214 research outputs found

    Maturing into My Disease

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    Qualitative Study of Factors Contributing to Fertility Service Use Among Cancer Survivors of Reproductive Age in the US

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    Cancer remains the second leading cause of death in the United States; however, there has been a decline in incidence and mortality due to advances in screening and treatment. Currently 16.9 million survivors are thriving within the United States, and the population of cancer survivors has been projected to grow to 22.2 million by 2030. Although cancer survivors report an increased surge of vitality and vigor, they often face physical, mental, psychosocial, or financial challenges that threaten their quality of life. A late treatment effect of particular concern for cancer survivors of reproductive age that has both physical and psychosocial implications is infertility. Current guidelines are in place to ensure that survivors are made aware of how treatment can impact their plans for building a family and pose viable options for preserving their fertility; however, studies indicate under-utilization of fertility preservation among cancer survivors. The aim of this study was to examine how a cancer diagnosis influenced parenthood motivation and family building strategies among individuals of reproductive age. The study identified contributors to access and use of fertility services by using a conceptual model based on Andersen’s Behavioral Model of Health Services, Lea’s model of Age-appropriate Care, and Kilbourne’s Health Services Research Framework to Advance Health Disparities. The conceptual model elucidates factors that impact cancer survivors’ use of fertility services, equitable access to services, and policy actions that assure equitable access to fertility services. A phenomenological qualitative study was conducted to allow deep exploration of these issues through the review and analysis of survivors’ stories as told through online narratives and in-depth interviews. Study findings showed a cancer diagnosis had not altered an individual’s desire to have children. Although fertility preservation was not always utilized by cancer survivors of reproductive age to conceive or sire a child, most survivors sought out some form of fertility service post treatment. Access and subsequent use of fertility services was grossly dependent on both survivor and provider factors as well as successful clinical encounters between the patient and the provider. These findings have implications for clinical care, public health policy, practice, and research

    Response to Intervention: A Program Evaluation of Implementation in a Rural School District

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    The acquisition of reading skills is a key component to a student’s academic progress and success in life. Effectively implemented early intervention programs have been shown to improve reading performance of struggling readers. The purpose of this study was to conduct a CIPP program evaluation of the implementation of a Response to Intervention (RTI) Program in a rural school district. The focus of this study was an RTI program in its second year of full implementation in kindergarten and first grade in 15 elementary schools. This mixed-method study utilized data gathered from reading achievement and special education referral data, district-level and school-level administrator interviews, a teacher survey, and focus groups. Findings from this study indicated there was no significant difference in reading achievement and special education referral data in the 2 years of program implementation. Administrators and teachers demonstrated knowledge of the purpose and key elements of an RTI program, but fidelity of program implementation was an area identified for improvement. Recommendations included clearly defining and communicating program expectations to improve fidelity of implementation. In addition, careful review, selection, and alignment of screening tools, intervention resources, and progress monitoring measures were recommended to improve consistency of implementation from school to school. The RTI program evaluated in this study was in its second year of implementation. Results of this program evaluation provided formative assessment data of the program’s strengths and weaknesses. The results of this study could be useful to district- and school-level administrators and teachers as they continue to work to implement an effective RTI program designed to meet the needs of struggling kindergarten and first-grade readers

    Student Awareness of Models in First-Year Engineering Courses

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    Contribution: This study assesses more than 800 students\u27 awareness of engineering model types before and after taking two first-year engineering courses across two semesters and evaluates the effect of each course. Background: All engineers must be able to apply and create models to be effective problem solvers, critical thinkers, and innovative designers. To help them develop these skills, as a first step, it is essential to assess how to increase students\u27 awareness of engineering models. According to Bloom\u27s taxonomy, the lower remember and understand levels, which encompass awareness, are necessary for achieving the higher levels, such as apply, analyze, evaluate, and create. Research Questions: To what extent did student awareness of model types change after taking introductory engineering courses? To what extent did student awareness of model types differ by course or semester? Methodology: In this study, a survey was designed and administered at the beginning and end of the semester in two first-year engineering courses during two semesters in a mid-sized private school. The survey asked students questions about their definition of engineering modeling and different types of models. Findings: Overall, student awareness of model types increased from the beginning of the semester toward the end of the semester, across both semesters and courses. There were some differences between course sections, however, the students\u27 awareness of the models at the end of the academic year was similar for both groups

    Types of Models Identified by First-Year Engineering Students

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    This is a Complete Research paper. Understanding models is important for engineering students, but not often taught explicitly in first-year courses. Although there are many types of models in engineering, studies have shown that engineering students most commonly identify prototyping or physical models when asked about modeling. In order to evaluate students\u27 understanding of different types of models used in engineering and the effectiveness of interventions designed to teach modeling, a survey was developed. This paper describes development of a framework to categorize the types of engineering models that first-year engineering students discuss based on both previous literature and students\u27 responses to survey questions about models. In Fall 2019, the survey was administered to first-year engineering students to investigate their awareness of types of models and understanding of how to apply different types of models in solving engineering problems. Students\u27 responses to three questions from the survey were analyzed in this study: 1. What is a model in science, technology, engineering, and mathematics (STEM) fields?, 2. List different types of models that you can think of., and 3. Describe each different type of model you listed. Responses were categorized by model type and the framework was updated through an iterative coding process. After four rounds of analysis of 30 different students\u27 responses, an acceptable percentage agreement was reached between independent researchers coding the data. Resulting frequencies of the various model types identified by students are presented along with representative student responses to provide insight into students\u27 understanding of models in STEM. This study is part of a larger project to understand the impact of modeling interventions on students\u27 awareness of models and their ability to build and apply models

    An essential bifunctional enzyme in Mycobacterium tuberculosis for itaconate dissimilation and leucine catabolism

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    Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis. One-fourth of the global population is estimated to be infected with Mtb, accounting for ∌1.3 million deaths in 2017. As part of the immune response to Mtb infection, macrophages produce metabolites with the purpose of inhibiting or killing the bacterial cell. Itaconate is an abundant host metabolite thought to be both an antimicrobial agent and a modulator of the host inflammatory response. However, the exact mode of action of itaconate remains unclear. Here, we show that Mtb has an itaconate dissimilation pathway and that the last enzyme in this pathway, Rv2498c, also participates in L-leucine catabolism. Our results from phylogenetic analysis, in vitro enzymatic assays, X-ray crystallography, and in vivo Mtb experiments, identified Mtb Rv2498c as a bifunctional ÎČ-hydroxyacyl-CoA lyase and that deletion of the rv2498c gene from the Mtb genome resulted in attenuation in a mouse infection model. Altogether, this report describes an itaconate resistance mechanism in Mtb and an L-leucine catabolic pathway that proceeds via an unprecedented (R)-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) stereospecific route in nature

    The Mycobacterium tuberculosis sRNA F6 Modifies Expression of Essential Chaperonins, GroEL2 and GroES.

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    Almost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of posttranscriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA F6 and shown it to be dependent on SigF for expression and significantly induced in starvation conditions in vitro and in a mouse model of infection. Further exploration of F6 using an in vitro starvation model of infection indicates that F6 affects the expression of the essential chaperonins GroEL2 and GroES. Our results point toward a role for F6 during periods of low metabolic activity typically associated with long-term survival of M. tuberculosis in human granulomas. IMPORTANCE Control of gene expression via small regulatory RNAs (sRNAs) is poorly understood in one of the most successful pathogens, Mycobacterium tuberculosis. Here, we present an in-depth characterization of the sRNA F6, including its expression in different infection models and the differential gene expression observed upon deletion of the sRNA. Our results demonstrate that deletion of F6 leads to dysregulation of the two essential chaperonins GroEL2 and GroES and, moreover, indicate a role for F6 in the long-term survival and persistence of M. tuberculosis in the human host

    The mycobacterium tuberculosis sRNA F6 modifies expression of essential chaperonins, GroEL2 and GroES

    Get PDF
    Almost 140 years after the identification of Mycobacterium tuberculosis as the etiological agent of tuberculosis, important aspects of its biology remain poorly described. Little is known about the role of posttranscriptional control of gene expression and RNA biology, including the role of most of the small RNAs (sRNAs) identified to date. We have carried out a detailed investigation of the M. tuberculosis sRNA F6 and shown it to be dependent on SigF for expression and significantly induced in starvation conditions in vitro and in a mouse model of infection. Further exploration of F6 using an in vitro starvation model of infection indicates that F6 affects the expression of the essential chaperonins GroEL2 and GroES. Our results point toward a role for F6 during periods of low metabolic activity typically associated with long-term survival of M. tuberculosis in human granulomas. IMPORTANCE Control of gene expression via small regulatory RNAs (sRNAs) is poorly understood in one of the most successful pathogens, Mycobacterium tuberculosis. Here, we present an in-depth characterization of the sRNA F6, including its expression in different infection models and the differential gene expression observed upon deletion of the sRNA. Our results demonstrate that deletion of F6 leads to dysregulation of the two essential chaperonins GroEL2 and GroES and, moreover, indicate a role for F6 in the long-term survival and persistence of M. tuberculosis in the human host

    Recruiting equal numbers of indigenous and non-indigenous participants to a ‘polypill’ randomized trial

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    Introduction. Māori are disproportionately affected by cardiovascular disease (CVD), which is the main reason for the eight year difference in life expectancy between Māori and non-Māori. The primary care-based IMPACT (IMProving Adherence using Combination Therapy) trial evaluates whether fixed dose combination therapy (a "polypill") improves adherence to guideline-based therapy compared with current care among people at high risk of CVD. Interventions shown in trials to be effective do not necessarily reduce ethnic disparities, and may in fact widen them. Indigenous populations with poorer health outcomes are often under-represented in trials so the effect of interventions cannot be assessed for them, specifically. Therefore, the IMPACT trial aimed to recruit as many Māori as non-Māori to assess the consistency of the effect of the polypill. This paper describes the methods and results of the recruitment strategy used to achieve this. Methods. Experienced Māori researchers were involved in trial governance throughout trial development and conduct. The trial Steering Committee included leading Māori researchers and was committed to equal recruitment of Māori and non-Māori. Additional funding and Māori research nurses were sought to allow home-based assessment, establishment of the relationship between research nurse and participant, more family involvement prior to enrollment, continuity of the research nurse-participant relationship, and acknowledgement of other Māori culturally important procedures, interactions, language and manners. Primary care practices with high enrollment of Māori were targeted, with over-sampling of potentially eligible Māori patients, lower thresholds for screening of Māori and 6 months continued Māori recruitment after non-Māori recruitment had finished. Results: A total of 257 Māori and 256 non-Māori participants were randomized. Four Māori and eight non-Māori participants were randomized per research nurse per month. Potentially eligible Māori were more likely than non-Māori to proceed to subsequent stages of recruitment. Differences between randomized Māori and non-Māori were evident (e.g. Maori were less likely to have established coronary artery disease). Conclusions: Recruitment of equal numbers of indigenous and non-indigenous participants is possible if it is prioritised, adequately resourced and self-determination is supported. Trial registration. The trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN12606000067572. © 2013 Selak et al.; licensee BioMed Central Ltd

    LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages

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    Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associ- ated with Parkinson’s disease, chronic inflammation and mycobac- terial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages. Moreover, inhibition of LRRK2 kinase activity in mouse and human macrophages enhanced Mycobacterium tuberculosis phagosome maturation and mycobac- terial control independently of autophagy. In vivo, LRRK2 defi- ciency in mice resulted in a significant decrease in M. tuberculosis burdens early during the infection. Collectively, our findings provide a molecular mechanism explaining genetic evidence linking LRRK2 to mycobacterial diseases and establish an LRRK2- dependent cellular pathway that controls M. tuberculosis replica- tion by regulating phagosome maturation
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