Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

Background: Preoperative radiochemotherapy (RCT) with 5-FU or capecitabine is the standard of care for patients with locally advanced rectal cancer (LARC). Preoperative RCT achieves pathological complete response rates (pCR) of 10-15%. We conducted a single arm phase II study to investigate the feasibility and efficacy of addition of bevacizumab and oxaliplatin to preoperative standard RCT with capecitabine. Methods: Eligible patients had LARC (cT3-4; N0/1/2, M0/1) and were treated with preoperative RCT prior to planned surgery. Patients received conventionally fractionated radiotherapy (50.4 Gy in 1.8 Gy fractions) and simultaneous chemotherapy with capecitabine 825 mg/m2 bid (d1-14, d22-35) and oxaliplatin 50 mg/m2 (d1, d8, d22, d29). Bevacizumab 5 mg/kg was added on days 1, 15, and 29. The primary study objective was the pCR rate. Results: 70 patients with LARC (cT3-4; N0/1, M0/1), ECOG < 2, were enrolled at 6 sites from 07/2008 through 02/2010 (median age 61 years [range 39–89], 68% male). At initial diagnosis, 84% of patients had clinical stage T3, 62% of patients had nodal involvement and 83% of patients were M0. Mean tumor distance from anal verge was 5.92 cm (± 3.68). 58 patients received the complete RCT (full dose RT and full dose of all chemotherapy). During preoperative treatment, grade 3 or 4 toxicities were experienced by 6 and 2 patients, respectively: grade 4 diarrhea and nausea in one patient (1.4%), respectively, grade 3 diarrhea in 2 patients (3%), grade 3 obstipation, anal abscess, anaphylactic reaction, leucopenia and neutropenia in one patient (1.4%), respectively. In total, 30 patients (46%) developed postoperative complications of any grade including one gastrointestinal perforation in one patient (2%), wound-healing problems in 7 patients (11%) and bleedings in 2 patients (3%). pCR was observed in 12/69 (17.4%) patients. Pathological downstaging (ypT < cT and ypN ≤ cN) was achieved in 31 of 69 patients (44.9%). All of the 66 operated patients had a R0 resection. 47 patients (68.1%) underwent sphincter preserving surgery. Conclusions: The addition of bevacizumab and oxaliplatin to RCT with capecitabine was well tolerated and did not increase perioperative morbidity or mortality. However, the pCR rate was not improved in comparison to other trials that used capecitabine or capecitabine/oxaliplatin in preoperative radiochemotherapy

Effects of Electroweak Instantons In High-Energy Neutrino Telescopes

We demonstrate that next generation high-energy neutrino telescopes may reveal the existence of interactions induced by standard model electroweak instantons. The energy spectrum, the angular distribution, and the quark and lepton multiplicity of events in the detector each provide signatures which can indicate the presence of these interactions. High-energy neutrino telescopes may be capable of searching for signals at energies far beyond the reach of the next generation colliders.Comment: Version to appear in PL

Priorities for Africa's food and nutrition security post-covid-19. A contribution from the Task Force Rural Africa (TFRA) to the AU-EU Summit, October 2020

A deep sense of concern about the impact of the COVID-19 pandemic on the lives and livelihoods of Africa’s people has inspired the writing of this contribution. As members of the Task Force Rural Africa (TFRA), we produced a report in March 2019 on what we thought was needed to transform Africa’s agriculture and rural economy. Less than one year later, COVID-19 struck Africa and the rest of the world with devastating effect. Another important change since March 2019 has been the shift on climate policy, represented by the EU Commission proposal in December 2019 of the European Green Deal (EGD). This ambitious vision, aimed at making Europe the first climate-neutral continent by 2050, will have implications for Africa – Europe relations. The combination of COVID-19’s impact on Africa and the EU’s climate policy change has led us to re-examine the analysis and the recommendations in our original report. We have drawn one central conclusion from our work: that food and nutrition security has become of such fundamental political, economic and social importance that it must be at the centre of all future policy and planning. We have built our report on this conclusion and produced a set of short and long-term recommendations we believe are relevant to the new world shaped by the COVID-19 pandemic. We hope our contribution may help in the preparation of the AU-EU Summit in October 2020. The Summit will seek to agree the long-term basis for partnership between Africa and the EU. It will meet at a crucially important time, shortly before the US Presidential election, when the world will be looking to see how Africa and Europe, separately and in partnership, can contribute to an effective multilateral response to global challenges and the current COVID-19 crisis. We wish the leaders well in their efforts

Consumer Decision Making and Store Patronage Behaviour in Traditional Chinese Medicine (TCM) Halls in Singapore

This paper examines who patronises Traditional Chinese Medicine (TCM) halls in Singapore and for what purpose. A quantitative study of 400 respondents identifies that TCMs are used primarily for the improvement of health and well being rather than the treatment of more serious medical conditions. While the patronage of TCM stores is not restricted to the Chinese population, traditional Mom-and-Pop outlets have come under increasing pressure from new market entrants. When choosing a TCM outlet, customers consider price and quality to be important factors while trust in the store keeper was also identified as a key determinant of store choice

The symmetric heavy-light ansatz

The symmetric heavy-light ansatz is a method for finding the ground state of any dilute unpolarized system of attractive two-component fermions. Operationally it can be viewed as a generalization of the Kohn-Sham equations in density functional theory applied to N-body density correlations. While the original Hamiltonian has an exact Z_2 symmetry, the heavy-light ansatz breaks this symmetry by skewing the mass ratio of the two components. In the limit where one component is infinitely heavy, the many-body problem can be solved in terms of single-particle orbitals. The original Z_2 symmetry is recovered by enforcing Z_2 symmetry as a constraint on N-body density correlations for the two components. For the 1D, 2D, and 3D attractive Hubbard models the method is in very good agreement with exact Lanczos calculations for few-body systems at arbitrary coupling. For the 3D attractive Hubbard model there is very good agreement with lattice Monte Carlo results for many-body systems in the limit of infinite scattering length.Comment: 38 pages, 13 figures, revised manuscript includes results for 1D, 2D, and 3

Pion-Production in Heavy-Ion Collisions at SIS energies

We investigate the production of pions in heavy-ion collisions in the energy range of $1$ - $2$ GeV/A. The dynamics of the nucleus-nucleus collisions is described by a set of coupled transport equations of the Boltzmann-Uehling-Uhlenbeck type for baryons and mesons. Besides the $N(938)$ and the $\Delta(1232)$ we also take into account nucleon resonances up to masses of $1.9 GeV/c^2$ as well as $\pi$-, $\eta$- and $\rho$-mesons. We study in detail the influence of the higher baryonic resonances and the $2\pi$-production channels ($NN\to NN \pi\pi$) on the pion spectra in comparison to $\pi^-$ data from $Ar + KCl$ collisions at $1.8$ GeV/A and $\pi^0$-data for $Au+Au$ at 1.0 GeV/A. We, furthermore, present a detailed comparison of differential pion angular distributions with the BEVALAC data for Ar + KCl at 1.8 GeV/A. The general agreement obtained indicates that the overall reactions dynamics is well described by our novel transport approach.Comment: 31 pages, 18 figures (inlcuded), to appear in Z. Phys.

Electroweak instantons as a solution to the ultrahigh energy cosmic ray puzzle

We propose a scenario in which a simple power-like primary spectrum for protons with sources at cosmological distances leads to a quantitative description of all the details of the observed cosmic ray spectrum for energies from 10^{17} eV to 10^{21} eV. As usual, the ultrahigh energy protons with energies above E_{GZK} ~ 4 x 10^{19} eV loose a large fraction of their energies by the photoproduction of pions on the cosmic microwave background, which finally decay mainly into neutrinos. In our scenario, these so-called cosmogenic neutrinos interact with nucleons in the atmosphere through Standard Model electroweak instanton-induced processes and produce air showers which are hardly distinguishable from ordinary hadron-initiated air showers. In this way, they give rise to a second contribution to the observed cosmic ray spectrum -- in addition to the one from above mentioned protons -- which reaches beyond E_{GZK}. Since the whole observed spectrum is uniquely determined by a single primary injection spectrum, no fine tuning is needed to fix the ratio of the spectra below and above E_{GZK}. The statistical analysis shows an excellent goodness of this scenario. Possible tests of it range from observations at cosmic ray facilities and neutrino telescopes to searches for QCD instanton-induced processes at HERA.Comment: 14 pages, 7 figure