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Other Publications (52)

Articles by Mark Brady in JoVE

 JoVE Neuroscience

Creating Objects and Object Categories for Studying Perception and Perceptual Learning

1Brain and Behavior Discovery Institute, Georgia Health Sciences University, 2Vision Discovery Institute, Georgia Health Sciences University, 3Department of Opthalmology, Georgia Health Sciences University, 4Intelligent Systems Laboratory, Palo Alto Research Center, 5Pattern Recognition Systems, Palo Alto Research Center, 6Department of Psychology, University of Minnesota


JoVE 3358

We describe a novel methodology for creating naturalistic 3-D objects and object categories with precisely defined feature variations. We use simulations of the biological processes of morphogenesis and phylogenesis to create novel, naturalistic virtual 3-D objects and object categories that can then be rendered as visual images or haptic objects.

Other articles by Mark Brady on PubMed

MCP-1 but Not CINC Synthesis is Increased in Rat Pancreatic Acini in Response to Cerulein Hyperstimulation

Inflammatory mediators including chemokines play a critical role in acute pancreatitis. The precise nature of early inflammatory signals within the pancreas remains, however, unclear. We examined the ability of isolated pancreatic acini to synthesize CC chemokine monocyte chemotactic protein-1 (MCP-1) and CXC chemokine cytokine-induced neutrophil chemoattractant (CINC) and the response to the secretagogue cerulein at physiological and supraphysiological concentrations. Isolated rat pancreatic acini maintained in short-term (< or =48 h) primary culture constitutively synthesized MCP-1 and CINC. Cerulein (10(-7) M; supramaximal dose) increased production of MCP-1 but not CINC. Cerulein-induced increase in MCP-1 synthesis was accompanied by increase in nuclear factor (NF)-kappaB activation shown by EMSA. Pretreatment with NF-kappaB inhibitors N-acetylcysteine (NAC) and N-tosylphenyalanine chloromethyl ketone (TPCK) blocked cerulein-induced NF-kappaB activation and abolished cerulein's effect on MCP-1 synthesis. Pretreatment with calcium antagonist BAPTA-AM also blocked cerulein's effect on MCP-1 synthesis. These results indicate that isolated acini synthesize MCP-1 and CINC and support the idea of acinar-derived chemokines as early mediators of inflammatory response in acute pancreatitis. Although cerulein hyperstimulation increased MCP-1 synthesis by a calcium-dependent mechanism involving NF-kappaB activation, CINC synthesis was not affected. This suggests that regulation of CC and CXC chemokines within acinar cells may be quite different.

Energy Recovery from New York City Municipal Solid Wastes

This work was part of a major study that examined the policy and technology implications of alternatives for managing the municipal solid wastes (MSW) of New York City. At this time, of the 4.1 million metric tons of MSW collected by the City annually, 16.6% are recycled, 12.4% are combusted in Waste-to-Energy (WTE) plants, and the remaining 71% are landfilled. Despite the heterogeneity of organic materials in MSW, the composite molecular structure can be approximated by the organic compound C6H10O4. A formula was derived that allows the prediction of the heating value of MSW as a function of moisture and glass/metal content and compares well with experimentally derived values. The performance of a leading Waste-to-Energy plant that utilises suspension firing of shredded MSW, processes one million tons of MSW per year, and generates a net of 610 kWh/metric ton was examined. The results of this study showed that WTE processing of the MSW reduces fossil fuel consumption and is environmentally superior to landfilling.

Expression of the Chemokines MCP-1/JE and Cytokine-induced Neutrophil Chemoattractant in Early Acute Pancreatitis

Inflammatory mediators play a critical role in acute pancreatitis. The precise role played by members of the chemokine family remains unclear.

Nitrogen in the Baltic Sea--policy Implications of Stock Effects

We develop an optimal control model for cost-effective management of pollution, including two state variables, pollution stock and ecosystem quality. We apply it to Baltic Sea pollution by nitrogen leachates from agriculture. We present a sophisticated, non-linear model of leaching abatement costs, and a simple model of nitrogen stocks. We find that significant abatement is achievable at reasonable cost, despite the countervailing effects of existing agricultural policies such as price supports. Successful abatement should lead to lower nitrogen stocks in the sea in 5 years or less. However, the rate of ecosystem recovery is less certain. The results are highly dependent on the rate of self-cleaning of the Baltic Sea, and less so on the discount rate. Choice of target has a radical effect on the abatement path chosen. Cost-effectiveness demands such a choice, and should therefore be used with care when stock effects are present.

Large-scale Mapping and Predictive Modeling of Submerged Aquatic Vegetation in a Shallow Eutrophic Lake

A spatially intensive sampling program was developed for mapping the submerged aquatic vegetation (SAV) over an area of approximately 20,000 ha in a large, shallow lake in Florida, U.S. The sampling program integrates Geographic Information System (GIS) technology with traditional field sampling of SAV and has the capability of producing robust vegetation maps under a wide range of conditions, including high turbidity, variable depth (0 to 2 m), and variable sediment types. Based on sampling carried out in August-September 2000, we measured 1,050 to 4,300 ha of vascular SAV species and approximately 14,000 ha of the macroalga Chara spp. The results were similar to those reported in the early 1990s, when the last large-scale SAV sampling occurred. Occurrence of Chara was strongly associated with peat sediments, and maximal depths of occurrence varied between sediment types (mud, sand, rock, and peat). A simple model of Chara occurrence, based only on water depth, had an accuracy of 55%. It predicted occurrence of Chara over large areas where the plant actually was not found. A model based on sediment type and depth had an accuracy of 75% and produced a spatial map very similar to that based on observations. While this approach needs to be validated with independent data in order to test its general utility, we believe it may have application elsewhere. The simple modeling approach could serve as a coarse-scale tool for evaluating effects of water level management on Chara populations.

Pilot Evaluation of High-dose Carboplatin and Paclitaxel Followed by High-dose Melphalan Supported by Peripheral Blood Stem Cells in Previously Untreated Advanced Ovarian Cancer: a Gynecologic Oncology Group Study

To evaluate the efficacy and safety of multiple cycles of high-dose carboplatin and paclitaxel and one consolidation cycle of high-dose melphalan with all cycles supported by hematopoietic stem cells and cytokine, in previously untreated patients with optimally debulked stage III epithelial ovarian cancer.

Extraovarian Peritoneal Serous Papillary Carcinoma: a Phase II Trial of Cisplatin and Cyclophosphamide with Comparison to a Cohort with Papillary Serous Ovarian Carcinoma-a Gynecologic Oncology Group Study

The goals of this study were first, to assess the clinical effectiveness of cisplatin and cyclophosphamide in a phase II study involving a well-defined group of women with extraovarian peritoneal serous papillary carcinoma (EPSPC); and second, to compare these results with those of a group of patients with papillary serous ovarian carcinoma (PSOC) who received identical therapy.

Expression of Tip60, an Androgen Receptor Coactivator, and Its Role in Prostate Cancer Development

Prostate cancer (CaP) is initially androgen sensitive and responsive to hormone ablation therapy. However, cancer growth recurs despite androgen deprivation in the majority of cases of advanced disease. The molecular basis of this progression still remains unknown. The significance of androgen receptor (AR) coactivator proteins in this androgen-dependent malignancy is only beginning to emerge. In the present study, we examined the role of Tat interactive protein, 60 kDa (Tip60), an AR coactivator, in CaP progression. In hormone refractory CaP biopsies, we observed a nuclear accumulation of Tip60 expression in contrast to a more diffuse distribution pattern observed in benign prostate hyperplasia and primary CaP. Furthermore, in both the prostate xenograft model CWR22 and the LNCaP CaP cell line, we observed that androgen withdrawal promoted upregulation of Tip60 as well as nuclear accumulation. In contrast, androgen exposure resulted in decreased Tip60 expression that was more closely linked to a cytoplasmic presence. Chromatin immunoprecipitation analysis revealed Tip60's recruitment to the PSA gene promoter in both androgen-dependent and -independent cell lines. Thus, in vitro and in vivo data support a possible role for Tip60 in the molecular pathway leading to the development of androgen-independent CaP following long-term androgen deprivation therapy.

Phase III Trial of Paclitaxel at Two Dose Levels, the Higher Dose Accompanied by Filgrastim at Two Dose Levels in Platinum-pretreated Epithelial Ovarian Cancer: an Intergroup Study

To determine if increasing the dose of paclitaxel increases the probability of clinical response, progression-free survival, or overall survival in women who have persistent or recurrent ovarian cancer, and whether doubling the dose of prophylactic filgrastim accompanying the higher paclitaxel dose decreases the frequency of neutropenic fever.

Bootstrapped Learning of Novel Objects

Recognition of familiar objects in cluttered backgrounds is a challenging computational problem. Camouflage provides a particularly striking case, where an object is difficult to detect, recognize, and segment even when in "plain view." Current computational approaches combine low-level features with high-level models to recognize objects. But what if the object is unfamiliar? A novel camouflaged object poses a paradox: A visual system would seem to require a model of an object's shape in order to detect, recognize, and segment it when camouflaged. But, how is the visual system to build such a model of the object without easily segmentable samples? One possibility is that learning to identify and segment is opportunistic in the sense that learning of novel objects takes place only when distinctive clues permit object segmentation from background, such as when target color or motion enables segmentation on single presentations. We tested this idea and discovered that, on the contrary, human observers can learn to identify and segment a novel target shape, even when for any given training image the target object is camouflaged. Further, perfect recognition can be achieved without accurate segmentation. We call the ability to build a shape model from high-ambiguity presentations bootstrapped learning.

Adjuvant Treatment for Early Ovarian Cancer: a Randomized Phase III Trial of Intraperitoneal 32P or Intravenous Cyclophosphamide and Cisplatin--a Gynecologic Oncology Group Study

To conduct a prospective study of intraperitoneal radioactive chromic phosphate (32P) versus cyclophosphamide-cisplatin (CP) in women with early ovarian cancer at high risk for recurrence (International Federation of Gynecology and Obstetrics stage Ia or Ib grade 3 or Ic or stage II, no macroscopic residual disease) and to compare cumulative incidence of recurrence, overall survival, and relative toxicity. Materials and

The Ethics of Reporting and Disseminating Results of Clinical Research Trials

Analysis of CHEK2 Gene for Ovarian Cancer Susceptibility

A deletion variant in the CHEK2 gene (del1100C) has been implicated as a low-penetrance risk factor for breast cancer. We sought to determine contribution of CHEK2 mutations to the etiology of ovarian cancer (OvCa).

Phase III Trial of Doxorubicin with or Without Cisplatin in Advanced Endometrial Carcinoma: a Gynecologic Oncology Group Study

Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone.

Secondary Surgical Cytoreduction for Advanced Ovarian Carcinoma

We evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy on progression-free survival and overall survival among patients who had advanced ovarian cancer and residual tumor exceeding 1 cm in diameter after primary surgery.

Regulation of P53 and MDM2 Activity by MTBP

p53 is a critical coordinator of a wide range of stress responses. To facilitate a rapid response to stress, p53 is produced constitutively but is negatively regulated by MDM2. MDM2 can inhibit p53 in multiple independent ways: by binding to its transcription activation domain, inhibiting p53 acetylation, promoting nuclear export, and probably most importantly by promoting proteasomal degradation of p53. The latter is achieved via MDM2's E3 ubiquitin ligase activity harbored within the MDM2 RING finger domain. We have discovered that MTBP promotes MDM2-mediated ubiquitination and degradation of p53 and also MDM2 stabilization in an MDM2 RING finger-dependent manner. Moreover, using small interfering RNA to down-regulate endogenous MTBP in unstressed cells, we have found that MTBP significantly contributes to MDM2-mediated regulation of p53 levels and activity. However, following exposure of cells to UV, but not gamma-irradiation, MTBP is destabilized as part of the coordinated cellular response. Our findings suggest that MTBP differentially regulates the E3 ubiquitin ligase activity of MDM2 towards two of its most critical targets (itself and p53) and in doing so significantly contributes to MDM2-dependent p53 homeostasis in unstressed cells.

P53 Regulation and Function in Renal Cell Carcinoma

Loss of p53 function is a critical event in tumor evolution. This occurs through a range of molecular events, typically a missense p53 mutation followed by loss of heterozygosity. In many cancers, there is compelling evidence that cells that can compromise p53 function have a selective advantage. The situation in renal cell carcinoma is unclear. It has recently been suggested that p53 function is unusually compromised in renal carcinoma cells by a novel dominant, MDM2/p14ARF-independent mechanism. This is hard to reconcile with other recent studies that have identified p53 as an important prognostic indicator. Indeed, one of these latter studies found that the best predictor of poor outcome was the presence of high levels of both p53 (usually indicative of p53 mutation) and MDM2. Thus, it is important that we gain a clearer understanding of the regulation of p53 and the role of MDM2 in renal cell cancer. To address this, we have investigated the transcriptional activity of p53 in a panel of renal cell carcinoma cell lines and the contribution of MDM2 and p14ARF to p53 regulation. We have found that p53 is functional in p53 wild-type renal cell carcinoma cells and that this activity is significantly regulated by MDM2 and to a much lesser extent by p14ARF. Moreover, following induction of DNA damage with UV, the p53 response in these cells is intact. Thus, future studies of renal cell carcinoma that focus on p53 and MDM2 and their role in determining disease outcome will be required to create a better understanding of this notoriously difficult to manage disease.

Pretreatment CA-125 and Risk of Relapse in Advanced Ovarian Cancer

A previous report suggested the nadir serum CA-125 level within the group of patients with ovarian cancer who achieved normalization of CA-125 accurately defined the risk of relapse. Using similar CA-125 subgroups, we sought to determine if the baseline CA-125 level before initiation of maintenance chemotherapy in women achieving a clinically-defined complete response to primary chemotherapy would be of prognostic value.

Randomized Phase III Trial of Three Versus Six Cycles of Adjuvant Carboplatin and Paclitaxel in Early Stage Epithelial Ovarian Carcinoma: a Gynecologic Oncology Group Study

Compared to 3 cycles, to determine if 6 cycles of adjuvant carboplatin (C) and paclitaxel (P) significantly lower the rate of recurrence in surgically staged patients with stage IA grade 3, IB grade 3, clear cell, IC, and completely resected stage II epithelial ovarian cancer (EOC); and to compare toxicities.

Intraperitoneal Therapy for Ovarian Cancer: a Treatment Ready for Prime Time

Survey of Orthopaedic and Sports Medicine Physicians Regarding Use of Medrol Dosepak for Sports Injuries

To study the use of a methylprednisolone taper (Medrol Dosepak; Pfizer, New York, NY) short-term oral corticosteroid treatment modality by sports medicine physicians; included is discussion on indications, perceived efficacy, and complications.

Effects of Initial Graft Tension on the Tibiofemoral Compressive Forces and Joint Position After Anterior Cruciate Ligament Reconstruction

The initial tension applied to an anterior cruciate ligament graft at the time of fixation modulates knee motion and the tibiofemoral compressive loads.

Any Given Sunday. Paramedics Assist Trainers and Physicians in the NFL's Largest Stadium

Directly Observed Highly Active Antiretroviral Therapy for HIV-infected Children in Cambodia

Antiretroviral medications are becoming available for HIV-infected children in resource-limited settings. Maryknoll, an international Catholic charity, provided directly observed antiretroviral therapy to HIV-infected children in Phnom Penh, Cambodia. Child care workers administered generic antiretroviral drugs twice daily to children, ensuring adherence. Treatment began with 117 late-stage HIV-infected children; 22 died of AIDS during the first 6 months. The rest were treated for at least 6 months and showed CD4 count increases comparable to those achieved in US and European children. Staffing cost for this program was approximately US $5 per child per month, or 15% more than the price of the medications. Drug toxicities were uncommon and easily managed. Directly observed antiretroviral therapy appears to be a promising, low-cost strategy for ensuring adherent treatment for HIV-infected children in a resource-limited setting.

An Early Signal of CA-125 Progression for Ovarian Cancer Patients Receiving Maintenance Treatment After Complete Clinical Response to Primary Therapy

For ovarian cancer patients receiving maintenance treatment after complete clinical response to primary therapy, we tested the predictive value of the following early signal of progressive disease (EPD) criterion based on serum CA-125: for patients with CA-125 nadir or= 20 U/mL serves as an early signal of CA-125 progression; for patients with nadir more than 10 U/mL, a value >or= 2x nadir that is confirmed predicts progression. PATIENTS AND METHODS The EPD criterion was tested on Southwest Oncology Group trial 9701/Gynecologic Oncology Group trial 178 patients (n = 288) and compared with Gynecologic Cancer Intergroup criterion.

A Gynecologic Oncology Group Randomized Phase III Trial of Whole Abdominal Irradiation (WAI) Vs. Cisplatin-ifosfamide and Mesna (CIM) As Post-surgical Therapy in Stage I-IV Carcinosarcoma (CS) of the Uterus

After initial surgery, there has been no established consensus regarding adjunctive therapy for patients with uterine carcinosarcoma (CS). This study was designed to compare patient outcome following treatment with adjuvant whole abdominal irradiation (WAI) versus (vs.) chemotherapy for patients with this rare group of female pelvic malignancies.

Phase III Randomized Trial of Intravenous Cisplatin Plus a 24- or 96-hour Infusion of Paclitaxel in Epithelial Ovarian Cancer: a Gynecologic Oncology Group Study

This study was undertaken to assess if prolonged paclitaxel administration in combination with cisplatin improves overall survival (OS) in epithelial ovarian cancer (EOC).

Corticosteroids Reduce Postoperative Morbidity After Third Molar Surgery: a Systematic Review and Meta-analysis

The purpose of this study was to apply meta-analytical methods to measure the effect of corticosteroids (CS) on edema, trismus, and pain at early and late postoperative periods after third molar (M3) removal.

Speeding Up the Evaluation of New Agents in Cancer

Despite both the increase in basic biologic knowledge and the fact that many new agents have reached various stages of development during the last 10 years, the number of new treatments that have been approved for patients has not increased as expected. We propose the multi-arm, multi-stage trial design as a way to evaluate treatments faster and more efficiently than current standard trial designs. By using intermediate outcomes and testing a number of new agents (and combinations) simultaneously, the new design requires fewer patients. Three trials using this methodology are presented.

Tibiofemoral Compression Force Differences Using Laxity- and Force-based Initial Graft Tensioning Techniques in the Anterior Cruciate Ligament-reconstructed Cadaveric Knee

Our purpose was to document the tibiofemoral (TF) compression forces produced during clinical initial graft tension protocols.

Camera Calibration for Natural Image Studies and Vision Research

A dominant theme in vision research is that important characteristics of the visual pathway evolved to be effective in processing natural scenes. Given this perspective, one can learn about the nature of visual processing from a quantitative analysis of natural images. Such analysis can benefit from the camera as a measuring device. As such, the camera should not introduce arbitrary artifacts into the image formation process. This paper describes how to correct a number of unnecessary artifacts associated with obtaining natural scene statistics with a digital camera. For artifacts that are inherently part of image formation, and where elimination is not possible or appropriate, we describe methods for transformation and quantification.

Evaluation of New Platinum-based Treatment Regimens in Advanced-stage Ovarian Cancer: a Phase III Trial of the Gynecologic Cancer Intergroup

To determine if incorporation of an additional cytotoxic agent improves overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma who receive carboplatin and paclitaxel.

Survival After Second-line Intraperitoneal Therapy for the Treatment of Epithelial Ovarian Cancer: the Gynecologic Oncology Group Experience

To assess the association between patient-disease characteristics and overall survival (OS) after second-line intraperitoneal (IP) treatment of ovarian cancer.

Congenital Trypanosoma Cruzi Transmission in Santa Cruz, Bolivia

We conducted a study of congenital Trypanosoma cruzi infection in Santa Cruz, Bolivia. Our objective was to apply new tools to identify weak points in current screening algorithms, and find ways to improve them.

Aciclovir Neurotoxicity is an Important Side Effect of Therapy in Patients with Renal Impairment

Microscopic Observation Drug Susceptibility Assay for Tuberculosis Screening Before Isoniazid Preventive Therapy in HIV-infected Persons

Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons.

The Role of Primary Care in Managing Chronic Kidney Disease

Prognostic Relevance of Uncommon Ovarian Histology in Women with Stage III/IV Epithelial Ovarian Cancer

The prognostic relevance of uncommon epithelial ovarian cancer (EOC) histological subtypes remains controversial. The Gynecologic Cancer InterGroup (GCIG) initiated this meta-analysis to assess the relative prognosis of women with a diagnosis of rare EOC histologies from completed, prospectively randomized studies performed by cooperative GCIG study groups.

Randomized Phase III Trial of Tamoxifen Versus Thalidomide in Women with Biochemical-recurrent-only Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma After a Complete Response to First-line Platinum/taxane Chemotherapy with an Evaluation of Serum Vascular Endothelial Growth Factor (VEGF): A Gynecologic Oncology Group Study

To compare progression-free survival (PFS), overall survival (OS) and toxicities of thalidomide versus tamoxifen and to evaluate serum vascular endothelial growth factor (VEGF) in biochemical-recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube carcinoma (EOC/PPC/FTC).

Advanced Stage Mucinous Adenocarcinoma of the Ovary is Both Rare and Highly Lethal: a Gynecologic Oncology Group Study

Primary mucinous adenocarcinomas of the ovary are uncommon, and their biological behavior is uncertain. Retrospective studies have suggested that many mucinous carcinomas initially diagnosed as primary to the ovary have in fact metastasized from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes.

EORTC 55971: Does It Apply to All Patients with Advanced State Ovarian Cancer?

Improved Survival in Non-Ashkenazi Jewish Ovarian Cancer Patients with BRCA1 and BRCA2 Gene Mutations

Previous studies report a survival advantage in ovarian cancer patients with Ashkenazi Jewish (AJ) breast cancer gene (BRCA) founder mutations. The purpose of this study was to determine if this association exists in patients with non-Ashkenazi Jewish (non-AJ) BRCA mutations. We also sought to account for "survival bias" by minimizing lead time that may exist between diagnosis and genetic testing.

Nuclear P27 Expression in Benign, Borderline (LMP) and Invasive Tumors of the Ovary and Its Association with Prognosis: a Gynecologic Oncology Group Study

Nuclear p27 expression was examined in non-invasive and invasive ovarian tumors from a cross-sectional study, and clinical relevance of p27 was evaluated in the primary tumors from women participating in two randomized phase III treatment trials.

Back to the Future: Changes in the Dialysis Delivery Model in the UK

A Randomized Phase III Trial of IV Carboplatin and Paclitaxel × 3 Courses Followed by Observation Versus Weekly Maintenance Low-dose Paclitaxel in Patients with Early-stage Ovarian Carcinoma: a Gynecologic Oncology Group Study

To compare the recurrence-free interval (RFI) and safety profile in patients with completely resected high-risk early-stage ovarian cancer treated with intravenous (IV) carboplatin and paclitaxel with or without maintenance low-dose paclitaxel for 24 weeks.

Clinical Trials in Recurrent Ovarian Cancer

The 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup was held in Vancouver, Canada, in June 2010. Representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. Group C, 1 of the 3 discussion groups, examined recurrent ovarian cancer, and we report the consensus reached regarding 4 questions. These included the following: (1) What is the role of cytoreductive surgery for recurrent ovarian cancer? (2) How do we define distinct patient populations in need of specific therapeutic approaches? (3) Should end points for trials with recurrent disease vary from those of first-line trials? (4) Is CA-125 progression alone sufficient for entry/eligibility into clinical trials?

Macrophage Reactivity to Different Polymers Demonstrates Particle Size- and Material-specific Reactivity: PEEK-OPTIMA(®) Particles Versus UHMWPE Particles in the Submicron, Micron, and 10 Micron Size Ranges

Biologic reactivity to orthopedic implant debris is generally the main determinant of long-term clinical performance where released polymeric particles of Ultra-high molecular weight polyethylene (UHMWPE) remain the most prevalent debris generated from metal-on-polymer bearing total joint arthroplasties. Polymeric alternatives to UHMWPE such as polyetherether-ketone (PEEK) may have increased wear resistance but the bioreactivity of PEEK-OPTIMA particles on peri-implant inflammation remains largely uncharacterized. We evaluated human monocyte/macrophage responses (THP-1s and primary human) when challenged by PEEK-OPTIMA, UHMWPE, and X-UHMWPE particles of three particle sizes (0.7 um, 2 um, and 10 um) at a dose of 20 particles-per-cell at 24- and 48-h time points. Macrophage responses were measured using cytotoxicity assays, viability assays, proliferation assays and cytokine analysis (IL-1b, IL-6, IL-8, MCP-1, and TNF-α). In general, there were no significant differences between PEEK-OPTIMA, UHMWPE, and X-UHMWPE particles on macrophage viability or proliferation. However, macrophages demonstrated greater cytotoxicity responses to UHMWPE and X-UHMWPE than to PEEK-OPTIMA at 24 and 48 h, where 0.7 μm-UHMWPE particles produced the highest amount of cytotoxicity. Particles of X-UHMWPE more than PEEK-OPTIMA and UHMWPE induced IL-1β, IL-6, MCP-1, and TNF-α at 24 h, p < 0.05 (no significant differences at 48 h). On average, cytokine production was more adversely affected by larger 10 μm particles than by 0.7 and 2 μm sized particles. While limitations of in vitro analysis apply to this study, PEEK-OPTIMA particles were more biocompatible than UHMWPE particles, in that they induced less inflammatory cytokine responses and thus, in part, demonstrates that PEEK-OPTIMA implant debris does not represent an increased inflammatory risk over that of UHMWPE. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.

Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer

Vascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy.

CA125 Regression in Ovarian Cancer Patients Treated with Intravenous Versus Intraperitoneal Platinum-based Chemotherapy: A Gynecologic Oncology Group Study

CA125 is a non-specific marker of peritoneal irritation which has the potential for false elevation during intraperitoneal treatment. The purpose of this study is to identify the rate of CA125 regression during intraperitoneal (IP) versus intravenous (IV) chemotherapy for ovarian cancer.

Object Recognition in Clutter: Cortical Responses Depend on the Type of Learning

Theoretical studies suggest that the visual system uses prior knowledge of visual objects to recognize them in visual clutter, and posit that the strategies for recognizing objects in clutter may differ depending on whether or not the object was learned in clutter to begin with. We tested this hypothesis using functional magnetic resonance imaging (fMRI) of human subjects. We trained subjects to recognize naturalistic, yet novel objects in strong or weak clutter. We then tested subjects' recognition performance for both sets of objects in strong clutter. We found many brain regions that were differentially responsive to objects during object recognition depending on whether they were learned in strong or weak clutter. In particular, the responses of the left fusiform gyrus (FG) reliably reflected, on a trial-to-trial basis, subjects' object recognition performance for objects learned in the presence of strong clutter. These results indicate that the visual system does not use a single, general-purpose mechanism to cope with clutter. Instead, there are two distinct spatial patterns of activation whose responses are attributable not to the visual context in which the objects were seen, but to the context in which the objects were learned.

How to Design a Targeted Agricultural Subsidy System: Efficiency or Equity?

In this paper we appraise current agricultural subsidy policy in the EU. Several sources of its inefficiency are identified: it is inefficient for supporting farmers' incomes or guaranteeing food security, and irrational transfer payments decoupled from actual performance that may be negative for environmental protection, social cohesion, etc. Based on a simplified economic model, we prove that there is "reverse redistribution" in the current tax-subsidy system, which cannot be avoided. To find a possible way to distribute subsidies more efficiently and equitably, several alternative subsidy systems (the pure loan, the harvest tax and the income contingent loan) are presented and examined.

Cytokine Use and Survival in the First-line Treatment of Ovarian Cancer: A Gynecologic Oncology Group Study

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) and erythropoietin stimulating agents (ESA) may be used to support patients during chemotherapy. We assessed whether G-CSF or ESA were associated with progression or death in patients with ovarian cancer. METHODS: Patients with ovarian cancer following surgery, were on a protocol to evaluate bevacizumab with chemotherapy. Guidelines for administering G-CSF and ESA were specified in the protocol. Overall survival (OS) was analyzed with landmark procedures and multivariate, time-dependent hazard models. RESULTS: Eighteen-hundred-seventy-three women were enrolled, with no differences in clinical and pathologic variables among treatment group. Performance status, hemoglobin, and white cell counts were associated with G-CSF and/or ESA usage during treatment. Nine patients received no protocol directed therapy, leaving 1864 patients for this review. One-thousand-one-hundred-twenty-five patients received neither ESA nor G-CSF; 311 received G-CSF but no ESA; 241 received ESA but no G-CSF; and 187 received both. Median survival following a five month landmark from the start of treatment was 34 versus 38months for those who did versus did not receive ESA (multivariate hazard ratio: 0.989; 95% confidence interval: 0.849-1.15) and 40 versus 37months for those who did versus did not receive G-CSF (multivariate hazard ratio: 0.932; 95% confidence interval: 0.800-1.08). CONCLUSIONS: Neither ESA nor G-CSF had a negative impact on survival after adjustment of prognostic factors among patients with ovarian cancer receiving chemotherapy. ESA may appear to be associated with shorter survival in univariate analyses because factors prognostic for ESA use are also prognostic for progression-free survival.

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