Compensation of scintillator sensitivity loss due to irradiation damage

International audienceComputed tomography reconstruction methods consider a normalized input signal. Images must be corrected using both a flat field record and a dark field record. Whereas there is no physical reason why the dark field would evolve during the experiment, the flat field may vary with time. One possible cause for flat field variation is irradiation damage which indeed occurs on the camera considered in this study. This paper considers different methods for taking into account the evolution of flat field due to irradiation damage. The aim is to keep the error resulting from bias on flat field at the same level than signal to noise ratio on fully illuminated areas of images, that is to say an error of 1%. Though this is still a work in progress, the methods proposed will be discussed and compared

The relationship between traits optimism and anxiety and health-related quality of life in patients hospitalized for chronic diseases: data from the SATISQOL study.

International audienceBACKGROUND: The impact of psychological factors is often taken into account in the evaluation of quality of life. However, the effect of optimism and trait anxiety remains controversial and they are rarely studied simultaneously. We aimed to study the effect of this factor on health-related quality of life (HRQOL) of patients after a hospitalization in relation with their chronic disease. METHODS: Using cross-sectional data from the SATISQOL cohort, we conducted a multicentric study, including patients hospitalized for an intervention in connection with their chronic disease. Six months after hospitalization, patients completed a generic HRQOL questionnaire (SF-36), and the STAI and LOT-R questionnaires to evaluate optimism and trait anxiety. We studied the effect of each trait on HRQOL separately, and simultaneously, taking account of their interaction in 3 models, using an ANOVA. RESULTS: In this study, 1529 patients were included in three participating hospitals and there existed wide diversity in the chronic diseases in our population. The HRQOL score increased for all dimensions of SF36 between 15,8 and 44,5 when the level of anxiety decreased (p < 0.0001) for the model 1, assessing the effect of anxiety on HRQOL and increased for all dimensions of SF36 between 3.1 and 12.7 with increasing level of optimism (< 0.0001) in the model 2 assessing the effect of optimism on HRQOL. In the model 3, assessing the effect of both anxiety and optimism on HRQOL, and their interaction, the HRQOL score for all dimensions of the SF36 increased when the level of anxiety decreased (p < 0.0001). It increased with increasing level of optimism (p < 0.006) in the model for all dimensions of SF36 except the Role Physical dimension. In this model, interaction between anxiety and optimism was significant for the Social Functioning dimension (p = 0.0021). CONCLUSIONS: Optimism and trait anxiety appeared to be significantly correlated with HRQOL. Furthermore, an interaction existed between the trait anxiety and optimism for some dimensions of SF36. Contrary to optimism, it seems essential to evaluate trait anxiety in future studies about HRQOL, since it could represent a confounding factor

High-Performance Multi-Rail Support with the NewMadeleine Communication Library

International audienceThis paper focuses on message transfers across multiple heterogeneous high-performance networks in the NewMadeleine Communication Library. NewMadeleine features a modular design that allows the user to easily implement load-balancing strategies efficiently exploiting the underlying network but without being aware of the low-level interface. Several strategies are studied and preliminary results are given. They show that performance of network transfers can be improved by using carefully designed strategies that take into account NIC activity

NewMadeleine: An Efficient Support for High-Performance Networks in MPICH2

International audienceThis paper describes how the NewMadeleine communication library has been integrated within the MPICH2 MPI implementation and the benefits brought. NewMadeleine is integrated as a Nemesis network module but the upper layers and in particular the CH3 layer has been modified. By doing so, we allow NewMadeleine to fully deliver its performance to an MPI application. NewMadeleine features sophisticated strategies for sending messages and natively supports multirail network configurations, even heterogeneous ones. It also uses a software element called PIOMan that uses multithreading in order to enhance reactivity and create more efficient progress engines. We show various results that prove that NewMadeleine is indeed well suited as a low-level communication library for building MPI implementations

Effects of age, sex, body mass index and APOE genotype on cardiovascular biomarker response to an n-3 polyunsaturated fatty acid supplementation

Objectives: To test whether age, sex, body mass index (BMI), and the apolipoprotein E (APOE) genotype are associated with the metabolic response to an n-3 polyunsaturated fatty acid (PUFA) supplementation. Methods: 210 subjects followed a 2-week run-in period based on Canada’s Food Guide and underwent a 6-week 5 g/day fish oil supplementation (1.9 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Cardiovascular disease risk factors were measured. Results: n-3 PUFA supplementation was associated with a decrease of plasma triglyceride levels (p = 0.0002) as well as with an increase of fasting glucose (FG) levels (p = 0.02). Age was associated with post-intervention plasma total cholesterol (p = 0.01), low-density lipoprotein cholesterol (p = 0.007), apolipoprotein B (p = 0.04), and insulin (p = 0.002) levels. Sex was associated with post-intervention plasma high-density lipoprotein cholesterol levels (p = 0.02). BMI was associated with plasma FG (p = 0.02) and insulin levels (p < 0.0001) after the supplementation. APOE genotype was associated with FG (p = 0.001) and C-reactive protein levels (p = 0.03) after the supplementation. Conclusion: Results suggest that age, sex, BMI, and the APOE genotype contribute to the inter-individual variability observed in the metabolic response to an n-3 PUFA supplementation

Haematopoietic stem cell transplantation in South Africa : current limitations and future perspectives

The growing need for haematopoietic stem cell transplantation (HSCT) is reflected in the increasing number of transplants performed globally each year. HSCT provides life-changing and potentially curative therapy for a range of pathologies including haematological malignancies; other indications include certain congenital and acquired disorders of the haematopoietic system, autoimmune conditions and hereditary diseases. The primary goals of HSCT are either to replace haematopoietic stem and progenitor cells (HSPC) following myeloablative chemotherapy or to cure the original pathology with allogeneic HSPCs. Success depends on optimal outcomes at various stages of the procedure including mobilisation of marrow stem/progenitor cells for harvesting from the patient or donor, long-term and sustainable engraftment of these cells in the recipient, and prevention of graft-versus-host disease in the case of allogeneic HSCT. Challenges in South Africa include high cost, limited infrastructure and lack of appropriately trained staff, as well as limitations in securing suitable haematopoietic stem cell donors. This review aims to provide an overview of HSCT and some of the challenges that are faced in the South African context.http://www.samj.org.zapm2020ImmunologyPhysiolog

Cell fate following irradiation of MDA-MB-231 and MCF-7 breast cancer cells pre-exposed to the setrahydroisoquinoline sulfamate microtubule disruptor STX3451

The compound STX3451 is not commercially available.SUPPLEMENTARY MATERIAL : TABLE S1: Data analysis comparing flow cytometric quantification of individual cell cycle phases across 24-h and 48-h timelines. TABLE S2: Data analysis of flow cytometric quantification of the cell cycle distribution in MCF-7 cells exposed to STX3451 and radiation. TABLE S3: Statistical analysis of cell cycle distribution in MCF-7 cells exposed to STX3451 and radiation. TABLE S4: Data analysis comparing flow cytometric quantification of individual cell cycle phases across 24-h and 48-h timelines in MDA-MB-231 cells. TABLE S5: Statistical analysis of cell cycle progression in MDA-MB-231 cells exposed to STX3451 and radiation. TABLE S6: Statistical analysis of cell cycle distribution in MDA-MB-231 cells exposed to STX3451 and radiation. TABLE S7: Annexin-V analysis of MCF-7 cells 48-h. TABLE S8: Annexin-V statistical analysis of MDA-MB-231 48-h. TABLE S9: Colony formation in MCF-7 cells. TABLE S10: Colony formation in MDA-MB-231 cells. TABLE S11: The total number of Mn in MCF-7 cells that were terminated 2- and 24-h after radiation. TABLE S12: The total number of Mn in MDA-MB-231 cells terminated 2- and 24-h after radiation. TABLE S13: Number of Mn per cell in MCF-7 cells terminated 2-h after radiation. TABLE S14: Number of Mn per cell in MCF-7 cells terminated 24-h after radiation. TABLE S15: Number of Mn per cell in MDA-MB-231 cells terminated 2-h after radiation. TABLE S16: The number of Mn per cell in MDA-MB-231 cells that were terminated 24-h after radiation. TABLE S17: Superoxide detection in MCF-7 cells treated with the various modalities. TABLE S18: Superoxide detection in pre-sensitized MDA-MB-231 cells. TABLE S19: Statistical analysis of ATM expression in combination treated MCF-7 and MDA-MB-231 cells 2- and 24-h post-radiation. TABLE S20: Nontumored animal toxicity assay; VIDEO S1: not applicable.Atetrahydroisoquinoline (THIQ) core is able tomimic theAand B rings of 2-methoxyestradiol (2ME2), an endogenous estrogen metabolite that demonstrates promising anticancer properties primarily by disrupting microtubule dynamic instability parameters, but has very poor pharmaceutical properties that can be improved by sulfamoylation. The non-steroidal THIQ-based microtubule disruptor 2-(3-bromo-4,5-dimethoxybenzyl)-7-methoxy-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (STX3451), with enhanced pharmacokinetic and pharmacodynamic profiles, was explored for the first time in radiation biology. We investigated whether 24 h pre-treatment with STX3451 could pre-sensitize MCF-7 and MDA-MB-231 breast cancer cells to radiation. This regimen showed a clear increase in cytotoxicity compared to the individual modalities, results that were contiguous in spectrophotometric analysis, flow cytometric quantification of apoptosis induction, clonogenic studies and microscopy techniques. Drug pre-treatment increased radiation-induced DNA damage, with statistically more double-strand (ds) DNA breaks demonstrated. The latter could be due to the induction of a radiation-sensitive metaphase block or the increased levels of reactive oxygen species, both evident after compound exposure. STX3451 pre-exposure may also delay DNA repair mechanisms, as the DNA damage response element ataxia telangiectasia mutated (ATM) was depressed. These in vitro findings may translate into in vivo models, with the ultimate aim of reducing both radiation and drug doses for maximal clinical effect with minimal adverse effects.The Research Committee of the University of Pretoria, the Struwig-Germeshuysen Trust, the Cancer Association of South Africa (CANSA), the National Research Foundation (NRF) and the Research Development Programme of the University of Pretoria (RDP-UP).https://www.mdpi.com/journal/moleculesam2023Physiolog

Rapidly developed, optimized, and applied wastewater surveillance system for real-time monitoring of low-incidence, high-impact MPOX outbreak

Recent MPOX viral resurgences have mobilized public health agencies around the world. Recognizing the significant risk of MPOX outbreaks, large-scale human testing, and immunization campaigns have been initiated by local, national, and global public health authorities. Recently, traditional clinical surveillance campaigns for MPOX have been complemented with wastewater surveillance (WWS), building on the effectiveness of existing wastewater programs that were built to monitor SARS-CoV-2 and recently expanded to include influenza and respiratory syncytial virus surveillance in wastewaters. In the present study, we demonstrate and further support the finding that MPOX viral fragments agglomerate in the wastewater solids fraction. Furthermore, this study demonstrates that the current, most commonly used MPOX assays are equally effective at detecting low titers of MPOX viral signal in wastewaters. Finally, MPOX WWS is shown to be more effective at passively tracking outbreaks and/or resurgences of the disease than clinical testing alone in smaller communities with low human clinical case counts of MPOX

Toxicity Associated with Stavudine Dose Reduction from 40 to 30 mg in First-Line Antiretroviral Therapy

To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors

Wastewater-based surveillance identifies start to the pediatric respiratory syncytial virus season in two cities in Ontario, Canada

IntroductionDetection of community respiratory syncytial virus (RSV) infections informs the timing of immunoprophylaxis programs and hospital preparedness for surging pediatric volumes. In many jurisdictions, this relies upon RSV clinical test positivity and hospitalization (RSVH) trends, which are lagging indicators. Wastewater-based surveillance (WBS) may be a novel strategy to accurately identify the start of the RSV season and guide immunoprophylaxis administration and hospital preparedness.MethodsWe compared citywide wastewater samples and pediatric RSVH in Ottawa and Hamilton between August 1, 2022, and March 5, 2023. 24-h composite wastewater samples were collected daily and 5 days a week at the wastewater treatment facilities in Ottawa and Hamilton, Ontario, Canada, respectively. RSV WBS samples were analyzed in real-time for RSV by RT-qPCR.ResultsRSV WBS measurements in both Ottawa and Hamilton showed a lead time of 12 days when comparing the WBS data set to pediatric RSVH data set (Spearman’s ρ = 0.90). WBS identify early RSV community transmission and declared the start of the RSV season 36 and 12 days in advance of the provincial RSV season start (October 31) for the city of Ottawa and Hamilton, respectively. The differing RSV start dates in the two cities is likely associated with geographical and regional variation in the incidence of RSV between the cities.DiscussionQuantifying RSV in municipal wastewater forecasted a 12-day lead time of the pediatric RSVH surge and an earlier season start date compared to the provincial start date. These findings suggest an important role for RSV WBS to inform regional health system preparedness, reduce RSV burden, and understand variations in community-related illness as novel RSV vaccines and monoclonal antibodies become available