Search for long lived charged massive particles in pp collisions at s-hat = 1.8TeV

We report a search for the production of long-lived charged massive particles in a data sample of 90   pb-1 of √s=1.8   TeV pp̅ collisions recorded by the Collider Detector at Fermilab. The search uses the muonlike penetration and anomalously high ionization energy loss signature expected for such a particle to discriminate it from backgrounds. The data are found to agree with background expectations, and cross section limits of O(1) pb are derived using two reference models, a stable quark and a stable scalar lepton

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

SRC tyrosine kinase is frequently overexpressed and activated in late-stage, poor prognosis ovarian tumours, and preclinical studies have supported the use of targeted SRC inhibitors in the treatment of this disease. The SAPPROC trial investigated the addition of the SRC inhibitor saracatinib (AZD0530) to weekly paclitaxel for the treatment of platinum resistant ovarian cancer; however, this drug combination did not provide any benefit to progression free survival (PFS) of women with platinum resistant disease. In this study we aimed to identify mechanisms of resistance to SRC inhibitors in ovarian cancer cells. Using two complementary strategies; a targeted tumour suppressor gene siRNA screen, and a phospho-receptor tyrosine kinase array, we demonstrate that activation of MAPK signalling, via a reduction in NF1 (neurofibromin) expression or overexpression of HER2 and the insulin receptor, can drive resistance to AZD0530. Knockdown of NF1 in two ovarian cancer cell lines resulted in resistance to AZD0530, and was accompanied with activated MEK and ERK signalling. We also show that silencing of HER2 and the insulin receptor can partially resensitize AZD0530 resistant cells, which was associated with decreased phosphorylation of MEK and ERK. Furthermore, we demonstrate a synergistic effect of combining SRC and MEK inhibitors in both AZD0530 sensitive and resistant cells, and that MEK inhibition is sufficient to completely resensitize AZD0530 resistant cells. This work provides a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials

First evidence of coherent K+K^{+} meson production in neutrino-nucleus scattering

Neutrino-induced charged-current coherent kaon production, $\nu_{\mu}A\rightarrow\mu^{-}K^{+}A$, is a rare, inelastic electroweak process that brings a $K^+$ on shell and leaves the target nucleus intact in its ground state. This process is significantly lower in rate than neutrino-induced charged-current coherent pion production, because of Cabibbo suppression and a kinematic suppression due to the larger kaon mass. We search for such events in the scintillator tracker of MINERvA by observing the final state $K^+$, $\mu^-$ and no other detector activity, and by using the kinematics of the final state particles to reconstruct the small momentum transfer to the nucleus, which is a model-independent characteristic of coherent scattering. We find the first experimental evidence for the process at $3\sigma$ significance.Comment: added ancillary file with information about the six kaon candidate

Infectious disease and health systems modelling for local decision making to control neglected tropical diseases

Most neglected tropical diseases (NTDs) have complex life cycles and are challenging to control. The “2020 goals” of control and elimination as a public health programme for a number of NTDs are the subject of significant international efforts and investments. Beyond 2020 there will be a drive to maintain these gains and to push for true local elimination of transmission. However, these diseases are affected by variations in vectors, human demography, access to water and sanitation, access to interventions and local health systems. We therefore argue that there will be a need to develop local quantitative expertise to support elimination efforts. If available now, quantitative analyses would provide updated estimates of the burden of disease, assist in the design of locally appropriate control programmes, estimate the effectiveness of current interventions and support ‘real-time’ updates to local operations. Such quantitative tools are increasingly available at an international scale for NTDs, but are rarely tailored to local scenarios. Localised expertise not only provides an opportunity for more relevant analyses, but also has a greater chance of developing positive feedback between data collection and analysis by demonstrating the value of data. This is essential as rational program design relies on good quality data collection. It is also likely that if such infrastructure is provided for NTDs there will be an additional impact on the health system more broadly. Locally tailored quantitative analyses can help achieve sustainable and effective control of NTDs, but also underpin the development of local health care systems