A phase I/II study of gemcitabine during radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma

The purpose of this phase I/II, open-label, single-arm trial is to investigate the safety, tolerability, maximum tolerated dose and preliminary efficacy of the potential radiosensitizer gemcitabine, administered concomitantly to radiotherapy, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Six doses of weekly gemcitabine were administered intravenously, concomitantly to 6 weeks of hyperfractionated radiotherapy. Successive cohorts received increasing doses of 140, 175 and 200 mg/m2 gemcitabine, respectively, following a 3 + 3 dose-escalation schedule without expansion cohort. Dose-limiting toxicities (DLT) were monitored during treatment period. Clinical response was assessed using predefined case report forms and radiological response was assessed using the modified RANO criteria. Quality of life (QoL) was assessed using PedsQL questionnaires. Between June 2012 and December 2016, nine patients were enrolled. Treatment was well tolerated, and no DLTs were observed up to the maximum dose of 200 mg/m2. All patients experienced reduction of tumor-related symptoms. QoL tended to improve during treatment. PFS and MOS were 4.8 months (95% CI 4.0–5.7) and 8.7 months (95% CI 7.0–10.4). Classifying patients according to the recently developed DIPG survival prediction model, intermediate risk patients (n = 4),

Marketing digital y fidelización de clientes en el desarrollo de la sostenibilidad comercial de la región Junín

Objective. To determine the relationship between digital marketing and customer loyalty in the development of commercial sustainability in the province of Tarma, Junín region (Peru). Methods. The research had a quantitative approach and was of basic type, correlational level and non-experimental-cross-sectional design; two instruments were used: the digital marketing questionnaire and the customer loyalty questionnaire. The first questionnaire consisted of 12 items referring to the dimensions of digital marketing and the second consisted of 15 items referring to the dimensions of customer loyalty. The sample consisted of 120 customers of commercial establishments in the province of Tarma. Results. 47.5 % of respondents considered that the implementation of digital marketing in commercial establishments is regular, 36.7 % considered that there is a low implementation and only 15.8 % considered that there is a high implementation of digital marketing. Referring to the customer loyalty questionnaire, 63.3 % considered that customer loyalty in commercial establishments occurs regularly, 21.7 % considered that customer loyalty is high and 15 % considered that customer loyalty is low. Conclusion. There is a direct and statistically significant relationship between digital marketing and customer loyalty in the development of sustainability in the province of Tarma, Junín region.Objetivo. Determinar la relación entre marketing digital y fidelización de clientes en el desarrollo de la sostenibilidad comercial de la provincia de Tarma, región Junín (Perú). Métodos. La investigación tuvo un enfoque cuantitativo y fue de tipo básico, nivel correlacional y diseño no experimental-transversal; se emplearon dos instrumentos: el cuestionario de marketing digital y el cuestionario de fidelización de clientes. El primer cuestionario constó de 12 ítems referidos a las dimensiones de marketing digital y el segundo constó de 15 ítems referidos a las dimensiones de la fidelización de clientes. La muestra estuvo conformada por 120 clientes de establecimientos comerciales de la provincia de Tarma. Resultados. El 47,5 % de encuestados consideró que la implementación del marketing digital en los establecimientos comerciales se da de forma regular, el 36,7% consideró que hay una baja implantación y solo el 15,8 % consideró que hay una alta implantación del marketing digital. Referente al cuestionario de fidelización de clientes, el 63,3 % consideró que la fidelización de clientes en los establecimientos comerciales se da de forma regular, el 21,7 % consideró que la fidelización de clientes es alta y el 15% considera que la fidelización de clientes es baja. Conclusión. Existe relación directa y estadísticamente significativa entre marketing digital y fidelización de clientes en el desarrollo de la sostenibilidad de la provincia de Tarma, región Junín

Measurement of the muon anti-neutrino double-differential cross section for quasi-elastic scattering on hydrocarbon at~Eν∼3.5E_\nu \sim 3.5 GeV

We present double-differential measurements of anti-neutrino quasi-elastic scattering in the MINERvA detector. This study improves on a previous single differential measurement by using updated reconstruction algorithms and interaction models, and provides a complete description of observed muon kinematics in the form of a double-differential cross section with respect to muon transverse and longitudinal momentum. We include in our signal definition zero-meson final states arising from multi-nucleon interactions and from resonant pion production followed by pion absorption in the primary nucleus. We find that model agreement is considerably improved by a model tuned to MINERvA inclusive neutrino scattering data that incorporates nuclear effects such as weak nuclear screening and two-particle, two-hole enhancements.Comment: 47 pages, 31 figure

Measurement of Total and Differential Cross Sections of Neutrino and Antineutrino Coherent π±\pi^\pm Production on Carbon

Neutrino induced coherent charged pion production on nuclei, $\overline{\nu}_\mu A\to\mu^\pm\pi^\mp A$, is a rare inelastic interaction in which the four-momentum squared transfered to the nucleus is nearly zero, leaving it intact. We identify such events in the scintillator of MINERvA by reconstructing |t| from the final state pion and muon momenta and by removing events with evidence of energetic nuclear recoil or production of other final state particles. We measure the total neutrino and antineutrino cross sections as a function of neutrino energy between 2 and 20 GeV and measure flux integrated differential cross sections as a function of $Q^2$, $E_\pi$ and $\theta_\pi$. The $Q^2$ dependence and equality of the neutrino and anti-neutrino cross-sections at finite $Q^2$ provide a confirmation of Adler's PCAC hypothesis

Early postoperative MRI overestimates residual tumour after resection of gliomas with no or minimal enhancement

Standards for residual tumour measurement after resection of gliomas with no or minimal enhancement have not yet been established. In this study residual volumes on early and late postoperative T2-/FLAIR-weighted MRI are compared. A retrospective cohort included 58 consecutive glioma patients with no or minimal preoperative gadolinium enhancement. Inclusion criteria were first-time resection between 2007 and 2009 with a T2-/FLAIR-based target volume and availability of preoperative, early (<48 h) and late (1-7 months) postoperative MRI. The volumes of non-enhancing T2/FLAIR tissue and diffusion restriction areas were measured. Residual tumour volumes were 22% smaller on late postoperative compared with early postoperative T2-weighted MRI and 49% smaller for FLAIR-weighted imaging. Postoperative restricted diffusion volume correlated with the difference between early and late postoperative FLAIR volumes and with the difference between T2 and FLAIR volumes on early postoperative MRI. We observed a systematic and substantial overestimation of residual non-enhancing volume on MRI within 48 h of resection compared with months postoperatively, in particular for FLAIR imaging. Resection-induced ischaemia contributes to this overestimation, as may other operative effects. This indicates that early postoperative MRI is less reliable to determine the extent of non-enhancing residual glioma and restricted diffusion volumes are imperativ

Segment-Specific Neuronal Subtype Specification by the Integration of Anteroposterior and Temporal Cues

To address the question of how neuronal diversity is achieved throughout the CNS, this study provides evidence of modulation of neural progenitor cell “output” along the body axis by integration of local anteroposterior and temporal cues

Development of the SIOPE DIPG network, registry and imaging repository : a collaborative effort to optimize research into a rare and lethal disease

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.Peer reviewe