National Institute Research Articles

Moving at the Speed of Business: A Possible Path to First Nation Prosperity Starts with Efficiency

First Nation economic self-determination strategies are constrained by high investment facilitation transaction costs and high jurisdictional implementation switching costs. This paper summarizes a First Nation-led strategy to overcome these constraints. This strategy, which began 55 years ago, uses federal legislation such as the First Nations Fiscal Management Act (FMA) and the Framework Agreement on First Nations Land Management (FA). It is supported by First Nation institutions such as the First Nations Tax Commission, First Nations Financial Management Board, First Nations Land Management Resource Centre, First Nations Finance Authority, and the newly established First Nations Infrastructure Institute. Preliminary observations suggest the FMA-FA strategy has successfully reduced transaction and switching costs on First Nation lands and could accelerate economic self-determination for interested First Nations.

NIAGADS: A Comprehensive National Data Repository for Alzheimer's Disease and Related Dementia Genetics and Genomics Research.

NIAGADS is the National Institute on Aging (NIA) designated national data repository for human genetics research on Alzheimer's Disease and related dementia (ADRD). NIAGADS maintains a high-quality data collection for ADRD genetic/genomic research and supports genetics data production and analysis. NIAGADS hosts whole genome and exome sequence data from the Alzheimer's Disease Sequencing Project (ADSP) and other genotype/phenotype data, encompassing 209,000 samples. NIAGADS shares these data with hundreds of research groups around the world via the Data Sharing Service, a FISMA moderate compliant cloud-based platform that fully supports the NIH Genome Data Sharing Policy. NIAGADS Open Access consists of multiple knowledge bases with genome-wide association summary statistics and rich annotations on the biological significance of genetic variants and genes across the human genome. NIAGADS stands as a keystone in promoting collaborations to advance the understanding and treatment of Alzheimer's disease.

Chronic Kidney Disease Predisposes to Acute Congestive Heart Failure, Cardiogenic Shock, and Mortality in Patients Undergoing Percutaneous Coronary Intervention

The relations between degrees of chronic kidney disease (CKD) and congestive heart failure (CHF) events after percutaneous coronary intervention (PCI) are not well characterized. We sought to determine the relation between different stages of CKD and acute CHF events, including HF and cardiogenic shock (CS), and the impact of CKD stages on all-cause mortality after PCI. Patients who underwent PCI from 2009 to 2017 were identified from our institution's National Cardiovascular Disease Registry CathPCI Database. Patients were stratified by CKD stage 1 (estimated glomerular filtration rate [eGFR] ≥90 ml/min/1.73 m2), 2 (60 to 89), 3a (45 to 59), 3b (30 to 44), 4 (16 to 29), 5 (≤15), and current dialysis. The primary end point was composite HF events defined as acute HF or CS within 30 days after PCI, or in-hospital mortality, stratified by CKD and analyzed by multivariable regression after screening with univariate analysis (p <0.05 entry criteria). Patients with CKD stage 3a or worse had more composite HF events, with an increase in all components, compared with patients with CKD stages 1 to 2 (p <0.0001 for all comparisons). After multivariable adjustment, CKD stages 3a to 5 remained independent predictors of composite HF or in-hospital mortality events. eGFR remained a strong predictor of acute HF events after multivariable adjustment, with a model including eGFR and baseline and procedural characteristics achieving excellent discriminatory ability with area under the curve 0.92. In conclusion, baseline eGFR is a strong, independent predictor of acute HF events after PCI. CKD stages 3a to 5 independently predict HF events including HF decompensation and CS and are predictors of in-hospital mortality after PCI. Patients with baseline CKD may benefit from targeted interventions to limit acute HF events after PCI.

Association between sialic acid, sialidase activity and cholesterol of lipid-containing circulating immune complexes in the blood serum of patients with atherosclerosis

Atherosclerosis is the most common chronic non-infectious diseases, in the pathogenesis of which the accumulation of lipids in the subendothelial layer of the arteries and the local inflammatory reaction play a significant role. The source of lipid accumulation in the vascular wall is modified low-density lipoproteins. Desialylation is one of the known modifications that leads to the emergence of atherogenic properties in low-density lipoproteins. Enzymes that have sialidase activity circulate in human blood, i.e., the ability to cleave sialic acid from low-density lipoproteins. Desialylated low-density lipoproteins are autoantigens and induce the production of IgG autoantibodies, which form immune complexes with low-density lipoproteins, which aggravates the course of atherosclerosis. The purpose of the study was to establish associations between the levels of sialic acid in low-density lipoproteins, sialidase activity and the cholesterol content of lipid-containing circulating immune complexes in the blood serum of patients with atherosclerosis. Blood sera from patients with coronary heart disease were used as biological material to determine indicators of sialidase activity, cholesterol content of lipid-containing circulating immune complexes and sialic acid in low-density lipoproteins, which were isolated from blood serum. Serum samples were obtained from the laboratory of clinical biochemistry of the Institute of Clinical Cardiology, A.L. Myasnikov Federal State Budgetary Institution National Medical Research Center of Cardiology named after Academician E.I. Chazov as unutilized residues after performing routine biochemical tests. Fifty-one samples of blood serum and low-density lipoproteins isolated from it were analyzed. A significant positive relationship was revealed between the cholesterol content of circulating immune complexes and sialidase activity in the blood serum (r = 0.305 at p = 0.029). At the same time, no correlation was found between the content of sialic acid in low-density lipoproteins and sialidase activity in the blood serum, as well as between the cholesterol content of circulating immune complexes in the blood serum and sialic acid in low-density lipoproteins. It should be assumed that increased sialidase activity in the blood serum leads to the formation of desialylated immunogenic low-density lipoproteins with the subsequent appearance of autoantibodies and the formation of lipid-containing circulating immune complexes.

Preoperative cerebral angiography nearly doubles the rate of diffusion-weighted imaging lesion detection following minimally invasive surgery for intracerebral hemorrhage

BackgroundDiffusion-weighted imaging (DWI) lesions have been linked to poor outcomes after intracerebral hemorrhage (ICH). We aimed to assess the impact of cerebral digital subtraction angiography (DSA) on the presence of...

Clive Palmer’s claims against Australia for billions renew pressure to remove investor rights to sue governments from trade agreements

Abstract The Australian debate over Investor-State Dispute Settlement (ISDS) sharpened in 2023 because Australian mining billionaire Clive Palmer, having previously registered his mining company in Singapore, has claimed to be a Singaporean investor. He is using ISDS provisions in the 2012 ASEAN-Australia-New Zealand Free Trade Agreement and the amended 2017 Singapore-Australia Free Trade Agreement to sue the Australian government for a total of A$410 billion in three separate claims. This article uses Cox’s critical theory framework developed by Schneiderman to explain the historical development and power dynamics of ISDS, the contest between its business supporters and social movement critics, and the impact of this contest on governments. It then analyses the Palmer claims and explores the global debate about ISDS, including its increased use by fossil fuel companies against government regulation of carbon emissions, which has led to increased resistance from social movements and governments. ISDS is also being reviewed by the United Nations and World Bank institutions which provide arbitrators for its tribunals and by the Organisation for Economic Co-operation and Development. The conclusion assesses the debate over whether ISDS can be reformed and its future viability.

Herbal Technological Prospects of Morus nigra L.: A Systematic Patent Analysis Review.

Morus nigra L. is a plant with significant potential for drug development due to the presence of numerous bioactive compounds in its various parts. This article aims to compile the technological perspectives of Morus nigra L. towards drug development and therapeutic indications based on registered patents in databases. The study analyzed patents published within the last five years, focusing on products derived from different parts of the Morus nigra L. plant. Patent databases such as the European Patent Office (EPO), the United States Patent and Trademark Office (USPTO), the World Intellectual Property Organization (WIPO), and the National Institute of Industrial Property Databases (INPI) were examined. A total of 45 patents were categorized by country of origin, type of applicant, extraction method, and therapeutic indications. China had the highest number of patent filings (43.48%), and private companies were the primary technology patent holders (38.64%). Noteworthy extraction methods included ultrasound-assisted extraction, decoction, infusion, and maceration. The most utilized plant parts were leaves (44.44%), followed by fruits (35.56%), root bark (15.56%), and stems (4.44%). The main therapeutic indications identified were the treatment of hyperglycemia and dyslipidemia (43.33%), along with digestive problems, cosmetics, nutrition, and cleaning applications. The study of patents covers discoveries and advancements often absent in scientific articles, making a review focused on this advanced information crucial for expanding existing scientific knowledge. Even if some therapies have been explored previously, patents can reveal innovative approaches and fresh perspectives that contribute to sustained scientific progress.

Tobacco control research on the African continent: a 22-year literature review and network analysis

ObjectiveDescribe the landscape of tobacco-related topics, funders and institutional networks in Africa.Data sourcesWe searched PubMed, Embase and African Index Medicus for published articles from January 1996 to August 2018 in...

Establishment and Clinical Application in Stroke of a Serum Copeptin Time-Resolved Fluorescence Immunoassay.

The serum biomarker copeptin, an innovative and stable substitute biomarker of vasopressin, is associated with stroke. Therefore, establishing a highly sensitive time-resolved fluorescence immunoassay for copeptin (copeptin-TRFIA) is helpful to measure stroke and evaluate its value in clinical applications. Double antibody sandwich was used to establish copeptin-TRFIA. The established method was then assessed. Two coated and Eu3+-labeled copeptin monoclonal specific antibodies targeting different antigen epitopes were employed. The serum fluorescence counts of patients with stroke and healthy volunteers were detected by using thewell-established copeptin-TRFIA. Serum copeptin levels were measured and analyzed statistically. The actual measurement linearity range of the proposed method was 0.13-44.66 ng/mL. Copeptin-TRFIA had the inter-assay coefficient of variation (CV) of 6.49%-9.08% and the intra-assay CV of 4.75%-7.77%. Patients with cerebral infarction (CI) and intracerebral hemorrhage (ICH) had significantly higher serum copeptin levels than healthy subjects. Copeptin concentrations in the serum of patients with stroke were significantly correlated with the scores of the National Institute for Healthy Stroke Scale (NIHSS) and modified Rankin Scale (mRS). A highly sensitive copeptin-TRFIA was successfully established. Serum copeptin has a certain value in the clinical diagnosis and prognosis of stroke.

Racial and ethnic disparities in potentially inappropriate medication use in patients with dementia.

Racial and ethnic disparities in potentially inappropriate medication (PIM) use among older adults with dementia are unclear. Data were drawn from the baseline visits of participants who were ≥60 years old and diagnosed with dementia in the National Alzheimer's Coordinating Center Uniform Data Set (NACCUDS) recruited from National Institute on Aging (NIA)-funded Alzheimer's Disease Research Centers (ADCs) throughout the United States. PIM utilization was evaluated using the 2019 American Geriatrics Society Beers Criteria for PIM Use in Older Adults. We estimated the association between race and ethnicity and the following outcomes and estimation models: (1) any PIM use, any PIM in each drug class, and any PIM best avoided in dementia patients using logistic regression models, (2) total number of medications, total number of PIMs, and anticholinergic burden scale (ACBS) using Poisson or negative binomial regression models, and (3) proportion of total medications that were PIMs using generalized linear models (GLM). Compared to White participants, Black, Hispanic, and Asian participants reported taking fewer total medications (incidence rate ratio [IRR] ± standard error[SE] = 0.903 ± 0.017, 0.875 ± 0.021, and 0.912 ± 0.041, respectively, all p < 0.01). Asian participants were less likely to be exposed to any PIM (odds ratio [OR] ± SE = 0.619 ± 0.118, p < 0.05). Compared to White participants, Black participants were less likely to be exposed to benzodiazepine (OR ± SE = 0.609 ± 0.094, p < 0.01) and antidepressant (OR ± SE = 0.416 ± 0.103, p < 0.001) PIMs, but greater antipsychotic (OR ± SE = 1.496 ± 0.204, p < 0.01), cardiovascular (OR ± SE = 2.193 ± 0.255, p < 0.001), and skeletal muscle relaxant (OR ± SE = 2.977 ± 0.860, p < 0.001) PIMs. Hispanic participants were exposed to greater skeletal muscle relaxant PIMs and had lower anticholinergic burden. Asian participants were exposed to fewer benzodiazepine PIMs. Significant racial and ethnic disparities in exposure to PIMs and PIMs by medication category in dementia research participants who have access to dementia experts found in the study suggest that disparities may be wider in the larger community.

Endovascular thrombectomy first-pass reperfusion and ancillary device placement

BackgroundRecent randomized trials have demonstrated the efficacy of mechanical thrombectomy in treating acute ischemic stroke, however, further research is required to optimize this technique. We aimed to evaluate the impact...

Endovascular therapy for acute intracranial large vessel occlusion due to atherothrombosis: Multicenter historical registry

BackgroundAtherothrombotic stroke-related large vessel occlusion (AT-LVO) is caused by two etiologies, the intracranial artery occlusion due to in situ occlusion (intracranial group) or due to embolism from cervical carotid occlusion...

Racial disparities in functional outcomes following mechanical thrombectomy in a cohort of patients with ischemic stroke

BackgroundNon-Hispanic Black (NHB) patients experience increased prevalence of stroke risk factors and stroke incidence compared with non-Hispanic White (NHW) patients. However, little is known about >90-day post-stroke functional outcomes following...

Endovascular therapy in acute ischemic stroke with poor reperfusion is associated with worse outcomes compared with best medical management: a HERMES substudy

BackgroundFunctional outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion (LVO) undergoing endovascular treatment (EVT) with poor reperfusion were compared with patients with AIS-LVO treated with best...

15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN.

This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer's disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2) genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset. Data and specimens collected are derived from full clinical assessments, including neurologic and physical examinations, extensive cognitive batteries, structural and functional neuro-imaging, amyloid and tau pathological measures using positron emission tomography (PET), flurordeoxyglucose (FDG) PET, cerebrospinal fluid and blood collection (plasma, serum, and whole blood), extensive genetic and multi-omic analyses, and brain donation upon death. This comprehensive evaluation of the human nervous system is performed longitudinally in both mutation carriers and family non-carriers, providing one of the deepest and broadest evaluations of the human brain across decades and through AD progression. These extensive data sets and samples are available for researchers to address scientific questions on the human brain, aging, and AD.

STDNet: Rethinking Disentanglement Learning With Information Theory.

Disentangled representation learning is typically achieved by a generative model, variational encoder (VAE). Existing VAE-based methods try to disentangle all the attributes simultaneously in a single hidden space, while the separation of the attribute from irrelevant information varies in complexity. Thus, it should be conducted in different hidden spaces. Therefore, we propose to disentangle the disentanglement itself by assigning the disentanglement of each attribute to different layers. To achieve this, we present a stair disentanglement net (STDNet), a stair-like structure network with each step corresponding to the disentanglement of an attribute. An information separation principle is employed to peel off the irrelevant information to form a compact representation of the targeted attribute within each step. Compact representations, thus, obtained together form the final disentangled representation. To ensure the final disentangled representation is compressed as well as complete with respect to the input data, we propose a variant of the information bottleneck (IB) principle, the stair IB (SIB) principle, to optimize a tradeoff between compression and expressiveness. In particular, for the assignment to the network steps, we define an attribute complexity metric to assign the attributes by the complexity ascending rule (CAR) that dictates a sequencing of the attribute disentanglement in ascending order of complexity. Experimentally, STDNet achieves state-of-the-art results in representation learning and image generation on multiple benchmarks, including Mixed National Institute of Standards and Technology database (MNIST), dSprites, and CelebA. Furthermore, we conduct thorough ablation experiments to show how the strategies employed here contribute to the performance, including neurons block, CAR, hierarchical structure, and variational form of SIB.

Development and Assessment of a Sustainable PhD Internship Program Supporting Diverse Biomedical Career Outcomes.

A doctoral-level internship program was developed at the University of North Carolina at Chapel Hill with the intent to create customizable experiential learning opportunities for biomedical trainees to support career exploration, preparation, and transition into their post-graduate professional roles. We report the outcomes of this program over a five-year period. During that 5-year period, 123 internships took place at over 70 partner sites, representing at least 20 academic, for-profit, and non-profit career paths in the life sciences. A major goal of the program was to enhance trainees' skill development and expertise in careers of interest. The benefits of the internship program for interns, host/employer, and supervisor/principal investigator were assessed using a mixed-methods approach, including surveys with closed- and open-ended responses as well as focus group interviews. Balancing stakeholder interests is key to creating a sustainable program with widespread support; hence, the level of support from internship hosts and faculty members were key metrics analyzed throughout. We hypothesized that once a successful internship program was implemented, faculty culture might shift to be more accepting of internships; indeed, the data quantifying faculty attitudes support this. Furthermore, host motivation and performance expectations of interns were compared with results achieved, and this data revealed both expected and surprising benefits to hosts. Data suggests a myriad of benefits for each stakeholder group, and themes are cataloged and discussed. Program outcomes, evaluation data, policies, resources, and best practices developed through the implementation of this program are shared to provide resources that facilitate the creation of similar internship programs at other institutions. Program development was initially spurred by National Institutes of Health pilot funding, thereafter, successfully transitioning from a grant-supported model, to an institutionally supported funding model to achieve long-term programmatic sustainability.

Older Adults with Cancer and Common Comorbidities-Challenges and Opportunities in Improving Their Cancer Treatment Outcomes.

The older American population is rapidly increasing, and millions of older adults will be cancer survivors with comorbidities. This population faces specific challenges regarding treatment and has unique clinical needs. Recognizing this need, the National Cancer Institute (NCI), in collaboration with the National Institute on Aging (NIA), hosted a webinar series, entitled "Cancer, Aging, and Comorbidities." This commentary provides a reflection of five thematic areas covered by the webinar series, which was focused on improving cancer treatment for older adults with cancer and comorbidities: i) the impact of comorbidities on treatment tolerability and patient outcomes; ii) the impact of comorbidities on cancer clinical trial design; iii) the development of wearable devices in measuring comorbidities in cancer treatment; iv) the effects of nutrition and the microbiome on cancer therapy and; v) the role of senescence and senotherapy in age-related diseases. While advances have been made in these areas, many gaps and challenges exist and are discussed in this commentary. To improve cancer survivorship in older populations with comorbidities, aging and comorbidities must be jointly considered and incorporated across the spectrum of cancer research. This includes more basic research of the mechanisms linking comorbidities and cancer development and treatment response, building critical resources and infrastructure (eg, preclinical models and patient samples), conducting clinical trials focused on the older population, integrating geriatric assessment into cancer treatment, and incorporating novel technologies, such as wearable devices into clinical trials and cancer care.

The role of the Alzheimer's Disease Neuroimaging Initiative in establishing the Dominantly Inherited Alzheimer Network.

The Dominantly Inherited Alzheimer Network (DIAN) initially was funded by the National Institute on Aging (NIA) in 2008 and thus was able to adopt and incorporate the protocols developed by the Alzheimer's Disease Neuroimaging Initiative (ADNI) that had been established by the NIA in 2004. The use of ADNI protocols for DIAN neuroimaging studies and assays of biological fluids for Alzheimer disease (AD) biomarkers permitted examination of the hypothesis that autosomal dominant AD (ADAD), studied by DIAN, and "sporadic" late-onset AD (LOAD), studied by ADNI, shared the same pathobiological construct. In a collaborative effort, the longitudinal DIAN and ADNI databases were compared and the findings supported the conclusion that ADAD and LOAD share a similar pathophysiology. The importance of the DIAN study thus is amplified by its relevance to LOAD, as characterized by the "parent" ADNI program.

Isolamento e sensibilidade antimicrobiana de Staphylococcus sp. e Escherichia coli de peixe-boi-da-amazônia (Trichechus inunguis) em cativeiro

ABSTRACT: The Amazonian manatee (Trichechusinunguis) is an aquatic mammal threatened with extinction. However, few studies have investigated the pathogens in this species, which may affect both animal and human health. This study aimed to evaluate the frequency, distribution, and patterns of antimicrobial susceptibility of Staphylococcus spp. and Escherichiacoli colonizing the nasal and rectal cavities of Amazonian manatees kept in captivity at the National Institute for Amazonian Research (INPA) in the state of Amazonas, Brazil. Rectal and nasal swabs from 44 manatees of different ages were used in this study. The genus Staphylococcus was isolated from the nasal swabs of 32 (72.7%) animals, with two individuals harboring more than one species of Staphylococcus. S. sciuri was the most commonly isolated species. Resistance to penicillin was observed in 13 (40.6%) isolates, more frequent than the other antimicrobials tested (P = 0.01). E. coli was isolated from the rectal swabs of all animals, with phylogroup B1 being the most frequent among the strains obtained (P = 0.0008). Four isolates (6.8%) were positive for virulence factors, three of which were classified as enterotoxigenicE. coli (ETEC) and one as enteropathogenicE. coli (EPEC). To our knowledge, this is the first study to evaluate Staphylococcus spp. and E. coli in Amazonian manatee samples. This study revealed nasal colonization by Staphylococcus spp., mainly S. sciuri, and diarrheagenicE. coli isolates, including antimicrobial-resistant strains.