Minimizing Metastatic Risk in Radiotherapy Fractionation Schedules

Metastasis is the process by which cells from a primary tumor disperse and form new tumors at distant anatomical locations. The treatment and prevention of metastatic cancer remains an extremely challenging problem. This work introduces a novel biologically motivated objective function to the radiation optimization community that takes into account metastatic risk instead of the status of the primary tumor. In this work, we consider the problem of developing fractionated irradiation schedules that minimize production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming framework is utilized to determine the optimal fractionation scheme. We evaluated our approach on a breast cancer case using the heart and the lung as organs-at-risk (OAR). For small tumor $\alpha/\beta$ values, hypo-fractionated schedules were optimal, which is consistent with standard models. However, for relatively larger $\alpha/\beta$ values, we found the type of schedule depended on various parameters such as the time when metastatic risk was evaluated, the $\alpha/\beta$ values of the OARs, and the normal tissue sparing factors. Interestingly, in contrast to standard models, hypo-fractionated and semi-hypo-fractionated schedules (large initial doses with doses tapering off with time) were suggested even with large tumor $\alpha$/$\beta$ values. Numerical results indicate potential for significant reduction in metastatic risk.Comment: 12 pages, 3 figures, 2 table

Role of hospitals in recovery from COVID-19: Reflections from hospital managers and frontliners in the Eastern Mediterranean Region on strengthening hospital resilience

BackgroundCOVID-19 highlighted the critical role that hospitals play throughout the prolonged response and continuous recovery stages of the pandemic. Yet, there is limited evidence related to hospitals in the recovery stage, particularly capturing the perspectives of hospital managers and frontliners in resource-restrained and humanitarian settings.ObjectiveThis paper aims to capture the perspectives of hospital managers and frontliners across the Eastern Mediterranean Region on (1) the role of hospitals in recovering from COVID-19, (2) Hospitals' expectations from public health institutions to enable recovery from COVID-19, (3) the Evaluation of hospital resilience before and through COVID-19, and (4) lessons to strengthen hospital resilience throughout the COVID-19 recovery.MethodsA multi-methods approach, triangulating a scoping review with qualitative findings from 64 semi-structured key-informant interviews and survey responses (n = 252), was used to gain a deeper context-specific understanding. Purposeful sampling with maximum diversity supported by snowballing was used and continued until reaching data saturation. Thematic analysis was conducted using MAXQDA and simple descriptive analysis using Microsoft Excel.FindingsIn recovering from COVID-19, hospital managers noted hospitals' role in health education, risk reduction, and services continuity and expected human resource management, financial and material resource mobilization, better leadership and coordination, and technical support through the provision of updated clinical evidence-based information from their public health institutions. Qualitative findings also indicated that hospital managers attributed considerable changes in hospitals' resilience capacities to the pandemic and suggested that strengthening hospitals' resilience required resilient staff, sustainable finance, and adaptive leadership and management.ConclusionHospitals are the backbone of health systems and a main point of contact for communities during emergencies; strengthening their resilience throughout the various stages of recovery is critical. Hospitals cannot be resilient in silos but rather require an integrated-whole-of-society-approach, inclusive of communities and other health systems actors

A systematic review and meta-analysis of the prevalence of toxoplasmosis in hemodialysis patients in Iran

OBJECTIVES Toxoplasmosis is a parasitic disease that occurs worldwide, with a wide range of complications in immunocompromised patients. This systematic review and meta-analysis was performed to evaluate the seroprevalence of Toxoplasma gondii among patients undergoing hemodialysis in Iran. METHODS We searched English and Persian databases for studies reporting T. gondii seroprevalence in Iranian hemodialysis patients through December 31, 2017. Inclusion and exclusion criteria were applied. RESULTS A total of 10 studies containing 1,865 participants (1,048 patients and 817 controls) met the eligibility criteria. Immunoglobulin G (IgG) antibodies against T. gondii were found in 58% (95% confidence interval [CI], 46 to 70) of hemodialysis patients and 40% (95% CI, 31 to 50) of healthy controls, while immunoglobulin M (IgM) antibodies were found in 2% (95% CI, 0 to 6) of hemodialysis patients and 0% (95% CI, 0 to 1) of healthy controls. The meta-analysis showed that hemodialysis patients were significantly more likely to be seropositive for IgG (odds ratio [OR], 2.04; 95% CI, 1.54 to 2.70; p<0.001) and IgM (OR, 2.53; 95% CI, 1.23 to 5.22; p<0.001) antibodies against T. gondii infection than healthy individuals. CONCLUSIONS The current study revealed a high prevalence of T. gondii infection in hemodialysis patients. Since hemodialysis patients are immunocompromised and T. gondii can cause serious clinical complications, we recommend that periodic screenings for T. gondii infection should be incorporated into the routine clinical care of these patients

Occurrence of Dioctophyme renale (Goeze, 1782) in road-killed canids of Iran and its public health implication

Dioctophyme renale, is the largest of parasitic nematodes, which infects different species of fish-eating carnivores worldwide. The northern provinces of Iran (Guilan and Mazandaran) located in south of the Caspian Sea are suitable for parasitic infections due to the mild and humid climatic conditions. From separate surveys of road-killed canids in various parts of the Caspian Sea littoral area in Iran, 70 carcasses were collected along the roads of Guilan and Mazandaran from 2015 to 2017. Dioctophyme renale detected by direct observation and molecular methods based on Cytochrome c oxidase subunit 1 (COX1 gene) sequencing analysis. Molecular investigation was also performed to validate prevalence and reduce false negative concerns. Dioctophyme renale was found in eight of 70 carnivores, mostly in the right kidneys, as well as two cases in the abdominal cavity of a dog and a golden jackal. More carcasses on the roads were seen with lacerated internal organs. Given the frequent number of giant kidney worms in canids in the region, the transmission of this zoonotic helminth to humans seems possible, since the area is a tourism hub in the country. The infection burden of this helminth should be investigated using DNA analysis of kidney tissue of road-killed carnivores in Iran. Keywords: Giant kidney worm, COX1, gene Carnivores, Conventional PCR, One healt

Keys to Unlock the Enigma of Ocular Toxocariasis: A Systematic Review and Meta-analysis

ABSTRACT Purpose: Ocular toxocariasis (OT) is a zoonotic infection caused by larval stages of Toxocara canis and T. cati. The current review and meta-analysis aimed to evaluate the global prevalence of OT. Methods: Five English (PubMed, Scopus, Science Direct, Web of Science, and Google Scholar) databases were explored and 101 articles met the inclusion criteria. Results: The pooled prevalence (95% confidence interval) of OT was higher in immunological studies (9%. 6–12%) than in studies that applied ophthalmic examination (1%. 1–2%). The lower middle-income level countries had the highest prevalence (6%. 2–12%) as well as the African region (10%. 7–13%). The highest infection rate (4%. 2–7%) was detected in the 1–25 mean age group. Conclusion: Regular anthelminthic treatment of cats and dogs, and removal of animal feces from public places must be considered. KEYWORDS Toxocariasis; ocular larva migrans; public health; humans; zoonose

Optimization of Radiation Dosing Schedules

University of Minnesota Ph.D. dissertation. January 2017. Major: Industrial and Systems Engineering. Advisor: Kevin Leder. 1 computer file (PDF); ix, 164 pages.Cancer is the second leading cause of death in the United States, claiming the lives of more than half a million people every year. Cancer is aggressively treated with surgery, chemotherapy, and radiotherapy. The primary focus of this thesis is to assist clinicians with hypothesis generation to design novel radiotherapy and chemoradiotherapy fractionation schemes that can improve the results of current clinical practices. We find solutions for some important questions in radiotherapy and chemotherapy fractionation problem. Chapter 2 extends the model developed in the literature to consider radiotherapy fractionated schedules in glioblastomas to best minimize toxicity arising in early- and late-responding tissues. To this end, we decomposed the problem into two separate solvable optimization tasks: optimal radiation schedule or the amount of radiation dose per fraction and optimization of the amount of time that passes between radiation doses. Chapter 3 proposes a method for determining the optimal fractionation in the presence of uncertainties in model parameters. We formulated our problem as a conservative model using robust optimization and a risk adjusted probabilistic formulation. A variable transformation and branch and bound algorithm is implemented to find the optimal regimen. Chapter 4 considers the radiotherapy fractionation problem with a new objective: minimizing production of metastatic cancer cells while keeping normal tissue damage below an acceptable level. A dynamic programming (DP) framework is utilized to determine the optimal fractionation scheme. In Chapter 5, we introduce a mathematical model to obtain optimal drug and radiation protocols in a chemoradiotherapy scheduling problem with two objectives: minimizing metastatic cancer cell populations at multiple potential sites and maintaining a minimum level of control to the primary tumor site. We derive closed-form expressions for optimal chemotherapy fractionation regimens in some special cases. A DP framework is used to determine the optimal radiotherapy fractionation regimen. Using discretization approach, the exact solution of the resulting DP algorithm is computationally intractable. We design efficient DP data structure and use some structural properties of the optimal solution to reduce the complexity of the resulting DP algorithm. In all chapters, we performed substantial numerical experiments to validate our results

Comprehensive performance study of magneto cantilevers as a candidate model for biological sensors used in lab-on-a-chip applications

In recent years, demand for biological sensors which are capable of fast and accurate detection of minor amounts of pathogens in real-time form has been intensified. Acoustic wave (AW) devices whose performance is determined by mass sensitivity parameters and quality factor are used in biological sensors as platforms with high quality. Yet, current AW devices are facing many challenges such as the low value of their quality factor in practical applications and also their difficulty to use in liquids. The main focus of this article is to study on the magnetostrictive sensors which include milli/microcantilever (MSMC) type. In comparison with AW devices, MSMC has a lot of advantages; (1) its actuation and sensing unit is wirelessly controlled. (2) Its fabrication process is easy. (3) It works well in liquids. (4) It has a high-quality factor (in the air > 500). Simulation results demonstrate that the amount of quality factor depends on environment properties (density and viscosity), MSMC geometry, and its resonant behavior of harmonic modes