Supersymmetry of Noncompact MQCD-like Membrane Instantons and Heat Kernel Asymptotics

We perform a heat kernel asymptotics analysis of the nonperturbative superpotential obtained from wrapping of an M2-brane around a supersymmetric noncompact three-fold embedded in a (noncompact) G_2-manifold as obtained in [1], the three-fold being the one relevant to domain walls in Witten's MQCD [2], in the limit of small "zeta", a complex constant that appears in the Riemann surfaces relevant to defining the boundary conditions for the domain wall in MQCD. The MQCD-like configuration is interpretable, for small but non-zero zeta as a noncompact/"large" open membrane instanton, and for vanishing zeta, as the type IIA D0-brane (for vanishing M-theory cicle radius). We find that the eta-function Seeley de-Witt coefficients vanish, and we get a perfect match between the zeta-function Seeley de-Witt coefficients (up to terms quadratic in zeta) between the Dirac-type operator and one of the two Laplace-type operators figuring in the superpotential. This is an extremely strong signature of residual supersymmetry for the nonperturbative configurations in M-theory considered in this work.Comment: 21 pages, LaTeX; v3: several clarifying remarks added, to appear in JHE

The Effectiveness of Maintenance Pharmacotherapies for Non-Small Cell Lung Cancer

Although current recommendations for the treatment of advanced non-small cell lung cancer (NSCLC) include a maximum of six cycles of platinum-based combination therapy as a first-line approach, most patients experience progression within 3–4 months. Therefore, a new treatment strategy, maintenance therapy, has been proposed, and several large randomized prospective controlled trials have shown benefits with maintenance therapy. Maintenance therapy can be classified as either continuation maintenance, which is defined as a prolongation of a part of the first-line chemotherapy or molecularly targeted agent until progression, or switch-maintenance, which is defined as the administration of a different cytotoxic chemotherapy or molecularly targeted agent immediately after induction therapy. In this article, recent results from large randomized phase III trials regarding maintenance therapy are reviewed in order to evaluate the role of maintenance therapy in NSCLC

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases

Un-oriented Quiver Theories for Majorana Neutrons

In the context of un-oriented open string theories, we identify quivers whereby a Majorana mass for the neutron is indirectly generated by exotic instantons. We discuss two classes of (Susy) Standard Model like quivers, depending on the embedding of SU(2)_W in the Chan-Paton group. In both cases, the main mechanism involves a vector-like pair mixing through a non-perturbative mass term. We also discuss possible relations between the phenomenology of Neutron-Antineutron oscillations and LHC physics in these models. In particular, a vector-like pair of color-triplet scalars or color-triplet fermions could be directly detected at LHC, compatibly with n-\bar{n} limits. Finally we briefly comment on Pati-Salam extensions of our models.Comment: More comments on phenomenology and fluxes, Re-discussion of SM-quivers compatible with n-cycles conditions Version accepted by JHE

Population-based differences in the outcome and presentation of lung cancer patients based upon racial, histologic, and economic factors in all lung patients and those with metastatic disease

To investigate the interrelation between economic, marital, and known histopathologic/therapeutic prognostic factors in presentation and survival of patients with lung cancer in nine different ethnic groups. A retrospective review of the SEER database was conducted through the years 2007-2012. Population differences were assessed via chi-square testing. Multivariable analyses (MVA) were used to detect overall survival (OS) differences in the total population (TP, N = 153,027) and for those patients presenting with Stage IV (N = 70,968). Compared to Whites, Blacks were more likely to present with younger age, male sex, lower income, no insurance, single/widowed partnership, less squamous cell carcinomas, and advanced stage; and experience less definitive surgery, lower OS, and lung cancer-specific (LCSS) survival. White Hispanics presented with younger age, higher income, lower rates of insurance, single/widowed partnership status, advanced stage, more adenocarcinomas, and lower rates of definitive surgery, but no difference in OS and LCSS than Whites. In the TP and Stage IV populations, MVAs revealed that OS was better or equivalent to Whites for all other ethnic groups and was positively associated with insurance, marriage, and higher income. Blacks presented with more advanced disease and were more likely to succumb to lung cancer, but when adjusted for prognostic factors, they had a better OS in the TP compared to Whites. Disparities in income, marital status, and insurance rather than race affect OS of patients with lung cancer. Because of their presentation with advanced disease, Black and Hispanics are likely to have increased benefit from lung cancer screening

Population-based differences in the outcome and presentation of lung cancer patients based upon racial, histologic, and economic factors in all lung patients and those with metastatic disease

To investigate the interrelation between economic, marital, and known histopathologic/therapeutic prognostic factors in presentation and survival of patients with lung cancer in nine different ethnic groups. A retrospective review of the SEER database was conducted through the years 2007-2012. Population differences were assessed via chi-square testing. Multivariable analyses (MVA) were used to detect overall survival (OS) differences in the total population (TP, N = 153,027) and for those patients presenting with Stage IV (N = 70,968). Compared to Whites, Blacks were more likely to present with younger age, male sex, lower income, no insurance, single/widowed partnership, less squamous cell carcinomas, and advanced stage; and experience less definitive surgery, lower OS, and lung cancer-specific (LCSS) survival. White Hispanics presented with younger age, higher income, lower rates of insurance, single/widowed partnership status, advanced stage, more adenocarcinomas, and lower rates of definitive surgery, but no difference in OS and LCSS than Whites. In the TP and Stage IV populations, MVAs revealed that OS was better or equivalent to Whites for all other ethnic groups and was positively associated with insurance, marriage, and higher income. Blacks presented with more advanced disease and were more likely to succumb to lung cancer, but when adjusted for prognostic factors, they had a better OS in the TP compared to Whites. Disparities in income, marital status, and insurance rather than race affect OS of patients with lung cancer. Because of their presentation with advanced disease, Black and Hispanics are likely to have increased benefit from lung cancer screening

Maintenance therapy in NSCLC: why? To whom? Which agent?

Maintenance therapy is emerging as a treatment strategy in the management of advanced non small cell lung cancer (NSCLC). Initial trials addressing the question of duration of combination chemotherapy failed to show any overall survival benefit for the prolonged administration over a fixed number of cycles with an increased risk for cumulative toxicity. Nowadays several agents with different ways of administration and a different pattern of toxicity have been formally investigated in the maintenance setting. Maintenance strategies include continuing with an agent already present in the induction regimen or switching to a different one. Taking into consideration that no comparative trials of maintenance with different chemotherapy drugs or targeted agents have been conducted, the choice and the duration of maintenance agents is largely empirical. Furthermore, it is still unknown and it remains an open question if this approach needs to be proposed to every patient in the case of partial/complete response or stable disease after the induction therapy. Here, we critically review available data on maintenance treatment, discussing the possibility to tailor the right treatment to the right patient, in an attempt to optimize costs and benefits of an ever-growing panel of different treatment options

Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for breast cancer

<p>Abstract</p> <p>Background</p> <p>It has been shown in in-vitro experiments that "withdrawal" of tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this is extrapolated into clinical context. We report our experience to verify the clinical relevance of "withdrawal therapy".</p> <p>Methods</p> <p>Breast cancer patients since 1998 who fulfilled the following criteria were selected from the departmental database and the case-notes were retrospectively reviewed: (1) estrogen receptor positive, operable primary breast cancer in elderly (age > 70 years), locally advanced or metastatic breast cancer; (2) disease deemed suitable for treatment by hormonal manipulation; (3) disease assessable by UICC criteria; (4) received "withdrawal" from a prior endocrine agent as a form of therapy; (5) on "withdrawal therapy" for ≥ 6 months unless they progressed prior.</p> <p>Results</p> <p>Seventeen patients with median age of 84.3 (53.7-92.5) had "withdrawal therapy" as second to tenth line of treatment following prior endocrine therapy using tamoxifen (n = 10), an aromatase inhibitor (n = 5), megestrol acetate (n = 1) or fulvestrant (n = 1). Ten patients (58.8%) had clinical benefit (CB) (complete response/partial response/stable disease ≥ 6 months) with a median duration of Clinical Benefit (DoCB) of 10+ (7-27) months. Two patients remain on "withdrawal therapy" at the time of analysis.</p> <p>Conclusion</p> <p>"Withdrawal therapy" appears to produce sustained CB in a significant proportion of patients. This applies not only to "withdrawal" from tamoxifen, but also from other categories of endocrine agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating option between endocrine agents to minimise resistance and provide additional line of therapy. It should be considered as part of the sequencing of endocrine therapy.</p