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"Story, David"
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The story of the Selma voting rights marches in photographs
\"Explores the Selma Voting Rights Marches of 1965, including the causes of the protests, the march organizers, the violence surrounding the events, and the impact the marches had on the passage of the Voting Rights Act\"--Provided by publisher.
Book
Implementability of healthcare interventions: an overview of reviews and development of a conceptual framework
Background
Implementation research may play an important role in reducing research waste by identifying strategies that support translation of evidence into practice. Implementation of healthcare interventions is influenced by multiple factors including the organisational context, implementation strategies and features of the intervention as perceived by people delivering and receiving the intervention. Recently, concepts relating to perceived features of interventions have been gaining traction in published literature, namely, acceptability, fidelity, feasibility, scalability and sustainability. These concepts may influence uptake of healthcare interventions, yet there seems to be little consensus about their nature and impact. The aim of this paper is to develop a testable conceptual framework of implementability of healthcare interventions that includes these five concepts.
Methods
A multifaceted approach was used to develop and refine a conceptual framework of implementability of healthcare interventions. An overview of reviews identified reviews published between January 2000 and March 2021 that focused on at least one of the five concepts in relation to a healthcare intervention. These findings informed the development of a preliminary framework of implementability of healthcare interventions which was presented to a panel of experts. A nominal group process was used to critique, refine and agree on a final framework.
Results
A total of 252 publications were included in the overview of reviews. Of these, 32% were found to be feasible, 4% reported sustainable changes in practice and 9% were scaled up to other populations and/or settings. The expert panel proposed that scalability and sustainability of a healthcare intervention are dependent on its acceptability, fidelity and feasibility. Furthermore, acceptability, fidelity and feasibility require re-evaluation over time and as the intervention is developed and then implemented in different settings or with different populations. The final agreed framework of implementability provides the basis for a chronological, iterative approach to planning for wide-scale, long-term implementation of healthcare interventions.
Conclusions
We recommend that researchers consider the factors acceptability, fidelity and feasibility (proposed to influence sustainability and scalability) during the preliminary phases of intervention development, evaluation and implementation, and iteratively check these factors in different settings and over time.
Journal Article
The story of Rosa Parks and the Montgomery Bus Boycott in photographs
\"Examines the Montgomery Bus Boycott through primary source photographs, including Rosa Parks' role in the effort, other important leaders, the daily struggles of the boycott, and the end of segregation on Montgomery's buses\"--Provided by publisher.
Book
Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery
Patients undergoing major abdominal surgery received restrictive or liberal intravenous fluids during surgery and up to 24 hours thereafter. The restrictive regimen did not improve disability-free survival and resulted in increased acute kidney injury.
Journal Article
The story of the Birmingham civil rights movement in photographs
\"Examines the Birmingham Civil Rights Movement, including the organizers of the protests, the movement's support from young people, the violence that occurred, and the integration of Birmingham\"--Provided by publisher.
Book
Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis
Axonal dysfunction is a common phenotype in neurodegenerative disorders, including in amyotrophic lateral sclerosis (ALS), where the key pathological cell-type, the motor neuron (MN), has an axon extending up to a metre long. The maintenance of axonal function is a highly energy-demanding process, raising the question of whether MN cellular energetics is perturbed in ALS, and whether its recovery promotes axonal rescue. To address this, we undertook cellular and molecular interrogation of multiple patient-derived induced pluripotent stem cell lines and patient autopsy samples harbouring the most common ALS causing mutation, C9orf72. Using paired mutant and isogenic expansion-corrected controls, we show that C9orf72 MNs have shorter axons, impaired fast axonal transport of mitochondrial cargo, and altered mitochondrial bioenergetic function. RNAseq revealed reduced gene expression of mitochondrially encoded electron transport chain transcripts, with neuropathological analysis of C9orf72-ALS post-mortem tissue importantly confirming selective dysregulation of the mitochondrially encoded transcripts in ventral horn spinal MNs, but not in corresponding dorsal horn sensory neurons, with findings reflected at the protein level. Mitochondrial DNA copy number was unaltered, both in vitro and in human post-mortem tissue. Genetic manipulation of mitochondrial biogenesis in C9orf72 MNs corrected the bioenergetic deficit and also rescued the axonal length and transport phenotypes. Collectively, our data show that loss of mitochondrial function is a key mediator of axonal dysfunction in C9orf72-ALS, and that boosting MN bioenergetics is sufficient to restore axonal homeostasis, opening new potential therapeutic strategies for ALS that target mitochondrial function.
Journal Article
Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability
Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening.
Journal Article
قصة الأصل : تاريخ جامع لكل شئ
هذا الكتاب رحلة جامحة عبر ال 13.8 مليار سنة التي صرنا نعرفها باسم \"التاريخ\" يكشف الخيوط الخفية التي تربط كل شيء معا من تشكل الكواكب إلى اختراع الزراعة والحرب النووية وما بعدها فيقدم رؤى مدهشة حول أصل الكون وبدايات الحياة وظهور البشر وما قد يأتي به المستقبل إنه قصة آسرة للكون من الانفجار العظيم إلى الديناصورات إلى العولمة الشاملة وما بعدها.
Book
Contributors to frailty in critical illness: Multi-dimensional analysis of the Clinical Frailty Scale
Frailty in critical illness is common and associated with poor outcomes, however little is known about contributing factors. We compared the Clinical Frailty Scale (CFS) with a multi-dimensional validated tool, the Edmonton Frail Scale (EFS), and investigated which health domains are affected by frailty in ICU.
This prospective cohort study enrolled patients aged ≥50 years admitted between February–June 2017, comparing the CFS and EFS using Spearman correlation and Kappa coefficients, assessing frailty status across health domains, and examining outcomes including mortality.
One hundred and sixty patients were enrolled, 33.8% were frail. Frail patients had greater in-hospital and 6-month mortality [25.9% vs. 8.5%; adjusted OR (95% CI) = 3.31 (1.17, 9.39), p = .024; and 40.4% vs. 17.3%; OR (95% CI) = 2.84 (1.18, 6.83), p = .020 respectively]. CFS and EFS scales were highly correlated [Spearman correlation coefficient = 0.85 (95% CI 0.81–0.88)], with high agreement [kappa coefficient = 0.78 (95% CI: 0.68–0.88)]. Frail patients had worse health status across the spectrum of frailty domains, in particular functional dependence, malnutrition, and prior hospital admissions.
Frailty in the critically ill affects a range of health deficits, adequately measured via the CFS.
•Frailty in critical illness affects the full range of health domains.•The Clinical Frailty Scale is a valid measure of frailty in ICU.•Functional dependence, malnutrition, and poor physical performance are common.•Frail ICU patients have greater mortality, and discharge to non-home location.
Journal Article