Quantification of the radiosensitization effect of high-Znanoparticles on photon irradiated cells: combining Monte Carlo simulations and an analytical approach to the local effect model.

In vitroexperiments show significant reduction in the survival fraction of cells under irradiation treatments assisted with high-Znanoparticles (NPs). In order to predict the radiosensitization effect of NPs, a modification of the local effect model (LEM), in which the energy deposition from NPs is assessed by Monte Carlo (MC) radiation transport codes, has been employed in the past. In this work, a combined framework that splits the consideration of the radiosensitization effect into two steps is proposed. The first step is the evaluation of the radial dose distribution (RDD) around a single NP ionized by a photon beam with given energy spectrum using MC simulation. Thereafter, an analytical approach based of the LEM and the calculated RDD is used for evaluation of the average dose and the average number of lethal lesions in a cell target due to a set of ionized NPs. The explicit expressions were derived for the case of a spherical cell target and the RDD describing by the power law function. RDDs around gold NPs (GNPs) of different radii were simulated using the MC technique and fitted by a power law function. The fitted RDD and the derived expressions were applied for calculation of the survival curves and relative biological effectiveness of a spherical MDA-MB-231 cell loaded with GNPs and irradiated with monoenergetic photons of 10-150 keV. The proposed framework provides a practical alternative to time-consuming MC simulations, enabling the assessment of the response of cell cultures to an irradiation treatment assisted with NPs for a wide variety of cell geometries, NP distributions and irradiation schemes.

Incidence and outcomes of healthcare-associated COVID-19 infections: significance of delayed diagnosis and correlation with staff absence.

BACKGROUND: The sudden increase in COVID-19 admissions in hospitals during the SARS-CoV-2 pandemic of 2020 led to onward transmissions among vulnerable inpatients. AIMS: This study was performed to evaluate the prevalence and clinical outcomes of healthcare-associated COVID-19 infections (HA-COVID-19) during the 2020 epidemic and study factors which may promote or correlate with its incidence and transmission in a Teaching Hospital NHS Trust in London, UK. METHODS: Electronic laboratory, patient and staff self-reported sickness records were interrogated from 1st March to 18th April 2020. HA-COVID-19 was defined as COVID-19 with symptom onset within >14 days of admission. Test performance of a single combined throat and nose swab (CTNS) for patient placement was calculated. The effect of delayed RNA positivity (DRP, defined as >48 h delay), staff self-reported COVID-19 sickness absence, hospital bed occupancy, and community incidence of COVID-19 was compared for HA-COVID-19. The incidence of other significant hospital-acquired bacterial infections (HAB) was compared with previous years. RESULTS: Fifty-eight HA-COVID-19 (7.1%) cases were identified. When compared with community-acquired admitted cases (CA-COVID-19), significant differences were observed in age (P=0.018), ethnicity (P<0.001) and comorbidity burden (P<0.001) but not in 30-day mortality. CTNS-negative predictive value was 60.3%. DRP was associated with greater mortality (P=0.034) and incidence of HA-COVID-19 correlated positively with DRP (R = 0.7108) and staff sickness absence (R = 0.7815). For the study period HAB rates were similar to the previous 2 years. CONCLUSIONS: Early diagnosis and isolation of COVID-19 patients would help to reduce transmission. A single CTNS has limited value in segregating patients into positive and negative pathways.

Nanoscale dose deposition in cell structures under X-ray irradiation treatment assisted with nanoparticles: An analytical approach to the relative biological effectiveness.

In this study, an analytical model for the assessment of the modification of cell culture survival under ionizing radiation assisted with nanoparticles (NPs) is presented. The model starts from the radial dose deposition around a single NP, which is used to describe the dose deposition in a cell structure with embedded NPs and, in turn, to evaluate the number of lesions formed by ionizing radiation. The model is applied to the calculation of relative biological effectiveness values for cells exposed to 0.5mg/g of uniformly dispersed NPs with a radius of 10nm made of Fe, I, Gd, Hf, Pt and Au and irradiated with X-rays of energies 20keV higher than the element K-shell binding energy.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

[Model for estimating costs per student at the medical sciences campus]. / Modelo para estimar costo por estudiante en el recinto de ciencias médicas.

The information about cost is considered at present essential for decision making in institutions of higher education. The way this information is collected, and the determination of the variables and cost objectives to be considered on the model depend on the particular characteristics and the objectives of the institution. This article describes the model developed for estimating costs per student and per year of study in the program, in the Medical Sciences Campus of the University of Puerto Rico. The information about costs is never completely precise yet, the model presented has tried to consider, whenever possible, all the cost elements that contribute to approximate the estimates to the real costs.