Simplicial complexes in Macaulay2

We highlight some features of the SimplicialComplexes package in Macaulay2.Comment: 8 pages, 2 figure

Small molecules and targeted therapies in distant metastatic disease

Chemotherapy, biological agents or combinations of both have had little impact on survival of patients with metastatic melanoma. Advances in understanding the genetic changes associated with the development of melanoma resulted in availability of promising new agents that inhibit specific proteins up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Although often studied as single agents with disappointing results, new targeted drugs should be more thoroughly evaluated in combination therapies. The future of rational use of new targeted agents also depends on successful application of analytical techniques enabling molecular profiling of patients and leading to selection of likely therapy responder

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Seismic refraction measurements in the Atlantic Ocean Basin (Part one)

A reversed seismic refraction measurement was made 120 miles northwest of Bermuda (400 miles east of Cape Hatteras) in 2,800 fathoms of water. A velocity of 24,800 feet per second (7.58 km/sec.) for the second layer was identified with the ultrabasic layer of earthquake seismology. Assuming a velocity of 5,600 feet per second (1.70 km/sec.), clearly indicated by earlier measurements, a thickness of 4,500 feet was obtained for the sedimentary layer. The granitic and intermediate layers were absent

The Importance of Ethics and Ethical Leadership in the Accounting Profession

The emergence of the twenty-first century was plagued with extensive, evasive and disheartening leadership failures. Despite the accounting profession’s standards of professional ethics, it was also tainted with ethical leadership indiscretions during this era. In response to these ethical leadership failings, renewed interest in developing accounting professionals with strong ethical principles and ethical leadership behaviors has emerged. In many firms training and development of ethical behavior is now at the forefront of the firm’s communications and professional development efforts. The question remains however, can the profession instill in its members the importance of ethical conduct? Can ethical leaders be developed that model and monitor ethical behavior? In response to the call for leaders who are ethical and moral, this research examined a model that examines ethical leadership and its impact on leader effectiveness for leaders within the accounting industry. The analysis shows that ethical and transformational leadership make incremental independent contributions in explaining leader effectiveness. The study comments on how the findings that ethically and morally focused leaders may impact the accounting profession and restore an industry tarnished with accusations of unethical behavior to one that regains its original prominence based on consistent, moral, ethical, and effective leaders