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About Prostate Cancer
Living With Prostate Cancer
Understanding Prostate Cancer
July 2011 Advances
2011 American Society of Clinical Oncology (ASCO)
Annual Meeting Highlights
June 3 – June 7, 2011
The 2011 American Society of Clinical Oncology Annual (ASCO) meeting witnessed compelling data on 3 new drugs heading rapidly towards FDA review and approval for metastatic prostate cancer: cabozantinib, Alpharadin and MDV3100. We also saw the first data from hundreds of patients showing that counting circulating tumor cells (CTCs) in blood outperform the prostate specific antigen (PSA) test in predicting whether an experimental treatment is working. More innovation was also reported. For example, a 1992 FDA-approved drug called itraconazole, a toenail fungus antibiotic, emerged as an important antagonist in micro-metastatic prostate cancer. It blocks the "Sonic Hedgehog pathway," a biochemical growth signal in cancer stem cells.
ASCO annually convenes the largest oncology meeting in the world. The meeting provides an optimal opportunity for oncology practitioners to learn the latest scientific advances in a collective setting. ASCO has 30,000 members. Add drug and pharmaceutical attendees, and McCormick Place bustled with approximately 40,000 attendees from more than 130 different countries.
The theme of the 2011 ASCO Annual Meeting, "Patients, Pathways, Progress" was reflected in many different aspects of the ASCO program, especially in the area of prostate cancer research. Achievements of PCF-supported cancer researchers were represented in the 30 out of 218 total prostate cancer papers presented at ASCO. Of these 30 papers, 16 were the work of PCF Young Investigators mentored by PCF senior investigators.
ASCO meetings are designed to update oncology practitioners on new clinical trial findings and trends and how to better care for problems that patients experience. While it is impossible to summarize all of the new science presented at the meeting, what follows below are the most relevant highlights which concern 10 new drugs as well as three new trends in biomarker research. These are promising developments that patients with advanced disease will want to track and stay informed of with their physicians.
New Agents in the Pipeline and Entering Practice
1. Cabozantinib (XL184) – Exelixis, Inc.
Andrew Pollack recently reported from ASCO in The New York Times, that cabozantinib, formerly XL184, "seems to be able to virtually eradicate bone metastases in some patients, at least as measured by bone scans, something no other drug has done." Below is a prostate cancer patient bone scan before and after treatment with cabozantinib:
PCF-funded investigator Maha Hussain from the University of Michigan, Ann Arbor presented interim data from a phase II study showing that cabozantinib (XL184) reduced bone metastases in 76% of prostate cancer patients with advanced castration-resistant disease. No other drug has done this to abnormal bone scans before in prostate oncology. The current standard of care for metastatic castration-resistant prostate cancer (mCRPC) is a combination of the chemotherapy drug docetaxel and the steroid prednisone. Docetaxel regimens have a limited impact on bone metastases and what they look like on bone scans.
While most chemotherapy is administered intravenously, cabozantinib, by contrast, is a small molecule tyrosine kinase inhibitor (TKI) that can be taken orally. Tyrosine kinases are part of the complex network of proteins involved in many different kinds of cancer cell functions, including several that drive prostate cancer cells to replicate. There are over 518 kinases found in the human genome. All 518 of them are potentially drug targets for diseases as often a disease state is "signaled" by an abnormal kinase. Specifically, cabozantinib is a "multi-kinase inhibitor" of specific kinds of tyrosine kinases: c-Met (MET) and the vascular endothelial growth factor receptor (VEGFR-2) and, at least in a test tube, kinases called RET, KIT and TEK.
Exelixis chemists designed cabozantinib, originally called XL184, to block the promotion of angiogenesis, the process by which tumors actually induce new blood vessels to form within them so that they can receive nutrients. Unexpectedly, as described below in the abstract, the drug can also affect the bone cells (osteoclasts and osteoblasts) that support the survival of prostate cancer cell clones within a bone metastasis.
In the University of Michigan study, 168 patients with metastatic PCa were treated with a 100mg dosage of cabozantinib daily. Overall, 71% of patients benefited and 86% of patients showed bone effects indicative of improvement. Of the patients treated, 51% required a dose reduction due to severe fatigue, high blood pressure, and "hand and foot syndrome" (burning sensation). Ten percent of patients had side effects at a 100mg per day dose that were so difficult they could not cope with the treatment. None of the side effects, as reported by careful grading, appeared life-threatening for the men on this trial. Sixty-four percent had marked improvement in pain at the site of bone metastases. Forty-six percent of patients were able to cease taking pain killers for bone metastases. Another striking observation was that anemic patients had improvements in their red blood cell counts. Many experts believe 100mg may be too high a dose, and further research is underway to find the optimal dose as well as whether or not patients should come on and off the drug periodically, rather than have it administered continuously.
2. Alpharadin® (radium-223 chloride) – AlgetaRL
A lesser known area of radiation oncology is radiopharmaceutical therapy. This approach involves the injection of a radioactive substance, such as strontium-89 or samarium-153, intravenously for systemic distribution to cancer cells. These two radiopharmaceuticals are atomically like calcium in the periodic table of the elements. As minerals, they are actively deposited by the body into areas of bone that contain cancer metastases where damaged bone matrix is exposed to blood flow. Providing radiation from a deposit of radiopharmaceuticals in this way can irradiate and destroy cancer cells in the bone, and subsequently relieve pain from bone metastases. Common side effects of strontium-89 and samarium-153 include dangerously lowered levels of normal platelets, and white and red blood cells, as they are radiated and killed.
Radium-223 is different. Radium-223 is a new type of radiopharmaceutical therapy that may produce fewer side effects. It does so by delivering its cell killing action over a very "short range" via an alpha particle (2 protons and 2 neutrons) of radiation in its nuclear decay—rather than through a beta particle (an electron). Alpha particles for prostate cancer cell killing in the bone are "first in field" and distinctive. In contrast, gamma rays from external beam radiation are so energetic they pass through the body if they do not hit molecules. Beta particles can penetrate many cell diameters away from the cancer deposit and kill radiation ultra-sensitive normal red blood cell and platelet-forming cells in the bone marrow.
From 1997-2000, PCF funded Dr. Logothetis, at the University of Texas MD Anderson Cancer Center, to test the concept of radiopharmaceutical targeting of bone metastatic prostate cancer with beta particles from strontium-89. Two important, PCF-funded papers were published from Dr. Logothetis' group in 2001 and 2003 confirming that a) prostate cancer bone metastases can be controlled and, in some cases, eradicated in the bone with radiopharmaceuticals and b) side effects on bone marrow in many patients make it impossible to safely use Sr89 routinely in combination with existing cell-killing drugs. Building on this clinical scholarship, a Norwegian cancer therapeutics company, Algeta, presented data in 2007 from a phase II study that showed a remarkable two-year survival advantage with bone-targeting alpha particles from radium-223 when used as a treatment for castrate-resistant prostate cancer. What then followed was a phase III trial with the significant U.S. leadership of Dr. Oliver Sartor at Tulane University.
On Monday, June 6, 2011 at ASCO, Algeta's partner, Bayer Healthcare, announced promising results for Alpharadin (radium-223 chloride). In that phase III clinical trial, four intravenous doses of radium-223 alone improved overall survival by 3 months for patients with extensive bone metastatic castration-resistant prostate cancer. The radiopharmaceutical treatment period was 12 weeks. The clinical trial was a randomized, double-blind, multi-dose, placebo-controlled international study that included 922 patients. The primary endpoint of the study was overall survival.
Side effects were very similar to those seen in the Algeta phase II trial where platelet counts, white cell counts and red cell counts were not significantly lowered and patients remained as outpatients. Based on a recommendation by the Independent Data Monitoring Committee (IDMC) for the FDA, the clinical radium-223 trial was stopped and patients on the placebo arm were proposed to be given the drug. Based on these data, Bayer-Algeta is re-evaluating its timeline for gaining FDA approval and looking at supply chain issues for distribution globally.
Among public and private biomedical research funding entities, PCF was the only Foundation to fund the "proof of concept" of radiopharmaceuticals at the University of Texas MD Anderson Cancer Center.
3. Zytiga® (abiraterone) – Johnson & Johnson
In early May, the Food and Drug Administration approved abiraterone, a new targeted therapy in the class of androgen production blockers. The drug improves overall survival by nearly four months for men with metastatic, castration-resistant prostate cancer after being treated with docetaxel chemotherapy.
In total, PCF invested $8.2 million in research (PCF Creativity and Challenge Awards 2007-2010) for fast forwarding treatment science research around abiraterone. The PCF research support was global, and it was funded in independent, university research laboratories. Most of that research focused on abiraterone's mechanism of action, discovery of biomarkers to predict patient response, e.g. circulating tumor cells, and identification of mechanisms of resistance. All this research occurred prior to Johnson & Johnson's acquisition of the drug. Pivotal clinical trials led by Dr. Johann de Bono at The Royal Marsden Hospital in London were enabled by critical contributions of a "star" cast of PCF Prostate Cancer Clinical Trials Consortium (PCCTC) collaborators including: Howard Scher, MD, at Memorial Sloan-Kettering Cancer Center; Gerhardt Attard, MD, PhD, The Susan and James Blair PCF Young Investigator 2008-2011 at The Royal Marsden Hospital; Peter Nelson, MD, at the Fred Hutchinson Cancer Research Center; Eric Small, MD, and Charles Ryan, MD, at the University of California, San Francisco and Christopher Logothetis, MD, and Eleni Efstathiou, MD, PhD, GenProbe PCF Young Investigator 2008-2011 at MD Anderson. When the pivotal clinical trial (comprised of 1,195 patients) was published, over 34 clinical investigators were listed on the New England Journal of Medicine paper which Dr. de Bono published. That paper gives the results and provides the details on how clinicians should use abiraterone in the clinic.
Abiraterone works in about 60% of men with metastatic prostate cancer following docetaxel chemotherapy, but studies are ongoing about its use earlier in the disease and in combination with new agents. Dr. Logothetis presented additional findings on abiraterone. In a study of 797 patients randomized to abiraterone with prednisone (5mg twice a day) and 398 to placebo, abiraterone markedly delayed "SREs" (skeletal related events) and delayed the time or need for palliative radiation therapy of painful bone metastases. Pain relief from bone metastases and delay of painful recurrence were striking with abiraterone. These findings of increased symptom-free survival were observed in men with the most advanced, docetaxel-treated, and then refractory, metastatic hormone refractory disease. Dr. Logothetis educated the ASCO audience on the concept of "intracrine" androgens, production of testosterone within the tumor cell and around the metastatic site. He also suggested to drug developers in the industry that with this data, abiraterone—in addition to being used earlier in the disease course—should be integrated in co-targeting strategies with other bone targeting therapies.
Dr. Charles Ryan of the University of California, San Francisco (UCSF) also presented a paper on the use of abiraterone in men who had been treated with ketoconazole for at least 28 days in the "pre-abiraterone FDA-approved era." Ryan reported 63% of those UCSF patients responded to abiraterone after ketoconazole treatment. This important single-institution study, supported by PCF's PCCTC, suggests that some tumors stay "Cyp17 pathway dependent" (which abiraterone inhibits better than ketoconazole). Pathways where continued "dependency" or "addiction" are demonstrated in the clinic, have been places for the research and development of better "second generations" of drugs than the "first generation." The work of PCF-funded scientists in San Francisco, Seattle, London, Boston and Houston has collectively supported the thinking that intracrine androgen signaling must be completely blocked in patients whose tumors are "addicted" to androgen for survival.
4. TAK-700 – Takeda Pharmaceuticals
Takeda Pharmaceuticals has introduced another molecule into clinical trials to disrupt intracrine testosterone synthesis in metastatic prostate cancer. TAK-700 is a pill like abiraterone that has a unique chemical structure enabling it to inhibit a key enzyme called the 17,20 lyase enzyme. The 17,20 lyase is a key enzyme in the production of the common precursor molecules derived from cholesterol for male and female sex steroid hormones which normally are synthesized in both the testes and the adrenal glands.
TAK-700 showed significant activity in 96 patients in a phase I/II trial. Patients had metastatic, castration-resistant prostate cancer with a median age of 70 years and median PSA at treatment of 22 ng/ml. At every TAK-700 dose tested, at least 50% of patients treated had PSA declines over 50% by 12 weeks of treatment. In those patients who had not received ketoconazole, 62% of patients had a PSA decline of >50% by 12 weeks on the drug. Patients experienced the predicted significant reduction of testosterone and DHEA-S in their blood; those findings should occur if the 17,20 lyase enzyme was being blocked adequately. Circulating tumor cell data from CellSearch systems was also illustrative of antitumor activity.
At 12 weeks after the start of treatment, 48 of 61 evaluable patients either had shifts from >5 cells/7.5mls (unfavorable) to <5 cells/7.5mls (favorable or retained favorable CTC counts). The drug also has toxicities. Seventy-one percent of patients reported fatigue, and nausea as an issue. Management of severe blood potassium levels was required in 6% of patients. TAK-700 is now in global phase III trials in docetaxel untreated, and docetaxel pre-treated patients on LHRH treatment.
5. MDV3100 – Medivation
In the laboratory, MDV3100 is a superior molecule to Casodex for inhibiting the androgen receptor. MDV3100 binds to the androgen receptor with 5x the affinity of Casodex. PCF supported significant molecular pharmacology around MDV3100 in Dr. Charles Sawyer's laboratory at UCLA. MDV3100 is currently in phase III clinical trials, and there was no new clinical data presented at this ASCO. However, Dr. Eleni Efstathiou presented a provocative treatment sciences paper in CT-guided, serial biopsies of bone metastases in 47 MD Anderson patients who were treated with MDV3100 in earlier clinical trials. With drug treatment, nuclear androgen receptor levels were reduced by MDV3100 in the bone metastasis clones—but with this was evidence of increased intracrine androgen production in the bone (observed by tandem mass spectroscopy). Increased phosphorylated-src oncogene as a research biomarker appeared to be correlated with MDV3100 treatment resistance. By studying patient volunteers in "real time," and by interrogating their bone metastases directly after biopsy in a protocol, Dr. Efstathiou has elevated a molecular rationale into an imperative: co-targeting of increased intracrine androgen production, which can be blocked by abiraterone, with MDV3100 treatment. It is possible that the two international phase III trials for MDV3100 called AFFIRM and PREVAIL, respectively, will have available data for presentation at the 2012 ASCO meeting in Orlando.
6. Jevtana® (cabazitaxel) – Sanofi-Aventis
For practitioners caring for advanced prostate cancer patients, additional data was presented on the newly FDA-approved chemotherapy drug Jevtana from Sanofi-Aventis. Patient data from the 755 patient phase III trial suggests that even in men treated with docetaxel—who responded and then had tumor progression—25 mg/m2 of Jevtana treatment every 3 weeks confers additional survival. Both Jevtana and docetaxel are in the taxane class of chemotherapeutic drugs. The data from the Sanofi-Aventis clinical trial suggests that even though castration-resistant prostate cancer (CRPCA) may become docetaxel resistant, it is not necessarily taxane resistant. These data open up new questions about the pathway mechanism of action of taxanes in hormone resistant prostate cancer. Using the same logic that MDV3100 is a superior molecule than Casodex, researchers are now studying Jevtana as a molecule superior to docetaxel for disrupting microtubule dynamics in prostate cancer cells. Microtubules in prostate cancer cells seem to be integral in prostate cancer cell survival. Dr. Johann de Bono from The Royal Marsden Hospital presented new data on Jevtana that suggested a survival advantage for patients who were treated with Jevtana regardless of when docetaxel treatment was stopped. The New York Times captured the theme of that data: specifically that there is still evidence that research on more efficient (and likely more costly) chemotherapy may confer greater survival with acceptable side effects for certain sets of patients.
7. Xgeva (denosumab) – Amgen
Xgeva (denosumab) was FDA approved for prostate cancer in November 2010. The drug is superior to Zometa in delaying or preventing skeletal related events in patients with known bone metastases. PCF-funded researcher and professor, Matthew R. Smith, MD, PhD, director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center championed the clinical research. PCF invested more than $1.8 million in Dr. Smith and his team's critical research projects on denosumab and treatment sciences on improving survivorship. The more than $1.8 million in funding support for Dr. Smith and denosumab from the Prostate Cancer Foundation came from peer-reviewed, non-corporate academic grants starting in 1997. Denosumab prevents cancerous cells from recruiting normal cells to assist in adhering to bone and forming metastatic tumors. The treatment does this through the inhibition of RANK Ligand, a protein that activates signals that lead to the breakdown of bones in a bone metastasis of prostate cancer.
Denosumab treatment also increased the time it takes to first bone metastasis and the time it takes to develop asymptomatic bone metastases. "Denosumab provides a new therapeutic strategy that is complimentary to other forms of treatment for men with prostate cancer," said Dr. Smith at ASCO. "In addition to providing a potential new treatment option, the study results widen the perception of metastasis prevention as a much more attractive area for research and an effective path for new drug development."
Despite the FDA approval and significant implications of the drug in the field of research on RANK Ligand in the cancer microenvironment and metastasis prevention or delay, denosumab was controversial at ASCO 2011 with respect to both cost of treatment and degree of patient survival benefit.
8. Provenge (sipuleucel–T) – Dendreon
It was a quiet ASCO for any new data following FDA approval of Provenge, especially for those looking for data on how the treatment works at the cellular level of apoptosis; destruction of cancer.
Knowing more specifically how Provenge extends survival without causing remissions is one of the privotal new questions in prostate cancer oncology. Research is ongoing on how to vaccinate a patient and then sculpt and redirect the key cancer-killing immune cells to the metastatic site. However, Dr. Gomella from Thomas Jefferson University presented a provocative follow up of data on what happened to patients on the placebo arm of the positive phase III FDA approval trial. These "placebo arm" patients were treated with their own, autologous, cellular immunotherapy at the time of disease progression. Those patients who "crossed over," and then were treated with Provenge, had a median survival of 23.6 months compared with 12.7 months median survival in men on the placebo arm who, for various reasons, were not treated.
9. Novel Agent [except it is an "old drug for something else"]: Itraconazole
At ASCO, novel data was presented on the FDA-approved oral antifungal drug itraconazole in an exploratory clinical trial in men with advanced prostate cancer. Itraconazole is an "old drug" most commonly used to treat nail fungus and approved by the FDA in 1992.
Supported by PCF-funding, itraconazole was identified as a potential anti-prostate cancer drug after Hopkins scientists led by Drs. Michael Carducci and Emmanuel Antonarakis tested a library of more than 3,000 FDA-approved drugs for diseases other than prostate cancer for potential anti-prostate cancer use. Itraconazole scored an unequivocal "hit" as an unexpected anti-prostate cancer drug in a dish. Laboratory testing by Johns Hopkins University investigator Jun Liu, PhD, demonstrated that human prostate tumors implanted in mice regress impressively when treated with itraconazole at doses that can be achieved in humans. In that research, itraconazole appeared to inhibit angiogenesis (the development of blood supply) around the tumors—the only drug in its chemical and antifungal class to act that way. Even more intriguingly, the Hopkins group discovered that the antifungal inhibits a key cancer stem cell activating-pathway called Hedgehog. PubMed has at least 105 research papers on Hedgehog signaling pathway in prostate cancer biology, but itraconazole is the first agent to enter the clinic in Baltimore as a "first-in-field" anti-Hedgehog molecule to target this pathway.
Dr. Antonarakis and colleagues tracked prostate cancer progression-free survival over 24 weeks of daily treatment with oral itraconazole in patients with CRPCA. Evidence of worsening disease was measured by a 25% increase in their blood level of prostate specific antigen (PSA). Early in the trial, preliminary analysis of 17 men with CRPCA received lower doses of itraconazole and 2/17 had stable or declining PSA. However, 11 of 24 (48.4%) men taking high doses of itraconazole, 600mg/day, had stable or declining PSA levels lasting at least 24 weeks. In addition, nearly a third of men taking the high dose had PSA reductions of 30% or more. Itraconazole did not affect blood testosterone levels or DHEA (a testosterone precursor). Interestingly, 12/14 men taking high doses of itraconazole had lower levels of CTCs in their blood after therapy, compared with their baseline levels. Side effects included lowered potassium, hypertension and fluid retention, but were manageable in the outpatient setting.
Translational research will now continue to interrogate blood and skin samples taken from patients on the trial to assess levels of proteins linked to both tumor blood vessel formation and inhibition of the Hedgehog pathway. In addition to Dr. Antonarakis, other investigators within PCF's PCCTC participated in the study. High-dose itraconazole is now slated for clinical research in larger studies of men with CRPCA.
10. Novel Agent [First Lead to Treat ETS fusion+Castration-Resistant Prostate Cancer]: Oliparb
More than 50% of prostate cancers have ETS gene chromosomal fusions according to the University of Michigan "Rosetta Stone" of human prostate cancer clonotypes. ETS fusions are now viewed as "driving mutations." Such driving mutations have generated game-changing drugs in other cancers such as Gleevec for the BCR-ABL protein in chronic myelogenous leukemia, Herceptin for breast cancer, and most recently crizonitib for ALK fusion lung cancer. The Stewart Rahr-PCF Young Investigator, Dr. Felix Feng, and his mentor Dr. Arul Chinnaiyan, reported that ETS fusions in prostate cancer confer sensitivity of cancer cells to an experimental drug class being investigated in ovarian cancer and breast cancer therapeutics called PARP inhibitors. According to the NCI, six different PARP inhibitors are being developed in biotech and pharma. Thus, an extensive body of work in breast and ovarian therapeutics research now has implications for research on ETS-fusion positive prostate cancer patients therapeutics.
Conversely, research in ETS-fusion prostate cancer is likely to have applications to "DNA damage-repair therapeutics" for breast cancer and ovarian cancer. These are direct consequences of research on DNA fusions in prostate cancer at the University of Michigan. Dr. Feng and colleagues' findings also motivate the use of PARP1 inhibitors as radiosensitizers in clinical trials of patients with localized ETS fusion-positive prostate cancers getting radiation therapy. Furthermore, for patients with bone metastatic disease facing the near-term possibility of FDA approval of radium-223, the co-targeting of PARP, with PARP inhibitors combined with radium-223 therapeutics, has a very strong rationale
Three Important New Trends
1. Intermittent Androgen Deprivation Therapy for Prostate Cancer
The results of intermittent androgen treatment in a large phase III randomized, controlled trial were presented at ASCO in a way that can be thought to be "practice changing." The trial was run by the National Cancer Institute of Canada and Dr. Juanita Crook presented the data. The patient group tested were those men whose PSA recurs with no evidence of metastatic disease on scans—and after primary tumor treatment, either radiation therapy or radical prostatectomy. Eligible patients had a PSA of >3.0 ng/ml at more than 12 months following either surgery, radiation following surgery, or primary radiation therapy. The two arms of the randomized trial were equally balanced for multiple variables and 1,386 men participated. The median follow up for all patients was 6.9 years and the intermittent androgen treated patients received between 1-9 cycles of treatment with the median number being 2 cycles of hormonal therapy between periods of discontinuation. Median survival was 8.8 years for the intermittent patients and 9.1 years for the patients treated continuously. The median age of the treated men was 74.2 years. In quality of life measures, intermittent antiandrogen treated patients complained of fewer hot flashes and 35% of them had full recovery of serum testosterone; myocardial events and osteoporotic fracture events were equal basically in both arms.
Here are the five key take away points for patients and clinicians:
- Intermittent androgen suppression was given for eight months then stopped and restarted only when PSA reached >3 ng/ml when off the treatment, compared to men treated with continuous androgen deprivation (called CAD).
- Intermittent antiandrogen treatment was equivalent to continuous antiandrogen treatment with similar overall survival and quality of life measures.
- Biostatiscally, intermittent therapy was called "a non-inferior" arm of the trial [non-inferiority is admittedly a double negative but is the language of the ASCO clinical trialist realm].
- Intermittent androgen suppression offers "cost-saving" to health systems as both patients and the systems pay only 27% of the cost of CAD.
- ASCO 2011 endorsed the concept that IAD now be presented to patients at the time of "biochemical PSA recurrence" in the absence of metastatic disease on scans.
2. Use of PSA and Prostate Cancer Screening "Rationally" in a Health System
While the PSA test cannot be made "prostate cancer specific," and over diagnosis and cost of treating indolent, non-life-threatening prostate cancer is the dominant discussion in the press, interesting data from Sweden was presented by a Swedish-American research group led by Drs. Hans Lilja and Peter Scardino. The paper is comprehensive and provided below. The major question raised in the discussion at ASCO 2011 was: since the U.S. is not Sweden, are the results applicable here?
3. Circulating Tumor Cells "Version 1.0" Outperforms PSA for Predicting Treatment Benefit
PCF has funded research on several different biotechnologies and university teams to capture, measure and analyze Circulating Tumor Cells (CTCs) as progression biomarkers. The purpose of this emphasis in the PCF Research Enterprise is to provide to patients new "surrogacy measures" that are specific to prostate cancer disease activity. See "Evans Test for Prostate Cancer CTCs" at www.pcf.org. With "survival surrogacy" markers new experimental therapies can be evaluated for efficacy quickly and earlier in the disease course—when measuring overall patient survival alone might require years to a decade to get a convincing answer. For example, it took nearly a decade to get a rigorous answer of "non-inferiority" of treatment, with intermittent androgen suppression, versus continuous treatment.
As of ASCO 2011, CTCs are now the best platform so far ever seen for surrogacy of treatment and survival benefit. There are several "versions" of the CTC technology, and more being "pitched" to PCF by bioengineers. At ASCO 2011, the Veridex CellSearch system was used in the abiraterone phase III trial to show CTCs could be a predictive surrogate for patient benefit and survival with abiraterone. The Veridex CellSearch test is approved by the FDA for breast, colon and prostate cancer as being "analytically valid' (reproducible). A very simplistic cutoff for analysis was used: CTC levels >5 /7.5mls (unfavorable) versus CTC levels <5/7.5mls (unfavorable). For the first time, Dr. Howard Scher presented results of the correlation reducing CTC counts after treatment where an experimental treatment conferred an overall survival improvement. In 972 of 1,195 patients participating in the abiraterone phase III clinical trial called COU-AA-301 CTC, data was generated prospectively.
Here are the key findings:
- Baseline CTC count and LDH was prognostic for overall survival but PSA was not.
- Conversion rates from unfavorable to favorable CTC at all specified time points in the trial (4 weeks, 8 weeks, 12 weeks) were higher for abiraterone than placebo and were statistically significant at every time point.
One trial is insufficient evidence, and the current use of "below or above 5/7.5mls" is likely to be improved by better quantification technologies. Nevertheless, it is a big first. "Proof of concept" came at ASCO 2011 that the use of prostate cancer CTC counts can be used as a surrogate to predict "winners" for new drugs for patients. With activism from PCF and the "boost" from ASCO 2011, the sponsors of the following have already agreed to support CTC testing and analysis: MDV3100, dasatinib, ipilimumab, Jevtana and TAK-700.
ASCO is about more than just papers and tracking progress towards patients. PCF runs a very significant "knowledge exchange" of unpublished data. Expanding on that role this year, PCF's Chief Science Officer Howard Soule, PhD, met with 13 PCF-funded Young Investigators in addition to another 22+ recipients of PCF funding from 2000-2011. During the 5 days in Chicago, PCF had 16 meetings with leaders in the biotechnology and pharmaceutical fields. The LeFrak PCF-funded Young Investigator Himisha Beltran, MD, presented a paper on a new target in high Gleason grade prostate cancers and expressed a provocative drug target called Aurora Kinase. At least 30 PCF-funded investigators were there in the room taking notes on Aurora Kinase. Dr. Beltran shared: "the new relationships formed during this year's ASCO highlighted the shared enthusiasm amongst prostate cancer researchers as we make new and exciting advancements in the field. Listening to researchers as they share prominent new data is encouraging to one's own work."
Anyone in any oncology specialty who read or listened to ASCO papers left this year's ASCO understanding that advanced, metastatic prostate cancer patients can now be treated with targeted medicines against defined receptors and kinases?and survive longer. This should improve prostate cancer clinical trial participation for advanced prostate cancer patients. In that way, ASCO 2011 represented a watershed for biotech and pharmaceutical executives who will now be told by their business development analysts that effective drugs can be produced profitably for prostate cancer.
As reported in The New York Times: "Dr. Christopher J. Logothetis, of the MD Anderson Cancer Center, predicted further progress. It's beyond the individual drugs," he said. "One sees a manual now on how to go forward.'"
As satisfying as ASCO 2011 was, Dr. Michael Morris of Memorial Sloan-Kettering Cancer Center soberly pointed out to the full genitourinary oncology audience assembled that none of the recent FDA approved medicines by itself has conferred a 12 month survival improvement as a new single agent. Co-targeting and rational combinations of new agents will have to be accelerated. Furthermore, the prostate cancer treatment pipeline is still in danger with federal cancer research funding cutbacks looming at the very moment CTCs may be delivering a speedier and less expensive way to discover "winners" from "losers" in prostate cancer new-drug development.
There is much more for prostate cancer researchers to do and tantalizing new targets and questions. Many promising projects are currently unfunded, but PCF will work to fast forward as many of them as possible.
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text: You know what's really hot about a Japanese porn cartoon ? It's the fact that the babes aren't real. You might think that would mean reality pornstars are hotter, but in sex toons , the chicks are drawn in a way that makes them so sexy that no real woman can hold a candle to them. Their breasts are impossibly perfect regardless of the size and level of firmness, while their hair silkier than silk itself and their smiling faces warmer than the afternoon sun. Speaking of warmth, you'll get hot under the collar when you see how they're always willing able to take dozens of inches of cock deep down their throats. Not to mention how wide their pussy lips will spread in order to take a hardcore double vaginal penetration. If you think that makes for a wild threesome, wait until you see how some like to get fucked by tentacle monsters.

subset: commoncrawl


text:
The following countdown details start-or-sit scenarios for Week 8, factoring in competitions at quarterback, running back and wide receiver.
For the most part, the rushing and receiving conundrums were broken down with standard-scoring leagues in mind.
But as routinely stated on The Fantasy Blog, it's hard to make rational decisions about wideouts and tight ends without factoring in receiving targets.
Enjoy the show!
Fantasy Football: Jeremy Maclin Leads 'Start-or-Sit' Scenarios for Week 8
By Jay Clemons ,
In his last two games against the Falcons, Eagles WR Jeremy Maclin boasts absurd averages of 10 catches, 165 yards and two touchdowns.
The following countdown details start-or-sit scenarios for Week 8, factoring in competitions at quarterback, running back and wide receiver.
2012 Stats: 1,674 Yards Passing, 10 Total TD
Week 8 Opponent: Titans (Away)
Fantasy Reasons To Start
1. Through six games, Andrew Luck has either accounted for 280 yards passing or two touchdowns in every game.
2. Luck has thrown for 300 yards three times this season—twice at home, once on the road.
3. The Colts QB already has a great rapport with Reggie Wayne, an elite fantasy receiver in standard-scoring and points-per-reception leagues.
2012 Stats: 1,359 Yards Passing, 8 TD
Week 8 Opponent: Carolina (Home)
Fantasy Reasons To Bench
1. In standard-scoring leagues, Jay Cutler has a universal ranking outside the top 20 quarterbacks.
2. Cutler has eclipsed the 20-completion mark only twice in six games, with a pedestrian season high of 23 in Week 5.
3. To date, only Brandon Marshall and Matt Forte have been consistently good within the Bears' passing game.
4. Against Carolina last year, Cutler threw for only 102 yards (on nine completions).
2012 Stats: 574 Total Yards (434 Rushing), 3 TD
Week 8 Opponent: Jets (Away)
Fantasy Reasons To Start
1. Through six games, Reggie Bush has racked up 100 total yards and/or one touchdown three times.
2. In his only matchup against the Jets last year, Bush tallied 6.5 yards per touch.
3. The Jets have the NFL's No. 30 rush defense, yielding 147.4 yards per game.
4. I don't live in fear of New York getting 'revenge' on Bush for his thinly veiled what-goes-around-comes-around comments regarding Darrelle Revis' major injury (against Miami in Week 3).
5. Bush is easily the Dolphins' No. 1 playmaker, and he's due for another breakout performance.
2012 Stats: 553 Total Yards (408 Rushing), 2 TD
Week 8 Opponent: Vikings (Away)
Fantasy Reasons To Bench
1. In two road games, Doug Martin has blah averages of 70 total yards and 0.5 touchdowns.
2. The Vikings currently have the NFL's 11th-ranked run defense, allowing only 100.3 rush yards per game.
And Minnesota's status would be considerably higher if Robert Griffin III hadn't called his number on a game-breaking, 73-yard scoring run a few weeks ago.
2012 Stats: 20 Catches, 295 Yards, 3 TD
Week 8 Opponent: Falcons (Home)
Fantasy Reasons To Start
1. Despite being slowed by injuries for a good chunk of the season, Jeremy Maclin still has three outings of eight-plus targets. In the last two weeks, he's accrued 18 targets.
2. Maclin caught six balls for 130 yards and one touchdown against the Lions two weeks ago—the healthiest he had been since suffering a hip injury in September.
3. Here's a track record-based stat of Chris Johnson-against-Buffalo proportions: In his last two games against the Falcons, Maclin boasts absurd averages of 10 catches, 165 yards and two touchdowns!
2012 Stats: 28 Catches, 471 Yards
Week 8 Opponent: Bears (Away)
Fantasy Reasons To Bench
1. Steve Smith has yet to find the end zone this season. The six-game drought is his longest in two years.
2. Since Week 3, Smith has per-game averages of only 4.5 catches and 65 yards.
3. The Bears easily rank as the NFL's No. 1 defense. The unit registered five touchdowns in a three-game span (Weeks 3-5).
4. To demonstrate how far the Carolina offense has fallen, Smith caught eight balls for 181 yards against Chicago last year...but the chances of replicating that performance are nil.
2012 Stats: 14 Catches, 333 Yards, 4 TD
Week 8 Opponent: Chargers (Home)
Fantasy Reasons To Start
1. Josh Gordon has scored a touchdown in three straight games (four in that span).
2. Gordon has seen a significant targets uptick in recent weeks as well, collecting eight in Week 5 and 10 last Sunday.
3. Looking ahead, Gordon has a realistic shot at nine or 10 touchdowns by season's end.
4. The Chargers have the NFL's 26th-ranked pass defense, allowing 268 yards per game.
Going further, San Diego has surrendered averages of 330 yards passing and 33 team points in its last two games.
2012 Stats: 34 Catches, 368 Yards, 1 TD
Week 8 Opponent: Cardinals (Away)
Fantasy Reasons To Bench
1. In four of his last five games, Michael Crabtree has accounted for 40 or fewer receiving yards and zero scores.
2. Crabtree has yet to tally double-digit targets at any point this season (he had five last year, including the NFC playoffs).
3. The 49ers are a run-first operation, and when they pass, tight end Vernon Davis logs the most red-zone targets.
4. Arizona boasts the NFL's No. 4 pass defense (198 yards per game)—a remarkable stat, considering that Miami receiver Brian Hartline rolled for 253 catches and one TD against the Cards in Week 4.
2012 Stats: 25 Catches, 435 Yards, 2 TD
Week 8 Opponent: Dolphins (Home)
Fantasy Reasons To Start
1. Jeremy Kerley is just days removed from his coming-out party at receiver, catching seven balls for 120 yards against the Patriots. He also collected a personal-high 11 targets.
2. The Jets aren't blessed with great depth at receiver, meaning that Kerley and rookie Stephen Hill will likely be granted every chance to succeed (and occasionally fail) this season.
3. There is some trepidation here since Kerley has yet to catch five balls for back-to-back weeks. He has never racked up 70-plus receiving yards on consecutive weekends, either.
But that status will change on Sunday.
2012 Stats: 19 Catches, 240 Yards, 4 TD
Week 8 Opponent: Steelers (Away)
Fantasy Reasons To Bench
1. Santana Moss hasn't caught five balls at any point this season. Basically, if he doesn't find the end zone—like he did twice against the Giants last week—fantasy points are hard to come by. Especially in PPR leagues.
2. The Steelers have the NFL's second-best defense against the pass (only 185 yards per game).
3. Along those lines, Pittsburgh held Cincinnati's No. 1 receiver (A.J. Green) to one catch and eight yards last week.
2012 Stats: 1,752 Yards Passing, 10 TD
Week 8 Opponent: Redskins (Home)
Fantasy Reasons To Start
1. Through six games, Ben Roethlisberger has crossed the QB-elite threshold of 275 total yards and/or three touchdowns four times.
2. Roethlisberger has attempted 37-plus passes in all but one game this season.
3. Big Ben has three superb passing options (Mike Wallace, Antonio Brown, Heath Miller) at his regular disposal.
4. The Redskins have the NFL's worst pass defense, surrendering 328 yards per game.
2012 Stats: 1,592 Yards Passing, 8 Total TD
Week 8 Opponent: Patriots (Neutral Field—London)
Fantasy Reasons To Bench
1. Sam Bradford already has three passing games of fewer than 200 yards.
2. When playing away from the Edward Jones Dome in St. Louis, Bradford has middling per-game averages of 222 yards passing and 0.66 TDs.
3. Bradford has four outings of 18 or fewer completions this season.
4. Unofficially, the Rams have a bottom-five receiving corps. Very little consistency among the group.


text:
View this article in Icelandic | bilingual
I try to be
kind to the children
so they'll tend my grave
when the time comes
crumble biscuits in the grass
on my birthday
and recite the poem about
the gambolling cows
themselves grown old and grey
All the same I will
know them again
by the heavenly smell of the stable
may they always be fragrant as the Jesus child
Translation of "Skagafjörður." © Gerdur Kristný. By arrangement with the author. Translation copyright 2011 by Victoria Cribb. All rights reserved.
This copy is for your personal, noncommercial use only. You can order presentation-ready copies for distribution by contacting us at email@example.com.


text:
Men's Tennis Splits a Pair of Matches in Ohio
April 2, 2012
Duquesne's men's team faced its last two Atlantic 10 opponents of the season before the Atlantic 10 Championship and came home with a split among the two Ohio schools.
The Dukes defeated Dayton, 5-2 on March 31 and fell to Xavier, 4-3 on April 1.
Pete Carpenter won both of his matches at number two singles and Alex Aleman went 2-0 at fifth singles. The duo also teamed up to win both of their doubles matches at number two. Rich Robbie also won both of his singles matches and went 1-1 at second doubles.
"Against Dayton, I feel like we improved upon several things that we had not been doing well the past few weeks," head coach Rob Castille said. "Dayton is much improved so we know we needed to play well to beat them and I am happy we were able to come away with the win."
"Xavier is always tough and we knew going in we would have to compete really well to beat them," Castille continued. "It's disappointing to come up just short but I think we can take a lot of positives away from this and apply them in our next match and in the A10 tournament."
The Dukes wrap up the regular season on April 6 at Niagara.


text:
This event occurs monthly, on day 1 of every 1 month(s).
Join us for a Sunday Soiree with Bob & Dave, on Sunday May 19, 2013 and Sunday June 9, 2013 from 3:00pm-5:00pm. Everyone is welcome!
Bob and Dave joined musical forces back in 2008 after playing together occasionally for a few years. Bob's musical background spans 40 years of playing a wide variety of both acoustic and electric guitar styles and singing both lead and harmony for a number of New Jersey based bands. Dave has been playing the fiddle for the past 40 years, mandolin for about 15 years, and sings lead vocals.
Both Bob and Dave have played in a variety of different band ensembles over the years playing everything from Acoustic Rock, Bluegrass, Swing, Standards, Country, Western Swing, Bossa Nova, from the 1930's to the present day. Their sweet spot is music from the era they grew up in, especially well known standards from the 50's, 60's and 70's. They've developed their own style employing unique arrangements and a personal touch to each song.
The music they play appeals to a wide range of ages and musical preferences, orchestrated with Bob on Guitar, Dave on Fiddle and Mandolin, complete with lead vocals and harmonies. Their music is enjoyed at area festivals, events, nursing homes and private parties. Bob and Dave both of Fairfield will also be playing at the 2013 Fairfield Dogwood Festival and the 2013 Fairfield Half Marathon.
Visit us @ www.facebook.com/FairfieldUBookstore
Fairfield University Bookstore
203-255-7756Ext. 501
Nancy L Quinn
We make every effort to ensure the accuracy of this information. However, you should always call ahead to confirm dates, times, location, and other information.


text:
This event has expired. This may be a recurring event, so please check the calendar in the future for updated occurrences.
Milwaukee Chamber Theatre presents "Art"
Set in present day Paris, 'ART' begins as Serge buys an extremely expensive painting – which is rather minimalist in style. He never suspects how much the purchase will strain his friendship with Marc and Yvan - testing their relationship to the max! Reza's comedy raises intriguing questions about art and friendship.


text:
Each month, direct to your email inbox, we'll send the best camping news, tips, recipes and more, to enhance the camping lifestyle that you love so much. Learn More
"The greatest meeting of land and water," a coastal California dream trip p...
Delicious homemade pizza meets camping in this easy grilling recipe.
Learn tips for proper RV lubrication in our latest RV maintenance video.
Plan the perfect trip from home or on the road with the official KOA app. Learn More
Open May 15 - October 15
Reserve: 800-562-7452
Info: 902-674-2145
3779 New Harris Road
New Harris, NS B1X 1T1 CanadaGet Directions
Located on south side of Trans-Canada Hwy 105: West side of Seal Island Bridge, at base of Kelly's Mountain. 35 km (22 miles) east of Baddeck, 29 km (18 miles) west of North Sydney. On Trans-Canada Hwy (turn is "between" Exits 12 & 13).Get Google Directions
All Sites
Check-out: 11:00 am
Camper Rating 4.5 out of 5


text:
In article
julien a
:After 2 hours using my "well new ;-)" SGI Indy, I done my first big mistake,
:and what a mistake ...
:I changed the refresh rate of the screen to a lower one but ... unsupported
:by my screen.
:I'm running IRIX 6.5 . Do someone know a solution to boot it in a "rescue"
:graphic mode, like the "VGA mode" under Windows NT on PeeCee ??
Connect a PC with terminal emulator program and "null modem cable"
to serial port #1 on the Indy. Use a Mac modem cable to plug in to the
Indy. Connect at 9600 bps. Power cycle and you should see some text
on the screen. When it says it is starting up, press escape. That will
give you a menu with 5 or 6 items. choose 5 to go into the prom.
Type the command single there and wait for it to boot into single
user mode. The command you have to use from there is setmon
with the -x option; look at the setmon man page via techpubs.sgi.com
to see what parameters to use.
Will you ask your master if he wants to join my court at Camelot?!


text:
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Oaklawn Park boosts purses for sixth consecutive year
Oaklawn Park in Hot Springs, Ark., announced purse increases for a number of key overnight categories for its 57-date meet that opens Jan. 10. The increases are being made for a sixth consecutive year at the track, which offers electronic gaming. Oaklawn previously announced a stakes schedule featuring 31 races worth a track-record $6.1 million.
Oaklawn will open its meet with maiden special weight races worth $55,000, up from $53,000 during the meet that closed in April. The track's allowance races will start at $56,000, compared with $54,000 at the most recent meet. All other overnight races will get a boost of at least $1,000 from their starting level in 2013.
Oaklawn also announced that the minimum purse for the meet has been increased from $15,500 to $17,000.
"It's exciting to be part of a racing program that continually bucks the national trend and gets better and better each year," David Longinotti, director of racing for Oaklawn, said in a release.
Longinotti and Pat Pope, the racing secretary at Oaklawn, will begin recruiting stables from around the country in the near future. They plan to make trips to California, Illinois, Kentucky, Louisiana, New Jersey, New York, and Oklahoma.
Oaklawn is quickly becoming one of the best betting opportunities in the winter
I would like to see Oaklawn re-do it a bit so more money goes to route races as opposed to sprints, perhaps with maiden specials for instance being $52,000 going short and $57,000 going long and N1x allowance events being $55,000 going short and $60,000 going long.
Very nice....for the management of Oaklawn risen purses up again, now how about an increase for the workers of Oaklawn, like the security guards,in charge of the stable area,keeping an eye on the barns and the horses and making sure that only authorized people come through the stable gate.
I wonder how these recruiting trips to the other states are received by the respective racing secretaries? They cannot have open arms for this?
turf track would boost business to the moon
This comment has been deleted


text:
The Ohio High School Athletic Association
2013 OHSAA Foundation Student
Leadership Conference
Home |
School Resources |
Eligibility |
Sports |
News |
Contact Us
OHSAA Foundation Student Leadership
Conference Information
and Location
The one day conference will be held at the Ohio Union on the campus
of The Ohio State University on Tuesday, October 1, 2013.
Member schools are encouraged to send student athletes that have
demonstrated or have potential for leadership roles in your school. Each
school group must be accompanied by at least one adult supervisor. The
first 900 applicants will be accepted free of charge for this yearís
conference. Student-athletes in grades 9 through 12 for the 2013 fall
semester are eligible to register.
Conference Activities
The conference will include several national keynote speakers. In
addition, five sessions will be provided for student-athletes. Over six
different topics will be presented and among these topics are: ìThe Role
of the Student Athlete,î Bullying and Hazing,î Developing Team
Captains,î ìHealthy Lifestylesî and ìSportsmanship.î All of the speakers
are invited to join the after lunch open panel discussion with questions
and answers form the participants. Information will be given to all
students on the OHSAA project ìCommunity Service and Your School.î
We will be filming an OHSAA video during the sessions of the
conference. We encourage participating schools to bring their school
colors (banners, jackets, etc.) for the video. This will be a fun way to
get the day started and we will post it on the OHSAA Student Leadership
Conference web page!
Schools may register an unlimited number of student-athletes. Up to
two adult supervisors may accompany the student athletes if four or more
students are attending.
We are revising the way schools will register this year. On August 15,
2013, schools will be able to register their student athletes and adults
for the conference. A link to the Student Leadership Conference will
appear on your school tab on the www.ohsaa.org by August 15, 2013. All
participants must register for the conference by Friday September 6,
8:00 ñ 8:30 am Registration Check-in and
Name Badges
8:30 ñ 9:00am Welcome ñ Opening Session
9:00 ñ 9:30am General Session Speaker
Harvey Alston
9:30 ñ 10:00 am General Session ñ Speaker ñThe
Role of the Student Athlete
10:00 ñ 10:30 am General Session ñ Speaker ñ Bullying
and Hazing
10:30 ñ 11:00 am General Session ñ Speaker ñ Role of
Team Captains
11:00 ñ 11:30 am General Session ñ Speaker ñ Healthy
11:30 ñ 12:00 General Session
ñ Speaker ñ Sportsmanship
12:45 ñ 1:15 pm Panel Discussion with all
1:15 ñ 1:30 pm Community Service Projects
1:30 ñ 2:00 pm Closing Session
* Lunch will be provided at the Ohio Union from 12:00 pm ñ 12:45 pm


text:
Carlisle Apartment Building Fire Ruled Accidental
No One Hurt In West High Street Blaze
UPDATED 3:30 AM EDT Mar 27, 2012
A fire damaged an apartment building in Carlisle, Cumberland County, late Monday night.
The fire was discovered shortly before midnight in the first block of West High Street.
A business is located on the first floor and apartments are on the second floor.
A state police fire marshal ruled the blaze, which was an electrical fire in the second-floor ceiling, accidental.
No one was hurt.
Copyright 2012 by WGAL.com. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


text:
A two-year-old boy was hit by a vehicle in southwest Oklahoma City, police said.
The incident happened Monday afternoon after 3 p.m. in the 500 block of Southwest 44th Street.
KOCO's Morgan Chesky is reporting that the boy suffered some scrapes and bruises and was taken to a local hospital as a precaution.
Stay with KOCO.com for live, local, latebreaking news.


text:
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Strong champion.
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Your post gets more ridiculous as it goes!
the only reason a "wing chun" master doesn't take off cain velasquez or alistair overeem and win the MMA HW belt is because he's too dangerous and would break his bones!
nothing to do with the fact that cain velasquez is an actual fighter who would rip his head off or anything
or that the reem would literally rape him
if you really need it i'll get some footage of "Karate masters" fighting
there is some on youtube
it exists
one example shows a rudimentary practitioner of BJJ cracking an arm in half
they flail away like old men
they clearly never spar in the gym
it's considered wrong for a master to spar his pupils, anyway
boxers spar tens, sometimes even a hundred or more rounds to prepare for each fight at the top
the guys at the top often have tens if not hundreds of AM fights
some guys have 300, 400 am fights
thats a fighter
if you want to fight with your "martial arts"
or they fight MMA
in which case they get rid of ALL of the karate that they have learned
and adopt ACTAUL combat martial arts
based on combat
and not aesthetic movements
Last edited by New England; 05-17-2011 at 04:34 PM.
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I've been punched in the larynx and it's awful. Hurts for weeks.
I'd much rather take one on the temple or square on the chin, tbh.
The only worse places to get hit IMO would be the family jewels and the liver.
Last edited by IntentionalButt; 05-17-2011 at 04:23 PM.
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I dont know why more fighters dont aim for the throat. If i was fighting someone like Wlad/Vitali who are tall I would aim all my jabs and punches to the throat and the chest area. Too many people trying to go for the head get punished and they have to aim up, just punch as your normally would forward so it hits the throat/high chest area. Would this not work in theory?
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if you could hit the throat, you would be doing a lot of damage
i dont think anybody is not aiming for the throat if they are aiming for the chin
check out an exchange in slow motion from a close angle where somebody is landing (usually the kind of stuff you see between rounds of a pacquiao fight work :-D )
the way most fighters hold their shoulders and more importantly the chin doesn't allow for clean angles at the throat
you see lesser quality fighters missing targets in four round undercards and hitting the shoulder and neck sometimes
if somebody is dumb enough to keep his throat exposed his opponent is likely to take advantage and end the fight quickly by hitting him on his chin which will be open by default
it would be wiser to try and damage the chin with clean punches rather than the throat or neck, especially with a gloved hand
and thus you don't see people targeting it habitually
you aim for the chin if it is available
or other parts of the head if they are open and you can actually take advantage (punching around a guard intelligently is something only top fighters can do, again, you can think pacquiao against clottey, margarito)
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what's wrong with my question? i was just curious; I mean because it is such a vulnerable area and certainly in a boxing match it has to have occurred before. no reason to attack for just asking a random question out of curiosity.
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Seriously, this happens all the time...maybe not direct obvious hits that are shown on replay, but I'd say it's definitely not uncommon in bouts that are high paced, esp in boxing.
a recent one i can remember that was pretty obvious and shown on replay was JMM/Katsidis
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Wilfredo Gómez suffered permanent damage in the throath when he was Owned by Azumah Nelson.
Even today he can´t talk well.
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In one of HBO's slow motion replays, JMM uppercuts Katsidis in the throat.
Skip to 3:59
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|EcommerceBytes-NewsFlash, Number 2575 - June 29, 2011 - ISSN 1539-5065 3 of 3
Google is launching the Google+ project, a social networking initiative that is currently by invitation only. In its announcement about the project, Google identified problems with current social networking sites - online we hear from everyone all the time; every online conversation (with over 100 friends) is a public performance; and, we lose the nuance between "friend" and "family."
The Google Plus project will use Plus Circles (+Circles), explaining:
"Google+ Circles helps you organize everyone according to your real-life social connections - say, "family," "work friends," "music buddies," and "alumni". Then, you can share relevant content with the right people, and follow content posted by people you find interesting. For example, you might post an announcement about your engagement and show it only to people in your friends and family circles, or maybe you see a post from the circle you created for your book club that there's a recent article on your favorite author."
Google then built features around the Circles, including an online sharing engine called Sparks - "simply add your interests, and you'll always have something to watch, read and share - with just the right circle of friends."
Other features include Plus Hangouts,Plus Mobile, Plus Huddle ("a group messaging experience that lets everyone inside the circle know what's going on, right this second"), and Instant Upload.
You can learn more about the Google+ project on this page.
About the author:
Ina Steiner is co-founder and Editor of EcommerceBytes and has been reporting on ecommerce since 1999. She's a widely cited authority on marketplace selling and is author of "Turn eBay Data Into Dollars" (McGraw-Hill 2006). Her blog was featured in the book, "Blogging Heroes" (Wiley 2008). Follow her on Twitter at @ecommercebytes and send news tips to firstname.lastname@example.com.
You may quote up to 50 words of any article on the condition that you attribute the article to
EcommerceBytes.com and either link to the original article or to www.EcommerceBytes.com.
All other use is prohibited.
Email this story to a friend.
3 of 3
Online Merchants Should Check Google Product Data Feeds - October 27, 2011
Facing Challenge from Facebook, Google to Focus on G-Plus - October 19, 2011
Webinar Offers Retailers Info on Google Product Search - October 14, 2011
Google Adds Visual Shopping Technology to Product Search - September 23, 2011


text:
Published (in a shorter version) in The Globe and Mail, February 5, 2004, p. A-21.
Now It Seems We Need a Passport Inside Canada
Pierre Lemieux
Canadians have recently become accustomed to produce "government-issued photo ID" before boarding domestic flights. But contrary to what most people think, this requirement is not mandated by any law or regulation. I know because I refused to show any government ID and was able to board three Air Canada flights over a two day period – after short discussions with dumb-founded airline personnel.
I complained to Robert Milton, Air Canada's CEO, who replied: "The requirement for individuals to produce 'government-issued personal photo identification' for all flights departing from airports in Canada is set out in a Security Measures Order issued by the Minister of Transport. Disclosure of the order is prohibited by subsection 4.8(1) of the Aeronautics Act."
I filed an Access to Information request about the "secret order." A Transport Canada official wrote to me that "security measures require that domestic travelers present travel documents, i.e., a ticket and boarding pass upon check-in. These security measures do not require passengers to provide government-issued photo identification for domestic flights in Canada." I was not able to get a copy of the secret regulation; indeed, it appears that even a MP cannot see it.
Confronted with the evidence, Mr. Milton's changed his story. "I can confirm," he wrote in a second e-mail, "that the now since amended security measures did indeed contain provisions which required airlines to request the production of government issued identification for domestic flights. Air Canada has chosen to maintain that requirement in order to ensure the safety and security of our customers which Air Canada is entitled to do under its tariffs in order to establish 'positive identification'. … Adult customers refusing to provide such identification may be denied boarding."
Do we get this right? Air Canada had never realized that requesting government-issued ID was necessary for its passengers' safety until they got a secret order from Big Brother himself. Then, they saw the light. The light was so brilliant that, even after Big Brother secretly rescinded the secret ID requirement on domestic flights, they second-guessed him. Yet, they continue to hide behind the pre-secret-amendment secret order and require ID papers in a country where they legally don't exist.
Virtually all Canadian airlines do the same. The only exception is WestJet which accepts "personal identification in the form of photo or non-photo id," including credit cards and ATM cards.
Since 9/11, official ID is required to board domestic flights in most countries. Among the major countries, we could only find the U.K. where this is not the case, although some British airports now insist on ID. It is only in the U.S. that an official legal requirement exist. Since the mid 90s, American regulations require passengers to show government-issued photo ID, but the requirement is not absolute: if a passenger does not provide such ID, he will be interrogated by security personnel and may be allowed to board his flight.
According to a Library of Parliament report dated December 22, 2003, the 1985 Aeronautics Act provided the legal basis for the 2000 Canadian Aviation Security Regulations which authorized the Minister of Transport to issue the secret Air Carrier Security Measures Order. It is not clear when exactly the order was issued. One airline spokesman claimed that it is only in May 2003 that the order was amended to force passengers to show "government-issued ID" on domestic flights, and that this requirement was revoked in July or August.
Since we are dealing with a secret order, the disclosure of which is punishable by one year in jail, this is as much as I was able to find. It is easy to understand why the rule of law, when it prevailed, required laws and regulations to be public.
Columnist George Jonas recently dealt the final blow to the security argument. Airline personnel are not trained to distinguish false ID, and concentrating on ID papers diverts attention from what could be real signs of danger. I would add that it is only worth fighting the "war on terror" if the goal is to protect our traditional liberties. The absence of ID papers is very much part of them.
Why are Canadian airlines requiring government ID on domestic flights? One argument is that it prevents trading tickets, and scalping. The secretly amended secret order has given them the opportunity to enforce a self-interested requirement that was otherwise unenforceable. The problem with this argument is that it is not clear, from an economic point of view, why it would be in a carrier's interest to do this: boosting the flights' occupancy rate would seem to be the paramount consideration.
Another, probably more fruitful, hypothesis is that the airlines are so heavily regulated that they are not private companies in any meaningful sense. They depend more on the state than on their customers, are very inefficient, and are used to passing the buck to the state. This would also explain why old Air Canada is more inflexible than young Westjet.
To the extent that airlines are private companies, it is difficult to argue against their right to ask whatever contractual terms they want, including official ID papers. But this justifies the traditional Canadian opposition: once government has issued any photo ID, it is too tempting for private parties to take advantage of it, thereby making it more and more indispensable.
Indeed, Québec law forbids requesting the driver's licence or the medicare card, except for the purposes for which such ID documents were created. Private firms and government bureaucracies circumvent the well-intentioned law by saying that they don't "request" any specifically forbidden ID document, and that any government-issued photo ID will do. However, a spokesman for the Commission d'accčs ŕ l'information confirms that it may be illegal to put a person in a position where he must provide either his driver's licence or his medicare card.
Therefore, airlines operating in Québec are probably violating Québec law, except to the extent that the Canadian passport provides a third alternative. But this would mean that the Canadian passport has become an interior passport.
There was a time when passports were even not even required to travel internationally, at least in the civilized world. Reflecting on the pre-World War I period, British economist Lord Maynard Keynes wrote, "The inhabitant of London … could secure forthwith, if he wished, cheap and comfortable means of transit to any country or climate without passport or other formality." For the benefit of a citizen traveling to uncivilized countries, his own state would issue a passport that was a warning to foreign tyrants not to mess with him.
Now, we need an interior passport to travel in our own country. "I swear," said a friend and former cop who works in the federal Parliament, "we're getting more like the Soviet Union every year."
Jayant Bhandari contributed to this article.


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Madworld will probably get GOTY. No More Heroes 2 comes out this year right? If so it'll be close between the two.
I don't even like golf but this game makes me want to play golf. Madworld is too short to be Game of the Year and COD6 will probably be just more maps and weapons. Conduit or Killzone 2, maybe but getting tired of FPS. I'm sure this game will probably be around 9.0-9.5 from most reviewers. Not perfect because of the Wii's graphics but who cares. WiiMotionPlus is going to make everything better except maybe fighting games. I believe that it is the future of console gaming. Analog sticks will be ancient in a few years like joysticks.
Madworld will probably get GOTY. No More Heroes 2 comes out this year right? If so it'll be close between the two.
Lets get a few months into the year before saying "ZOMG GAME OF THE YEAR"
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Corrections officer booked into jail
Jeffrey Miller accused of providing impression of key
UPDATED 9:44 PM EDT Jul 31, 2013
A corrections officer was charged Wednesday with trying to help a jail inmate escape.
Authorities said Cpl. Jeffrey Miller, who worked at the Tyger River Correctional Institution, was booked into the Spartanburg County Sheriff's Office Detention Center.
Investigators said Miller helped an inmate by providing a plastic foam impression of keys that could have been used to escape.
Officials said no one escaped and jail security was not compromised. The locks and keys were changed.
Miller resigned on July 28 during the investigation. He had been on the job for less than a year and was still on mandatory probation.
Copyright 2013 by WYFF All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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STATEN ISLAND, N.Y. -- An sport utility vehicle overturned on Four Corners Road near Flagg Place in Dongan Hills during the morning rush hour on Wednesday.
The accident was reported at 6:52 a.m. near 25 Four Corners Road. A person in the car suffered a minor injury and was transported in stable condition to Staten Island University Hospital in Ocean Breeze, according to Fire Press.


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Comprehensive DescriptionRead full entry
BiologyFound in streams, rivers, and estuaries. Ovoviviparous (Ref. 205). The male carries the eggs in a brood pouch which is found under the tail (Ref. 205). Males may be brooding at 11.25 cm SL.
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The Killers Documentary From 'Jack Reacher' Villain- Werner Herzog
The eyes of a genius or a mad man? Werner Herzog will bring a terrifying chill to movie screens this December as 'The Zec' in the upcoming action crime drama, 'Jack Reacher.' As we discussed in a previous post, Werner is a modern day Renassiance man when it comes to the arts; actor, writer, producer. But his most respected role is as an Academy Award nominated documentary filmmaker. The Killers: Brandon Flowers, Mark…
September 19, 2012
Jack Reacher's Other Man of Menace: Werner Herzog, The Villain…
…evil counterpart to Reacher's man of rough justice, will impact the screen with his own brand of bad. And bringing him to life. will be none other than the highly respected German director/actor and jack-of-all-trades, Werner Herzog. Herzog may be unfamiliar to many of you. His widest acclaim comes as a writer and director of films and documentaries, but he also directs opera and theatre, writes books, runs the Rogue Film School, which according…
July 19, 2012
2nd Official 'Jack Reacher' Movie Trailer Serves Up Justice
…acher the Army sniper could have been the victim of a setup, Reacher sets out to confirm for himself the absolute certainty of the man's guilt, but comes up with more than he bargained for. Read our previous blog about Werner Herzog. Almost as exciting as seeing Tom completely transform into the intense, truth seeking vigilant is the first time we're being shown Werner Herzog in all of his villainous glory! Scott Collura of IGN, said…
October 17, 2012
The FIRST 'Jack Reacher' Movie Poster Is Launched Internationally!
…ion packed crime drama is scheduled to open in the U.S. December 21, 2012. It's written and directed by Christopher McQuarrie, adapted from Lee Child's novel, 'One Shot,' and co-starring Robert Duval, Werner Herzog, Rosamund Pike and of course, Alexander Rhodes as the suspicious onlooker. And in Russian… In the meantime, check out Tom's fearless fighting as the mysterious 'Jack Reacher' in the of…
October 4, 2012
…serious vigilante justice as the ex-Army major, 'Jack Reacher.' We also have the two latest 'Jack Reacher' TV spots that will put any action-lover in the mood for Tom's new thriller, co-starring Werner Herzog, Robert Duvall and Rosamund Pike. Check 'em out by clicking here. Join the 'Jack Reacher' Online Community at These Official Sites: Join the Jack Reacher online fan community at these official…
November 21, 2012
Aspiring Filmmakers Take Heart: Passion for Directing & Screenwriting Can Lead To The Top
…ly diverse global filmmakers who compete for prizes ranging from $15,000 in cash and exposure through distribution or airing films on television. Some of the panel of judges at Filmaka include Academy Award-nominated director Werner Herzog, directors Neil LaBute, Wim Wenders and Paul Schrader, along with Academy Award nominated actor Colin Firth. Founded by Oscar-winning director and noted auteur Francis Ford Copolla, American Zoetrope has been…
August 17, 2010
UPDATE: Watch The Google CHAT With 'Jack Reacher' Author Lee Child
…serious vigilante justice as the ex-Army major, 'Jack Reacher.' We also have the two latest 'Jack Reacher' TV spots that will put any action-lover in the mood for Tom's new thriller, co-starring Werner Herzog, Robert Duvall and Rosamund Pike. Check 'em out by clicking here. Join the Jack Reacher online fan community at these official sites: 'Jack Reacher' Website: http://www.JackReacherMovie.com &…
November 28, 2012
'Jack Reacher' UK Red Carpet Premiere LIVE!
WELCOME TO THE TOMCRUISE.COM TEAM LIVE COVERAGE OF THE 'JACK REACHER' UK PREMIERE! TeamTC will be on the 'Jack Reacher' UK red carpet TODAY, Dec 10th w/LIVE coverage of the premiere at 4pm GMT, 8am PT, 11am ET!!! Follow #JackReacherUK on Twitter and check back regularly for live info, pic and video updates of all the excitement and stars including, exclusive video of Tom answering YOUR questions about 'Jack Reacher&…
December 10, 2012


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Here's a time lapse of the News 9 crew setting up the Granite State Debates set for debates Oct. 29, Oct. 30 and Nov. 1.
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text by Brian Moynahan
In this photographic history of Russia's 20th century, Brian Moynahan, a historian and former European editor of the London Sunday Times, tells us that under Communism even the elements could be a state secret: No weather reports were published in Soviet newspapers until the late 1970s. So it goes without saying that photographs, with all of their potential for contradicting the official version of things, were under strict party control.
And when the walls of the old system finally crumbled in the early 1990s, hundreds of pictures came tumbling out like escaped prisoners. Photo researchers Annabel Merullo and Sarah Jackson, who gathered the images for this book, drew much of their material from Soviet archives and photo' collections that had never been opened before to Russians, much less to Westerners.
The photographs, all of them black-and-white, give Russian history, already a story of endless turmoil, an even deeper dimension of bleakness, whether it's in scenes of starvation during the revolution to black-market thuggery in Boris Yeltsin's post-Communist Moscow. Moynahan's accompanying history paints a too rosy picture of Russian life before the revolution and takes a tabloid pleasure in emphasizing brutalities like those during the civil war that followed the Bolshevik takeover, when agents of the Cheka, a precursor of the KGB, rolled their anti-Soviet victims in nail-encrusted barrels.
The photographs, too, are prone to zoom in on the frozen corpse or the hanged man, while in other places humdrum group shots of party officials are hyped with purplish prose captions. It's unnecessary. This book's most unnerving vision of Russia is its least melodramatic: a serene-looking Stalin crosses a street with ordinary Russians, his white tunic gleaming—the monster at ease among his victims. (Random House, $45)
Picks and Pans Review: The Russian Century
updated 01/09/1995 AT 01:00 AM EST
•originally published 01/09/1995 AT 01:00 AM EST


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First of all, how is the game? what kinda stuff can you do and are there any objectives?
Online mode, how does it all work? Is it good? How do you communicate in online modes?
Wii Sports, Red Steel (27%), Zelda : Twilight Princess (Forest Temple), Resident Evil 4 : Wii Edition (3-1), Trauma Center : Second Opinion (Ch2 1), Super Paper Mario (Ch 3-1), Mario Strikers Charged Football, MoH Heroes 2


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Jerome Velez: Probation violation.
Yerwinson Arvelo-Arias: Resisting arrest without violence.
Ivonne Aleman: Battery.
Cory Mindock: Marijuana possession.
Richard Anicola: Sexual battery by a 24-year-old on a 16/17-year-old.
Jose Aguilar: DUI.
Carlos Alfaro-Lemus: Grand theft.
Marvin Alvarez: Battery.
Tory Johnson: Driving with a suspended license.
Heath Barton: Marijuana possession.
Rosemarie Bowie: Resisting arrest.
Jeffrey Chin: Resisting arrest.
Jose Deleon: Driving with a suspended license.
Donald Camp: Petit theft.
Keith Eaton: Driving with a suspended license.
Roberto Gonzalez-Broche: Failure to obey law enforcement.
Steven Frese-Maldonado: Resisting arrest.
Sarah Goodwin: Out of county warrant.
Justin Hazley: Failure to appear.
Ava Jones: Probation violation.
Yashira Ortiz-Hernandez: Operating a motor vehicle without a license.
Jose Melendez: Wrongfully obtaining property.
Hector Marcano-Olmedo: Driving with a suspended license.
Kenny Sinanan: Marijuana possession.
Kristopher Mora: Battery.
Lord Mercado: Battery.
Matthew Montgomery: Battery.
Luis Paulino: Battery.
Angel Saniago: Probation violation.
Robert Payne: Out of county warrant.
Tahnee Rolles: DUI.
Miguel Resto: Order of transport.
Leeroy Sheppard: Battery.
Chad Stadler: Probation violation.
Fernando Torres: Out of county warrant.
Carl Thomas: Non-support.
Rex Thomas: Battery.
Guillermo Torres-Colon: DUI and battery.
Cadina Williams: Probation violation.
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by Mike Bleech
photos-Mike Bleech
One minute the broad Allegheny Reservoir valley
was visible from Kinzua Creek to well beyond the New York border. The next minute a storm rolled over the hills from the
west and wind-driven snow obliterated my closest tip-ups. I turned my back to the wind, hunkering down on a plastic
bucket, pulled the draw cord tight in the coyote ruff hood of my goose down parka, and waited it out. If I have learned
anything from many years of ice fishing at the Allegheny Reservoir--more commonly called Kinzua--it is to dress
properly. Cold blasts from the northwest are the rule, not the exception.
When the snow and wind passed, all of my tip-up flags were up. I assumed all had been tripped by the wind. I had been there since early morning without a bit of fish action. Indeed, the first two tip-ups I checked were untouched. But at the third, I found slack line, a lot of slack line, and when I came to the end of the slack line there was movement. Something was swimming with my bait in its mouth.
I was patient. The fish was moving toward me. You have to be patient in midwinter. Fish are typically tentative. I waited until the fish started moving away. Then I set the hook. The fish did not seem like anything special at first. It obviously had some weight, but it came toward the hole without a lot of fuss. I peered through the hole, waiting to grab the fish when its head broke water.
The instant the fish became visible, I knew I would never catch it. It was far too big to be pulled through the seven-inch hole. Instead of the walleye I was attempting to catch, it was a musky. I will not make any estimate of its size because I never saw more than a small portion of it while it made that one brief visit to the hole. It just glided by, and then it was gone. There was no struggle. It just took all of my line. Then, fortunately for its sake, it cut the line close to the hook.
Just about everyone who regularly ice fishes Kinzua has a story like that. Walleye numbers have slowly improved during the past several years to the point at which ice anglers often catch limits. Perch have returned. But panfish are not the mainstay here as they are at most ice fishing lakes. Big fish get folks excited herebig trout, big muskies, big pike and big walleyes.
One such fish was the 12-pound, 33-inch walleye Mark Papalia pulled through the ice last winter, during the last weekend of January. It struck a shiner on a tip-up set in about 12 feet of water in the lower main arm.
Mark Papalia hauled this 12-pound walleye through the ice late last January. A catch like this is what lures ice anglers to Kinzua.
Kinzua has a history of giving up huge walleyes since the mid-1970s. Most of the largest were caught through the ice. These fish were sometimes the largest walleyes caught in Pennsylvania each year. In 1976, a 13-pound, 12-ounce walleye caught from the Kinzua Arm was the largest.
The state record was approached several times. It was finally broken in 1979 by a 16-pound, 12-ounce, 34 1/4-inch walleye. The following year, Mike Holly, of Bradford, pulled the current record, 17 pounds, 9 ounces, 36 1/2 inches, through Kinzua ice.
A walleye just two ounces shy of the record was caught in 1991 through the ice in the Kinzua Arm. The New York state record walleye, 16 pounds, 7 ounces, was also caught at Kinzua in 1994. However, this fish was not caught through the ice.
If you want a tip-up spread that is ready for any Kinzua big fish, run your tip-ups in a line, or a J shape, out from shore to a depth of no more than 30 feet.
Kinzua also produced the current state record northern pike. It was not caught through the ice, yet ice fishing for pike is excellent. Some groups have been placing Christmas trees in the lake, so pike fishing has improved considerably.
Last winter, two age classes comprised most of the northern pike catch. One group was about keeper size, 24 inches. The other included fish of 32 to 36 inches. Of course, they will be larger still this winter. The potential for catching a trophy pike through the ice has probably never been better.
Trout, mostly browns, are a regular part of the ice fishing catch, though they are not caught as frequently as walleyes or pike. Trout up to 6 pounds are common. One of the largest was an 11-pound brown caught in late January by Carl Zimmer, a Sheffield angler who spends much time on Kinzua ice. Zimmer was fishing in Sugar Bay in about 18 feet of water during the very warm 1998 winter.
The only ice on Kinzua when Zimmer caught his big brown trout was toward the heads of the bays. Just a week before, a 41 1/2-pound musky was caught from open water in the main arm. Muskies are sometimes hooked by ice anglers, but the bigger ones are too large to pull through the six-inch to eight-inch holes drilled by most ice anglers.
Kinzua also occasionally gives up other big fish
through its ice. Rainbow trout are stocked regularly, but they are not caught as often as browns. Channel catfish up to
12 pounds were fairly common during the late 1970s, but they are unusual now. Lake trout and Atlantic salmon have also
been stocked here in small numbers, though not recently.
Ice anglers at the Allegheny Reservoir rely more on tip-ups than ice anglers on most other Pennsylvania lakes. Most use at least four tip-ups and no more than one jigging rod. Any jigging rod left unattended here is likely to be pulled through the ice. Many regulars use tip-ups almost exclusively.
Emerald shiners are the favorite tip-up bait so much so that some of the most successful ice anglers will not fish without them. Fortunately, they are usually available at most area bait shops. The favorite bait size of anglers who concentrate on big game is four to six inches.
There is considerable disagreement about how shiners should be hooked, and which type of hook, treble or single wide-gap, is best. Some veteran ice anglers hook their shiners through the lips, believing that fish generally turn the shiner head-first to swallow it. Some hook them near the dorsal fin, thinking this is the most likely place to get the hook into the mouth of a fish. Early or late in the ice fishing season when fish are generally most active, it probably does not matter. But during midwinter when many of the largest walleyes are caught, hooking shiners near the dorsal fin with a treble hook probably has the advantage.
Talk to a dozen Kinzua ice fishing veterans and you will probably get a dozen different strategies on patterns for setting tip-ups. But if you combine several strategies, you arrive at a strategy that covers several bases.
Kinzua Tip-Up Spread
Set tip-ups at a variety of depths if you hope to catch a variety of Kinzuas big fish. Tip-up A is set near a shoreline boulder. The bait is about five feet under the ice. This is a great set-up for pike, trout or muskies. Tip-ups B, C and D are intended primarily for walleyes, but they might catch anything. These baits are set about a foot above the bottom. Tip-up E is set just a few feet under the ice over deep water. It is intended to catch trout primarily, but maybe pike. Move B, C and D into about the same depth if a pattern develops.
Start your tip-up pattern near shore, and near some type of steep structure such as a steep point, a cliff, or a large boulder. Pike and trout are the reason for this starting point. Pike and trout often roam just a few feet under the ice, and pike, especially, near shore. Set the bait about three to five feet beneath the ice. If pike are your primary objective, set two or three tip-ups close to shore with a reasonable distance between tip-ups, and if the water is deep enough, vary the depths of the baits. For example, if the depth is about 15 feet, set one at three feet, one at eight feet, and another at 12 feet.
Keep in mind that the fishing regulations require that tip-ups be close enough to be under your immediate control.
If you want a tip-up spread that is ready for any Kinzua big fish, run your tip-ups in a line, or a J shape, out from shore to a depth of no more than 30 feet. Beyond 30 feet you will catch mostly smaller walleyes, and bringing them up from depths greater than about 33 feet will kill most. If the bottom slope is relatively gentle, the line should be roughly perpendicular to the shoreline. On steeper slopes, run the line at a more acute angle so you can spread the holes at least 20 feet apart. This will cover a reasonable amount of water, and it will usually avoid fish tangling two lines. Walleyes seldom take out more than 10 to 15 feet of line. Pike and trout often take much more.
Setting the depth of the bait depends on the fish
you hope to catch. For walleyes, the bait should usually be set within a foot of the bottom. If trout are your
objective, set at least a couple of baits no more than five feet under the ice, no matter what the depth.
Once you establish a pattern, if most hits come on one or two tip-ups, concentrate more of your rigs in that same depth range. I prefer, regardless of the pattern, to keep at least one tip-up close to shore.
I also reserve one of my five allotted rigs for jigging. Several holes are drilled for this purpose with at least one close to each tip-up--no more than five feet away--so I can jig there if it appears that a school of walleyes is in the area. On the flip side of that formula, if I locate fish by jigging, I move tip-ups into the same area.
At most lakes, you might sometimes notice that one
particular hole gets hot, but you cannot catch a nibble from any other hole no matter how close they are. I assume in a
case like this that the hole is just close enough, and on the correct side, of a very good piece of structure or cover.
Countless boulders, stumps and sunken logs are scattered on the bottom of Kinzua.
Where to go
Access is the major obstacle to ice fishing at Kinzua. The lake is large with few good access points. At some access points, a treacherous walk down a very steep bank is required.
On the west side of the lake, the only good access is at Webbs Ferry, close to the New York border. Even here, unless you have a 4x4 with chains, you might have to walk a few hundred yards to the ice. There is another road to the ice at Roper Hollow, but this long, steep, narrow road is not maintained during winter.
Along the east side, many anglers walk to the ice from Route 59 between the dam and the bridge over the Kinzua Arm, and at the swimming beach on the north side of the Route 59 bridge. Ice anglers coming from the Bradford area have good success by walking to the ice from Route 321 near the head of Sugar Bay. Willow Bay, just south of the New York border along Route 346, is another popular area.
The area close to the New York border generally is best early in the ice fishing season. But currents can make the ice treacherous there. Later in the season, the better action often moves down the lake. Some anglers get to the ice at Webbs Ferry or Willow Bay and walk down the lake on the ice.
Kinzua is notorious for weak spots, even when most of the ice is very thick. Many of these weak spots are caused by gas escaping from old wells. Never strike out alone. Carry rope and ice spikes. Some smart ice anglers wear life jackets.
Snowmobiles, ATVs and all other motorized vehicles are prohibited from operating on the ice at Kinzua, and from driving to the edge of the ice.
For More Information
For local information about the Allegheny Reservoir area, contact the following:
Allegheny National Forest Vacation Bureau
P.O. Drawer G, Junction 219 & 770
Custer City, PA 16725
phone: 814-368-9370
Northern Alleghenies Vacation Region
315 Second Avenue
Warren, PA 16365
phone: 814-726-1222
U.S. Army Corps of Engineers
Kinzua Dam, 1205 Kinzua Road
Warren, PA 16365
phone: 814-726-0661
PDF file of this article
January/February 2001 Angler & Boater
Commonwealth of Pennsylvania Web Privacy and Security Policies


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A Photo A Day: Katie, from Lomography Canada2013-05-07 6 Share Tweet
Instant Month is upon us and we'll be sharing an instant photo a day from our Lomography Canada office and the Lomography Gallery Store Toronto. Here is our intern, Katie!
Name: Katie Shim
Lomohome: katieshim
What you do at Lomography: Have FUN! Oh, and I'm also the Public Relations Intern
What would get you running in an instant?: If someone in a gorilla suit was chasing me
What would put you to sleep instantly?: Long car rides
Name something you can do in an instant: Snap a picture!
What gets you instantly happy?: Sunny days and Superkid ice cream from Laura Secord
What gets you instantly sad?: Cold, rainy days
What is your favourite instant camera to use?: The Classic Polaroid!
Anyone have a gorilla suit?
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written by ashleyaang on 2013-05-07 #instant #month #lifestyle #polaroid #gallery-store #day #photo #canada #toronto #analogue-photography


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Red Rose rocked after Anderson five
Click here for exclusive match highlights from every day's play, latest scores, reports, news and interviews during the LV= County Championship campaign
England fast bowler James Anderson recovered from illness and injury to claim 5-82 for Lancashire at Old Trafford, but another abject batting display from the hosts put Nottinghamshire in total control at the end of day three.
Chris Read's men reduced their opponents to 39 for five after being bowled out for 304 in their second innings to set a stiff victory target of 328.
Stuart Broad - another member of England's pace attack - picked up two wickets in an accurate new-ball spell, while Andre Adams, who returned 7-32 in the first innings, also struck twice.
Bad light ended play 21 overs early to deny Nottinghamshire the opportunity of completing victory inside three days.
However, after storming to a memorable LV= County Championship title triumph last summer, an off-colour Lancashire appeared almost certain to register a third defeat in four games. They trailed by 289 heading into the fourth and final day.
Nottinghamshire's evening breakthroughs followed half-centuries from Michael Lumb and Read.
Their second-innings total would have been larger had Anderson not dismissed four of the last five batsmen as Notts lost their last six wickets for 39 runs.
While the Burnley-born seamer enjoyed catching Broad off Simon Kerrigan, he probably derived greater satisfaction from exacting his revenge on Graeme Swann, whom he bowled for 12.
Anderson also had reason to be grateful to his opponents after confusion over when he would be allowed to bowl after his illness on Thursday had been resolved by a compromise which only delayed his participation by 11 minutes.
Nottinghamshire's early dominance was firmly established by two vital partnerships between their middle-order batsmen. The most productive of these was a 100-run stand for the fifth wicket between James Taylor and his skipper Read, but Lumb, who made 62, and Samit Patel did much of the hard work in a testing morning session by putting on 76 for the third wicket.
Paul Horton compounded Lancashire's problems by dropping both Taylor and Read after lunch.
By mid-afternoon, when Taylor had been caught down the leg side off Kerrigan for 46 and Read had been brilliantly taken by Gareth Cross off Anderson for 54, Nottinghamshire's lead was already a formidable 312.
Anderson quickly added the wicket of Paul Franks and returned after a rain break to take a hand in the dismissals of his England team-mates as Nottinghamshire suffered a collapse which should have little impact on the outcome of the match.
Broad removed Horton for a second-ball duck and Karl Brown for seven when Lancashire batted for a second time, while Adams accounted for Stephen Moore and Steven Croft either side of Swann having Ashwell Prince caught at slip for 14 in his first over.
Want to know what's happening at your county? Interested in how your rivals are faring? Look no further than ecb.co.uk's county-by-county page