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Spinal muscular atrophy (SMA) is a neuromuscular disorder arising from biallelic non-functional survival motor neuron 1(SMN1) genes with variable copies of partially functional SMN2gene. Intrathecal onasemnogene abeparvovec administration, at fixed, low doses, may enable treatment of heavier patients ineligible for weight-based intravenous dosing. STRONG (NCT03381729) assessed the safety/tolerability and efficacy of intrathecal onasemnogene abeparvovec for sitting, nonambulatory SMA patients. Sitting, nonambulatory SMA patients (biallelic SMN1loss, three SMN2copies, aged 6–<60 months) received a single dose of intrathecal onasemnogene abeparvovec. Patients were enrolled sequentially into one of three (low, medium, and high) dose cohorts and stratified into two groups by age at dosing: younger (6–<24 months) and older (24–<60 months). Primary endpoints included safety/tolerability, independent standing ≥3 seconds (younger group), and change in Hammersmith Functional Motor Scale Expanded (HFMSE) from baseline (older group) compared with historic controls. Thirty-two patients were enrolled and completed the study (medium dose, n = 25). All patients had one or more treatment-emergent adverse events, with one serious and related to treatment (transaminase elevations). No deaths were reported. One of 13 patients (7.7%) in the younger group treated with the medium dose achieved independent standing. At Month 12 for the older group receiving the medium dose, change from baseline in HFMSE was significantly improved compared with the SMA historic control population (P < 0.01). Intrathecal onasemnogene abeparvovec was safe and well-tolerated. Older patients treated with the medium dose demonstrated increases in HFMSE score greater than commonly observed in natural history.

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder arising from biallelic non-functional survival motor neuron 1(SMN1) genes with variable copies of partially functional SMN2gene. Intrathecal onasemnogene abeparvovec administration, at fixed, low doses, may enable treatment of heavier patients ineligible for weight-based intravenous dosing.Objective: STRONG (NCT03381729) assessed the safety/tolerability and efficacy of intrathecal onasemnogene abeparvovec for sitting, nonambulatory SMA patients.Methods: Sitting, nonambulatory SMA patients (biallelic SMN1loss, three SMN2copies, aged 6–<60 months) received a single dose of intrathecal onasemnogene abeparvovec. Patients were enrolled sequentially into one of three (low, medium, and high) dose cohorts and stratified into two groups by age at dosing: younger (6–<24 months) and older (24–<60 months). Primary endpoints included safety/tolerability, independent standing =3 seconds (younger group), and change in Hammersmith Functional Motor Scale Expanded (HFMSE) from baseline (older group) compared with historic controls.Results: Thirty-two patients were enrolled and completed the study (medium dose, n?=?25). All patients had one or more treatment-emergent adverse events, with one serious and related to treatment (transaminase elevations). No deaths were reported. One of 13 patients (7.7%) in the younger group treated with the medium dose achieved independent standing. At Month 12 for the older group receiving the medium dose, change from baseline in HFMSE was significantly improved compared with the SMA historic control population (P?

Modern nursing is supported by a rich ethical tradition dating back to the mid-19th century. Moving illustrations of nursing practice and “the highest morals” (McIsaac, 1901) relay the distinguished history and distinctives of nursing ethics from the 1860s to the present day. Of note is that nursing ethics is relationally focused, virtue-based, preventative, and central to the identity of nursing. A brief history of how bioethics emerged in the mid-20th century and an overview of the development of nursing ethics unveils differences between the two ethical paradigms.

AbstractPast studies examining sponsorship have primarily focused on the sponsor and not the sporting event. The current study seeks to analyze how sponsorship associations are interpreted by consumers toward the event through the Elaboration Likelihood Advertising Model (ELAM). The purpose of this study is to: (1) examine consumers’ perceptions of authenticity and unauthenticity stemming from sport sponsor-event partnerships and the effects of each partnership on consumers’ elaboration, attitude, and emotion; and (2) assess the impact of consumer attitudes and emotions toward the sporting event on event-related behavioral intentions based on perceived authentic and unauthentic partnerships. Significant differences were found among healthy, unhealthy and CSR experiments for authenticity, elaboration, and attitude but not for emotion. In addition, emotion was positive and significantly related to event-related behavioral intentions for all three experiments, while attitude was positive and significantly related to event-related behavioral intentions for the healthy experiment only. Findings provide evidence that sponsorship associations affect consumer evaluations toward the event.

The COVID-19 pandemic and subsequent development of COVID vaccines have resulted in unique challenges for nurses. Nurses are being asked to make recommendations about vaccinations that have only been available since December 2020 even as vaccine information evolves on an almost daily basis. Standards of professional care and a Christian perspective on nursing to help guide nurses' practice in the current climate are discussed in this article. An overview of information and research findings published up to October 31, 2021 about COVID-19 vaccination is given to assist nurses in answering vaccination questions.

Acute trauma stimulates local repair mechanisms but can also impact structures distant from the injury, for example through the activity of circulating factors. To study the responses of remote tissues during tissue regeneration, we profiled transcriptomes of zebrafish brains after experimental cardiac damage. We found that the transcription factor gene cebpdwas upregulated remotely in brain ependymal cells as well as kidney tubular cells, in addition to its local induction in epicardial cells. cebpdmutations altered both local and distant cardiac injury responses, altering the cycling of epicardial cells as well as exchange between distant fluid compartments. Genome-wide profiling and transgenesis identified a hormone-responsive enhancer near cebpdthat exists in a permissive state, enabling rapid gene expression in heart, brain and kidney after cardiac injury. Deletion of this sequence selectively abolished cebpdinduction in remote tissues and disrupted fluid regulation after injury, without affecting its local cardiac expression response. Our findings suggest a model to broaden gene function during regeneration in which enhancer regulatory elements define short- and long-range expression responses to injury.

Infertility, the inability to conceive and/or carry a baby to term, is an agonizing experience for many. Both the experience and pain of infertility are ancient, shared by women and men of the Bible and by couples today. An insider's look into infertility can help nurses understand the suffering that occurs, suggest what can be said and done that can be helpful as well as hurtful, and offer insight into what can be gained personally and spiritually through the experience of infertility.

Purpose: In 2017, the National Basketball Association (NBA) became the first major professional North American sport league to adopt jersey sponsorship. While professional leagues across the globe have allowed this practice for decades, the NBA's decision marked what may be the start of a new trend in North American sport sponsorship. With this in mind, the current study sought to assess the impact of fans' perceptions of these sponsorships on sponsor- and team-related outcomes. Design/methodology/approach: An online sample of 301 NBA fans across the United States was conducted through Amazon's MTurk. Findings: Results exhibited the importance of sponsorship authenticity, which maintained the strongest influence on sponsor- and team-related outcomes. Brand–team fit, sponsorship familiarity and sponsorship identification were also assessed, with mixed results for each factor. Originality/value: Results of these findings related to sponsorship authenticity and consequent practical and theoretical implications are discussed, and areas for future research are provided.

As vehicle automation continues to become a more prevalent part of everyday life, remote operators may be able to contribute to making this technology safer and more efficient. Such operators could be expected to monitor vehicles until it is necessary for them to intervene. In recent years several countries have passed legislation mandating the implementation of remote operation, making it a plausible scenario. For many practical reasons, operators may monitor more than one vehicle. This study provides an initial look into how remote operators might perform when asked to attend to multiple concurrent displays using simulated automated vehicles. The initial results indicate that participants retained a comparable level of accuracy in detecting failures in automation as the number of vehicles they monitored rose from one to two, albeit with a higher workload. The results and the methodology provide insights into potential task designs for remote operators of automated vehicles.

AbstractBackground:Neuromuscular disorders are a phenotypically and genotypically diverse group of diseases that can be difficult to diagnose accurately because of overlapping clinical features and nonspecific muscle pathology. Next-generation sequencing (NGS) is a high-throughput technology that can be used as a more time- and cost-effective tool for identifying molecular diagnoses for complex genetic conditions, such as neuromuscular disorders. Methods:One hundred and sixty-nine patients referred to a Canadian neuromuscular clinic for evaluation of possible muscle disease were screened with an NGS panel of muscular dystrophy–associated genes. Patients were categorized by the reason of referral (1) muscle weakness (n=135), (2) recurrent episodes of rhabdomyolysis (n=18), or (3) idiopathic hyperCKemia (n=16). Results:Pathogenic and likely pathogenic variants were identified in 36.09% of patients (61/169). The detection rate was 37.04% (50/135) in patients with muscle weakness, 33.33% (6/18) with rhabdomyolysis, and 31.25% (5/16) in those with idiopathic hyperCKemia. Conclusions:This study shows that NGS can be a useful tool in the molecular workup of patients seen in a neuromuscular clinic. Evaluating the utility of large panels of a muscle disease-specific NGS panel to investigate the genetic susceptibilities of rhabdomyolysis and/or idiopathic hyperCKemia is a relatively new field. Twenty-eight of the pathogenic and likely pathogenic variants reported here are novel and have not previously been associated with disease.

To examine practices for addressing moral distress, a collaborative project was developed by the Johns Hopkins Berman Institute of Bioethics, the Johns Hopkins School of Nursing, the American Journal of Nursing, and the Journal of Christian Nursing, along with the American Association of Critical-Care Nurses and the American Nurses Association. Its purpose was to identify strategies that individuals and systems can use to mitigate the detrimental effects of moral distress and foster moral resilience. On August 11 and 12, 2016, an invitational symposium, State of the Science: Transforming Moral Distress into Moral Resilience in Nursing, was held at the Johns Hopkins School of Nursing in Baltimore, Maryland. Forty-five nurse clinicians, researchers, ethicists, organization representatives, and other stakeholders took part. The result of the symposium was group consensus on recommendations for addressing moral distress and building moral resilience in four areas: practice, education, research, and policy. Participants and the organizations represented were energized and committed to moving this agenda forward. The full report is available online at http://journals.lww.com/ajnonline/Pages/Moral-Distress-Supplement.aspx

Anything toxicis poisonous and harmful—including a toxic workplace. Surveys of hundreds of individuals and organizations reveal three primary areas that are common in unhealthy work environments: sick systems, toxic leaders, and dysfunctional colleagues. This article draws from research and offers practical steps on how to survive, if not change and thrive, in toxic workplaces.A toxic workplace has unhealthy characteristics in three primary areas: sick systems, toxic leaders, and dysfunctional colleagues. Discover practical steps on how to survive, if not thrive, and impact all three areas.