| 1. |
- Hay, S. I., et al.
(författare)
-
Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016 : A systematic analysis for the Global Burden of Disease Study 2016
- 2017
-
Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1260-1344
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). Methods: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE difered from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. Findings: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs ofset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the fve lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. Interpretation: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs ofset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention eforts, and development assistance for health, including fnancial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
|
|
| 2. |
- Vos, T., et al.
(författare)
-
Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
-
Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259
-
Tidskriftsartikel (refereegranskat)abstract
- Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
|
|
| 3. |
- Gakidou, E., et al.
(författare)
-
Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
-
Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1345-1422
-
Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
|
|
| 4. |
- Naghavi, M., et al.
(författare)
-
Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
-
Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1151-1210
-
Tidskriftsartikel (refereegranskat)abstract
- Background Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72.3% (95% uncertainty interval [UI] 71.2-73.2) of deaths in 2016 with 19.3% (18.5-20.4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8.43% (8.00-8.67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16-age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1.80 million deaths (95% UI 1.59 million to 1.89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2.89%); the median annualised rate of change for all other causes was lower (a decrease of 1.59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Wang, Haidong, et al.
(författare)
-
Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Woitowich, N. C., et al.
(författare)
-
Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome
- 2018
-
Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 5:Part 5, s. 619-634
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruitingbody formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.
|
|
| 16. |
- Edlund, Petra, et al.
(författare)
-
The room temperature crystal structure of a bacterial phytochrome determined by serial femtosecond crystallography
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 angstrom resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 angstrom resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
|
|
| 17. |
- Hossain, I., et al.
(författare)
-
Admission Levels of Total Tau and β-Amyloid Isoforms 1–40 and 1–42 in Predicting the Outcome of Mild Traumatic Brain Injury
- 2020
-
Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to investigate if admission levels of total tau (T-tau) and β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42) could predict clinical outcome in patients with mild traumatic brain injury (mTBI). Methods: A total of 105 patients with mTBI [Glasgow Coma Scale (GCS) ≥ 13] recruited in Turku University Hospital, Turku, Finland were included in this study. Blood samples were drawn within 24 h of admission for analysis of plasma T-tau, Aβ40, and Aβ42. Patients were divided into computed tomography (CT)-positive and CT-negative groups. The outcome was assessed 6–12 months after the injury using the Extended Glasgow Outcome Scale (GOSE). Outcomes were defined as complete (GOSE 8) or incomplete (GOSE < 8) recovery. The Rivermead Post Concussion Symptoms Questionnaire (RPCSQ) was also used to assess mTBI-related symptoms. Predictive values of the biomarkers were analyzed independently, in panels and together with clinical parameters. Results: The admission levels of plasma T-tau, Aβ40, and Aβ42 were not significantly different between patients with complete and incomplete recovery. The levels of T-tau, Aβ40, and Aβ42 could poorly predict complete recovery, with areas under the receiver operating characteristic curve 0.56, 0.52, and 0.54, respectively. For the whole cohort, there was a significant negative correlation between the levels of T-tau and ordinal GOSE score (Spearman ρ = −0.231, p = 0.018). In a multivariate logistic regression model including age, GCS, duration of posttraumatic amnesia, Injury Severity Score (ISS), time from injury to sampling, and CT findings, none of the biomarkers could predict complete recovery independently or together with the other two biomarkers. Plasma levels of T-tau, Aβ40, and Aβ42 did not significantly differ between the outcome groups either within the CT-positive or CT-negative subgroups. Levels of Aβ40 and Aβ42 did not significantly correlate with outcome, but in the CT-positive subgroup, the levels of T-tau significantly correlated with ordinal GOSE score (Spearman ρ = −0.288, p = 0.035). The levels of T-tau, Aβ40, and Aβ42 were not correlated with the RPCSQ scores. Conclusions: The early levels of T-tau are correlated with the outcome in patients with mTBI, but none of the biomarkers either alone or in any combinations could predict complete recovery in patients with mTBI. © Copyright © 2020 Hossain, Mohammadian, Takala, Tenovuo, Azurmendi Gil, Frantzén, van Gils, Hutchinson, Katila, Maanpää, Menon, Newcombe, Tallus, Hrusovsky, Wilson, Gill, Blennow, Sanchez, Zetterberg and Posti.
|
|
| 18. |
- Posti, J. P., et al.
(författare)
-
Admission Levels of Interleukin 10 and Amyloid beta 1-40 Improve the Outcome Prediction Performance of the Helsinki Computed Tomography Score in Traumatic Brain Injury
- 2020
-
Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Blood biomarkers may enhance outcome prediction performance of head computed tomography scores in traumatic brain injury (TBI). Objective: To investigate whether admission levels of eight different protein biomarkers can improve the outcome prediction performance of the Helsinki computed tomography score (HCTS) without clinical covariates in TBI. Materials and methods: Eighty-two patients with computed tomography positive TBIs were included in this study. Plasma levels of beta-amyloid isoforms 1-40 (A beta 40) and 1-42 (A beta 42), glial fibrillary acidic protein, heart fatty acid-binding protein, interleukin 10 (IL-10), neurofilament light, S100 calcium-binding protein B, and total tau were measured within 24 h from admission. The patients were divided into favorable (Glasgow Outcome Scale-Extended 5-8, n = 49) and unfavorable (Glasgow Outcome Scale-Extended 1-4, n = 33) groups. The outcome was assessed 6-12 months after injury. An optimal predictive panel was investigated with the sensitivity set at 90-100%. Results: The HCTS alone yielded a sensitivity of 97.0% (95% CI: 90.9-100) and specificity of 22.4% (95% CI: 10.2-32.7) and partial area under the curve of the receiver operating characteristic of 2.5% (95% CI: 1.1-4.7), in discriminating patients with favorable and unfavorable outcomes. The threshold to detect a patient with unfavorable outcome was an HCTS > 1. The three best individually performing biomarkers in outcome prediction were A beta 40, A beta 42, and neurofilament light. The optimal panel included IL-10, A beta 40, and the HCTS reaching a partial area under the curve of the receiver operating characteristic of 3.4% (95% CI: 1.7-6.2) with a sensitivity of 90.9% (95% CI: 81.8-100) and specificity of 59.2% (95% CI: 40.8-69.4). Conclusion: Admission plasma levels of IL-10 and A beta 40 significantly improve the prognostication ability of the HCTS after TBI.
|
|
| 19. |
- Posti, J. P., et al.
(författare)
-
Correlation of Blood Biomarkers and Biomarker Panels with Traumatic Findings on Computed Tomography after Traumatic Brain Injury
- 2019
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 36:14, s. 2178-89
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of beta-amyloid isoforms 1-40 (A beta 40) and 1-42 (A beta 42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative (n = 65) and CT-positive (n = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.
|
|
| 20. |
- Koivikko, P., et al.
(författare)
-
Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury
- 2022
-
Ingår i: Emergency Medicine Journal. - : BMJ. - 1472-0205 .- 1472-0213. ; 39, s. 206-212
-
Tidskriftsartikel (refereegranskat)abstract
- Background There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting. Methods Adult patients (>= 18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011-2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13-15 was classified as mild (mTBI); GCS 9-12 as moderate (moTBI) and GCS 3-8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed. Results Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls. Conclusions S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.
|
|
| 21. |
- Lagerstedt, L., et al.
(författare)
-
Interleukin 10 and Heart Fatty Acid-Binding Protein as Early Outcome Predictors in Patients With Traumatic Brain Injury
- 2020
-
Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Patients with traumatic brain injury (TBI) exhibit a variable and unpredictable outcome. The proteins interleukin 10 (IL-10) and heart fatty acid-binding protein (H-FABP) have shown predictive values for the presence of intracranial lesions. Aim:To evaluate the individual and combined outcome prediction ability of IL-10 and H-FABP, and to compare them to the more studied proteins S100 beta, glial fibrillary acidic protein (GFAP), and neurofilament light (NF-L), both with and without clinical predictors. Methods:Blood samples from patients with acute TBI (all severities) were collected 6 months post injury using the Glasgow Outcome Scale Extended (GOSE) score, dichotomizing patients into: (i) those with favorable (GOSE >= 5)/unfavorable outcome (GOSE <= 4) and complete (GOSE = 8)/incomplete (GOSE <= 7) recovery, and (ii) patients with mild TBI (mTBI) and patients with TBIs of all severities. Results:When sensitivity was set at 95-100%, the proteins' individual specificities remained low. H-FABP showed the best specificity (%) and sensitivity (100%) in predicting complete recovery in patients with mTBI. IL-10 had the best specificity (50%) and sensitivity (96%) in identifying patients with favorable outcome in patients with TBIs of all severities. When individual proteins were combined with clinical parameters, a model including H-FABP, NF-L, and ISS yielded a specificity of 56% and a sensitivity of 96% in predicting complete recovery in patients with mTBI. In predicting favorable outcome, a model consisting IL-10, age, and TBI severity reached a specificity of 80% and a sensitivity of 96% in patients with TBIs of all severities. Conclusion:Combining novel TBI biomarkers H-FABP and IL-10 with GFAP, NF-L and S100 beta and clinical parameters improves outcome prediction models in TBI.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Berntsson, Oskar, 1989, et al.
(författare)
-
Sequential conformational transitions and alpha-helical supercoiling regulate a sensor histidine kinase
- 2017
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Sensor histidine kinases are central to sensing in bacteria and in plants. They usually contain sensor, linker, and kinase modules and the structure of many of these components is known. However, it is unclear how the kinase module is structurally regulated. Here, we use nano- to millisecond time-resolved X-ray scattering to visualize the solution structural changes that occur when the light-sensitive model histidine kinase YF1 is activated by blue light. We find that the coiled coil linker and the attached histidine kinase domains undergo a left handed rotation within microseconds. In a much slower second step, the kinase domains rearrange internally. This structural mechanism presents a template for signal transduction in sensor histidine kinases.
|
|
| 29. |
- Cellini, Andrea, 1991, et al.
(författare)
-
The three-dimensional structure of Drosophila melanogaster (6-4) photolyase at room temperature
- 2021
-
Ingår i: Acta Crystallographica Section D-Structural Biology. - : International Union of Crystallography (IUCr). - 2059-7983. ; 77, s. 1001-1009
-
Tidskriftsartikel (refereegranskat)abstract
- (6-4) photolyases are flavoproteins that belong to the photolyase/cryptochrome family. Their function is to repair DNA lesions using visible light. Here, crystal structures of Drosophila melanogaster (6-4) photolyase [Dm(6-4)photolyase] at room and cryogenic temperatures are reported. The room-temperature structure was solved to 2.27 angstrom resolution and was obtained by serial femtosecond crystallography (SFX) using an X-ray free-electron laser. The crystallization and preparation conditions are also reported. The cryogenic structure was solved to 1.79 angstrom resolution using conventional X-ray crystallography. The structures agree with each other, indicating that the structural information obtained from crystallography at cryogenic temperature also applies at room temperature. Furthermore, UV-Vis absorption spectroscopy confirms that Dm(6-4)photolyase is photoactive in the crystals, giving a green light to time-resolved SFX studies on the protein, which can reveal the structural mechanism of the photoactivated protein in DNA repair.
|
|
| 30. |
- Claesson, Elin, 1989, et al.
(författare)
-
The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser
- 2020
-
Ingår i: eLife. - 2050-084X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.
|
|
| 31. |
- Hossain, I., et al.
(författare)
-
Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury
- 2023
-
Ingår i: BMC Neurology. - 1471-2377. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI.MethodsNinety-three patients with mTBI (GCS & GE; 13), blood sample for NF-L within 24 h of admission, and DW-MRI & GE; 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups.ResultsThe levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001-p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found.ConclusionIn patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.
|
|
| 32. |
- Möller, Per Werner, et al.
(författare)
-
Right atrial pressure and venous return during cardiopulmonary bypass
- 2017
-
Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 313:2
-
Tidskriftsartikel (refereegranskat)abstract
- The relevance of right atrial pressure (RAP) as the backpressure for venous return (QVR) and mean systemic filling pressure as upstream pressure is controversial during dynamic changes of circulation. To examine the immediate response of QVR (sum of caval vein flows) to changes in RAP and pump function, we used a closed-chest, central cannulation, heart bypass porcine preparation (n ± 10) with venoarterial extracorporeal membrane oxygenation. Mean systemic filling pressure was determined by clamping extracorporeal membrane oxygenation tubing with open or closed arteriovenous shunt at euvolemia, volume expansion (9.75 ml/kg hydroxyethyl starch), and hypovolemia (bleeding 19.5 ml/kg after volume expansion). The responses of RAP and QVR were studied using variable pump speed at constant airway pressure (PAW) and constant pump speed at variable PAW. Within each volume state, the immediate changes in QVR and RAP could be described with a single linear regression, regardless of whether RAP was altered by pump speed or PAW (r2 ± 0.586–0.984). RAP was inversely proportional to pump speed from zero to maximum flow (r2 ± 0.859– 0.999). Changing PAW caused immediate, transient, directionally opposite changes in RAP and QVR (RAP: P ≤ 0.002 and QVR: P ≤ 0.001), where the initial response was proportional to the change in QVR driving pressure. Changes in PAW generated volume shifts into and out of the right atrium, but their effect on upstream pressure was negligible. Our findings support the concept that RAP acts as backpressure to QVR and that Guyton’s model of circulatory equilibrium qualitatively predicts the dynamic response from changing RAP. NEW & NOTEWORTHY Venous return responds immediately to changes in right atrial pressure. Concomitant volume shifts within the systemic circulation due to an imbalance between cardiac output and venous return have negligible effects on mean systemic filling pressure. Guyton’s model of circulatory equilibrium can qualitatively predict the resulting changes in dynamic conditions with right atrial pressure as backpressure to venous return. © 2017 the American Physiological Society.
|
|
| 33. |
- Newcombe, Virginia F J, et al.
(författare)
-
Post-acute blood biomarkers and disease progression in traumatic brain injury.
- 2022
-
Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 145:6, s. 2064-2076
-
Tidskriftsartikel (refereegranskat)abstract
- There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein and neurofilament light have been widely explored in characterising acute traumatic brain injury, their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following traumatic brain injury. Two-hundred and three patients were recruited in two separate cohorts; six months post-injury (n=165); and >5 years post-injury (n=38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n=199) and magnetic resonance imaging (n=172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualised Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at six months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualised brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. Glial fibrillary acid protein and neurofilament light levels can remain elevated months to years after traumatic brain injury, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify traumatic brain injury survivors who are at high risk of progressive neurological damage.
|
|
| 34. |
- Liu, S. C., et al.
(författare)
-
Effects of Trendelenburg position and increased airway pressure on hepatic regional blood flow of normal and resected liver
- 2020
-
Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 128:3, s. 667-680
-
Tidskriftsartikel (refereegranskat)abstract
- High portal venous blood flow (Qpv) may contribute to posthepatectomy liver failure. Both Trendelenburg position (TP) and elevated airway pressure (Paw) increase backpressure to venous return and may thereby reduce Qpv. The aim of this study was to evaluate the effects of TP and increased Paw on hepatosplanchnic hemodynamics before and after major liver resection. Arterial and venous blood pressures, Qpv, extrasplanchnic inferior vena cava (Qivc), superior mesenteric (Qsma), hepatic (Qha), and carotid artery blood flows (Qca) were measured in 14 anesthetized and mechanically ventilated pigs in supine and 30 degrees TP during end-expiratory hold at 5 cmH(2)O positive end-expiratory pressure (PEEP) and during inspiratory hold with Paw of 15, 20, 25, and 30 cmH(2)O. After major liver resection, the interventions were repeated in seven randomly selected animals. At baseline, TP increased right atrial pressure (Pra) and Qpv but not Qivc or Qsma. With increased Paw in the supine position, Pra increased and all regional blood flows decreased. TP during increasing Paw attenuated the decrease in Qpv, Qsma, and Qivc but not in Qha or Qca. After liver resection, the effects of TP during increasing Paw remained, albeit at higher portal vein pressures. However, TP alone did not increase IVC venous return. Increasing Paw in supine position reduces Qpv and all other regional flows, while the reduction in Qpv is attenuated in TP, suggesting partly preserved liver waterfall or decreased intrahepatic resistance. Liver resection, despite resulting in major intrahepatic blood flow changes, does not fundamentally influence the interaction of increasing Paw and TP on regional perfusion. NEW & NOTEWORTHY In Trendelenburg position (TP), liver blood flow is the only contributor to increased venous return measured in the inferior vena cava (IVC), which attenuates the decreased IVC venous return induced by increasing airway pressure. After liver resection, TP similarly attenuated effects of increasing airway pressure.
|
|
| 35. |
- Möller, Per Werner, et al.
(författare)
-
Effect of volume status on the estimation of mean systemic filling pressure
- 2019
-
Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 126:6, s. 1503-1513
-
Tidskriftsartikel (refereegranskat)abstract
- Various methods for indirect assessment of mean systemic filling pressure (MSFP) produce controversial results compared with MSFP at zero blood flow. We recently reported that the difference between MSFP at zero flow measured by right atrial balloon occlusion (MSFPRAO) and MSFP estimated using inspiratory holds depends on the volume status. We now compare three indirect estimates of MSFP with MSFPRAO in euvolemia, bleeding. and hypervolemia in a model of anesthetized pigs (n = 9) with intact circulation. MSFP was estimated using instantaneous beat-to-beat venous return during tidal ventilation (MSFPinst_VR). right atrial pressure-flow data pairs at flow nadir during inspiratory holds (MSFPnadir_hold), and a dynamic model analog adapted to pigs (MSFPa). MSFPRAO was underestimated by MSFPnadir_(hold) and MSFP a in all volume states. Volume status modified the difference between MSFPRAO and all indirect methods (method X volume state interaction. P <= 0.020). All methods tracked changes in MSFPRAO concordantly, with the lowest bias seen for MSFPa [bias (confidence interval): -0.4 (-0.7 to -0.0) mmHg]. We conclude that indirect estimates of MSFP are unreliable in this experimental setup. NEW & NOTEWORTHY For indirect estimations of MSFP using inspiratory hold maneuvers, instantaneous beat-to-beat venous return. or a dynamic model analog, the accuracy was affected by the underlying volume state. All methods investigated tracked changes in MSFPRAO concordantly.
|
|
| 36. |
- Möller, Per Werner, et al.
(författare)
-
Experimental validation of a mean systemic pressure analog against zero-flow measurements in porcine VA-ECMO
- 2022
-
Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 132:3, s. 726-736
-
Tidskriftsartikel (refereegranskat)abstract
- The mean systemic pressure analog (Pmsa), calculated from running hemodynamic data, estimates mean systemic filling pressure (MSFP). This post hoc study used data from a porcine veno-arterial extracorporeal membrane oxygenation (ECMO) model [n = 9; Sus scrofa domesticus; ES breed (Schweizer Edelschwein)] with eight experimental conditions; Euvolemia [a volume state where ECMO flow produced normal mixed venous saturation (SVO2) without vascular collapse]; three levels of increasing norepinephrine infusion (Vasoconstriction 1-3); status after stopping norepinephrine (Post Vasoconstriction); and three steps of volume expansion (10 mL/kg crystalloid bolus) (Volume Expansion 1-3). In each condition, Pmsa and a "reduced-pumpspeed-Pmsa" (Pmsared) were calculated from baseline and briefly reduced pump speeds, respectively. We calculated agreement for absolute values (per condition) and changes (between consecutive conditions) of Pmsa and Pmsared, against MSFP at zero ECMO flow. Euvolemia venous return driving pressure was 5.1 +/- 2.0 mmHg. Bland-Altman analysis for Pmsa vs. MSFP (all conditions; 72 data pairs) showed bias (confidence interval) 0.5 (0.1-0.9) mmHg; limits of agreement (LoA) -2.7 to 3.8 mmHg. Bias for DPmsa vs. DMSFP (63 data pairs): 0.2 (-0.2 to 0.6) mmHg, LoA -3.2 to 3.6 mmHg. Bias for Pmsared vs. MSFP (72 data pairs): 0.0 (-0.3 to -0.3) mmHg; LoA -2.3 to 2.4 mmHg. Bias for DPmsared vs. DMSFP (63 data pairs) was 0.2 (-0.1 to 0.4) mmHg; LoA -1.8 to 2.1 mmHg. In conclusion, during veno-arterial ECMO, under clinically relevant levels of vasoconstriction and volume expansion, Pmsa accurately estimated absolute and changing values of MSFP, with low between-method precision. The within-method precision of Pmsa was excellent, with a least significant change of 0.15 mmHg. NEW & NOTEWORTHY This is the first study ever to validate the mean systemic pressure analog (Pmsa) against the reference mean systemic filling pressure (MSFP) determined at full arterio-venous pressure equilibrium. Using a porcine ECMO model with clinically relevant levels of vasoconstriction and volume expansion, we showed that Pmsa accurately estimated absolute and changing values of MSFP, with a poor between-method precision. The within-method precision of Pmsa was excellent.
|
|
| 37. |
- Oresic, Matej, 1967-, et al.
(författare)
-
Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury
- 2016
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 12, s. 118-126
-
Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n=22), moderate (moTBI; n=14) or mild TBI (mTBI; n=108) according to Glasgow Coma Scale. The control group (n=28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n=23), moTBI (n=7), mTBI (n=37) patients and controls (n=27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC=0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified 'TBI metabotype' in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new venue for the development of diagnostic and prognostic markers of broad spectrum of TBIs. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
|
|
| 38. |
- Takala, S., et al.
(författare)
-
Practice patterns in diagnostics, staging, and management strategies of gallbladder cancer among Nordic tertiary centers
- 2023
-
Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 112:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Gallbladder cancer (GBC) is a rare malignancy in the Nordic countries and no common Nordic treatment guidelines exist. This study aimed to characterize the current diagnostic and treatment strategies in the Nordic countries and disclose differences in these strategies. Methods: This was a survey study with a cross-sectional questionnaire of all 19 university hospitals providing curative-intent surgery for GBC in Sweden, Norway, Denmark, and Finland. Results: In all Nordic countries except Sweden, neoadjuvant/downstaging chemotherapy was used in GBC patients. In T1b and T2, majority of the centers (15-18/19) performed extended cholecystectomy. In T3, majority of the centers (13/19) performed cholecystectomy with resection of segments 4b and 5. In T4, majority of the centers (12-14/19) chose palliative/oncological care. The centers in Sweden extended lymphadenectomy beyond the hepatoduodenal ligament, whereas all other Nordic centers usually limited lymphadenectomy to the hepatoduodenal ligament. All Nordic centers except those in Norway used adjuvant chemotherapy routinely for GBC. There were no major differences between the Nordic centers in diagnostics and follow-up. Conclusions: The surgical and oncological treatment strategies of GBC vary considerably between the Nordic centers and countries.
|
|
| 39. |
- Nyberg, Annette, 1967, et al.
(författare)
-
Time- and dose-related regional fluxes of tissue-type plasminogen activator in anesthetized endotoxemic pigs.
- 2008
-
Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 52:1, s. 57-64
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute endotoxinemia elicits an early fibrinolytic response. This study analyzes the effects of the dose and duration of endotoxin infusion on arterial levels of tissue-type plasminogen activator (tPA) and pulmonary, mesenteric and hepatic plasma tPA fluxes. METHODS: Pigs were randomized to receive an acute, high-dose (for 6 h, n=13, high ETX) or a prolonged, low-dose (for 18 h, n=18, low ETX) infusion of endotoxin or saline vehicle alone (for 18 h, n=14, control). All animals were fluid resuscitated to maintain a normodynamic circulation. Systemic and regional blood flows were measured and arterial, pulmonary arterial, portal and hepatic venous blood samples were analyzed to calculate regional net fluxes of tPA. Plasma tumor necrosis factor (TNF-alpha) levels were analyzed. RESULTS: Mesenteric tPA release and hepatic uptake increased maximally at 1.5 h in ETX groups related to dose. Maximal mesenteric tPA release [high ETX 612 (138-1185) microg/min/kg, low ETX 72 (32-94) microg/min/kg, median+/-interquartile range] and hepatic tPA uptake [high ETX -1549 (-1134 to -2194) microg/min/kg, low ETX -153 (-105 to -307) microg/min/kg] correlated to TNF-alpha levels. Regional tPA fluxes returned to baseline levels at 6 h in both ETX groups and also remained low during sustained low ETX. No changes were observed in control animals. CONCLUSIONS: Endotoxemia induces an early increase in mesenteric tPA release and hepatic tPA uptake related to the severity of endotoxemia. The time patterns of changes in mesenteric and hepatic tPA fluxes are similar in acute high-dose endotoxemia and sustained low-dose endotoxemia.
|
|
| 40. |
- Posti, Jussi P., et al.
(författare)
-
SERUM METABOLITES ASSOCIATE WITH HEAD COMPUTED TOMOGRAPHY FINDINGS FOLLOWING TRAUMATIC BRAIN INJURY
- 2018
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 35:16, s. A67-A67
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of bio-markers to determine the need for CT and to distinguish between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). The levels of glial fibrillary acidic protein and ubiquitin C-terminalhydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein bio-markers in patients with TBI, the model that determined the need for a CT scan validated poorly (AUC=0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, thre esugar derivatives and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC=0.77 in Turku patients and AUC=0.73 in Cambridge patients). Furthermore, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC=0.87 in Turku patients and AUC=0.68 in Cambridge pa-tients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.
|
|
| 41. |
- Raj, R, et al.
(författare)
-
Dynamic prediction of mortality after traumatic brain injury using a machine learning algorithm
- 2022
-
Ingår i: NPJ digital medicine. - : Springer Science and Business Media LLC. - 2398-6352. ; 5:1, s. 96-
-
Tidskriftsartikel (refereegranskat)abstract
- Intensive care for patients with traumatic brain injury (TBI) aims to optimize intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The transformation of ICP and CPP time-series data into a dynamic prediction model could aid clinicians to make more data-driven treatment decisions. We retrained and externally validated a machine learning model to dynamically predict the risk of mortality in patients with TBI. Retraining was done in 686 patients with 62,000 h of data and validation was done in two international cohorts including 638 patients with 60,000 h of data. The area under the receiver operating characteristic curve increased with time to 0.79 and 0.73 and the precision recall curve increased with time to 0.57 and 0.64 in the Swedish and American validation cohorts, respectively. The rate of false positives decreased to ≤2.5%. The algorithm provides dynamic mortality predictions during intensive care that improved with increasing data and may have a role as a clinical decision support tool.
|
|
| 42. |
- Takala, M., et al.
(författare)
-
Dielectric Properties and Partial Discharge Endurance of Polypropylene- Silica Nanocomposite
- 2010
-
Ingår i: IEEE Transactions on Dielectrics and Electrical Insulation. - 1558-4135 .- 1070-9878. ; 17:4, s. 1259-1267
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results of the dielectric properties and partial discharge endurance measurements conducted on polypropylene (PP)-silica nanocomposite. The material compounds were analyzed with micro-Raman spectroscopy, X-ray tomography and transmission electron microscopy (TEM). ac and dc breakdown strength of the materials was measured. Dielectric response, capacitance and loss factor of the film samples were measured as a function of temperature and frequency. Partial discharge (PD) endurance of the reference PP and PP Silica nanocomposite was studied as a function of ac voltage. Material surfaces were analyzed after PD stress with optical microscopy. All dielectric measurements were done for oriented thin films with a thickness of 11-23 μm. The results were analyzed statistically to determine the effects of the additive on the properties of PP. The paper discusses the potential of PP Silica nanocomposite with a view to high voltage applications, especially power capac itors. © 2010 IEEE.
|
|
| 43. |
- Takala, M., et al.
(författare)
-
Effect of low amount of nanosilica on dielectric properties of polypropylene
- 2010
-
Ingår i: Proceedings of the 2010 IEEE International Conference on Solid Dielectrics, ICSD 2010. - 9781424479443
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper presents the results of the dielectric properties measurements conducted on Silica-Polypropylene (PP) nanocomposites. According to prior investigations by the authors silica nanoparticles have improved the performance of the dielectric material considering capacitor applications. Especially breakdown strengths with ac and dc voltages and resistance against surface degradation have increased. The relative permittivity and dielectric losses have also been comparable to reference PP. In this paper the results of the dielectric measurements conducted on composites with 1-2 wt-% silica are compared with reference PP. Silica dispersion in PP was confirmed with transmission electron microscopy (TEM). Weibull analysis was applied to the breakdown strength measurement results with dc voltage. Capacitance and loss factor measurements were conducted as a function of temperature to study thermal behavior. The measurements were conducted at the high voltage laboratories of Tampere University of Technology and Chalmers University of Technology. Statistical analysis was applied to the results to determine the significance of the differences between the materials. ©2010 IEEE.
|
|
