Exploration of transitional life events in individuals with Friedreich ataxia: Implications for genetic counseling

<p>Abstract</p> <p>Background</p> <p>Human development is a process of change, adaptation and growth. Throughout this process, transitional events mark important points in time when one's life course is significantly altered. This study captures transitional life events brought about or altered by Friedreich ataxia, a progressive chronic illness leading to disability, and the impact of these events on an affected individual's life course.</p> <p>Methods</p> <p>Forty-two adults with Friedreich ataxia (18-65y) were interviewed regarding their perceptions of transitional life events. Data from the interviews were coded and analyzed thematically using an iterative process.</p> <p>Results</p> <p>Identified transitions were either a direct outcome of Friedreich ataxia, or a developmental event altered by having the condition. Specifically, an awareness of symptoms, fear of falling and changes in mobility status were the most salient themes from the experience of living with Friedreich ataxia. Developmental events primarily influenced by the condition were one's relationships and life's work.</p> <p>Conclusions</p> <p>Friedreich ataxia increased the complexity and magnitude of transitional events for study participants. Transitional events commonly represented significant loss and presented challenges to self-esteem and identity. Findings from this study help alert professionals of potentially challenging times in patients' lives, which are influenced by chronic illness or disability. Implications for developmental counseling approaches are suggested for genetic counseling.</p> <p>Background</p> <p>Human development can be described in terms of key transitional events, or significant times of change. Transitional events initiate shifts in the meaning or direction of life and require the individual to develop skills or utilize coping strategies to adapt to a novel situation <abbrgrp><abbr bid="B1">1</abbr><abbr bid="B2">2</abbr></abbrgrp>. A successful transition has been defined as the development of a sense of mastery over the changed event <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Transitions can be influenced by a variety of factors including one's stage of development, such as graduation from high school, historical events, including war, and idiosyncratic factors, such as health status <abbrgrp><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr></abbrgrp>. Of particular interest in the present study are transitional life events, brought about or altered by progressive chronic illness and disability, and the impact of these events on the lives of affected individuals.</p> <p>It has been recognized that the clinical characteristics of a chronic illness or disability may alter the course and timing of many developmentally-related transitional events <abbrgrp><abbr bid="B6">6</abbr></abbrgrp>. For example, conditions associated with a shortened lifespan may cause an individual to pursue a career with a shorter course of training <abbrgrp><abbr bid="B6">6</abbr></abbrgrp>. Specific medical manifestations may also promote a lifestyle incongruent with developmental needs <abbrgrp><abbr bid="B6">6</abbr><abbr bid="B7">7</abbr></abbrgrp>. For example, an adolescent with a disability may have difficulty achieving autonomy because of his/her physical dependence on others.</p> <p>In addition to the aforementioned effects of chronic illness and disability on developmentally-related transitional events, a growing body of literature has described disease-related transitional events: those changes that are a direct result of chronic illness and disability. Diagnosis has received attention as being a key disease-related transitional event <abbrgrp><abbr bid="B8">8</abbr><abbr bid="B9">9</abbr></abbrgrp>. Studies have also noted other disease transitions related to illness trajectory <abbrgrp><abbr bid="B10">10</abbr></abbrgrp>, as the clinical features of the disease may require the individual to make specific adaptations. Disease-related events have also been described in terms of accompanying psychological processes, such as one's awareness of differences brought about by illness <abbrgrp><abbr bid="B11">11</abbr></abbrgrp>.</p> <p>While disease-related events are seemingly significant, the patient's perception of the events is varied. Some events may be perceived as positive experiences for the individual. For example, a diagnosis may end years of uncertainty. Some individuals may perceive these transitional events as insignificant, as they have accommodated to the continual change brought about by a chronic disease <abbrgrp><abbr bid="B12">12</abbr><abbr bid="B13">13</abbr></abbrgrp>.</p> <p>The aforementioned impact of disability and chronic illness on transitional events may create psychological stress. Developed by Lazarus and Folkman, the Transitional Model of Stress and Coping describes the process of adaptation to a health condition <abbrgrp><abbr bid="B14">14</abbr></abbrgrp>. This model purports that individuals first appraise a stressor and then utilize a variety of coping strategies in order to meet the stressor's demands <abbrgrp><abbr bid="B14">14</abbr></abbrgrp>. Thus, in the context of chronic illness, the ability of the individual to cope successfully with the stress of a health threat contributes to the process of overall adaptation to the condition.</p> <p>The process of adaptation can be more complex when the chronic illness or disability is progressive. Each transition brought about or altered by the disability may also represent additional loss, including the loss of future plans, freedom in social life and the ability to participate in hobbies <abbrgrp><abbr bid="B15">15</abbr></abbrgrp>. These losses may be accompanied by grief, uncertainty, and a continual need for adaptation <abbrgrp><abbr bid="B16">16</abbr><abbr bid="B17">17</abbr></abbrgrp>.</p> <p>Friedreich ataxia (FRDA) is one example of a progressive disorder, leading to adolescent and adult onset disability. To better understand patients' perceptions of key transitional events and the factors perceived to facilitate progression through these events, individuals with FRDA were interviewed.</p> <p>FRDA is a rare, progressive, neurodegenerative disorder affecting approximately one in 30,000 people in the United States <abbrgrp><abbr bid="B18">18</abbr></abbrgrp>. It equally affects both men and women. Individuals with FRDA experience progressive muscle weakness and loss of coordination in the arms and legs. For most patients, ataxia leads to motor incapacitation and full-time use of a wheelchair, commonly by the late teens or early twenties. Other complications such as vision and hearing impairment, dysarthria, scoliosis, diabetes mellitus and hypertrophic cardiomyopathy may occur <abbrgrp><abbr bid="B19">19</abbr><abbr bid="B20">20</abbr></abbrgrp>. Cardiomyopathy and respiratory difficulties often lead to premature death at an average age of 37 years <abbrgrp><abbr bid="B21">21</abbr></abbrgrp>. Currently, there are no treatments or cures for FRDA. Little is known about the specific psychological or psychosocial effects of the condition.</p> <p>FRDA is an autosomal recessive condition. The typical molecular basis of Friedreich ataxia is the expansion of a GAA trinucleotide repeat in both copies of the <it>FXN </it>gene <abbrgrp><abbr bid="B22">22</abbr></abbrgrp>. Age of onset usually occurs in late childhood or early adolescence. However, the availability of genetic testing has identified affected individuals with an adult form of the condition. This late-onset form is thought to represent approximately 10-15% of the total FRDA population <abbrgrp><abbr bid="B23">23</abbr></abbrgrp>.</p> <p>Health care providers of individuals with progressive, neurodegenerative disorders can help facilitate their patients' progression through transitional events. Data suggest that improvements should be made in the care of these individuals. Shaw et al. <abbrgrp><abbr bid="B24">24</abbr></abbrgrp> found that individualized care that helps to prepare patients for transition is beneficial. Beisecker et al. <abbrgrp><abbr bid="B25">25</abbr></abbrgrp> found that patients desire not only physical care from their providers, but also emotional and psychosocial support.</p> <p>Genetic counselors have an important opportunity to help patients with neuromuscular disorders progress through transitional events, as several of these conditions have a genetic etiology. Genetic counselors in pediatric and adult settings often develop long-term relationships with patients, due to follow-up care. This extended relationship is becoming increasingly common as genetic counselors move into various medical sub-specialties, such as neurology, ophthalmology, oncology and cardiology.</p> <p>The role of the genetic counselor in addressing the psychosocial needs of patients has been advocated, but rarely framed in the context of developmental events <abbrgrp><abbr bid="B26">26</abbr></abbrgrp>. Data suggest that patients may not expect a genetic counselor to address psychosocial needs <abbrgrp><abbr bid="B27">27</abbr></abbrgrp>. In a survey of genetic counseling patients, Wertz <abbrgrp><abbr bid="B28">28</abbr></abbrgrp> found a majority of respondents understood genetic conditions to have a moderate to serious effect on family life and finances, while almost half perceived there to be an effect on the spouse, quality of life, and the relationship between home and work. However, these topics were reportedly not discussed within genetic counseling sessions <abbrgrp><abbr bid="B27">27</abbr><abbr bid="B28">28</abbr></abbrgrp>. Overall, there is limited information about the experiences of transitional life events in FRDA, as well as a lack of recommendations for genetic counselors and other health care providers to assist patients through these events.</p> <p>Our study investigated perceptions of patients with Friedreich ataxia to 1) identify key transitional events and specific needs associated with events; 2) describe perception of factors to facilitate progression through the identified events; and 3) explore the actual or potential role of the health care provider in facilitating adaptation to the identified events. Data were used to make suggestions for developmental genetic counseling approaches in the context of ongoing care of clients with hereditary, progressive, neurodegenerative conditions.</p

The hard X-ray burst spectrometer event listing 1980-1987

This event listing is a comprehensive reference for the Hard X-ray bursts detected with the Hard X-ray Burst Spectrometer on the Solar Maximum Mission from the time of launch 14 February 1980 to December 1987. Over 8600 X-ray events were detected in the energy range from 30 to approx. 600 keV with the vast majority being solar flares. The listing includes the start time, peak time, duration and peak rate of each event

Adaptation to bipolar disorder and perceived risk to children: a survey of parents with bipolar disorder

Abstract Background Bipolar disorder (BPD) is a common condition associated with significant morbidity and reduced quality of life. In addition to challenges caused by their mood symptoms, parents affected with BPD harbor concerns about the mental health of their children. Among adult parents who perceive themselves to have BPD, this study aims to examine participants’ coping methods; identify predictors of adaptation; assess parental perceptions of risks for mood disorders among their children; and describe the relationships among illness appraisals, coping, adaptation to one’s own illness, and perceived risk to one’s children. Methods Parents who self-identified as having BPD completed a web-based survey that assessed dispositional optimism, coping, perceived illness severity, perceived etiology of BPD, perceived risk to offspring, and adaptation to BPD. Participants had at least one unaffected child who was 30 years of age or below. Results 266 parents were included in the analysis. 87% of parents endorsed a “somewhat greater” or “much greater” risk for mood disorders in one’s child(ren) than someone without a family history. Endorsing a genetic/familial etiology to BPD was positively correlated with perceived risk for mood disorders in children (r s = .3, p < 0.01) and active coping with BDP (r = .2, p < 0.01). Increased active coping (β = 0.4, p < 0.001) and dispositional optimism (β = 0.3, p < 0.001) were positively associated with better adaptation, while using denial coping was negatively associated with adaptation (β = −0.3, p < 0.001). The variables explained 55.2% of the variance in adaptation (F = 73.2, p < 0.001). Coping mediated the effect of perceived illness severity on adaptation. Conclusions These data inform studies of interventions that extend beyond symptom management and aim to improve the psychological wellbeing of parents with BPD. Interventions targeted at illness perceptions and those aimed at enhancing coping should be studied for positive effects on adaptation. Parents with BPD may benefit from genetic counseling to promote active coping with their condition, and manage worry about perceived risk to their children

Numerical Simulation of an EUV Coronal Wave Based on the February 13, 2009 CME Event Observed by STEREO

On 13 February 2009, a coronal wave -- CME -- dimming event was observed in quadrature by the STEREO spacecraft. We analyze this event using a three-dimensional, global magnetohydrodynamic (MHD) model for the solar corona. The numerical simulation is driven and constrained by the observations, and indicates where magnetic reconnection occurs between the expanding CME core and surrounding environment. We focus primarily on the lower corona, extending out to $3R_{\odot}$; this range allows simultaneous comparison with both EUVI and COR1 data. Our simulation produces a diffuse coronal bright front remarkably similar to that observed by STEREO/EUVI at 195 \AA. It is made up of \emph{two} components, and is the result of a combination of both wave and non-wave mechanisms. The CME becomes large-scale quite low ($<$ 200 Mm) in the corona. It is not, however, an inherently large-scale event; rather, the expansion is facilitated by magnetic reconnection between the expanding CME core and the surrounding magnetic environment. In support of this, we also find numerous secondary dimmings, many far from the initial CME source region. Relating such dimmings to reconnecting field lines within the simulation provides further evidence that CME expansion leads to the "opening" of coronal field lines on a global scale. Throughout the CME expansion, the coronal wave maps directly to the CME footprint. Our results suggest that the ongoing debate over the "true" nature of diffuse coronal waves may be mischaracterized. It appears that \emph{both} wave and non-wave models are required to explain the observations and understand the complex nature of these events

\u3cem\u3eDENND5B\u3c/em\u3e Regulates Intestinal Triglyceride Absorption and Body Mass

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common DENND5B variant, p.(R52K), is correlated with body mass index. These studies establish an important role for DENND5B in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism

Statistical Survey of Type III Radio Bursts at Long Wavelengths Observed by the Solar TErrestrial RElations Observatory (STEREO)/Waves Instruments: Radio Flux Density Variations with Frequency

We have performed a statistical study of $152$ Type III radio bursts observed by Solar TErrestrial RElations Observatory (STEREO)/Waves between May 2007 and February 2013. We have investigated the flux density between $125$kHz and $16$MHz. Both high- and low-frequency cutoffs have been observed in $60\,$ of events suggesting an important role of propagation. As already reported by previous authors, we observed that the maximum flux density occurs at $1$MHz on both spacecraft. We have developed a simplified analytical model of the flux density as a function of radial distance and compared it to the STEREO/Waves data.Comment: published in Solar Physic

The PiGeOn project: Protocol for a longitudinal study examining psychosocial, behavioural and ethical issues and outcomes in cancer tumour genomic profiling

© 2018 The Author(s). Background: Genomic sequencing in cancer (both tumour and germline), and development of therapies targeted to tumour genetic status, hold great promise for improvement of patient outcomes. However, the imminent introduction of genomics into clinical practice calls for better understanding of how patients value, experience, and cope with this novel technology and its often complex results. Here we describe a protocol for a novel mixed-methods, prospective study (PiGeOn) that aims to examine patients' psychosocial, cognitive, affective and behavioural responses to tumour genomic profiling and to integrate a parallel critical ethical analysis of returning results. Methods: This is a cohort sub-study of a parent tumour genomic profiling programme enrolling patients with advanced cancer. One thousand patients will be recruited for the parent study in Sydney, Australia from 2016 to 2019. They will be asked to complete surveys at baseline, three, and fivemonths. Primary outcomes are: knowledge, preferences, attitudes and values. A purposively sampled subset of patients will be asked to participate in three semi-structured interviews (at each time point) to provide deeper data interpretation. Relevant ethical themes will be critically analysed to iteratively develop or refine normative ethical concepts or frameworks currently used in the return of genetic information. Discussion: This will be the first Australian study to collect longitudinal data on cancer patients' experience of tumour genomic profiling. Findings will be used to inform ongoing ethical debates on issues such as how to effectively obtain informed consent for genomic profiling return results, distinguish between research and clinical practice and manage patient expectations. The combination of quantitative and qualitative methods will provide comprehensive and critical data on how patients cope with 'actionable' and 'non-actionable' results. This information is needed to ensure that when tumour genomic profiling becomes part of routine clinical care, ethical considerations are embedded, and patients are adequately prepared and supported during and after receiving results

From Predicting Solar Activity to Forecasting Space Weather: Practical Examples of Research-to-Operations and Operations-to-Research

The successful transition of research to operations (R2O) and operations to research (O2R) requires, above all, interaction between the two communities. We explore the role that close interaction and ongoing communication played in the successful fielding of three separate developments: an observation platform, a numerical model, and a visualization and specification tool. Additionally, we will examine how these three pieces came together to revolutionize interplanetary coronal mass ejection (ICME) arrival forecasts. A discussion of the importance of education and training in ensuring a positive outcome from R2O activity follows. We describe efforts by the meteorological community to make research results more accessible to forecasters and the applicability of these efforts to the transfer of space-weather research.We end with a forecaster "wish list" for R2O transitions. Ongoing, two-way communication between the research and operations communities is the thread connecting it all.Comment: 18 pages, 3 figures, Solar Physics in pres

The PiGeOn project: Protocol of a longitudinal study examining psychosocial and ethical issues and outcomes in germline genomic sequencing for cancer

© 2018 The Author(s). Background: Advances in genomics offer promise for earlier detection or prevention of cancer, by personalisation of medical care tailored to an individual's genomic risk status. However genome sequencing can generate an unprecedented volume of results for the patient to process with potential implications for their families and reproductive choices. This paper describes a protocol for a study (PiGeOn) that aims to explore how patients and their blood relatives experience germline genomic sequencing, to help guide the appropriate future implementation of genome sequencing into routine clinical practice. Methods: We have designed a mixed-methods, prospective, cohort sub-study of a germline genomic sequencing study that targets adults with cancer suggestive of a genetic aetiology. One thousand probands and 2000 of their blood relatives will undergo germline genomic sequencing as part of the parent study in Sydney, Australia between 2016 and 2020. Test results are expected within12-15 months of recruitment. For the PiGeOn sub-study, participants will be invited to complete surveys at baseline, three months and twelve months after baseline using self-administered questionnaires, to assess the experience of long waits for results (despite being informed that results may not be returned) and expectations of receiving them. Subsets of both probands and blood relatives will be purposively sampled and invited to participate in three semi-structured qualitative interviews (at baseline and each follow-up) to triangulate the data. Ethical themes identified in the data will be used to inform critical revisions of normative ethical concepts or frameworks. Discussion: This will be one of the first studies internationally to follow the psychosocial impact on probands and their blood relatives who undergo germline genome sequencing, over time. Study results will inform ongoing ethical debates on issues such as informed consent for genomic sequencing, and informing participants and their relatives of specific results. The study will also provide important outcome data concerning the psychological impact of prolonged waiting for germline genomic sequencing. These data are needed to ensure that when germline genomic sequencing is introduced into standard clinical settings, ethical concepts are embedded, and patients and their relatives are adequately prepared and supported during and after the testing process