Endurance and Resistance Training in Radically Treated Respiratory Cancer patients: A Pilot Study

Introduction. Respiratory cancer and its treatment are known to contribute to muscle weakness and functional impairment. Aim. To assess the effects of rehabilitation in patients with respiratory cancer. Methods. Radically treated respiratory cancer patients were included in a 12-week multidisciplinary rehabilitation program. Results. 16 patients (age: 61 ± 7 years; FEV1: 57 ± 16% pred.) showed a reduced exercise tolerance (VO2max: 56 ± 15% pred.; 6 MWD: 67 ± 11% pred.), muscle force (PImax: 54 ± 22% pred.; QF: 67 ± 16% pred.), and quality of life (CRDQd: 17 ± 5 points; CRDQf: 16 ± 5 points). Exercise tolerance, muscle force, and quality of life improved significantly after rehabilitation. Conclusion. Radically treated patients with respiratory cancer have a decreased exercise capacity, muscle force, and quality of life. 12 weeks of rehabilitation leads to a significant improvement in exercise capacity, respiratory muscle force, and quality of life

Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study

To improve the prognosis of limited stage small cell lung cancer (LS-SCLC) the addition of concurrent thoracic radiotherapy to a platinum-containing regimen is important. In the Netherlands, we initiated a multicenter, phase II study, of the combination of four cycles of carboplatin (AUC 5), paclitaxel (200 mg m−2) and etoposide (2 × 50 mg orally for 5 days) combined with 45 Gy (daily fractions of 1.8 Gy). The radiation was given to the involved field and concurrently with the second and third chemotherapy cycle. Patients with a partial or complete response received prophylactic cranial irradiation to a dose of 30 Gy. From January 1999 to December 2001, 37 of the 38 patients with LS-SCLC entered were eligible for toxicity analysis and response. Grade 3 and 4 haematological toxicity occurred in 57% (21/37) with febrile neutropenia in 24% (9/37). There were no treatment-related deaths or other grade 4 toxicity. Grade 3 toxicities were oesophagitis (27%), radiation pneumonitis (6%), anorexia (14%), nausea (16%), dyspnea (19%) and lethargy (22%). The objective response rate was 92% (95% confidence interval (CI) 80–98%) with a median survival time of 19.5 months (95% CI 12.8–29.2). The 1-, 2- and 5-year survival rate was 70, 47 and 27%, respectively. In field local recurrences occurred in six patients. Distant metastases were observed in 19 patients of which 13 in the brain. This study indicates that combination chemotherapy with concurrent involved-field radiation therapy is an effective treatment for LS-SCLC. Despite PCI, the brain remained the most important site of recurrence

A new silicon detector for microdosimetry applications in proton therapy

A silicon-on-insulator diode array with a sensitive depth of 10 microns has been developed for microdosimetry in proton therapy. The detector was coupled to a radiation-hard charge sensitive amplifier with the probe assembly capable of measuring an LET down to 1.2 keV/μm. The device has been successfully tested at two proton therapy centers. The 230 MeV Northeastern Proton Therapy Center, Boston and the 250 MeV Proton Medical Research Center at Tsukuba, Japan. The device offers much improved spatial resolution compared with a proportional gas counter particularly in the critical high dose region around the proton Bragg peak. Due to its small cross-sectional area (0.04 cm2) measurements may also be made in facilities with short high intensity beams

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient dis- ruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, in- trinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional che- motherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequence-specific targeting of mRNAs causing mRNA degradation or translational repression. Accumulating evidence suggests that impairment of candidate miRNAs may be involved in the acquisition of tumor cell resistance to conventional chemotherapy and novel biological agents by affecting the drug sensitivity of cancer cells. The modulation of these miR- NAs, using antagomiRs or miRNA mimics, can restore key gene networks and signaling pathways, and optimize anti- cancer therapies by inhibition of tumor cell proliferation and increasing the drug sensitivity. Therefore, miRNA-based therapeutics provides an attractive anti-tumor approach for developing new and more effective individualized therapeutic strategies, improving drug efficiency, and for predicting the response to different anticancer drugs. In this review, we pre- sent an overview on the role of miRNAs in resistance mechanisms of NSCLC, discussing the main studies on the aberra- tions in apoptosis, cell cycle and DNA damage repair pathways, as well as in novel drug targets

Nonlinear and delayed impacts of climate on dengue risk in Barbados: A modelling study

Background: Over the last 5 years (2013–2017), the Caribbean region has faced an unprecedented crisis of co-occurring epidemics of febrile illness due to arboviruses transmitted by the Aedes sp. mosquito (dengue, chikungunya, and Zika). Since 2013, the Caribbean island of Barbados has experienced 3 dengue outbreaks, 1 chikungunya outbreak, and 1 Zika fever outbreak. Prior studies have demonstrated that climate variability influences arbovirus transmission and vector population dynamics in the region, indicating the potential to develop public health interventions using climate information. The aim of this study is to quantify the nonlinear and delayed effects of climate indicators, such as drought and extreme rainfall, on dengue risk in Barbados from 1999 to 2016. Methods and findings: Distributed lag nonlinear models (DLNMs) coupled with a hierarchal mixed-model framework were used to understand the exposure–lag–response association between dengue relative risk and key climate indicators, including the standardised precipitation index (SPI) and minimum temperature (Tmin). The model parameters were estimated in a Bayesian framework to produce probabilistic predictions of exceeding an island-specific outbreak threshold. The ability of the model to successfully detect outbreaks was assessed and compared to a baseline model, representative of standard dengue surveillance practice. Drought conditions were found to positively influence dengue relative risk at long lead times of up to 5 months, while excess rainfall increased the risk at shorter lead times between 1 and 2 months. The SPI averaged over a 6-month period (SPI-6), designed to monitor drought and extreme rainfall, better explained variations in dengue risk than monthly precipitation data measured in millimetres. Tmin was found to be a better predictor than mean and maximum temperature. Furthermore, including bidimensional exposure–lag–response functions of these indicators—rather than linear effects for individual lags—more appropriately described the climate–disease associations than traditional modelling approaches. In prediction mode, the model was successfully able to distinguish outbreaks from nonoutbreaks for most years, with an overall proportion of correct predictions (hits and correct rejections) of 86% (81%:91%) compared with 64% (58%:71%) for the baseline model. The ability of the model to predict dengue outbreaks in recent years was complicated by the lack of data on the emergence of new arboviruses, including chikungunya and Zika. Conclusion: We present a modelling approach to infer the risk of dengue outbreaks given the cumulative effect of climate variations in the months leading up to an outbreak. By combining the dengue prediction model with climate indicators, which are routinely monitored and forecasted by the Regional Climate Centre (RCC) at the Caribbean Institute for Meteorology and Hydrology (CIMH), probabilistic dengue outlooks could be included in the Caribbean Health-Climatic Bulletin, issued on a quarterly basis to provide climate-smart decision-making guidance for Caribbean health practitioners. This flexible modelling approach could be extended to model the risk of dengue and other arboviruses in the Caribbean region

Breath analysis by gas chromatography-mass spectrometry and electronic nose to screen for pleural mesothelioma : a cross-sectional case-control study

Rationale: Malignant pleural mesothelioma (MPM) is mainly caused by previous exposure to asbestos fibers and has a poor prognosis. Due to a long latency period between exposure and diagnosis, MPM incidence is expected to peak between 2020-2025. Screening of asbestos-exposed individuals is believed to improve early detection and hence, MPM management. Recent developments focus on breath analysis for screening since breath contains volatile organic compounds (VOCs) which reflect the cell’s metabolism. Objectives: The goal of this cross-sectional, case-control study is to identify VOCs in exhaled breath of MPM patients with gas chromatography-mass spectrometry (GC-MS) and to assess breath analysis to screen for MPM using an electronic nose (eNose). Methods: Breath and background samples were taken from 64 subjects: 16 healthy controls (HC), 19 asymptomatic former asbestos-exposed (AEx) individuals, 15 patients with benign asbestos-related diseases (ARD) and 14 MPM patients. Samples were analyzed with both GC-MS and eNose. Results: Using GC-MS, AEx individuals were discriminated from MPM patients with 97% accuracy, with diethyl ether, limonene, nonanal, methylcyclopentane and cyclohexane as important VOCs. This was validated by eNose analysis. MPM patients were discriminated from AEx+ARD participants by GC-MS and eNose with 94% and 74% accuracy, respectively. The sensitivity, specificity, positive and negative predictive values were 100%, 91%, 82%, 100% for GC-MS and 82%, 55%, 82%, 55% for eNose, respectively. Conclusion: This study shows accurate discrimination of patients with MPM from asymptomatic asbestos-exposed persons at risk by GC-MS and eNose analysis of exhaled VOCs and provides proof-of-principle of breath analysis for MPM screening

European climate optimum and enhanced Greenland melt during the Last Interglacial

The Last Interglacial climatic optimum, ca. 128 ka, is the most recent climate interval signifi cantly warmer than present, providing an analogue (albeit imperfect) for ongoing global warming and the effects of Greenland Ice Sheet (GIS) melting on climate over the coming millennium. While some climate models predict an Atlantic meridional overturning circulation (AMOC) strengthening in response to GIS melting, others simulate weakening, leading to cooling in Europe. Here, we present evidence from new proxy-based paleoclimate and ocean circulation reconstructions that show that the strongest warming in western Europe coincided with maximum GIS meltwater runoff and a weaker AMOC early in the Last Interglacial. By performing a series of climate model sensitivity experiments, including enhanced GIS melting, we were able to simulate this confi guration of the Last Interglacial climate system and infer information on AMOC slowdown and related climate effects. These experiments suggest that GIS melt inhibited deep convection off the southern coast of Greenland, cooling local climate and reducing AMOC by ~24% of its present strength. However, GIS melt did not perturb overturning in the Nordic Seas, leaving heat transport to, and thereby temperatures in, Europe unaffected. © 2012 Geological Society of America