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| 2. |
- Abramson, Alex, et al.
(författare)
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Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors
- 2021
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 40:1, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system.
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| 3. |
- Cappellini, Enrico, et al.
(författare)
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Resolution of the type material of the Asian elephant, Elephas maximus Linnaeus, 1758 (Proboscidea, Elephantidae)
- 2014
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Ingår i: Zoological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4082 .- 1096-3642. ; 170:1, s. 222-232
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Tidskriftsartikel (refereegranskat)abstract
- The understanding of Earth's biodiversity depends critically on the accurate identification and nomenclature of species. Many species were described centuries ago, and in a surprising number of cases their nomenclature or type material remain unclear or inconsistent. A prime example is provided by Elephas maximus, one of the most iconic and well-known mammalian species, described and named by Linnaeus (1758) and today designating the Asian elephant. We used morphological, ancient DNA (aDNA), and high-throughput ancient proteomic analyses to demonstrate that a widely discussed syntype specimen of E.maximus, a complete foetus preserved in ethanol, is actually an African elephant, genus Loxodonta. We further discovered that an additional E.maximus syntype, mentioned in a description by John Ray (1693) cited by Linnaeus, has been preserved as an almost complete skeleton at the Natural History Museum of the University of Florence. Having confirmed its identity as an Asian elephant through both morphological and ancient DNA analyses, we designate this specimen as the lectotype of E.maximus. The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium with the data set identifier PXD000423.
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| 4. |
- Ishida, Marie, et al.
(författare)
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The Joint Effect of Physical Multimorbidity and Mental Health Conditions Among Adults in Australia
- 2020
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Ingår i: Preventing Chronic Disease. - 1545-1151 .- 2166-5435. ; 17:December 2020, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The prevalence of chronic physical and mental health conditions is rising globally. Little evidence exists on the joint effect of physical and mental health conditions on health care use, work productivity, and health-related quality of life in Australia. Methods We analyzed data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, waves 9 (2009), 13 (2013), and 17 (2017). Economic effects associated with multimorbidity were measured through health service use, work productivity loss, and health-related quality of life. We used generalized estimating equations to assess the effect of the association between physical multimorbidity and mental health conditions and economic outcomes. Results From 2009 through 2017 the prevalence of physical multimorbid-ity increased from 15.1% to 16.2%, and the prevalence of mental health conditions increased from 11.2% to 17.3%. The number of physical health conditions was associated with the number of health services used (general practitioner visits, incidence rate ratio = 1.41), work productivity loss (labor force participation, adjusted odds ratio = 0.71), and reduced health-related quality of life (SF-6D score: Coefficient = -0.03). These effects were exacerbated by the presence of mental health conditions and low so-cioeconomic status. Conclusion Having multiple physical health conditions (physical multimorbid-ity) creates substantial health and financial burdens on individuals, the health system, and society, including increased use of health services, loss of work productivity, and decreased health-related quality of life. The adverse effects of multimorbidity on health, quality of life, and economic well-being are exacerbated by the cooccurrence of mental health conditions and low socioeconomic status.
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| 5. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 6. |
- Lee, John Tayu, et al.
(författare)
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Functional limitation as a mediator of the relationship between multimorbidity on health-related quality of life in Australia: evidence from a national panel mediation analysis.
- 2023
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Ingår i: Frontiers in medicine. - 2296-858X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The inverse relationships between chronic disease multimorbidity and health-related quality of life (HRQoL) have been well-documented in the literature. However, the mechanism underlying this relationship remains largely unknown. This is the first study to look into the potential role of functional limitation as a mediator in the relationship between multimorbidity and HRQoL.This study utilized three recent waves of nationally representative longitudinal Household, Income, and Labor Dynamics in Australia (HILDA) surveys from 2009 to 2017 (n = 6,814). A panel mediation analysis was performed to assess the role of functional limitation as a mediator in the relationship between multimorbidity and HRQoL. The natural direct effect (NDE), indirect effect (NIE), marginal total effect (MTE), and percentage mediated were used to calculate the levels of the mediation effect.This study found that functional limitation is a significant mediator in the relationship between multimorbidity and HRQoL. In the logistic regression analysis, the negative impact of multimorbidity on HRQoL was reduced after functional limitation was included in the regression model. In the panel mediation analysis, our results suggested that functional limitation mediated ~27.2% (p < 0.05) of the link between multimorbidity and the composite SF-36 score for HRQoL. Functional limitation also mediated the relationship between the number of chronic conditions and HRQoL for each of the eight SF-36 dimensions, with a proportion mediated ranging from 18.4 to 28.8% (p < 0.05).Functional status has a significant impact on HRQoL in multimorbid patients. Treatment should concentrate on interventions that improve patients' functioning and mitigate the negative effects of multimorbidity.
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| 7. |
- Mi, Jun, et al.
(författare)
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Impact of health risk factors on healthcare resource utilization, work-related outcomes and health-related quality of life of Australians: a population-based longitudinal data analysis.
- 2023
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Ingår i: Frontiers in public health. - 2296-2565. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Health risk factors, including smoking, excessive alcohol consumption, overweight, obesity, and insufficient physical activity, are major contributors to many poor health conditions. This study aimed to assess the impact of health risk factors on healthcare resource utilization, work-related outcomes and health-related quality of life (HRQoL) in Australia.We used two waves of the nationally representative Household, Income, and Labor Dynamics in Australia (HILDA) Survey from 2013 and 2017 for the analysis. Healthcare resource utilization included outpatient visits, hospitalisations, and prescribed medication use. Work-related outcomes were assessed through employment status and sick leave. HRQoL was assessed using the SF-6D scores. Generalized estimating equation (GEE) with logit or log link function and random-effects regression models were used to analyse the longitudinal data on the relationship between health risk factors and the outcomes. The models were adjusted for age, sex, marital status, education background, employment status, equilibrium household income, residential area, country of birth, indigenous status, and socio-economic status.After adjusting for all other health risk factors covariates, physical inactivity had the greatest impact on healthcare resource utilization, work-related outcomes, and HRQoL. Physical inactivity increased the likelihood of outpatient visits (AOR = 1.60, 95% CI = 1.45, 1.76 p < 0.001), hospitalization (AOR = 1.83, 95% CI = 1.66-2.01, p < 0.001), and the probability of taking sick leave (AOR = 1.31, 95% CI = 1.21-1.41, p < 0.001), and decreased the odds of having an above population median HRQoL (AOR = 0.48, 95% CI = 0.45-0.51, p < 0.001) after adjusting for all other health risk factors and covariates. Obesity had the greatest impact on medication use (AOR = 2.02, 95% CI = 1.97-2.29, p < 0.001) after adjusting for all other health risk factors and covariates.Our study contributed to the growing body of literature on the relative impact of health risk factors for healthcare resource utilization, work-related outcomes and HRQoL. Our results suggested that public health interventions aim at improving these risk factors, particularly physical inactivity and obesity, can offer substantial benefits, not only for healthcare resource utilization but also for productivity.
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| 8. |
- Owolabi, Mayowa O., et al.
(författare)
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Primary stroke prevention worldwide : translating evidence into action
- 2022
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Ingår i: The Lancet Public Health. - 2468-2667. ; 7:1, s. 74-85
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Forskningsöversikt (refereegranskat)abstract
- Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.
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| 10. |
- Zhao, Yang, et al.
(författare)
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Out-Of-Pocket Expenditure Associated with Physical Inactivity, Excessive Weight, and Obesity in China: Quantile Regression Approach
- 2022
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Ingår i: Obesity Facts. - 1662-4025 .- 1662-4033. ; 15, s. 416-427
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Previous studies exploring associations of physical inactivity, obesity, and out-of-pocket expenditure (OOPE) mainly used traditional linear regression, and little is known about the effect of both physical inactivity and obesity on OOPE across the percentile distribution. This study aims to assess the effects of physical inactivity and obesity on OOPE in China using a quantile regression approach. Methods: Study participants included 10,687 respondents aged 45 years and older from the recent wave of the China Health and Retirement Longitudinal Study in 2015. Linear regression and quantile regression models were used to examine the association of physical activity, body weight with annual OOPE. Results: Overall, the proportion of overweight and obesity was 33.2% and 5.8%, respectively. The proportion of individuals performing high-level, moderate-level, and low-level physical activity was 55.2%, 12.7%, and 32.1%, respectively. The effects of low-level physical activity on annual OOPE were small at the bottom quantiles but more pronounced at higher quantiles. Respondents with low-level activity had an increased annual OOPE of 26.9 USD, 150.3 USD, and 1,534.4 USD, at the 10th, 50th, and 90th percentiles, respectively, compared with those with high-level activity. The effects of overweight and obesity on OOPE were also small at the bottom quantiles but more pronounced at higher quantiles. Conclusion: Interventions that improve the lifestyles and unhealthy behaviors among people with obesity and physical inactivity are likely to yield substantial financial gains for the individual and health systems in China.
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