Thermoregulation in P. Terraenovae aggregations, an agent-based approach

International audienceThis paper deals with an important issue of forensic entomology: the estimation of the temperature in a "maggot mass". An agent-based model of the thermoregulation behaviour of fly (Protophormia terraenovae) larvae is described. Simulation results show that the model reproduces an important observed pattern and thus, might be used in entomological expertises

Quality of life after the initial treatments of non-small cell lung cancer: a persistent predictor for patients' survival.

International audienceBACKGROUND: Health-related quality of life (HRQoL) before treatment may predict survival of patients with non-small-cell lung cancer (NSCLC). We investigated the predictive role of HRQoL after the initial treatments, on the survival of these patients. METHODS: A prospective multi-center study conducted in northeastern France. The SF-36 and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (QLQ C-30) were mailed to patients 3 months after the end of the diagnostic process. High scores for functioning dimensions on both questionnaires indicated better QoL, and low scores for symptom dimensions on the QLQ C-30 indicated few symptoms. Cox regression modeling was used to identify predictive factors of survival. RESULTS: In total, 230 (63.5%) patients responded to the SF-36 and QLQ C-30. Before completing the questionnaires, almost 60% of patients had undergone some chemotherapy, about 10% underwent radio/chemotherapy or both and more than 30% underwent surgery or surgery plus chemo/radiotherapy.On SF-36, the highest mean score was for social functioning dimension (55.5 ± 28), and the lowest was for the physical role dimension (17.9 ± 32.2).On QLQ C-30, for the functioning dimensions, the highest mean score was for cognitive functioning (74.6 ± 25.9) and the lowest was for role functioning (47.2 ± 34.1). For symptom dimensions, the lowest score was for diarrhoea (11.5 ± 24.2) and the highest was for fatigue (59.7 ± 27.7).On multivariate analysis, high bodily pain, social functioning and general health scores (SF-36) were associated with a lower risk of death (hazard ratio 0.580; 95% confidence interval [0.400-0.840], p = 0.004; HR 0.652 [0.455-0.935], p < 0.02; HR 0.625 [0.437-0.895] respectively). Better general QoL on QLQ C-30 was related to lower risk of death (HR 0.689 [0.501-0.946], p = 0.02). CONCLUSION: Adding to previous knowledge about factors that may influence patients QoL, this study shows a persisting relationship between better perceived health in HRQoL after the initial treatment of NSCLC and better survival

Item response theory and factor analysis as a mean to characterize occurrence of response shift in a longitudinal quality of life study in breast cancer patients.

International audienceBACKGROUND: The occurrence of response shift (RS) in longitudinal health-related quality of life (HRQoL) studies, reflecting patient adaptation to disease, has already been demonstrated. Several methods have been developed to detect the three different types of response shift (RS), i.e. recalibration RS, 2) reprioritization RS, and 3) reconceptualization RS. We investigated two complementary methods that characterize the occurrence of RS: factor analysis, comprising Principal Component Analysis (PCA) and Multiple Correspondence Analysis (MCA), and a method of Item Response Theory (IRT). METHODS: Breast cancer patients (n = 381) completed the EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires at baseline, immediately following surgery, and three and six months after surgery, according to the "then-test/post-test" design. Recalibration was explored using MCA and a model of IRT, called the Linear Logistic Model with Relaxed Assumptions (LLRA) using the then-test method. Principal Component Analysis (PCA) was used to explore reconceptualization and reprioritization. RESULTS: MCA highlighted the main profiles of recalibration: patients with high HRQoL level report a slightly worse HRQoL level retrospectively and vice versa. The LLRA model indicated a downward or upward recalibration for each dimension. At six months, the recalibration effect was statistically significant for 11/22 dimensions of the QLQ-C30 and BR23 according to the LLRA model (p ≤ 0.001). Regarding the QLQ-C30, PCA indicated a reprioritization of symptom scales and reconceptualization via an increased correlation between functional scales. CONCLUSIONS: Our findings demonstrate the usefulness of these analyses in characterizing the occurrence of RS. MCA and IRT model had convergent results with then-test method to characterize recalibration component of RS. PCA is an indirect method in investigating the reprioritization and reconceptualization components of RS

Incidence and main factors associated with early unplanned hospital readmission among French medical inpatients aged 75 and over admitted through emergency units

Background: among elderly patients, readmission in the month following hospital discharge is a frequent occurrence which involves a risk of functional decline, particularly among frail subjects. While previous studies have identified risk factors of early readmission, geriatric syndromes, as markers of frailty have not been assessed as potential predictors. Objective: to evaluate the risk of early unplanned readmission, and to identify predictors in inpatients aged 75 and over, admitted to medical wards through emergency departments. Design: prospective multi-centre study. Setting: nine French hospitals. Subjects: one thousand three hundred and six medical inpatients, aged 75 and older admitted through emergency departments (SAFES cohort). Methods: using logistic regressions, factors associated with early unplanned re-hospitalisation (defined as first unplanned readmission in the thirty days after discharge) were identified using data from the first week of hospital index stay obtained by comprehensive geriatric assessment. Results: data from a thousand out of 1,306 inpatients were analysed. Early unplanned readmission occurred in 14.2% of inpatients and was not related with sociodemographic characteristics, comorbidity burden or cognitive impairment. Pressure sores (OR=2.05, 95% CI = 1.0-3.9), poor overall condition (OR = 2.01, 95% CI = 1.3-3.0), recent loss of ability for self-feeding (OR = 1.9, 95% CI = 1.2-2.9), prior hospitalisation during the last 3 months (OR = 1.6, 95% CI = 1.1-2.5) were found to be risk factors, while sight disorders appeared as negatively associated (OR = 0.5, 95% CI = 0.3--0.8). Conclusions: markers of frailty (poor overall condition, pressure sores, prior hospitalisation) or severe disability (for self-feeding) were the most important predictors of early readmission among elderly medical inpatients. Early identification could facilitate preventive strategies in risk grou

Does the availability of positron emission tomography modify diagnostic strategies for solitary pulmonary nodules? An observational study in France

International audienceBACKGROUND: Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization. METHODS: In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002-2003, and 20,075 in an after-PET period, 2004-2005. Patients were followed through their physician, who was responsible for diagnostic management. RESULTS: We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups. CONCLUSION: In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches

The Athena X-ray Integral Field Unit (X-IFU)

The X-ray Integral Field Unit (X-IFU) is the high resolution X-ray spectrometer of the ESA Athena X-ray observatory. Over a field of view of 5' equivalent diameter, it will deliver X-ray spectra from 0.2 to 12 keV with a spectral resolution of 2.5 eV up to 7 keV on similar to 5 '' pixels. The X-IFU is based on a large format array of super-conducting molybdenum-gold Transition Edge Sensors cooled at similar to 90 mK, each coupled with an absorber made of gold and bismuth with a pitch of 249 mu m. A cryogenic anti-coincidence detector located underneath the prime TES array enables the non X-ray background to be reduced. A bath temperature of similar to 50 mK is obtained by a series of mechanical coolers combining 15K Pulse Tubes, 4K and 2K Joule-Thomson coolers which pre-cool a sub Kelvin cooler made of a He-3 sorption cooler coupled with an Adiabatic Demagnetization Refrigerator. Frequency domain multiplexing enables to read out 40 pixels in one single channel. A photon interacting with an absorber leads to a current pulse, amplified by the readout electronics and whose shape is reconstructed on board to recover its energy with high accuracy. The defocusing capability offered by the Athena movable mirror assembly enables the X-IFU to observe the brightest X-ray sources of the sky (up to Crab-like intensities) by spreading the telescope point spread function over hundreds of pixels. Thus the X-IFU delivers low pile-up, high throughput (> 50%), and typically 10 eV spectral resolution at 1 Crab intensities, i.e. a factor of 10 or more better than Silicon based X-ray detectors. In this paper, the current X-IFU baseline is presented, together with an assessment of its anticipated performance in terms of spectral resolution, background, and count rate capability. The X-IFU baseline configuration will be subject to a preliminary requirement review that is scheduled at the end of 2018. The X-IFU will be provided by an international consortium led by France, the Netherlands and Italy, with further ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Ireland, Poland, Spain, Switzerland and contributions from Japan and the United States.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival