​A RETROSPECTIVE CLINICAL AUDIT OF THE CLINICAL APPLICATION OF THE RAYPILOT REAL TIME MOTION MANAGEMENT SYSTEM AND THE FEASABILITY OF ITS USE FOR FURTHER DOSE ESCALATED STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER.

​Background and purpose ​Prostate cancer is one of the most prevalent malignancies within oncology cases. Intrafraction motion is an important consideration in the clinical delivery of radiotherapy and indeed, long-term outcome and toxicity for patients. The purpose of this retrospective clinical audit was to review the efficacy of the RayPilot® real time motion management system and the impact that this has on planning target margins in prostate stereotactic body radiotherapy to assess if the RayPilot® system could be used clinically to allow for further dose escalation and fractionation reduction. ​Materials and methods ​Intrafraction motion was measured and recorded using the RayPilot® real time motion management system in seven patients. The RayPilot® system collated intrafraction data thirty times per second during treatment delivery for each patient. The collected data was then used to replan the patient in the Eclipse treatment planning software using reduced planning target margins to assess if this was a feasible method of dose escalation by reducing treatment fractionation. ​Results ​The RayPilot® recorded data resulted in 54175 intrafraction motion measurements in total. Mean displacement (following removal of outliers >0.3cm) was 0.1cm (SD± 0.1cm), 0.1cm (SD± 0.1cm) and 0.1cm (SD± 0.1cm) in the lateral, longitudinal and vertical directions respectively. The Van Herk Margin recipe was used to calculate the required clinical margins using the intrafraction motion data resulting in lateral, longitudinal and vertical margins of 0.7cm, 0.7cm and 0.7cm respectively. These margins allowed for dose escalation of 2400cGy in three fractions with no detrimental effects or increase in patient toxicity using dose volume histogram analysis. ​Conclusion ​RayPilot® is an efficient method of monitoring and recording prostate intrafraction motion and allowed for a reduction in target volume margins resulting in dose escalation in prostate stereotactic body radiotherapy. However, further analysis and research must be carried out to assess the feasibility of it being used as a stand-alone monitoring modality

6 Ways to Celebrate Student Writing

Susan Adamson, executive director of the Indiana Partnership for Young Writers, shares a few of her favorite strategies for celebrating student writing at the end of a unit of study

Book review: Talking diversity with Teachers and Teacher educators

Book review of Cruz, B., Ellerbrock, C. R., Vásquez, A., & Howes, E. V. (2014). Talking diversity with teachers and teacher educators: Exercises and critical conversations across the curriculum. by Ryan Flessner and Susan C. Adamson

Blazing the Real: Writing by Indiana Children

I got my first camera when I was in third grade—a Brownie Hawkeye flash model with a snazzy little camera case. The instruction manual provided six simple steps for taking successful pictures. Hold the camera steady, supporting it underneath. Then, with the sun behind your back or over your shoulder, locate the subject in the finder. At the instant of exposure, hold your breath and press the shutter release with a gentle squeezing action (Brownie Hawkeye Instruction Manual). The camera came with two rolls of film, each with16 frames. I eagerly used them up and sent the exposed film off for developing and printing. Maybe because I didn’t hold my breath or squeeze the shutter release quite gently enough—I don’t know—but when the prints came back, I had (according to the manual) “fumbles”: double-exposures, complete blurs, specks on the images, a few close-ups of my finger or the camera strap, and plenty of shots where the subject was cut-off. I did have pictures, but not one that was good. Cameras now are nothing like my Brownie Hawkeye, but if you still point and shoot like I do, you have surely noticed that the beautiful sunset you see with your own eyes is nothing like the digital image you end up with. That’s because creating breathtaking photography is up to the photographers who are, in the words of Ansel Adams, blazing the poetry of the real (1930) – using shadow and light, focus, compositional elements, perspective, texture, and tone to illuminate what we see (and sometimes don’t see). For the longest time, we have used a point and shoot mentality in writing, too. You remember... follow the directions for writing a paper, hold your breath when you turn it in, then get it back in a few days with your “fumbles” clearly marked in red pen. Think about it. How much better would your writing have been if you had known how to create the illusion of motion or sound, manipulate the volume or inflection in a reader’s voice, make the reader your accomplice, or persuade her to think like you? That is the work of writing after all—to hold its own in the absence of the author, blazing the real of time and space. Knowing how to write well is not just the province of published authors anymore. It can’t be—too much is at stake. Workshop teachers take seriously this call to action, teaching the qualities of good writing every single day. In Blazing the Real, their students demonstrate that good writing comes from a deeper understanding of craft, of what writers know and do. These young writers understand that very specific, tangible details help them effectively express big, sometimes abstract concepts. They understand the power of creating intimacy with a reader by using second-person address. They understand that reflecting on topics immediately relevant to their own lives, stirs emotions that resonate broadly. And, they even understand how to manipulate the conventions of writing to provoke their audiences to respond in particular, intended ways. Breathe in the beauty of Blazing the Real—the splendor of meticulously crafted photographs inspired by the writing in each of four chapters, the artistry of language both written and drawn that is influenced by the work of real writers. And know, we are a very long way from point and shoot. -Susan C. Adamsonhttps://digitalcommons.butler.edu/iypw_books/1000/thumbnail.jp

A Genome-Wide Study of Homologous Recombination in Mammalian Cells Identifies RBMX, a Novel Component of the DNA Damage Response

Repair of DNA double-strand breaks is critical to the maintenance of genomic stability, and failure to repair these DNA lesions can cause loss of chromosome telomeric regions, complex translocations, or cell death. In humans this can lead to severe developmental abnormalities and cancer. A central pathway for double-strand break repair is homologous recombination (HR), a mechanism that operates during the S and G2 phases of the cell cycle and primarily utilizes the replicated sister chromatid as a template for repair. Most knowledge of HR is derived from work carried out in prokaryotic and eukaryotic model organisms. To probe the HR pathway in human cells, we performed a genome-wide siRNA-based screen; and through this screen, we uncovered cellular functions required for HR and identified proteins that localize to sites of DNA damage. Among positive regulators of HR, we identified networks of pre-mRNA-processing factors and canonical DNA damage response effectors. Within the former, we found RBMX, a heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with the spliceosome, binds RNA, and influences alternative splicing. We found that RBMX is required for cellular resistance to genotoxic stress, accumulates at sites of DNA damage in a poly(ADP-ribose) polymerase 1-dependent manner and through multiple domains, and promotes HR by facilitating proper BRCA2 expression. Screen data also revealed that the mammalian recombinase RAD51 is commonly off-targeted by siRNAs, presenting a cautionary note to those studying HR with RNAi and highlighting the vulnerability of RNAi screens to off-target effects in general. Candidate validation through secondary screening with independent reagents successfully circumvented the effects of off-targeting and set a new standard for reagent redundancy in RNAi screens

“Funerals aren’t nice but it couldn’t have been nicer”. The makings of a good funeral

There is growing comment in both academic and popular writing about the shape and content of funerals today, with general agreement that we are seeing marked changes with a growing trend towards secularisation and personalisation. Despite this, there is as yet relatively little systematic research on the topic. This article reports on a study funded by the Arts and Humanities Research Council UK into spirituality in contemporary funerals. This qualitative study centred around case studies of 46 funerals in the north of England and gathered data from observations of funeral arrangement meetings as well as the funeral and semi-structured interviews with bereaved families and funeral professionals. The way both sets of participants engaged with the funeral and its constituent elements in an active process of meaning-seeking, meaning-creating and meaning-taking was closely aligned with contemporary understandings of humanistic spirituality. There was, however, little evidence of adherence to formal religious belief systems or wider philosophical frameworks amongst the bereaved families but considerable evidence of drawing on religious tradition and specific beliefs to locate personal meaning-making. The authors conclude that the funeral remains a significant ceremonial event which is psycho-social-spiritual in character and purpose

Effect of Early Intervention with Combination Ledipasvir/Sofosbuvir (Harvoni®) in Patients with Chronic Hepatitis C Virus Infection

In the United States, hepatitis C virus (HCV) is the most common bloodborne infection with an estimated prevalence of 3.2 million people. Although new cases of HCV are declining since the 1980s there are still approximately 17,000 new cases diagnosed each year. There are multiple risk factors, however, in the United States the most common mode of transmission is intravenous drug use. Among infected individuals, approximately 55-85% will develop a chronic HCV infection. In this population, the risk of cirrhosis of the liver is 15-30% within 20 years and morbidity can be significant. HCV infection has become the most frequent reason for hepatologic consultation and the single leading indication for hepatic transplantation, accounting for 30% of such procedures in the United States. Until late 2013, the treatment of choice for chronic HCV was pegylated interferon-α plus ribavirin, which achieved a cure rate of 54%-63%. Recently, novel antiviral drugs that specifically target HCV have provided better options in HCV treatment. Use of ledipasvir, an HCV NS5A replication complex inhibitor in combination with sofosbuvir, a nucleotide analog HCV NS5B polymerase inhibitor, in patients with chronic HCV, achieves high rates of sustained viral response (SVR) with just 12-weeks of treatment. A fixed-dose combination of ledipasvir-sofosbuvir (90mg/400mg), or Harvoni® was approved for treatment of chronic HCV genotypes 1,4,5, and 6. Although extremely successful, the use of this medication is inhibited by high costs, upwards of $90,000 for each 12-week treatment

SUPER BOWL CITY: THE REAL FACES OF XLVI UNMASKED

poster abstract111.3 million viewers watched as Indianapolis went from Naptown to Super City when they hosted the 2012 Super Bowl XLVI. As visitors poured into Indianapolis, they were greeted with the smiling faces of Hoosiers. Throughout the weeks preceding the Super Bowl Indianapolis residents worked together to bring the Super Bowl legacy to life. While the media focused on Lucas Oil stadium and the events in Super Bowl Village because it grabbed the attention of the public, the lives of unnoticed Indianapolis residents were impacted by their involvement with the mega sports event. To investigate the effects of the Super Bowl on Indianapolis and its residents, we interviewed residents who were involved with the Super Bowl through the areas of philanthropy, low-wage workers, and the residents of the Near-East Side. Data was collected through interviews, participant observations, ethnographic research methods, surveys, and resources collected from residents and organizations. Our project is an ongoing process and is a start to understanding the impact of large sporting events on Indianapolis and its residents

Defects in translation-dependent quality control pathways lead to convergent molecular and neurodevelopmental pathology.

Translation-dependent quality control pathways such as no-go decay (NGD), non-stop decay (NSD), and nonsense-mediated decay (NMD) govern protein synthesis and proteostasis by resolving non-translating ribosomes and preventing the production of potentially toxic peptides derived from faulty and aberrant mRNAs. However, how translation is altered and the in vivo defects that arise in the absence of these pathways are poorly understood. Here, we show that the NGD/NSD factors Pelo and Hbs1l are critical in mice for cerebellar neurogenesis but expendable for survival of these neurons after development. Analysis of mutant mouse embryonic fibroblasts revealed translational pauses, alteration of signaling pathways, and translational reprogramming. Similar effects on signaling pathways, including mTOR activation, the translatome and mouse cerebellar development were observed upon deletion of the NMD factor Upf2. Our data reveal that these quality control pathways that function to mitigate errors at distinct steps in translation can evoke similar cellular responses

A Bioinformatics Method Identifies Prominent Off-targeted Transcripts in RNAi Screens

Because off-target effects hamper interpretation and validation of RNAi screens, we developed a bioinformatics method, Genome-wide Enrichment of Seed Sequence matches (GESS), to identify candidate off-targeted transcripts from direct analysis of primary screening data. GESS identified a prominent off-targeted transcript in several screens, including MAD2 in a screen for components of the spindle assembly checkpoint. We demonstrate how incorporation of the results of GESS analysis can enhance the validation rate in RNAi screens