Careful and Complete Observation of the Patient: Nurses and the Sociotechnical System of Medical Research, 1930-1962

ABSTRACT CAREFUL AND COMPLETE OBSERVATION OF THE PATIENT;” NURSES AND THE SOCIOTECHNICAL SYSTEM OF MEDICAL RESEARCH, 1930-1962 Amanda L. Mahoney, MS, RN Julie A. Fairman, PhD, RN, FAAN This study addresses the history of nurses working in medical research between 1930 and 1962, a time of tremendous growth in the use of experimentation to further clinical knowledge. Nurses were part of an intricate network of people, machines, knowledge and space—a socio-technical system—that made the clinical discoveries of the mid-20th century possible. Nurses were heavily involved in the day to day practices of medical research, thus this dissertation employs a microhistory approach, focusing on individual research projects conducted at the Hospital of the University of Pennsylvania (HUP) in Philadelphia, Pennsylvania. Archival sources related to clinical trials and nursing at HUP were examined as well as the historical records of funding agencies. Nurses performed important, skilled tasks including data collection and complex patient care. The requirements of research studies as well as the new technologies associated with clinical trials required nurses to develop methods and systems to accommodate an increased work load, collect data, and implement new treatments and techniques. This knowledge work was performed in the busy, understaffed world of the mid-20th century hospital. Nurses provided close observation and careful control of the patient, making metabolic research in particular feasible within hospitals. Nurses maintained the cooperation of research patients, a critical aspect to studies involving special diets. Within the hospital, nurses created a “zone of control” around the bedside of research patients, implementing research protocols, closely observing patients and gaining their compliance or cooperation. Using the work of bedside nurses as a historical lens reveals much about the world of medical research and the many factors that contributed to the growth and acceptance of experimentation as a normal part of clinical medicine. Marginalized actors have the agency and power to influence the success or failure of medical research even if they are denied official power. Nursing may hold the solutions to many of the challenges researchers face today

A Survey of Communication Sciences and Disorders Graduate Students\u27 Perceptions of Critical Appraisal Skills

Research shows that prerequisite courses prepare students for participation in more challenging coursework and more advanced future learning. Despite being a field that heavily relies on research evidence to inform clinical decisions as part of evidence-based practice, many undergraduate Communication Sciences and Disorder (CSD) programs do not include prerequisite undergraduate coursework dedicated to research methods. The purpose of the present study was to explore speech-language pathology and audiology graduate students’ experiences with and opinions about critical appraisal of research articles. A total of 201 graduate students from institutions nationwide completed an online survey with questions related to exposure to research appraisal, use of an appraisal tool, and perspectives on the importance of research appraisal and confidence in appraisal skills. Results indicated that nearly one-third of the respondents did not learn or could not remember learning about article appraisal in their undergraduate CSD programs, though almost all survey respondents reported that they had learned about article appraisal in their graduate classes. Over half of the students used an article appraisal tool to bolster their learning of article critiques, almost all of whom found it helpful. Most of the respondents recognized the importance of article appraisal knowledge prior to graduate school but suggested that many of their undergraduate instructors did not place importance on the skill. Respondents’ confidence in their article appraisal skills ranged from “least confident” to “most confident”. This study supports early and ongoing practice with article appraisal, which will provide these future clinicians with the confidence to communicate their knowledge and understanding when making evidence-informed clinical decisions. Additionally, instructors who teach article appraisal may consider using a hands-on appraisal tool since almost all students with experience using them believe they are helpful

Differential regulation of gene expression pathways with dexamethasone and ACTH after early life seizures.

Early-life seizures (ELS) are associated with persistent cognitive deficits such as ADHD and memory impairment. These co-morbidities have a dramatic negative impact on the quality of life of patients. Therapies that improve cognitive outcomes have enormous potential to improve patients\u27 quality of life. Our previous work in a rat flurothyl-induction model showed that administration of adrenocorticotropic hormone (ACTH) at time of seizure induction led to improved learning and memory in the animals despite no effect on seizure latency or duration. Administration of dexamethasone (Dex), a corticosteroid, did not have the same positive effect on learning and memory and has even been shown to exacerbate injury in a rat model of temporal lobe epilepsy. We hypothesized that ACTH exerted positive effects on cognitive outcomes through beneficial changes to gene expression and proposed that administration of ACTH at seizure induction would return gene-expression in the brain towards the normal pattern of expression in the Control animals whereas Dex would not. Twenty-six Sprague-Dawley rats were randomized into vehicle- Control, and ACTH-, Dex-, and vehicle- ELS. Rat pups were subjected to 60 flurothyl seizures from P5 to P14. After seizure induction, brains were removed and the hippocampus and PFC were dissected, RNA was extracted and sequenced, and differential expression analysis was performed using generalized estimating equations. Differential expression analysis showed that ACTH pushes gene expression in the brain back to a more normal state of expression through enrichment of pathways involved in supporting homeostatic balance and down-regulating pathways that might contribute to excitotoxic cell-damage post-ELS

Pretend Play and Social Engagement in Toddlers at High and Low Genetic Risk for Autism Spectrum Disorder

Toddlers with an older sibling with autism spectrum disorder (ASD) and low risk (LR) toddlers with typically-developing older siblings were observed during free play with a parent and elicited pretend with an examiner at 22-months. Functional and pretend play, children’s social engagement, and parent sensitivity were assessed during free play. Complexity of play was assessed during the elicited pretend task. Toddlers with an ASD diagnosis showed less pretend play across contexts and less social engagement with parents or the examiner than either LR toddlers or high risk toddlers without a diagnosis (HR-noASD). Lower levels of pretend play and social engagement were associated with symptom severity within the high risk group, reflecting emerging ASD in toddlerhood

A Novel Conserved Isoform of the Ubiquitin Ligase UFD2a/UBE4B Is Expressed Exclusively in Mature Striated Muscle Cells

Yeast Ufd2p was the first identified E4 multiubiquitin chain assembly factor. Its vertebrate homologues later referred to as UFD2a, UBE4B or E4B were also shown to have E3 ubiquitin ligase activity. UFD2a function in the brain has been well established in vivo, and in vitro studies have shown that its activity is essential for proper condensation and segregation of chromosomes during mitosis. Here we show that 2 alternative splice forms of UFD2a, UFD2a-7 and -7/7a, are expressed sequentially during myoblast differentiation of C2C12 cell cultures and during cardiotoxin-induced regeneration of skeletal muscle in mice. UFD2a-7 contains an alternate exon 7, and UFD2a-7/7a, the larger of the 2 isoforms, contains an additional novel exon 7a. Analysis of protein or mRNA expression in mice and zebrafish revealed that a similar pattern of isoform switching occurs during developmental myogenesis of cardiac and skeletal muscle. In vertebrates (humans, rodents, zebrafish), UFD2a-7/7a is expressed only in mature striated muscle. This unique tissue specificity is further validated by the conserved presence of 2 muscle-specific splicing regulatory motifs located in the 3′ introns of exons 7 and 7a. UFD2a interacts with VCP/p97, an AAA-type ATPase implicated in processes whose functions appear to be regulated, in part, through their interaction with one or more of 15 previously identified cofactors. UFD2a-7/7a did not interact with VCP/p97 in yeast 2-hybrid experiments, which may allow the ATPase to bind cofactors that facilitate its muscle-specific functions. We conclude that the regulated expression of these UFD2a isoforms most likely imparts divergent functions that are important for myogenisis

Cost-effectiveness of cognitive behaviour therapy versus talking and usual care for depressed older people in primary care

Background: Whilst evidence suggests cognitive behaviour therapy (CBT) may be effective for depressed older people in a primary care setting, few studies have examined its cost-effectiveness. The aim of this study was to compare the cost-effectiveness of cognitive behaviour therapy (CBT), a talking control (TC) and treatment as usual (TAU), delivered in a primary care setting, for older people with depression.Methods: Cost data generated from a single blind randomised controlled trial of 204 people aged 65 years or more were offered only Treatment as Usual, or TAU plus up to twelve sessions of CBT or a talking control is presented. The Beck Depression Inventory II (BDI-II) was the main outcome measure for depression. Direct treatment costs were compared with reductions in depression scores. Cost-effectiveness analysis was conducted using non-parametric bootstrapping. The primary analysis focussed on the cost-effectiveness of CBT compared with TAU at 10 months follow up.Results: Complete cost data were available for 198 patients at 4 and 10 month follow up. There were no significant differences between groups in baseline costs. The majority of health service contacts at follow up were made with general practitioners. Fewer contacts with mental health services were recorded in patients allocated to CBT, though these differences were not significant. Overall total per patient costs (including intervention costs) were significantly higher in the CBT group compared with the TAU group at 10 month follow up (difference 427 pound, 95% CI: 56 pound - 787 pound, p < 0.001). Reductions in BDI-II scores were significantly greater in the CBT group (difference 3.6 points, 95% CI: 0.7-6.5 points, p = 0.018). CBT is associated with an incremental cost of 120 pound per additional point reduction in BDI score and a 90% probability of being considered cost-effective if purchasers are willing to pay up to 270 pound per point reduction in the BDI-II score.Conclusions: CBT is significantly more costly than TAU alone or TAU plus TC, but more clinically effective. Based on current estimates, CBT is likely to be recommended as a cost-effective treatment option for this patient group if the value placed on a unit reduction in BDI-II is greater than 115 pound

Pretreatment Engineering Platform Phase 1 Final Test Report

Pacific Northwest National Laboratory (PNNL) was tasked by Bechtel National Inc. (BNI) on the River Protection Project, Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to conduct testing to demonstrate the performance of the WTP Pretreatment Facility (PTF) leaching and ultrafiltration processes at an engineering-scale. In addition to the demonstration, the testing was to address specific technical issues identified in Issue Response Plan for Implementation of External Flowsheet Review Team (EFRT) Recommendations - M12, Undemonstrated Leaching Processes.( ) Testing was conducted in a 1/4.5-scale mock-up of the PTF ultrafiltration system, the Pretreatment Engineering Platform (PEP). Parallel laboratory testing was conducted in various PNNL laboratories to allow direct comparison of process performance at an engineering-scale and a laboratory-scale. This report presents and discusses the results of those tests

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Careful and complete observation of the patient : Nurses and the Sociotechnical System of Medical Research, 1930-1962

This study addresses the history of nurses working in medical research between 1930 and 1962, a time of tremendous growth in the use of experimentation to further clinical knowledge. Nurses were part of an intricate network of people, machines, knowledge and space—a socio-technical system—that made the clinical discoveries of the mid-20th century possible. Nurses were heavily involved in the day to day practices of medical research, thus this dissertation employs a microhistory approach, focusing on individual research projects conducted at the Hospital of the University of Pennsylvania (HUP) in Philadelphia, Pennsylvania. Archival sources related to clinical trials and nursing at HUP were examined as well as the historical records of funding agencies. Nurses performed important, skilled tasks including data collection and complex patient care. The requirements of research studies as well as the new technologies associated with clinical trials required nurses to develop methods and systems to accommodate an increased work load, collect data, and implement new treatments and techniques. This knowledge work was performed in the busy, understaffed world of the mid-20th century hospital. Nurses provided close observation and careful control of the patient, making metabolic research in particular feasible within hospitals. Nurses maintained the cooperation of research patients, a critical aspect to studies involving special diets. Within the hospital, nurses created a “zone of control” around the bedside of research patients, implementing research protocols, closely observing patients and gaining their compliance or cooperation. Using the work of bedside nurses as a historical lens reveals much about the world of medical research and the many factors that contributed to the growth and acceptance of experimentation as a normal part of clinical medicine. Marginalized actors have the agency and power to influence the success or failure of medical research even if they are denied official power. Nursing may hold the solutions to many of the challenges researchers face today

Evaluation of giant african pouched rats for detection of pulmonary tuberculosis in patients from a high-endemic setting

This study established evidence about the diagnostic performance of trained giant African pouched rats for detecting Mycobacterium tuberculosis in sputum of well-characterised patients with presumptive tuberculosis (TB) in a high-burden setting.; The TB detection rats were evaluated using sputum samples of patients with presumptive TB enrolled in two prospective cohort studies in Bagamoyo, Tanzania. The patients were characterised by sputum smear microscopy and culture, including subsequent antigen or molecular confirmation of Mycobacterium tuberculosis, and by clinical data at enrolment and for at least 5-months of follow-up to determine the reference standard. Seven trained giant African pouched rats were used for the detection of TB in the sputum samples after shipment to the APOPO project in Morogoro, Tanzania.; Of 469 eligible patients, 109 (23.2%) were culture-positive for Mycobacterium tuberculosis and 128 (27.3%) were non-TB controls with sustained recovery after 5 months without anti-TB treatment. The HIV prevalence was 46%. The area under the receiver operating characteristic curve of the seven rats for the detection of culture-positive pulmonary tuberculosis was 0.72 (95% CI 0.66-0.78). An optimal threshold could be defined at ≥2 indications by rats in either sample with a corresponding sensitivity of 56.9% (95% CI 47.0-66.3), specificity of 80.5% (95% CI 72.5-86.9), positive and negative predictive value of 71.3% (95% CI 60.6-80.5) and 68.7% (95% CI 60.6-76.0), and an accuracy for TB diagnosis of 69.6%. The diagnostic performance was negatively influenced by low burden of bacilli, and independent of the HIV status.; Giant African pouched rats have potential for detection of tuberculosis in sputum samples. However, the diagnostic performance characteristics of TB detection rats do not currently meet the requirements for high-priority, rapid sputum-based TB diagnostics as defined by the World Health Organization