Perspective review of what is needed for molecular-specific fluorescence-guided surgery

Molecular image-guided surgery has the potential for translating the tools of molecular pathology to real-time guidance in surgery. As a whole, there are incredibly positive indicators of growth, including the first United States Food and Drug Administration clearance of an enzyme-biosynthetic-activated probe for surgery guidance, and a growing number of companies producing agents and imaging systems. The strengths and opportunities must be continued but are hampered by important weaknesses and threats within the field. A key issue to solve is the inability of macroscopic imaging tools to resolve microscopic biological disease heterogeneity and the limitations in microscopic systems matching surgery workflow. A related issue is that parsing out true molecular-specific uptake from simple-enhanced permeability and retention is hard and requires extensive pathologic analysis or multiple in vivo tests, comparing fluorescence accumulation with standard histopathology and immunohistochemistry. A related concern in the field is the over-reliance on a finite number of chosen preclinical models, leading to early clinical translation when the probe might not be optimized for high intertumor variation or intratumor heterogeneity. The ultimate potential may require multiple probes, as are used in molecular pathology, and a combination with ultrahigh-resolution imaging and image recognition systems, which capture the data at a finer granularity than is possible by the surgeon. Alternatively, one might choose a more generalized approach by developing the tracer based on generic hallmarks of cancer to create a more "one-size-fits-all" concept, similar to metabolic aberrations as exploited in fluorodeoxyglucose-positron emission tomography (FDG-PET) (i.e., Warburg effect) or tumor acidity. Finally, methods to approach the problem of production cost minimization and regulatory approvals in a manner consistent with the potential revenue of the field will be important. In this area, some solid steps have been demonstrated in the use of fluorescent labeling commercial antibodies and separately in microdosing studies with small molecules. (C) The Authors

Synchronous Strategies for Interactive Live Virtual Class Sessions that Engage Students and Build Community

Slides from the session "Synchronous Strategies for Interactive Live Virtual Class Sessions that Engage Students and Build Community," presented at the Education Beyond Tomorrow: Innovation in Pedagogy and Practice Virtual Conference on April 20, 2016. Session description: For new and experienced online instructors, or those who work with them, this session will give participants a chance to learn concrete activities and strategies that have been experience-tested during synchronous, live virtual class sessions. Participants will come away with something new for their virtual instruction toolkit. Throughout the presentation, participants will have the opportunity to share their own strategies, ask questions, and add to their toolkits of online institutional strategies. This will include the chance to experience innovative uses of chat and polling. The presentation will include a handout of strategies and concrete ideas to take home. This presentation draws from the following book chapter: Marquart, M., Fleming, M., Rosenthal, S., & Hibbert, M. (2016, April). Instructional Strategies for Synchronous Components of Online Courses. In S. D’Agustino (Ed.), Creating Teacher Immediacy in Online Learning Environments. Hershey, PA: IGI Global. Additional keywords: Adobe Connec

Fever in Neoplastic Disease

A comparison is made between incidence of fever in 132 patients with various types of disseminated cancer and 57 patients with diseases other than cancer during a 2- month observation period. Fifty-three febrile episodes were observed in cancer patients. Of these, 15 were of undetermined origin and 6 were noninfectious; none of the episodes occurred immediately following surgery. In the control group of 57 patients, there were 12 febrile episodes; of these, 7 were due to proven bacterial infection, 2 were due lo possible bacterial infection, and 3 were of undetermined etiology. All three febrile episodes in this latter group occurred postoperatively. The pathogenesis of fever is discussed, especially unexplained fever, in the absence of infection. Tissue necrosis, with the release of endogenous pyrogen, is suggested as a pathogenic mechanism in neoplastic fevers. It is of interest that unexplained fever was more prevalent in patients with demonstrable liver metastases. The metabolism of naturally occurring steroid hormones may be impaired by hepatic dysfunction. The role of steroid pyrogens remains undefined. Hepatic dysfunction may be a contributory factor

Drug resistance mediating Plasmodium falciparum polymorphisms and clinical presentations of parasitaemic children in Uganda.

BackgroundPlasmodium falciparum genetic polymorphisms that mediate altered drug sensitivity may impact upon virulence. In a cross-sectional study, Ugandan children with infections mutant at pfcrt K76T, pfmdr1 N86Y, or pfmdr1 D1246Y had about one-fourth the odds of symptomatic malaria compared to those with infections with wild type (WT) sequences. However, results may have been confounded by greater likelihood in those with symptomatic disease of higher density mixed infections and/or recent prior treatment that selected for WT alleles.MethodsPolymorphisms in samples from paired episodes of asymptomatic and symptomatic parasitaemia in 114 subjects aged 4-11 years were followed longitudinally in Tororo District, Uganda. Paired episodes occurred within 3-12 months of each other and had no treatment for malaria in the prior 60 days. The prevalence of WT, mixed, and mutant alleles was determined using multiplex ligase detection reaction-fluorescent microsphere assays.ResultsConsidering paired episodes in the same subject, the odds of symptomatic malaria were lower for infections with mutant compared to WT or mixed sequence at N86Y (OR 0.26, 95% CI 0.09-0.79, p = 0.018), but not K76T or D1246Y. However, symptomatic episodes (which had higher densities) were more likely than asymptomatic to be mixed (for N86Y OR 2.0, 95% CI 1.04-4.0, p = 0.036). Excluding mixed infections, the odds of symptomatic malaria were lower for infections with mutant compared to WT sequence at N86Y (OR 0.33, 95% CI 0.11-0.98, p = 0.046), but not the other alleles. However, if mixed genotypes were grouped with mutants in this analysis or assuming that mixed infections consisted of 50% WT and 50% mutant genotypes, the odds of symptomatic infection did not differ between infections that were mutant or WT at the studied alleles.ConclusionsAlthough infections with only the mutant pfmdr1 86Y genotype were associated with symptomatic infection, this association could primarily be explained by greater parasite densities and therefore greater prevalence of mixed infections in symptomatic children. These results indicate limited association between the tested polymorphisms and risk of symptomatic disease and highlight the value of longitudinal studies for assessing associations between parasite factors and clinical outcomes

Direct sums and the Szlenk index

For $\alpha$ an ordinal and $1<p<\infty$, we determine a necessary and sufficient condition for an $\ell_p$-direct sum of operators to have Szlenk index not exceeding $\omega^\alpha$. It follows from our results that the Szlenk index of an $\ell_p$-direct sum of operators is determined in a natural way by the behaviour of the $\epsilon$-Szlenk indices of its summands. Our methods give similar results for $c_0$-direct sums.Comment: The proof of Proposition~2.4 has changed, with some of the arguments transferred to the proof of an added-in lemma, Lemma~2.8. Changes have been made to the Applications sectio

Evaluation of Wildlife Reflectors in Reducing Vehicle-Deer Collisions on Indiana Interstate 80/90

The Indiana Department of Transportation is committed to reducing vehicle-deer collision incidents on the Indiana Interstate I-80/90 as well as on the other roads. Very few of the studies to reduce vehicle-deer collisions incorporated any sound and complete statistical design. Some states (California, Colorado, Maine, Ontario-Canada, Washington State and Wyoming) have found that the use of wildlife reflectors did not reduce vehicle-deer collisions. However, some other states (British Columbia-Canada, Iowa, Minnesota, Oregon, Washington State and Wisconsin) found that the use of wildlife reflectors did reduce vehicle-deer collisions. The main objective of this experimental study is to evaluate the effectiveness of the Reflectors in reducing vehicledeer collisions. The experimental design uses one-mile long road sections for each combination of reflector colors (red and blue/green), reflector spacing (30 m and 45 m), reflector design (single and dual reflectors), and median (one with and one without reflectors). In this design there are sixteen treatment combinations. A complete set of treatment combinations is called a replicate and the design had two replicates. Two one-mile control sections were placed at each end of each replicate. Data for the peak months of April, May, October and November was used in the data analyses. Poisson Regression models were used to analyze the data. No statistically significant differences among reflectors combinations or between reflectors and controls were found. When comparing all combined reflector sites with all combined control sites, the Poisson Regression Analyses indicate that the difference between the Poisson Mean (μ) of the all reflectors sections and all the control sections is statistically significant. The use of reflectors provides an expected reduction in deer-vehicle collisions of 19% with 95% confidence limits of 5% to 30%. Maximum reduction is associated with 100 ft spacing regardless of the reflector color, median with or without reflectors, single or double reflectors. The cost effectiveness of this reduction will be behind any decision to use reflectors to reduce vehicle-deer collisions

Effect of interfractional shoulder motion on low neck nodal targets for patients treated using volume modulated arc therapy (VMAT)

Purpose: To quantify the dosimetric impact of interfractional shoulder motion on targets in the low neck for head and neck patients treated with volume modulated arc therapy (VMAT).Methods: Three patients with head and neck cancer were selected. All three required treatment to nodal regions in the low neck in addition to the primary tumor site. The patients were immobilized during simulation and treatment with a custom thermoplastic mask covering the head and shoulders. One VMAT plan was created for each patient utilizing two full 360° arcs and a second plan was created consisting of two superior VMAT arcs matched to an inferior static AP supraclavicular field. A CT-on-rails alignment verification was performed weekly during each patient’s treatment course. The weekly CT images were registered to the simulation CT and the target contours were deformed and applied to the weekly CT. The two VMAT plans were copied to the weekly CT datasets and recalculated to obtain the dose to the deformed low neck contours.Results: The average observed shoulder position shift in any single dimension relative to simulation was 2.5 mm. The maximum shoulder shift observed in a single dimension was 25.7 mm. Low neck target mean doses, normalized to simulation and averaged across all weekly recalculations were 0.996, 0.991, and 1.033 (Full VMAT plan) and 0.986, 0.995, and 0.990 (Half-Beam VMAT plan) for the three patients, respectively. The maximum observed deviation in target mean dose for any individual weekly recalculation was 6.5%, occurring with the Full VMAT plan for Patient 3.Conclusion: Interfractional variation in dose to low neck nodal regions was quantified for three head and neck patients treated with VMAT. Mean dose was 3.3% higher than planned for one patient using a Full VMAT plan. A Half-Beam technique is likely a safer choice when treating the supraclavicular region with VMAT.-------------------------------------------Cite this article as: Casey K, Wang P, Tung S, Rosenthal D. Effect of interfractional shoulder motion on low neck nodal targets for patients treated using volume modulated arc therapy (VMAT). Int J Cancer Ther Oncol 2014; 2(2):020218. DOI: 10.14319/ijcto.0202.1