. Anderson Cancer Center and received NC before surgery. Patients were categorized as obese (BMI ≥ 30 kg/m2), overweight (BMI of 25 to < 30 kg/m2), or normal/underweight (BMI < 25 kg/m2). Logistic regression was used to examine associations between BMI and pathologic complete response (pCR). Breast cancer–specific, progression-free, and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. All statistical tests were two-sided.

Results

Median age was 50 years; 30% of patients were obese, 32% were overweight, and 38% were normal or underweight. In multivariate analysis, there was no significant difference in pCR for obese compared with normal weight patients (odds ratio [OR] = 0.78; 95% CI, 0.49 to 1.26). Overweight and the combination of overweight and obese patients were significantly less likely to have a pCR (OR = 0.59; 95% CI, 0.37 to 0.95; and OR = 0.67; 95% CI, 0.45 to 0.99, respectively). Obese patients were more likely to have hormone-negative tumors (P < .01), stage III tumors (P < .01), and worse overall survival (P = .006) at a median follow-up time of 4.1 years.

Conclusion

Higher BMI was associated with worse pCR to NC. In addition, its association with worse overall survival suggests that greater attention should be focused on this risk factor to optimize the care of breast cancer patients.
Expanding Circle of Inhibition: Small-Molecule Inhibitors of Bcl-2 as Anticancer Cell and Antiangiogenic Agents
Authors: Zeitlin Benjamin D. , Zeitlin Isaac J. , Nör Jacques E.
Published: November 2008

The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade. Bcl-2 is vital during development, much less so in adults. It has also been noted that some cancers evade apoptosis and obtain a survival advantage through aberrant expression of Bcl-2. The new and remarkably diverse class of drugs, small-molecule inhibitors of Bcl-2 (molecular weight approximately 400 to 800 Daltons), is examined herein. We present the activities of these compounds along with clinical observations, where available. The effects of Bcl-2 inhibition on attenuation of tumor cell growth are discussed, as are studies revealing the potential for Bcl-2 inhibitors as antiangiogenic agents. Despite an enormous body of work published for the Bcl-2 family of proteins, we are still learning exactly how this group of molecules interacts and indeed what they do. The small-molecule inhibitors of Bcl-2, in addition to their therapeutic potential, are proving to be an important investigative tool for understanding the function of Bcl-2.
Patient Education Level As a Predictor of Survival In Lung Cancer Clinical Trials
Authors: Herndon James E. , Kornblith Alice B. , Holland Jimmie C. , Paskett Electra D.
Published: November 2008

Purpose

To investigate the effect of socioeconomic status, as measured by education, on the survival of 1,577 lung cancer patients treated on 11 studies conducted by the Cancer and Leukemia Group B.

Patients and Methods

Sociodemographic data, including education, was reported by the patient at the time of clinical trial accrual. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival after adjustment for known prognostic factors.

Results

The patient population included 1,177 patients diagnosed with non–small-cell lung cancer (NSCLC; stage III or IV) and 400 patients diagnosed with small-cell lung cancer (SCLC; extensive or limited). Patients with less than an eighth grade education (13% of patients) were significantly more likely to be male, nonwhite, and older; have a performance status (PS) of 1 or 2; and have chest pain. Significant predictors of poor survival in the final model included male sex, PS of 1 or 2, dyspnea, weight loss, liver or bone metastases, unmarried, presence of adrenal metastases and high alkaline phosphatase levels among patients with NSCLC, and high WBC levels among patients with advanced disease. Education was not predictive of survival.

Conclusion

The physical condition of patients with low education who enroll onto clinical trials is worse than patients with higher education. Once enrolled onto a clinical trial, education does not affect the survival of patients with SCLC or stage III or IV NSCLC. The standardization of treatment and follow-up within a clinical trial, regardless of education, is one possible explanation for this lack of effect.
Stress-regulated kinase pathways in the recovery of tip growth and microtubule dynamics following osmotic stress inS. pombe
Authors: Robertson Alasdair M. , Hagan Iain M.
Published: November 2008

The cell-integrity and stress-response MAP kinase pathways (CIP and SRP, respectively) are stimulated by various environmental stresses. Ssp1 kinase modulates actin dynamics and is rapidly recruited to the plasma membrane following osmotic stress. Here, we show that osmotic stress arrested tip growth, induced the deposition of abnormal cell-wall deposits at tips and led to disassociation of F-actin foci from cell tips together with a reduction in the amount of F-actin in these foci. Osmotic stress also `froze' the dynamics of interphase microtubule bundles, with microtubules remaining static for approximately 38 minutes (at 30°C) before fragmenting upon return to dynamic behaviour. The timing with which microtubules resumed dynamic behaviour relied upon SRP activation of Atf1-mediated transcription, but not on either CIP or Ssp1 signalling. Analysis of the recovery of tip growth showed that: (1) the timing of recovery was controlled by SRP-stimulated Atf1 transcription; (2) re-establishment of polarized tip growth was absolutely dependent upon SRP and partially dependent upon Ssp1 signalling; and (3) selection of the site for polarized tip extension required Ssp1 and the SRP-associated polarity factor Wsh3 (also known as Tea4). CIP signalling did not impact upon any aspect of recovery. The normal kinetics of tip growth following osmotic stress of plo1.S402A/E mutants established that SRP control over the resumption of tip growth after osmotic stress is distinct from its control of tip growth following heat or gravitational stresses.
Nucleoplasmic mobilization of nucleostemin stabilizes MDM2 and promotes G2-M progression and cell survival
Authors: Meng Lingjun , Lin Tao , Tsai Robert Y. L.
Published: November 2008

Nucleolar disassembly occurs during mitosis and nucleolar stress, releasing several MDM2-interactive proteins residing in the nucleolus that share the common activity of p53 stabilization. Here, we demonstrate that mobilization of nucleostemin, a nucleolar protein enriched in cancer and stem cells, has the opposite role of stabilizing MDM2 and suppressing p53 functions. Our results show that nucleostemin increases the protein stability and nucleoplasmic retention of MDM2, and competes with L23 for MDM2 binding. These activities were significantly elevated when nucleostemin is released into the nucleoplasm by mutations that abolish its nucleolar localization or by chemotherapeutic agents that disassemble the nucleoli. Nucleostemin depletion decreases MDM2 protein, increases transcription activity without affecting the level of p53 protein, and triggers G2-M arrest and cell death in U2OS cells but not in H1299 cells. This work reveals that nucleoplasmic relocation of nucleostemin during nucleolar disassembly safeguards the G2-M transit and survival of continuously dividing cells by MDM2 stabilization and p53 inhibition.
The effect of indirect forging pressure of wrought aluminium alloys on material properties by varying solid fraction using electromagnetic stirring
Authors: Kang S S , Kang C G , Lee S M
Published: November 2008

The rheoforming of Al7075 using the electromagnetic stirring (EMS) approach is demonstrated. The mechanical properties, chemical composition, and microstructural observations are performed on the produced samples. The rheo-slurry produced by EMS of a 60 A stirring current was forged for 20 s at temperatures of 625 °C (solid fraction, fs = 35 per cent) and 615 °C ( fs = 50 per cent) under applied pressures of 170, 200, 220, and 250 MPa. The highest tensile strength of 404 MPa was recorded for a sample produced at a temperature of 615 °C and a pressure of 220 MPa that underwent a T6 heat treatment. The sample produced at 625 °C achieved its highest tensile strength for an applied pressure of 200 MPa and a T6 heat treatment. The improvement in the ductility observed in these samples is a result of the removal of a liquid phase that contains Cu and Si from the boundaries between grains of the pure α phase material. The elongation properties of the sample were investigated and correlated with the observed microstructures.
The effect of forging pressure on liquid segregation during direct rheoforging process of wrought aluminium alloys fabricated by electromagnetic stirring
Authors: Kang C G , Lee S M
Published: November 2008

This study demonstrated rheoforging of wrought aluminium alloys fabricated by means of electromagnetic stirring (EMS) and characterization of the rheoforged products. When EMS was applied under a stirring current of 60 A, infusion of surface oxides into the bulk material and porosities within the bulk material were both prevented and dendrites were crushed. Material rheoforged at a densification pressure of 150 MPa exhibited good mechanical strength and surface quality. The temperature of the rheological material during forging influences the formability of the material. When the solid fraction is below 70 per cent, the rheological material completely fills the die cavity and the pressure applied by the punch is transferred to the material at the bottom of the die cavity. Investigating the microstructural features and mechanical properties of the material, it is shown that the rheoforged material following EMS yields a fine and globular microstructure.
Computationally efficient predictive adaptive control for robotic operation in dynamic environments and task domains
Authors: Vaidyanathan R , Prince T S , Modarreszadeh M , Gupta L , Lisy F J
Published: November 2008

This paper presents a new adaptive predictive control algorithm and its refinement for robotic utility. The controller addresses the need for practical, computationally efficient, robust real-time adaptive control for multivariable robotic systems working in challenging industrial environments. It exploits a special matrix representation to obtain substantial reductions in the computational expense relative to standard methods. Controller performance is established for a simple robotic manipulator directing motion through sharply changing loading conditions and on an industrial robot loading heavy shells within the weapons magazine of a naval vessel. The new controller demonstrates the ability to adapt to varying actuator performance and rapidly changing sea states for which a classic proportional—integral—derivative controller cannot adjust. Control commands and parameter adjustments are executed in time frames suitable for real-time use, even on platforms and in environments with limited computational resources. Future work involves the implementation and testing of the controller on a prototype robot during facsimile naval operations. This work may serve as a foundation to address control issues for robots working in uncertain dynamic environments with varying task domains through the implementation of computationally efficient predictive adaptive control.
Study of the effect of process parameters in high-speed grinding on surface integrity by Barkhausen noise analysis
Authors: Vashista M , Paul S
Published: November 2008

An experimental study was undertaken to investigate the role of process parameters on the grindability of medium carbon steel in a high-speed grinding domain with particular emphasis on surface integrity. Surface residual stress on the ground specimens has been assessed using X-ray diffraction technique and Barkhausen noise analysis. High-speed grinding with cubic boron nitride (cBN) wheels, unlike conventional grinding, provided compressive residual stress throughout the experimental domain. This can be attributed to a desirable temperature control as the single layer cBN wheel with higher thermal conductivity than conventional wheels and grinding fluid took away a substantial part of the grinding heat flux. Micromagnetic or Barkhausen noise parameters correlated linearly with the residual stress, indicating its applicability in assessing the surface integrity of high-speed ground steel.
An experimental investigation of deep-hole microdrilling capability for a nickel-based superalloy
Authors: Imran M , Mativenga P T , Kannan S , Novovic D
Published: November 2008

This paper presents the results of an experimental investigation into the feasibility of deep-hole microdrilling a nickel-based superalloy. This material is very challenging to machine and current drilling methods are based on non-conventional machining technologies; the traditional view is that microdrills are too fragile to be used for drilling this high-strength aerospace alloy. The work investigated mechanical microdrilling under various cutting conditions. Mechanical microdrilling may offer the chance of improved hole quality and surface integrity. Initially a review of literature was undertaken with a view to identify the best drill geometry for the production of micro holes in nickel-based alloys. Based on this review the best available commercial micro drills were selected. A special strategy was introduced for selecting the pilot drill in order to ensure gradual loading of the twist drill and reduce the chance of drill breakage. For the cutting tests, 0.5 mm diameter twist drills were used in drilling tests to a depth of 5 mm. The effect of processing parameters such as drill feed rate, spindle speed, and peck depth were evaluated, and the tool wear mechanism was also investigated. The cutting performance was characterized by the number of holes produced before drill breakage. The results show that deep-hole mechanical microdrilling of nickel-based superalloys is technically feasible and offers good hole definition and potentially competitive lead times.
Hybrid forming process of AA 6108 T4 thin sheets: Modelling by neural network solutions
Authors: Barletta M , Gisario A , Guarino S
Published: November 2008

The highly non-linear deformation processes occurring in most dynamic sheet metal forming operations cause large amounts of elastic strain energy to be stored in the formed material and massive related springback phenomena. Therefore, this paper investigates how effective a laser source is in reducing the extent of springback in mechanical contact forming operations.

The hybrid forming process investigated was composed of using a high-power diode laser to induce local heating of mechanically bent AA 6108 T4 thin sheets in order to minimize the extent of the springback. In particular, experiments were carried out to assess the influence of the leading process parameters such as laser source power, scan speed, and starting elastic deformation of the mechanically bent sheets. It was found that the trends in the experimental response of residual deflection were always consistent with the operating parameters.

Artificial intelligence techniques were then used to model the hybrid forming process. The extent of the springback in the hybrid forming process of AA 6108 T4 thin sheets was predicted by using different neural network models and training algorithms. Lastly, the reliability of the best neural network solutions was checked by comparing these solutions with experimental results and by developing an ad hoc first approximation technical model.
Prediction of pulsed-laser powder deposits’ shape profiles using a back-propagation artificial neural network
Authors: Mahapatra M M , Li L
Published: November 2008

The cross-sectional shape profile geometry of blown powder clad deposit is important for overall structural integrity of the clad layer. The penetration zone of the clad deposit is represented within its shape profile geometry. The shape profile geometry of the clad deposit is also important for thermomechanical modelling. Although a rough estimation of blown powder clad deposit shape profile can be made based on the powder feeding parameters using empirical formulae, it may not be sufficiently accurate to be used in a thermomechanical model, as it may lead to inaccuracy in the prediction of temperature distributions, residual stresses, and distortion. The pulsed-laser blown powder deposition process is a highly coupled multivariable problem. Hence the deterministic numerical-methods-based prediction of pulsed-laser powder deposit shape profile geometry is time consuming, costly, and may not be adequate to predict the profile geometry over a wide range of varying process parameters. The present investigation deals with the cross-sectional shape profile geometry modelling of the pulsed-laser assisted superalloy powder deposition (PLPD) process using a soft computing approach. A simple yet effective mapping technique was used in the present work to map the experimentally obtained shape profiles of the powder deposits. The mapped characteristics of the powder deposits’ shape profiles were used in the back-propagation artificial neural network (ANN) modelling of the PLPD process. The present modelling technique can be conveniently used to incorporate the PLPD shape profile geometry parameters in thermomechanical analyses for accurate prediction of temperature distributions and residual stresses. Based on the present soft computing modelling methodology, an estimation of top reinforcement and penetration zone shape boundaries of a blown powder clad deposit can also be made.
Optimizing cutting parameters in minimum quantity of lubrication milling of hardened cold work tool steel
Authors: Iqbal A , Dar N U , He N , Khan I , Li L
Published: November 2008

Despite the numerous advantages offered by high-speed and high-performance cutting technologies, the issue of diminished tool life still remains profoundly concerning, especially in the case of machining hardened steels. Moreover, in finish machining, the requirement of improving workpiece surface finish also gains considerable importance. Application of the minimum quantity of lubrication (MQL) has delivered so many benefits that it has almost become part and parcel of turning, drilling, and milling technologies. In this research work, the high-speed milling of hardened cold work tool steel (62 HRc), under an MQL environment, was experimentally investigated and a response surface methodology was utilized to optimize the cutting parameters. A series of experiments was performed in order to quantify the effects of following three cutting parameters on tool life and arithmetic average surface roughness: cutting speed ( Vc), feed rate ( fz), and radial depth of cut ( ae). The surface roughness was measured in two directions: along the feed, Ra, and along the pick-feed, Ra(pick). Analysis of variance (ANOVA) performed on the data revealed that the effect of cutting speed was significant on tool life as well as on Ra. Moreover, the effects of feed rate and radial depth of cut on tool life and Ra(pick) respectively were found to be significant. Scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) analyses were performed to determine the dependence of different tool damage modes on levels of cutting parameters utilized. It was found that chipping and adhesion were the dominant tool damage modes in most of the experimental runs and their severity was dependent on levels of feed rate and cutting speed respectively.