The World Humanitarian Summit: A Pivot Point in Philanthropy's Contribution to Addressing Humanitarian Crises

This paper calls on the philanthropic community to take advantage of the opportunity offered by the first World Humanitarian Summit (WHS) in Istanbul in May 2016 to make important changes in the way it contributes its share of the global response to humanitarian crises. In Section 1, the paper looks at the challenges shared by all who contribute, including the philanthropy sector. Section 2 discusses philanthropy's current contributions and potential, including some of its shortcomings. Section 3 examines how the Summit is setting the stage for change -- change for which philanthropy can be a greater part. Section 4 concludes the paper with a set of actionable recommendations for how philanthropy's contribution to humanitarian crises can be greatly improved

The Effect of Docetaxel (Taxotere®) on Human Gastric Cancer Cells Exhibiting Low-Dose Radiation Hypersensitivity

Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells in the G2/M phase of the cell cycle. Some previous studies suggested that HRS might result from the abrogation of the early G2 checkpoint arrest. First we tested whether HRS occurs in gastric cancer—derived cells, and whether pre-treatment of cells with low docetaxel concentrations can enhance the magnitude of HRS in gastric cancer cells. The results demonstrated HRS at ~0.3 Gy and the synergy between 0.3 Gy and docetaxel (3 nM for 24 h), and the additivity of other drug/dose combinations. The synergistic effect was associated with a significant docetaxel-induced G2 accumulation. Next, we evaluated in time-course experiments ATM kinase activity and proteins associated with the induction and maintenance of the early G2 checkpoint. The results of multi-immunoblot analysis demonstrate that HRS does not correlate with the ATM-dependent early G2 checkpoint arrest. We speculate that G2 checkpoint adaptation, a phenomenon associated with a prolonged cell cycle arrest, might be involved in HRS. Our results also suggest a new approach for the improvement the effectiveness of docetaxel-based radiotherapy using low doses per fraction

Using Low-Dose Radiation to Potentiate the Effect of Induction Chemotherapy in Head and Neck Cancer: Results of a Prospective Phase 2 Trial

Purpose: Low-dose fractionated radiation therapy (LDFRT) induces effective cell killing through hyperradiation sensitivity and potentiates effects of chemotherapy. We report our second investigation of LDFRT as a potentiator of the chemotherapeutic effect of induction carboplatin and paclitaxel in locally advanced squamous cell cancer of the head and neck (SCCHN). Experimental Design: Two cycles of induction therapy were given every 21 days: paclitaxel (75 mg/m2) on days 1, 8, and 15; carboplatin (area under the curve 6) day 1; and LDFRT 50 cGy fractions (2 each on days 1, 2, 8, and 15). Objectives included primary site complete response rate; secondary included overall survival, progression-free survival (PFS), disease-specific survival, and toxicity. Results: A total of 24 evaluable patients were enrolled. Primary sites included oropharynx (62.5%), larynx (20.8%), oral cavity (8.3%), and hypopharynx (8.3%). Grade 3/4 toxicities included neutropenia (20%), leukopenia (32%), dehydration/hypotension (8%), anemia (4%), infection (4%), pulmonary/allergic rhinitis (4%), and diarrhea (4%). Primary site response rate was 23/24 (95.8%): 15/24 (62.5%) complete response, 8/24 (33.3%) partial response, and 1/24 (4.2%) stable disease. With median follow-up of 7.75 years, 9-year rates for overall survival were 49.4% (95% confidence interval [CI], 30.5-79.9), PFS was 72.2% (CI, 55.3-94.3), and disease-specific survival was 65.4% (44.3-96.4). Conclusion: Chemopotentiating LDFRT combined with paclitaxel and carboplatin is effective in SCCHN and provided an excellent median overall survival of 107.2 months, with median PFS not yet reached in this locally advanced SCCHN cohort. This compares favorably to prior investigations and caused fewer grade 3 and 4 toxicities than more intensive, 3-drug induction regimens. This trial demonstrates the innovative use of LDFRT as a potentiator of chemotherapy

Global glacier change in the 21st century: Every increase in temperature matters

Glacier mass loss affects sea level rise, water resources, and natural hazards. We present global glacier projections, excluding the ice sheets, for shared socioeconomic pathways calibrated with data for each glacier. Glaciers are projected to lose 26 ± 6% (+1.5°C) to 41 ± 11% (+4°C) of their mass by 2100, relative to 2015, for global temperature change scenarios. This corresponds to 90 ± 26 to 154 ± 44 millimeters sea level equivalent and will cause 49 ± 9 to 83 ± 7% of glaciers to disappear. Mass loss is linearly related to temperature increase and thus reductions in temperature increase reduce mass loss. Based on climate pledges from the Conference of the Parties (COP26), global mean temperature is projected to increase by +2.7°C, which would lead to a sea level contribution of 115 ± 40 millimeters and cause widespread deglaciation in most mid-latitude regions by 2100

Epidermal Growth Factor Receptor Inhibition Modulates the Microenvironment by Vascular Normalization to Improve Chemotherapy and Radiotherapy Efficacy

Background: Epidermal growth factor receptor (EGFR) inhibitors have shown only modest clinical activity when used as single agents to treat cancers. They decrease tumor cell expression of hypoxia-inducible factor 1-a (HIF-1a) and vascular endothelial growth factor (VEGF). Hypothesizing that this might normalize tumor vasculature, we examined the effects of the EGFR inhibitor erlotinib on tumor vascular function, tumor microenvironment (TME) and chemotherapy and radiotherapy sensitivity. Methodology/Principal Findings: Erlotinib treatment of human tumor cells in vitro and mice bearing xenografts in vivo led to decreased HIF-1a and VEGF expression. Treatment altered xenograft vessel morphology assessed by confocal microscopy (following tomato lectin injection) and decreased vessel permeability (measured by Evan’s blue extravasation), suggesting vascular normalization. Erlotinib increased tumor blood flow measured by Power Doppler ultrasound and decreased hypoxia measured by EF5 immunohistochemistry and tumor O2 saturation measured by optical spectroscopy. Predictin

Differentiation between rebound thymic hyperplasia and thymic relapse after chemotherapy in pediatric Hodgkin lymphoma

Rebound thymic hyperplasia (RTH) is a common phenomenon caused by stress factors such as chemotherapy (CTX) or radiotherapy, with an incidence between 44% and 67.7% in pediatric lymphoma. Misinterpretation of RTH and thymic lymphoma relapse (LR) may lead to unnecessary diagnostic procedures including invasive biopsies or treatment intensification. The aim of this study was to identify parameters that differentiate between RTH and thymic LR in the anterior mediastinum. After completion of CTX, we analyzed computed tomographies (CTs) and magnetic resonance images (MRIs) of 291 patients with classical Hodgkin lymphoma (CHL) and adequate imaging available from the European Network for Pediatric Hodgkin lymphoma C1 trial. In all patients with biopsy-proven LR, an additional fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT was assessed. Structure and morphologic configuration in addition to calcifications and presence of multiple masses in the thymic region and signs of extrathymic LR were evaluated. After CTX, a significant volume increase of new or growing masses in the thymic space occurred in 133 of 291 patients. Without biopsy, only 98 patients could be identified as RTH or LR. No single finding related to thymic regrowth allowed differentiation between RTH and LR. However, the vast majority of cases with thymic LR presented with additional increasing tumor masses (33/34). All RTH patients (64/64) presented with isolated thymic growth. Isolated thymic LR is very uncommon. CHL relapse should be suspected when increasing tumor masses are present in distant sites outside of the thymic area. Conversely, if regrowth of lymphoma in other sites can be excluded, isolated thymic mass after CTX likely represents RTH

Infância, exclusão social e educação como utopia realizável

A infância, como construção social, tem sofrido, no decurso da 2ª modernidade, processos de reinstitucionalização que, em larga medida, põem em causa as representações e imagens das crianças, dominantes nos últimos 200 anos. A análise da (re)construção das identidades sociais e das subjectividades infantis constitui, desse modo, uma tarefa teórica da mais exigente actualidade. O que, entretanto, aqui se assinala é que este processo de reinstitucionalização da infância, apesar da construção de consensos globais sobre os direitos das crianças, tem vindo a aumentar os factores e as condições de exclusão das gerações mais jovens face aos direitos sociais e da cidadania. Neste artigo inventariam-se alguns dos principais indicadores de exclusão, considerando diversos espaços estruturais, e assinalam-se alguns dos pontos de ruptura por onde pode passar a construção de uma educação escolar centrada na afirmação activa dos direitos das crianças.Along the second modernity, childhood, as a social construction, has undergone reinstatement processes that question the representations and images of children that have prevailed over last two hundred years. An analysis of the (re) construction of the social identities and childhood subjectivity thus constitute a theoretical task of the most contemporary exigence. Nevertheless, even though a global consensus about children’s rights has been constructed, the increase of factors and conditions that exclude the youngest generations from social rights and citizenship, induced by this reinstatement process of childhood, is here emphasized. This paper lists some of the main indicators of exclusion, considering different structural spaces, and pinpoints some turning points through which the construction of a school education centered on the active affirmation of the children’s rights could be attained.CIFPEC/CIEC - Centro de Investigação em Estudos da Criança, UM (UI 644 e 317 da FCT

Hodgkin lymphoma:hypodense lesions in mediastinal masses

Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with mediastinal involvement from the EuroNet-PHL-C1 trial and explored correlations of HDV with patient characteristics, mediastinal tumor volume and progression-free survival. HDV occurred in 350 of 1178 patients (29.7%), typically in larger mediastinal volumes. There were different patterns in appearance with single lesions found in 243 patients (69.4%), multiple lesions in 107 patients (30.6%). Well delineated lesions were found in 248 cases (70.1%), diffuse lesions were seen in 102 cases (29.1%). Clinically, B symptoms occurred more often in patients with HDV (47.7% compared to 35.0% without HDV (p = 0.039)) and patients with HDV tended to be in higher risk groups. Inadequate overall early-18F-FDG-PET-response was strongly correlated with the occurrence of hypodense lesions (p &lt; 0.001). Patients with total HDV &gt; 40 ml (n = 80) had a 5 year PFS of 79.6% compared to 89.7% (p = 0.01) in patients with HDV &lt; 40 ml or no HDV. This difference in PFS is not caused by treatment group alone. HDV is a common phenomenon in HL with mediastinal involvement.</p